Independently Tuned Frontier Orbital Energy Levels of 1,3,4,6,9b-Pentaazaphenalene Derivatives by the Conjugation Effect

Article abstract of DOI:10.1021/acs.joc.8b03161

Herein reported are syntheses and the unique substituent effect in 1,3,4,6,9b-pentaazaphenalene (5AP) derivatives. We developed the new synthetic route via (N,N-pyridine-2,6-diyl)bisamides, which enabled us to prepare a variety of substituted 5APs and to

Full text of DOI:10.1021/acs.joc.8b03161

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Article
Independently Tuned Frontier Orbital Energy Levels of
1,3,4,6,9b-Pentaazaphenalene Derivatives by Conjugation Effect
Hiroyuki Watanabe, Kazuo Tanaka, and Yoshiki Chujo
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b03161 • Publication Date (Web): 30 Jan 2019
Downloaded from http://pubs.acs.org on February 4, 2019
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Independently Tuned Frontier Orbital Energy Levels
of 1,3,4,6,9b-Pentaazaphenalene Derivatives by
Conjugation Effect
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Hiroyuki Watanabe, Kazuo Tanaka*, and Yoshiki Chujo
Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura,
Nishikyo-ku, Kyoto 615-8510, Japan
E-mail: tanaka@poly.synchem.kyoto-u.ac.jp
Key words: Azaphenalene; heterocycle; HOMO-LUMO gap; absorption
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ABSTRACT
Herein reported is syntheses and unique substituent effect in 1,3,4,6,9b-pentaazaphenalene
(5AP) derivatives. We developed the new synthetic route via (N,N-pyridine-2,6-diyl)bisamides,
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which enabled us to prepare a variety of substituted 5APs and to systematically investigate the
substituent effects on the electronic structures of the multi-N-heterocyclic 5APs using UV–vis
absorption spectroscopy, cyclic voltammetry and density functional theory calculations. From the
analyses, we found that the substituent effects regarding the electronic states of 5APs drastically
varied depending on the substitution position. It was revealed that the conjugation effects from
the substituents were specifically expressed either highest occupied molecular orbitals (HOMOs)
or lowest unoccupied molecular orbitals (LUMOs) by altering the substitution position at the
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AP ring. As a result, small HOMO–LUMO gap were accomplished only by elevating HOMOs
or by lowering LUMOs. Intrinsically separated HOMO and LUMO of 5AP is the origin of this
unique substituent effect. These results suggested that HOMOs and LUMOs can be
independently tuned by the conjugation effects in 5APs. This selective tunability of an either
frontier orbital is a desired character for application of organic molecules as modern
optoelectronic devices and advanced organic electronic materials.
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INTRODUCTION
Hückel’s [4n+2] rule is a basic concept in organic chemistry, which refers to the aromaticity of
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monocyclic π-conjugated systems. Extension of Hückel’s rule to polycyclic systems has been
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tried, and several theoretical models such as the perimeter models and the
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annulene-within-an-annulene (AWA) models were proposed. Although there are still much room
to be sophisticated in each model for improving applicability3–6 and removing limitations,4–6 it
should be stated that macrocyclic π-conjugated systems other than ordinary acenes show high
structure-dependency in their unique aromaticity and properties.7,8
Phenalenyl anion, cation and related isoelectronic species are a class of interesting macrocyclic
π-conjugated systems. They schematically have a 12π-electron system (“outside” electrons) in the
perimeter and the central atom (“inside” electrons, 9-C in the parent phenalenyl) interacts with
the perimeter. This situation of phenalenyls, the interaction between the “inside” and “outside”
electrons, is similar to that of the AWA model. Fowler and Jenneskens et al. called the
phenalenyl structure as “a magnetic chameleon”, referring to the interesting behavior of their
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aromaticity depending on the central atom. In terms of the magnetic properties (ring current,
nucleus-independent chemical shift (NICS), and magnetic susceptibility), phenalenyl cation and
anion show aromaticity, whereas 9b-boraphenalene and 9b-azaphenalene (isoelectronic to
phenalenyl cation and anion, respectively) show antiaromaticity. On the other hand, in terms of
energetic properties (aromatic stabilization energies (ASE)), all four species had positive ASE
values (indicated their aromaticity).
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In the course of our research on “element-blocks” (functional building blocks containing
heteroatoms),10,11 we have reported the introduction of novel π-conjugated building blocks to the
π-conjugated systems and their intriguing optical and electronic properties originating from each
element-block. Their unique performances of the element-block were also successfully reflected
in the π-conjugated systems.12,13 Therefore such an interesting behavior of phenalenyl and its
isoelectronic species motivated us to explore their properties as a building block of π-conjugated
system.
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As one of promising conjugated element-blocks, we have focused on
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,3,4,6,9b-pentaazaphenalene (Figure 1, 5AP) and its derivatives including π-conjugated
polymers.14–16 5AP has an isoelectronic structure of phenalenyl anion (PA) and substitution of
five carbon atoms to nitrogen atoms leads to the neutral and stable 5AP scaffold.17,18 PA and its
isoelectronic species including 5AP can be classified as non-benzenoid aromatic compounds
(NBAs) because they show energetic stabilization by π-conjugation which indicates its
aromaticity19,20 and their fourteen π-electrons delocalized over the triangle structure without
localization into any six-membered ring. After the first synthesis of 9b-azaphenalene by Farquhar
and Leaver,21 in the 1970s to 1980s, syntheses of azaphenalene (AP) derivatives were
achieved.18,22–24 The stability of AP derivatives were, especially in detail, theoretically
discussed17 and experimentally analyzed18,24 based on the theory of topological charge
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stabilization. On the other hand, the properties of APs as building blocks for π-conjugated
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organic materials were hardly investigated. One of the main reasons may be the limited synthetic
route toward AP derivatives.
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Figure 1. Structures of PA and azaphenalenes. The number of substituent positions is shown for
AP.
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In this research, we focused on 5AP among APs because of its high stability and functionality
to exhibit unique properties originating from the trigonally-fused 12π (peripheral [12]annulene) +
π (the central nitrogen atom) conjugated system. Although there have been a few reports on
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partial functionalization with the 5AP rings,22,23,25–29 it is still challenging to apply 5AP-based
π-conjugated systems for constructing optoelectronic materials according to preprogrammed
designs due to the limited number of chemical modification methods. We initially established a
versatile synthetic route for constructing the 5AP structure and subsequently discovered
fundamental optical and electrochemical characteristics from the series of 5APs. It was suggested
that frontier orbitals were differently affected by the conjugation effect in the case of
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,5-disubstituted 5APs (4a-e) and 7,9-disubstituted 5APs (6a-e). It means the dependency of the
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substituent effect on the position of the substituent. Theoretical calculation clarified that the
origin of the unique substituent effect was the spatially separated frontier orbitals, which
originated from the π-conjugated system of 5AP.
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RESULTS AND DISCUSSION
Firstly we tried to synthesize 5AP derivatives via the condensation of 2,6-diaminopyridine and
methyl N-cyanoimidates (1a and 1b, Scheme 1).23 Although non-substituted 5AP and
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2,5-dimethyl 5AP were synthesized in moderate yields in the literature, the method was not
suitable for our initial target molecules; 2,5-di(tert-butyl) 5AP (2a, 3% isolated yield) and
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,5-di(4-(tert-butyl)phenyl) 5AP (2b, 4% isolated yield). These results clearly indicated that
alternative synthetic route should be necessary for obtaining 2,5-disubstituted 5AP derivatives
which are expected to provide us with insight into electronically perturbed 5AP derivetives.
Shaw et al. suggested that the formation of 5AP from 2,6-diaminopyridine and
N-cyanoimidates is composed of the two steps. The intermolecular condensation of
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2,6-diaminopyridine was supposed to be the rate-determining step. Based on the assumption
that inefficient condensation could result in low reaction yields in the preliminary experiments,
we replaced the condensation step to the reaction with 2,6-diaminopyridine and acyl chlorides
(Scheme 2). The resulting amides (Scheme 2, 3a-g) were able to be transformed into the imidoyl
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chlorides. It was presumed that they can be further transformed into the plausible intermediate
by Shaw et al. (Scheme 2) after nucleophilic additions by two equivalents of cyanamide.
Addition of an excess amount of cyanamide to the imidoyl chloride smoothly afforded 5APs. It
should be noted that the plausible intermediate in our reaction was reported to be a precursor for
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vacuum pyrolysis synthesis of APs. Details of our design and plausible mechanism of this
efficient and versatile synthetic scheme of 5AP is described in Supporting Information (SI,
Section 1). As a consequence, 2a, the synthesis of which was difficult in the conventional
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scheme, was obtained in 69% isolated yield (Scheme 2). 2a was fully characterized by H and
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C{ H} NMR spectroscopy, high-resolution mass spectroscopy and single-crystal X-ray
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structure analysis (Figure 2). It is surprising since fused planar π-conjugated molecules are
prone to suffer from low solubility, meanwhile 2a was readily soluble in most of common
organic solvents even as methanol and hexane. 2b was also obtained by this reaction in 71%
isolated yield through our synthetic route.
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Figure 2 shows the crystal structure and packing of 2a determined from single-crystal X-ray
analysis. The sum of three C-N-C bond angles around the 9b (central) nitrogen atom was
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60.01°, which suggested the high planarity of 5AP scaffold. It agreed with the literatures
suggesting that the lone pair on 9b nitrogen atom contributes to the entire π-conjugated system24
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and does not have basicity . The packing was face-to-face and anti-parallel. The distance
between two faced 2a molecules was 4.03 Å (> sum of van der waals radii of two carbon atoms).
The π-π stacking of 2a might have been suppressed by steric hindrance between tert-butyl
groups on 2 and 5 positions of 5AP scaffold. The anti-parallel packing probably originated from
the polarity of 5AP core.
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Scheme 1. Synthesis of 2,5-substituted 5APs by the conventional scheme
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a)
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18.72°118.72°
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Figure 2. ORTEP (a) top, (b) side and (c,d) packing views of 2a obtained by single crystal
X-ray structure analysis. Thermal ellipsoid plot is shown at 50% probability level. All hydrogen
atoms are omitted for clarity. Details of the analysis is described in the CIF file (CCDC 1535792).
Crystallographic data is in Table S27.
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Various 2,5-substituted 5APs (Scheme 2) were prepared with the same procedure. A variety of
π-conjugated substituents having electron-withdrawing and electron-donating characters were
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introduced. As Shaw et al. and we
have reported, 7 and 9 positions of 5AP can be easily
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brominated by electrophilic aromatic substitution reaction. A wide range of substituents were
able to be introduced by subsequent Suzuki–Miyaura cross coupling reaction. 7,9-Disubstituted
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AP derivatives (Scheme 3) were also synthesized in order to be compared with 4a-e. All 4a-e
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and 6a-e were characterized by H and C{ H} NMR spectroscopy and high-resolution mass
measurements. These 5AP derivatives had good stability enough for evaluating optical and
electrochemical analyses to clarify substituent effects of NBAs on different positions and provide
general insight into electronic states of NBAs.
Scheme 2. Synthesis of 2,5-substituted 5APs from amide precursors and its plausible mechanism
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Isolated yields from corresponding amides. Refluxed for 24 h. PCl
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was used instead of PCl .
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Scheme 3. Synthesis of 7,9-substituted 5APs via Suzuki-Miyaura cross coupling reaction
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aIsolated yields from 5.
Optical properties of 5APs were investigated in chloroform solutions and the spectra of 5APs
with the same type of substituents were represented with the same colored line for clarity (Figure
3). The results of UV–vis absorption spectroscopy are summarized in Table 1. Quite different
features were obtained in the UV−vis absorption spectra of 2,5-substituted 5APs (4a-e; Figure 3a,
c) and 7,9-substituted 5APs (6a-e; Figure 3b, d). In 4a-e, red-shifted spectra were obtained when
electron-withdrawing substituents were introduced (i.e. 4a and 4b), whereas red-shifts of the
absorption bands of 6a-e were caused by electron-donating substituents (i.e. 6d and 6e). These
tendencies mean that the electronic properties of 5APs can be significantly influenced by the
position of the substituent. The weak absorption bands in the longer wavelength region were
assignable to the symmetry-forbidden HOMO–LUMO transition according to the previous
literatures.14,15,24 This assignment was also applicable in this study according to theoretical
calculations (See SI). It should be noted that the assignment is changed as the transition between
HOMO−2 and LUMO in the case of 4e although the character of the transition (the transition
from the HOMO of the 5AP moiety to the LUMO delocalized over the molecule) remained intact.
It is merely because the high HOMO energy levels of the 4-diphenylamine substituents is located
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over the intrinsic HOMO of the 5AP moiety in 4e
.
Thereby, the apparent assignment is different
from others, similarly to the 5AP-containing conjugated polymer where the LUMO of the 5AP
monomer was converted to the LUMO+2 only in the copolymer with benzothiadiazole because
1
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of intrinsically-low LUMO energy level of the benzothiadiazole unit. These spectra indicated
that the substituent of 5AP derivatives differently affected their HOMO–LUMO gaps depending
on the substituent position. Because the HOMO–LUMO transition of 5AP is symmetry-forbidden,
emission was hardly observed in this study.14,15,24
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Figure 3. UV–vis absorption spectra of (a) 2a, 4a-e and (b) 6a-e (1.0 × 10 M in chloroform).
−
4
Enlarged spectra in the visible region of (c) 2a, 4a-e and (d) 6a-e (1.0 × 10 M in chloroform).
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Table 1. Summary of optical properties
2,5-substituted series
short λa long λb
7,9-substituted series
short λa
long λ
b
Substituent Compound
Compound
λ
abs
ε
max
λ
abs
ε
max
−1
λ
abs
ε
max
−1
λ
abs
ε
max
−1 −1
−
1
−1
−1
−1
[
nm] [M cm ] [nm] [M cm ]
[nm] [M cm ] [nm] [M cm ]
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
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9
0
1
2
3
4
5
6
7
8
tBu
(4-CN)Ph
2a
4a
4b
4c
4d
4e
314 19 200
575
672
657
636
622
626
820
690
870
-
–
–
–
–
315 38 900
305 41 500
317 35 700
356 54 500
6a
6b
6c
6d
379 30 800
364 26 400
353 24 200
358 27 100
372 33 300
607 2 190
608 1 630
615 1 420
624 1 530
646 2 000
(
4-CF
Ph
4-OMe)Ph
3
)Ph
840
(
1 580
3 320
#
#
(4-NR
2
)Ph
347 26 200
6e
b
a
From absorption bands in the shorter wavelength region (λ < 400 nm). From weak absorption bands in the longer wavelength region.
#
##
R = Ph for 4e and R = Me for 6e. A strong peak at λabs = 450 nm had the large contribution from the local excitation in the
(4-diphenylamino)phenyl moiety, therefore instead we show the similar transition to other 2,5-substituted 5APs in this table. For the
details of the assignment, see Supporting Information (Section 6).
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6
Cyclic voltammetry was performed to independently evaluate the HOMO levels (EHOMO,CV
)
and the LUMO levels (ELUMO,CV) of 5APs using ferrocene/ferrocenium half-wave potential
3
3
(
–5.10 eV) as an external standard (Table S14,15 and Figure S45). It should be noted that the
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relationship between the electrochemical (onset or half-step) potential and the frontier molecular
33
energy levels has been still much debated. Here we estimated (not determine) the HOMO or
LUMO levels from the onset potential of first oxidation or reduction peaks. The estimated energy
levels are summarized as diagrams in Figure 4. Their absolute values have large uncertainties,
nevertheless it could be stated that they are useful for comparing the 5APs to evaluate the
differences originating from the substituent effects. It was shown that, substituents strongly
affected ELUMO,CV and weakly affected EHOMO,CV in 2,5-substituted 5APs (4a-e), while
completely-opposite tendency was observed from 7,9-substituted 5APs (6a-e). The optical
properties obtained from UV–vis absorption measurements can be rationalized by the
electrochemical data. Electron-withdrawing substituents in 4a-e especially lowered ELUMO,CV
,
which induced the red-shifted spectra. The substituents in 4a-e made a difference of 0.37 eV in
LUMOs, which is significantly larger than a difference of 0.26 eV in HOMOs. (Here we omitted
2
a because it does not have phenyl spacers and 4e because its HOMO was not from 5AP scaffold
but from triphenylamine units.) In contrast, electron-donating substituents in 6a-e upraised
HOMO,CV resulting in red-shifted spectra. The difference due to substituent effects were 0.57 eV
E
in HOMOs and 0.28 eV in LUMOs. It is clearly indicating that only one of the frontier molecular
orbitals should be strongly perturbed by the conjugation effect of the substituents. The substituent
effect on 5AP was completely different depending on the position.
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Figure 4. Energy levels of HOMOs and LUMOs estimated from cyclic voltammetry
measurements. The onset potentials were converted to the electron volt unit according to the
following formula: EHOMO (eV) = –5.10-Eox,onset, ELUMO (eV) = –5.10-Ered,onset.33
In our previous report on 5AP-containing π-conjugated polymers, it was found that
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π-conjugated system can be extended only through HOMO via the 7,9-positions of 5AP. It was
suggested that LUMOs of each unit were isolated even though they are incorporated and
connected in the same polymer main-chains. On the basis of this unique electronic structure, we
proposed that 5AP is the conjugated element-block creating the “isolated-LUMO” state in
conjugated polymers. The optical and electrochemical data suggest that the isolated-LUMO state
is also realized in 6a-e. To realize the “isolated-LUMO” state, it is essential to obtain the spatially
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separated HOMO and LUMO on the 5AP ring. To confirm the distributions of HOMOs and
LUMOs, the theoretical calculations were performed (Figure 5, S45 and S46). Apparently, in the
cases of 4a-e and 6a-e, distribution of the lobes of HOMO were different from those of LUMO.
In addition, when the substituents are introduced into the 2,5-positions of 5AP, the energy level
of LUMO of 5AP was strongly perturbed, whereas that of HOMO was hardly affected in terms of
the conjugation effect. Because not HOMO but LUMO exists at these positions, these changes in
the substituent effect should be induced. In the case of 7,9-substituted 5APs, the opposite effects
were observed because not LUMO but HOMO exists at positions where the substituents were
introduced. These unique extension of π-conjugated system either HOMO or LUMO of 5AP
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might be originated from the anti-aromatic nature of peripheral moiety of 5AP because the
HOMO and LUMO of 5AP have the character of the degenerated SOMOs of [12]annulene.24
a)
b)
c)
7
9
5
2
Figure 5. Frontier orbitals of (a) 2, (b) 4c and (c) 6c at B3LYP/6-31+G(d,p) level of theory.
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To obtain deep insight, quantitative evaluation by density functional theory (DFT) and
time-dependent DFT (TD-DFT) method using Gaussian 09 D.01 package34 at
B3LYP/6-31+G(d,p) level of theory was executed with experimental and theoretical data. In
Figure 6 and Tables S12 and S13, we compare the experimental data and the calculated values.
Although they do not absolutely match, the trends were reproduced so well that we are motivated
to calculate and analyze the difference originating from the electronic nature of substituents. (As
we describe the reason in the section of cyclic voltammetry, 2a and 4e were omitted for clarity.)
In the cases of EHOMOs and ELUMOs, we can compare 4a-d and 6a-e to conclude that the
substituents of 2,5-subsrtitued 5APs (4a-d) induced the experimental differences of 0.26 eV
(HOMO) and 0.37 eV (LUMO). Likewise, from theoretical data, the differences of 0.78 eV
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(HOMO) and 0.97 eV (LUMO) were proved to be induced by the substituent effects in
2
,5-subsrtitued 5APs (4a-d). Both of experimental and simulated differences indicated that the
substituent effects were stronger in LUMO than in HOMO. In contrast, the differences were
larger in HOMO about 7,9-substitued 5APs (6a-e), as follows: 0.57 eV (HOMO, experimental),
0
.28 eV (LUMO, experimental), 1.22 eV (HOMO, theoretical) and 0.86 eV (LUMO, theoretical).
These well agreements in the trends of EHOMOs and ELUMOs resulted in the reproduced trend in
HOMO–LUMO gaps and optical band gaps (Figures 6c-6f). As we described in this section, the
tendency of substituent effects in UV–vis absorption spectra and cyclic voltammetry were
qualitatively consistent with the calculation results. Other peaks than HOMO–LUMO transition
in UV–vis absorption spectra were able to be assigned based on the results of TD-DFT single
point calculations (Tables S1−S11). These agreements of the results from our experiments and
calculations strongly support validity of our discussion based on the spatially separated frontier
orbitals and resulting unique π-conjugated system of 5APs. We might have to mention about the
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energies of the localized orbital on 5AP (HOMOs of 4a-d and LUMOs of 6a-e), which differed a
little depending on the substituents. We assume that it might derive from the inductive effect of
substituent, which does not need the π-conjugation between the substituents and the 5AP
scaffold.
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Figure 6. Comparisons of (a,b) orbital energies of HOMOs and LUMOs estimated from CV
measurements (EHOMO,CV and ELUMO,CV) and calculated by the DFT method (EHOMO,DFT and
E
LUMO,DFT), (c,d) Eg,CV (ELUMO,CV − EHOMO,CV) and Eg,DFT (ELUMO,DFT − EHOMO,DFT) and (e,f) Eg,opt
(energy of the onset wavelengths in absorption spectra) and ES0−S1,DFT (the vertical excitation
energy from the ground state to the excited state 1 calculated by the TD-DFT method).;
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CONCLUSION
In this paper, new synthetic route to 5AP derivatives were developed. Consequently, electronic
states of 5APs were widely modulated by the substituents. The unique behaviors of UV–vis
absorption spectra, electrochemical measurements and theoretical calculations indicated that the
conjugation effects of substituents affected only one of the HOMO or LUMO level depending on
the substitution position. As an related example of the substituent effect in 5AP, Plattner pointed
out the substitution-position-dependent behavior of the methyl-substituted azulene derivatives.35
Moreover, several groups have implied that it was able to be attributed to the existence of either
frontier molecular orbital at the positions.36,37 Katagiri et al. stated that the extension of
π-conjugated system in terazulenes (trimer of azulene) depends on the regioregularity.38
Azulene-containing polymers have been reported to have different properties depending on the
connectivity between azulene and comonomers.39,40 It is still unclear whether such a behavior is
characteristic of NBAs because the number of extensive studies on NBAs are limited. In addition,
researches on porphyrin41,42 and pyrene43–46 systems suggested the dependency of substituent
effects on substituent positions is of importance in benzenoid π-conjugated system. In the case of
azulene derivatives, systematic investigation regarding a series of substituent positions and
electronically different substituents has not been achieved due to the limitation of the
functionalization method of the azulene scaffold. Therefore, it is no doubtful that there are much
room to examine the conjugation effect on NBAs. From this point of view, it could be stated that
this work on 5AP affords further electronic insight about NBAs. The advantage of 5AP-based
system would be the distance of the substituted positions. 1,3-positions and 2-positions
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(
functionalizations have been reported47,48) of azulene are too close to cooperatively exhibit
conjugation effects. These findings suggest that 5AP would be promising building materials
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based on novel π-conjugated systems where the HOMOs and the LUMOs are independently
affected by conjugation effect by substituents, though the inductive effect from substituents
inevitably affect the both HOMOs and LUMOs. Other types of 5APs including tri- and tetra-
substituted ones are currently investigated in our laboratory and will be reported in the near future.
They may open the way to full-tuning of the frontier orbital levels in organic materials. In the
organic electronic materials, fine-tuning of frontier orbital levels is needed for receiving high
efficiency. 5AP derivatives could be a promising building block for realizing such materials
through specific tuning of frontier orbital levels with the conjugation effect. The small molar
absorption coefficient of 5APs motivates us to apply them for carrier transport materials in
organic electronics. Researches toward the application of 5AP as carrier transport materials with
tunable HOMO / LUMO energies are now underway in our laboratory.
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Experimental section
General
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H (400 MHz) and C{ H} (100 MHz) NMR spectra were recorded on JEOL JNM-EX400 or
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1
JNM-AL400 spectrometers. H and C{ H} NMR spectra in CDCl
3
were recorded by using
tetramethylsilane (TMS) as an internal standard. H and C{ H} NMR spectra in CD Cl and
DMSO-d were recorded by using residual solvents as internal standards. High-resolution mass
spectra (HRMS) were obtained on a Thermo Fisher EXACTIVE Plus Fourier-transform
orbitrap) mass spectrometer for electron spray ionization (ESI). UV–vis absorption spectra were
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6
(
recorded on a Shimadzu UV-3600 spectrophotometer. Cyclic voltammetry (CV) was carried out
on a BAS ALS-Electrochemical-Analyzer Model 600D with a glassy carbon working electrode, a
+
Pt counter electrode, an Ag/Ag reference electrode, and the ferrocene/ferrocenium external
‒
1
reference at a scan rate of 0.1 Vs . All reactions were performed under argon atmosphere. X-ray
crystallographic analysis was carried out by Rigaku R-AXIS RAPID-F graphite-monochromated
Mo Kα radiation diffractometer with an imaging plate. The analysis was carried out with direct
4
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methods (SHELXT-2014, SHELXL-2014 ) using Yadokari-XG . Details of the structure
5
1
analysis are described in the CIF file (CCDC 1535792). The program Mercury was used to
generate the X-ray structural image with thermal ellipsoid plots.
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Materials
Reagents (pivalaldehyde, sodium tert-butoxide (tBuONa), 4-(tert-butyl)benzaldehyde,
,6-diaminopyridine, pivaloyl chloride, benzoyl chloride, 4-methoxybenzoyl chloride,
-(trifluoromethyl)benzoyl chloride, 4-cyanobenzoylchloride, 4-diphenylamino(benzaldehyde),
2
4
1
1
1
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potassium permanganate, oxalyl chloride, cyanamide, phosphorus pentachloride (PCl
N-bromosuccinimide,
2-dicyclohexylphosphino-2’,6’-dimethoxybiphenyl)[2-(2’-amino-1,1’-biphenyl)]palladium(II)
5
),
(
methanesulfonate dichloromethane adduct (SPhos Pd G3), benzeneboronic acid pinacol ester,
4-methoxybenzeneboronic acid, 4-(N,N-dimethylamino)benzeneboronic acid pinacol ester,
4
-(trifluoromethyl)benzeneboronic acid pinacol ester, 4-cyanobenzeneboronic acid pinacol ester
and cesium carbonate) and dry solvents (methanol, N,N-dimethylformamide, dichloromethane
and toluene) were purchased from commercial sources and used without further purification.
Tetrahydrofuran (THF), diethyl ether (Et
2
O) and triethylamine (NEt ) were purified using a
3
two-column solid-state purification system (Glasscontour System, Joerg Meyer, Irvine, CA).
Glyme (1,2-dimethoxyethane) was degassed by Ar bubbling prior to use. Water for the
Suzuki‒Miyaura cross coupling reactions was degassed by Ar bubbling prior to use.
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Synthetic procedures
Syntheses of 5APs via the condensation of 2,6-diaminopyridine and N-cyanomimidates.
N-Cyanomidates were synthesized according to the literature procedure.52
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•
Methyl N-cyanopivalimidate (1a)
tBuONa (22.4 g, 200 mmol) was charged in a two-neck round-bottom flask in the glovebox.
Dry MeOH (deoxidized) 300 mL was added. To this solution was added pivalaldehyde (5.52 mL,
.31 g, 50.0 mmol) and cyanamide (8.52 g, 203 mmol). After stirring for 0.5 h,
4
N-bromosuccinimide (36.5 g, 205 mmol) was added. Then the solution was warmed to 50 °C and
stirred 18 h. After the solution was cooled to room temperature, the reaction mixture was filtered
and the solvents were removed in vacuo. The residual oil was purified by column
chromatography on silica gel (eluent: hexane / EtOAc = 10:1 (v/v)) to afford the product as a
1
colorless oil (2.07 g, 14.8 mmol, 30% isolated yield). H NMR (CDCl
3
, ppm): δ 3.84 (s, 3H,
1
3
1
OMe), 1.41 (s, 9H, tBu). C{ H} NMR (CDCl
3
, ppm): δ 187.4, 112.4, 56.6, 41.5, 28.8. HRMS
+
(ESI-orbitrap) m/z: [M+Na] Calcd for C
7
H
12
N
2
ONa 163.0842; Found 163.0839.
• Methyl 4-(tert-butyl)-N-cyanobenzimidate (1b)
Following the procedure for the synthesis of methyl N-cyanopivalimidate, the product was
obtained from 4-(tert-butyl)benzaldehyde after the purification by column chromatography on
silica gel (eluent: hexane / EtOAc = 8:1 (v/v)) as a colorless oil (4.02 g, 18.6 mmol, 57% isolated
1
yield). H NMR (CDCl
3
, ppm): δ 8.04 (d, J = 8.8 Hz, 2H, Ar), 7.52 (s, J = 8.8 Hz, 2H, Ar), 4.04
1
3
1
(s, 3H, OMe), 1.34 (s, 9H, tBu). C{ H} NMR (CDCl , ppm): δ 174.8, 157.7, 128.6, 126.5,
3
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+
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25.8, 113.6, 56.6, 35.2, 31.0. HRMS (ESI-orbitrap) m/z: [M+H] Calcd for C13
H
17
2
N O
217.1335; Found 217.1334.
•
2,5-Di-tert-butyl-1,3,4,6,9b-pentaazaphenalene (2a)
A glyme (0.5 mL) solution of 2,6-diaminopyridine (0.151 g, 1.38 mmol) and methyl
N-cyanopivalimidate (0.48 g, 3.4 mmol) was stirred at 80 °C for 27 h. After it was allowed to
cool to room temperature, the reaction mixture was diluted by CHCl and washed by water three
times. The organic layer was dried over MgSO and then evaporated. After purification by
1
1
1
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column chromatography on silica gel, 2a was obtained as a red solid (12.1 mg, 0.043 mmol, 3%
isolated yield). Characterization data is shown in the following procedure of our synthetic
method.
• 2,5-Di-(4-tert-butylphenyl)-1,3,4,6,9b-pentaazaphenalene (2b)
A glyme (0.5 mL) solution of 2,6-diaminopyridine (0.412 g, 3.76 mmol) and methyl
4
-(tert-butyl)-N-cyanobenzimidate (2.06 g, 9.52 mmol) was stirred at 80 °C for 57 h. After it was
allowed to cool to room temperature, the reaction mixture was diluted by CHCl and washed by
water three times. The organic layer was dried over MgSO and then evaporated. After
purification by column chromatography on silica gel and recrystallization from CHCl / MeOH
70 °C), 3b was obtained as a purple solid (68.1 mg, 0.156 mmol, 4% isolated yield).
3
4
3
(
Characterization data is shown in the following procedure of our synthetic method.
Syntheses of amides (3a-g).
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Although some of them are reported in the literature, our modified experimental procedure
and characterization data are described.
•
N,N’-(Pyridine-2,6-diyl)bis(4-cyanobenzamide) (3a)
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An ice-cooled CH
10 mL, 7.6 g, 75 mmol) was stirred. To the solution was added a CH
-cyanobenzoyl chloride (10 g, 60 mmol) dropwise. After the addition was completed, the
reaction mixture was allowed to warm to room temperature and stirred for 22 h. Then the mixture
was poured into 200 mL H O and a colorless precipitate formed. The precipitate was washed by
MeOH. The organic layer was washed by brine, dried over MgSO . After filtration, the solvents
2
Cl
2
(50 mL) solution of 2,6-diaminopyridine (2.91 g, 26.7 mmol) and NEt
3
(
2
Cl (25 mL) solution of
2
4
2
4
were removed in vacuo. The residual solid was washed by hot EtOH (80 °C) and CH
2
Cl
2
. 3a was
, ppm):
1
obtained as a colorless solid (9.20 g, 25.1 mmol, 94% isolated yield). H NMR (DMSO-d
6
δ 10.82 (br s, 2H, NH), 8.11 (d, J = 8.5 Hz, 4H, Ph), 7.98 (d, J = 8.5 Hz, 4H, Ph), 7.87 (m, 3H,
13
1
Py). C{ H} NMR (DMSO-d
6
, ppm): δ 164.6, 150.1, 140.0, 138.1, 132.3, 128.6, 118.1, 114.1,
–
1
11.6. HRMS (ESI-orbitrap) m/z: [M–H] Calcd for C21
H
12
N
5
2
O 366.0996; Found 366.0999.
• N,N’-(Pyridine-2,6-diyl)bis(4-(trifluoromethyl)benzamide) (3b)
An ice-cooled CH
2
Cl
2
(150 mL) solution of 2,6-diaminopyridine (6.52 g, 59.7 mmol) and NEt
Cl (50 mL) solution of
-(trifluoromethyl)benzoyl chloride (24.7 g, 118 mmol) dropwise. After the addition was
3
(
17 mL, 12 g, 120 mmol) was stirred. To the solution was added a CH
2
2
4
completed, the reaction mixture was allowed to warm to room temperature and stirred for 21 h.
Precipitates formed and were collected by filtration. Hot filtration of the precipitate from EtOH
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(
80 °C) afforded 3b as colorless solid (24.2 g, 53.4 mmol, 89% isolated yield) after washing by
1
CH
2
Cl
2
and EtOH. H NMR (DMSO-d
6
, ppm): δ 10.80 (br s, 2H, NH), 8.17 (d, J = 8.2 Hz, 4H,
13
1
Ph), 7.88–7.95 (m containing d (J = 8.2 Hz), 7H, Ph and Py). C{ H} NMR (DMSO-d
6
, ppm): δ
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1
1
1
1
1
1
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64.9, 150.2, 140.7, 137.9, 131.5 (q, J = 32 Hz), 128.8, 123.0 (q, J = 272 Hz), 125.2 (br), 111.7.
–
HRMS (ESI-orbitrap) [M–H] Calcd for C21
H
12
F N
6 3
2
O 452.0839; Found 452.0837.
• N,N’-(Pyridine-2,6-diyl)dibenzamide (3c)
To an ice-cooled THF (50 mL) solution of 2,6-diaminopyridine (5.28 g, 48.4 mmol) and NEt
18 mL, 13 g, 130 mmol) was added a THF (30 mL) solution of benzoyl chloride (13 mL, 16 g,
10 mmol) dropwise. After the addition was completed, the reaction mixture was allowed to
3
(
1
warm to room temperature and stirred for 20 h. Precipitates formed and were removed by
filtration and washed by THF (5 × 10 mL). The solvents were removed from the filtrate and the
yellow solid was obtained. The residual solid was washed by hexane / EtOAc (80 °C) then EtOH
(80 °C). After filtration, 3c was obtained as a colorless solid (11.8 g, 37.1 mmol, 77% isolated
1
yield). H NMR (DMSO-d
6
, ppm): δ 10.65 (br s, 2H, NH), 8.01 (m, 4H, Ph), 7.93 (m, 1H, Py),
13
1
7.85 (m, 2H, Py), 7.61 (tt, J = 1.0 Hz, 7.3 Hz, 2H, Ph), 7.53 (t, J = 7.3 Hz, 4H, Ph). C{ H}
NMR (DMSO-d
6
, ppm): δ 165.9, 150.1, 140.3, 133.8, 132.0, 128.4, 127.8, 111.1. HRMS
+
(
ESI-orbitrap) m/z: [M+Na] Calcd for C19
H
15
N
3
O Na 340.1056; Found 340.1055.
2
•
N,N’-(Pyridine-2,6-diyl)bis(4-methoxybenzamide) (3d)
To an ice-cooled THF (150 mL) solution of 2,6-diaminopyridine (7.34 g, 67.2 mmol) and NEt
3
(23 mL, 17 g, 170 mmol) was added a THF (70 mL) solution of 4-methoxybenzoyl chloride (25.3
g, 148 mmol) dropwise. After the addition was completed, the reaction mixture was allowed to
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