Synthesisandpropertiesof5,7-Dihydropyrido[3,2-b:5,6-b′]diindoles

Article abstract of DOI:10.1002/ejoc.201403035

5,7-Dihydropyrido[3,2-b:5,6-b]diindoles were prepared by a highly efficient two-step synthesis that involved a site-selective Suzuki coupling reaction of 2,3,5,6-etrabromopyridine and a subsequent Pd-catalyzed cyclization that proceeded through a twofold C-N coupling reaction with aromatic and aliphatic amines. With the exception of the parent molecule, which was described in a patent without any characterization data, the 5,7-dihydropyrido[3,2-b:5,6-b]diindoles are a new chemical entity. Their electrochemical and photochemical properties were investigated. These pyridodiindoles show promising fluorescence properties with good quantum yields and interesting electrochemical behavior. The optical and electronical properties were analyzed and explained by using DFT calculations.

Full text of DOI:10.1002/ejoc.201403035

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FULL PAPER
DOI: 10.1002/ejoc.201403035
Synthesis and Properties of 5,7-Dihydropyrido[3,2-b:5,6-bЈ]diindoles
Tran Quang Hung,[a] Ngo Ngoc Thang,[a,b] Do Huy Hoang,[a,b] Tuan Thanh Dang,*[a]
Khurshid Ayub,[c] Alexander Villinger,[a] Stefan Lochbrunner,[d] Gerd-Uwe Flechsig,[a,e] and
Peter Langer*[a,b]
Keywords: Nitrogen heterocycles / Cross-coupling / Cyclization / Electrochemistry / UV/Vis spectroscopy / Fluorescence
spectroscopy
5,7-Dihydropyrido[3,2-b:5,6-bЈ]diindoles were prepared by a
data, the 5,7-dihydropyrido[3,2-b:5,6-bЈ]diindoles are a new
highly efficient two-step synthesis that involved a site-selec- chemical entity. Their electrochemical and photochemical
tive Suzuki coupling reaction of 2,3,5,6-tetrabromopyridine
and a subsequent Pd-catalyzed cyclization that proceeded
through a twofold C–N coupling reaction with aromatic and
aliphatic amines. With the exception of the parent molecule,
which was described in a patent without any characterization
properties were investigated. These pyridodiindoles show
promising fluorescence properties with good quantum yields
and interesting electrochemical behavior. The optical and
electronical properties were analyzed and explained by
using DFT calculations.
tached to a triphenylamine moiety, which have a longer life-
time than related derivatives with three carbazole moie-
ties.[1a] Recently, Lee et al. showed that related α- and β-
carbolines possess a higher quantum efficiency and a higher
triplet energy than isomeric γ-carbolines.[1f] The quantum
efficiency reached 22.1%.[1c]
Introduction
Carbolines (pyridoindoles) and their derivatives are used
as electronic transport units in host materials.[1] The re-
placement of a carbazole unit with a carboline moiety im-
proves electron mobility in these materials, and it is as-
sumed that the carbazole ring accelerates the electron-ac-
cepting properties because of its electron-deficient ring sys-
tem.[1a,1b,1e,2] The combination of the carbazole and carb-
oline units promotes the triplet energy, which results in high
quantum efficiency. Materials that contain a carboline moi-
ety have been studied for the development of new bipolar
host materials. In 2013, Lee et al. synthesized bi- and ter-
phenyl derivatives, which were substituted by carbazole and
carboline moieties (through the nitrogen atom). These com-
pounds show a 30% external quantum efficiency and high
triplet energy (2.90 eV) in blue phosphorescence organic
light-emitting diodes.[1b,2] Kwon et al. prepared new com-
pounds that contained three α-carbolinyl substituents at-
On the basis of their optical properties, organic materials
that contain acene and heteroacene core structures have
found many applications in organic photovoltaic cells,[3] or-
ganic light-emitting diodes (OLEDs),[4] and, especially, in
organic field-effect transitors (OFETs).[5] In this context,
pentacene and its heterocyclic derivatives have received much
attention in current research because of their excellent charge
mobility. In fact, pentacene-based OFETs show very high
charge mobilities in the range of 5–40 cm2/(V·s).[5b] How-
ever, pentacene derivatives are known to be easily oxidized
by air,[5c] which results in limitations to their practical appli-
cations. The replacement of the heteroatoms in pentacene
serves an important role in tuning the electronic properties,
solubility, stability, and molecular packing.[5] For example,
indolocarbazoles,[6] pentathienoacenes,[7] dibenzothieno-
pyrroles,[8] tetraazapentacenes,[9] N-heteropentacenes,[5] and
thiophene–benzene-annulated pentacenes[5,10] provide excel-
lent OFET applications.
Because of the importance of both N-heteropentacenes
and carbolines in the field of organic materials, we were
interested in the development of a new class of N-hetero-
pentacenes (5,7-dihydropyrido[3,2-b:5,6-bЈ]diindoles), which
combines the indole and δ-carboline core structures. Our
approach to 5,7-dihydropyrido[3,2-b:5,6-bЈ]diindoles in-
volved the Pd-catalyzed twofold C–N coupling of 3,5-di-
bromo-2,6-bis(2-bromophenyl)pyridine with 2 equiv. of the
corresponding amine. The Chida, Nozaki, and Verkade
[a] Institut für Chemie, Universität Rostock,
Albert-Einstein-Str. 3a, 18059 Rostock, Germany
E-mail: thanhtuandang@hotmail.com
peter.langer@uni-rostock.de
http://www.langer.chemie.uni-rostock.de/
[b] Leibniz Institut für Katalyse an der Universität Rostock e. V.
(LIKAT),
Albert-Einstein-Str. 29a, 18059 Rostock, Germany
[c] Department of Chemistry, COMSATS Institute of Information
Technology,
Abbottabad, Pakistan
[d] Institut für Physik, Universität Rostock,
Universitätsplatz 3, 18051 Rostock, Germany
[e] Division of Chemistry and Environmental Science, Manchester
Metropolitan University,
Chester Street, Manchester, M1 5GD, United Kingdom
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201403035.
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T. T. Dang, P. Langer et al.
FULL PAPER
groups successfully used this strategy to prepare carbazoles properties were not provided, and, therefore, the patent is
from 2,2Ј-dihalobiphenyl derivatives and amines (see Fig- of limited use to the chemical community.
ure 1).[11] Very recently, we also applied this method to the
synthesis of both 3,9Ј- and 2,9Ј-bis(carbazole)s, which are
present in many natural alkaloids and organic materials.[12a]
Wepreviouslyreportedthesynthesisofdiindolo[3,2-b:4,5-bЈ]-
Results and Discussion
2,3,5,6-Tetrabromopyridine (1) was prepared from 2,6-
diaminopyridine according to a procedure by Flowers.[14]
The Suzuki–Miyaura reaction of 2,3,5,6-tetrabromopyr-
idine with 2.2 equiv. of o-bromophenylboronic acid (2) in
the presence of 5 mol-% of Pd(PPh3)4 gave adduct 3 in 80%
isolated yield. The reaction proceeded with excellent site
selectivity. The Pd-catalyzed cyclization of 3 with amines
4a–4t by using the twofold C–N coupling reaction afforded
the desired 5,7-dihydropyrido[3,2-b:5,6-bЈ]diindoles in good
to excellent yields (see Figure 2).
thiophenes and indolo[2,3-b]quinoxalines on the basis of
the cyclization of o-bromophenylboronic acid with tetra-
bromothiophene and 2,3-dibromoquinoxaline, respec-
tively.[12b,12c] Herein, we report a new and efficient synthesis
of 5,7-dihydropyrido[3,2-b:5,6-bЈ]diindoles by what is, to
the best of our knowledge, the first site-selective Suzuki re-
action of 2,3,5,6-tetrabromopyridine with ortho-(bromo-
phenyl)boronic acid followed by a cyclization that involves
a twofold palladium-catalyzed C–N coupling reaction with
an amine. The products of this synthetic path exhibit excel-
lent fluorescence properties with good quantum yields. The
photophysical and electronic properties were studied in de-
tail experimentally and by using DFT calculations.
To optimize the reaction, we started with the annulation
reaction of adduct 3 with tert-butylaniline (4c) by using 1,4-
1
dioxane as an internal standard for the H NMR analysis
(see Table 1). The important parameters to examine in-
cluded the ligand, the precatalyst, the solvent, and the
reaction temperature. The employment of monodentate
phosphine ligands such as XPhos [2-(dicyclohexylphos-
pino)-2Ј,4Ј,6Ј-triisopropylbiphenyl], Xphos·tBu2, SPhos [2-
(dicyclohexylphosphino)-2Ј,6Ј-dimethoxybiphenyl], Dave-
Phos
[2-(dicyclohexylphosphino)-2Ј-(dimethylamino)bi-
phenyl], RuPhos [2-(dicyclohexylphosphino)-2Ј,6Ј-diiso-
propoxylbiphenyl], PCy3·HBF4 (Cy = cyclohexyl), or
P(tBu)3·HBF4 gave 5c in unsatisfactory yields (see Figure 3
and Table 1). Finally, we realized that the yields signifi-
cantly improved by using bidentate phosphine ligands such
as BINAP [2,2Ј-bis(diphenylphosphino)-1,1Ј-binaphthyl],
XantPhos [4,5-bis(diphenylphosphino)-9,9-dimethylxanth-
ene], DPEPhos, dppe [1,2-bis(diphenylphosphino)ethane],
or dppf (see Figure 3 and Table 1). Our optimization results
show that bidentate ligands with bite angles larger than 90°
gave the best yields. For example, product 5c was isolated
Figure 1. Retrosynthetic analysis of 5,7-dihydropyrido[3,2-b:5,6-bЈ]-
diindoles (OTf = trifluoromethanesulfonate).
The 5,7-dihydropyrido[3,2-b:5,6-bЈ]diindole core struc- in up to 90% yield when dppf was employed as the ligand
ture is rather new, and only the N-hydrogen-substituted par- in combination with Pd2dba3 (i.e., method A). The use of
ent molecule, 5,7-dihydropyrido[3,2-b:5,6-bЈ]diindole, has Pd(OAc)2 as the palladium source resulted in lower yields.
been reported so far. This compound was reported in a Ko- Toluene proved to be the best solvent. The success of
rean patent and was prepared by using a different and more BINAP, XantPhos, DPEPhos, dppe, and dppf can be ex-
complicated synthetic method.[13] However, the compound plained by their rigid structure and their bidentate charac-
characterization and details of the synthesis and physical ter[15] as well as by the influence of diphosphine back-bond-
Figure 2. Synthesis of 5,7-disubstituted 5,7-dihydropyrido[3,2-b:5,6-bЈ]diindoles 5a–5t. Reagents and conditions: (i) 2 (2.2 equiv.),
Pd(PPh3)4 (5 mol-%), NaOH (3 equiv.), tetrahydrofuran (THF), H2O, 70 °C, 4 h; (ii) 4 (3 equiv.), NaOtBu (6 equiv.), Pd2(dba)3 (5 mol-%;
dba = dibenzylideneacetone), ligand {method A: 10% of 1,1Ј-bis(diphenylphosphino)ferrocene (dppf); method B: 10% of bis[2-(diphenyl-
phosphino)phenyl] ether (DPEPhos)}, toluene, 100 °C, 7 h.
2
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Synthesis and Properties of 5,7-Dihydropyrido[3,2-b:5,6-bЈ]diindoles
Table 1. Optimization for the synthesis of 5c.[a]
Entry
Catalyst
Ligand
Solvent
Time [h]
Temperature [°C]
Yield [%]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd(OAc)2
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
BINAP
XantPhos
DPEPhos
dppe
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
dioxane
DMF[b]
toluene
toluene
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
7
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
110
80
73
84
52
40
90
13
35
31
37
12
45
32
34
25
0
dppf
PCy3·HBF4
P(tBu)3·HBF4
XPhos
XPhos·tBu2
SPhos
DavePhos
RuPhos
dppf
dppf
dppf
dppf
dppf
82
77
1
[a] Yield calculated by H NMR analysis of the crude product by using 1,4-dioxane as an internal standard. [b] DMF = N,N-dimethyl-
formamide.
Figure 3. Monodentate and bidentate ligands.
ing.[16] It has been previously reported that the dissociation
Table 2. Synthesis of 5a–5t.
of one P–Pd bond (arm-off mechanism)[17] leads to an
Product 5
R
Method
Yield [%]
acceleration of the reductive elimination with respect to the
β-hydride elimination.
5a
5b
5c
5d
5e
5f
5g
5h
5i
Ph
4-tBuC6H4
3,5-Me2C6H3
4-FC6H4
3-(F3C)C6H4
4-(MeO)C6H4
3,5-(MeO)2C6H3
4-(Et2N)C6H4
n-C7H15
A
A
A
A
A
A
A
A
B
B
B
B
B
B
B
B
B
B
B
B
83
84
85
66
70
93
95
69
80
86
71
84
70
60
53
52
75
56
68
55
With the optimized conditions (i.e., method A) in hand,
we explored the scope of our method. The employment of
various aniline derivatives afforded products 5a–5h in good
to excellent yields (see Table 2). In general, the yields were
higher with electron-rich anilines (more nucleophilic) than
with electron-poor ones. 4-(Diethylamino)aniline was an ex-
ception to the rule, presumably because of the interaction
of the diethylamino group with the catalyst.
However, low yields were obtained when method A was
applied to alkylamines. Therefore, further optimization for
the synthesis of derivative 5l was carried out (see Table 3).
The best yields of alkyl-substituted products were obtained
when DPEPhos was used as the ligand in combination with
Pd2(dba)3 (i.e., method B, see Table 3). Only bidentate li-
gands catalyzed these reactions, but no correlation between
their bite angle and the yields was observed.[17,18] Employ-
5j
5k
5l
n-C3H7
n-C12H25
allyl
Bn
5m
5n
5o
5p
5q
5r
5s
5t
4-(MeO)C6H4CH2
(4-FC6H4)CH2
3-(F3C)C6H4CH2
PhCH2CH2
3,4-(MeO)2C6H3CH2CH2
PhCH2CH2CH2
cyclohexyl
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Table 3. Optimization for the synthesis of 5l.[a]
Entry
Catalyst
Ligand
Solvent
Time [h]
Temperature [°C]
Yield [%]
1
2
3
4
5
6
7
8
9
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
BINAP
XantPhos
DPEPhos
dppe
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
7
7
7
7
7
7
7
7
7
7
7
7
100
100
100
100
100
100
100
100
100
100
100
100
11
17
74
58
41
0
6
4
7
8
dppf
PCy3·HBF4
P(tBu)3·HBF4
XPhos
XPhos·tBu2
10
11
12
SPhos
DavePhos
RuPhos
7
5
1
[a] Yield calculated by H NMR analysis of crude product by using 1,4-dioxane as an internal standard.
Table 4. Comparison of bond lengths and bond angles of 5j on the basis of DFT calculations and X-ray crystal structure analysis.
Bond length
Experimental [Å]
Theoretical [Å]
Bond Angle
Experimental [°]
Theoretical [°]
N-1–C-1
C-1–C-8
1.335
1.427
1.387
1.339
1.380
1.444
1.387
1.392
1.335
1.433
1.386
1.338
1.386
1.447
1.395
1.397
N-1–C-1–C-8
N-1–C-1–C-2
N-2–C-2–C-6
N-2–C-7–C-2
C-9–C-8–N-2
C-12–C-10–N-3
N-3–C-11–C-12
N-3–C-11–C-16
124.7
128.31
128.82
109.55
130.42
108.46
128.56
109.78
124.3
129.08
129.37
109.30
130.12
108.85
129.30
109.31
N-2–C-8
N-1–C-17
N-3–C-10
C-16–C-17
C-9–C-10
N-2–C-7
ment of the Pd2(dba)3 catalyst allowed for the synthesis of tal geometric parameters, which illustrates the validity of
products 5i–5t in good yields (see Table 2).
the computational method applied.
The structures of 5g and 5j were independently con-
firmed by X-ray crystal structure analyses (see Figures 4
and 5). Moreover, DFT calculations were performed to
compare the geometric parameters of the theoretical and
experimental structures. The heterocyclic core structure is
planar. Some selected calculated bond lengths and bond
angles of 5j (as an example) were compared with those of
the crystal structure (see Table 4). A maximum difference
of 0.008 Å in bond length was observed between the theo-
retical and experimental structures, whereas the difference
in bond angles reached a maximum of 0.7°. A good corre-
lation was observed between the theoretical and experimen-
Figure 5. Molecular structure of 5j.
Electrochemical Properties
The electrochemical properties of some of the δ-carbol-
ines were examined by means of a μAutolab III potentiostat
(Ecochemie, Utrecht, The Netherlands) to obtain cyclic vol-
tammetry (CV) and differential pulse voltammetry (DPV)
measurements at three different concentrations (1ϫ10–3,
3ϫ10–3, and 6ϫ10–3 molL–1) in DMF (see Figure 6).
These solutions also contained 0.01 molL–1 tetrabutyl-
ammonium hexafluorophosphate (TBAPF6) as a support-
ing electrolyte. All potentials were calibrated with the ferro-
cene/ferrocenium couple (Fc/Fc+) as the internal standard.
Oxidation and reduction energy levels were determined
from the better resolved DPV measurements (see Table 5).
Figure 4. Molecular structure of 5g.
4
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Synthesis and Properties of 5,7-Dihydropyrido[3,2-b:5,6-bЈ]diindoles
Figure 6. Cyclic voltammograms and differential pulse voltammograms of 5.
The formal potential of Fc/Fc+ versus a vacuum was as- ping background current. Therefore, the DPV method was
sumed to be –4.8 eV.
employed for the electrochemical investigations, which re-
Figure 6 depicts voltammograms of 5 with reversible and vealed the redox signals of the oxidized forms of 5 at ap-
well-defined redox peaks at around –2.2 V for the formation proximately +1.3 V. The results showed that the band gaps
and reoxidation of the reduced forms of 5. However, the were independent from the structure. It is assumed that the
corresponding redox peaks of the oxidized forms are hardly 5,7-dihydropyrido[3,2-b:5,6-bЈ]diindole core plays the key
visible in the cyclic voltammograms because of the overlap- role in the electrochemical properties. Compared to 4,4Ј-
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Table 5. Cyclic voltammetry and differential pulse voltammetry parameters and calculated energy values of 5.
[V vs. Fc/Fc+][a]
E
ox
[V vs. Fc/Fc+][b]
EHOMO [eV][c] ELUMO [eV][d] ΔEg [eV][e] ΔEgcal. [eV][f]
1/2
1/2
Compound
E
redox
5a
5b
5c
5d
5g
5i
5k
5l
5m
5n
5q
5r
–2.167
–2.171
–2.143
–2.056
–2.07
–2.268
–2.35
–2.197
–2.003
–2.256
–2.254
–2.264
–2.299
–2.191
–
1.4
–6.250
–6.207
–6.176
–6.221
–6.170
–6.063
–6.065
–6.112
–6.457
–6.112
–6.067
–6.041
–6.054
–6.104
–5.91
–2.683
–2.629
–2.657
–2.744
–2.730
–2.532
–2.450
–2.603
–2.797
–2.544
–2.546
–2.536
–2.501
–2.609
–2.51
3.567
3.578
3.519
3.477
3.440
3.531
3.615
3.509
3.660
3.568
3.521
3.505
3.553
3.495
3.40
4.107
4.096
4.057
4.112
4.117
4.103
4.102
4.124
4.132
4.123
4.107
4.07
1.407
1.376
1.421
1.37
1.263
1.265
1.312
1.657
1.312
1.267
1.241
1.254
1.304
–
5s
5t
CBP
4.105
4.105
–
1/2
1/2
[a] E
= Eredox + (Eampli/2). Eampli = 0.0501 V. Eredox values were determined by DPV in acetonitrile. [b] E = Eox + (Eampli/2). Eox
ox
redox
values were determined by DPV in acetonitrile; in V vs. Fc/Fc+ in tetrabutylammonium hexafluoroborate (TBABF6, 0.1 m). [c] The
HOMO levels were estimated from EHOMO = –(E
1/2
1/2
= +4.8) eV. [d] The LUMO levels were estimated from ELUMO = –(E
= +4.8) eV.
redox
redox
[e] Electrochemical band gaps ΔEg were estimated from ΔEg = ELUMO – EHOMO. [f] The band gaps ΔEgcal. were estimated from computa-
tional DFT calculations.
Figure 7. Isodensity plots of HOMO and LUMO orbitals of 5a, 5j, and 5m.
6
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Synthesis and Properties of 5,7-Dihydropyrido[3,2-b:5,6-bЈ]diindoles
bis(N-carbazolyl)-1,1Ј-biphenyl (CBP), which is commonly properly captured by DFT methods, which leads to overes-
used as a host material, 5 has lower HOMO and lower timated theoretical band gaps. The results in Table 5 indi-
LUMO levels and slightly larger band gaps. Phenyl-substi- cate that both theoretical and experimental band gaps are
tuted derivatives 5a and 5d have the lowest HOMO energy not much affected by structural modifications. The nitrogen
levels and band gaps. In contrast, substrates 5r and 5s, substituents of 5a–5t can mainly be categorized as aliphatic,
which are derived from aliphatic amines, have the highest benzylic, and phenyl moieties. No significant differences in
HOMO and highest LUMO level. The smallest band gap the HOMO–LUMO gaps have been observed in these com-
was observed in the case of 5d and 5e. Phenyl-substituted pounds that contain a variety of substituents, which sug-
groups located at the nitrogen position resulted in band gests that the HOMO and LUMO are not influenced by
gaps smaller than those of derivatives that contained ali- the substituents. Towards this end, we analyzed the HOMO
phatic substituents. This might be explained by some elec- and LUMO of 5a, 5j, and 5m, and the orbital diagrams are
tronic interaction between the central heterocyclic core and provided in Figure 7. As expected, the HOMO and LUMO
the phenyl substituents. However, it can be anticipated that of each compound are spread over the pyridodiindole skel-
this interaction is small because of the orthogonal twisting eton only and are not extended to the nitrogen substituents.
of the aryl groups.
The highest HOMO–LUMO band gap was calculated for
Density functional theory (DFT) calculations have also 5m (4.132 eV), which is consistent with the highest experi-
been performed to determine the values of the HOMO– mental band gap for the same compound (3.66 eV).
LUMO band gaps. A comparison of theoretical and experi-
Molecular orbitals and isodensity plots of HOMO–2 to
mental values is provided in Table 5. The calculated band LUMO+2 for N-phenylpyridodiindole 5a are shown as a
gaps are slightly higher than the experimental values, and representative example in Figure 8. The HOMO–1 and
the differences between the theoretical and experimental HOMO–2 are almost equal in energy and lie about 0.13 eV
band gaps have previously been discussed by us[19] and lower in energy relative to the HOMO. The HOMO–1 and
others.[20] The energy of the virtual orbitals (LUMO) is not HOMO–2 are mainly centered on the pyridodiindole skel-
Figure 8. Isodensity plots of HOMO–2 to LUMO+2 of 5a.
Eur. J. Org. Chem. 0000, 0–0
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T. T. Dang, P. Langer et al.
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Table 6. Absorption and emission spectroscopic data of 5.
max
max
max
max
max
max
max
Compound
λ
Logε λ
λ
Logε λ
λ
Logε λ
λ
em
Stokes shift Φfluo
1abs
1abs
2abs
2abs
3abs
3abs
[nm]
[nm]
[nm]
[nm]
[nm]
[%]
5a
5c
5d
5g
5j
5k
5l
5n
5o
5p
5t
290
291
288
290
291
291
288
289
288
288
292
4.557
4.743
4.694
4.712
4.674
4.649
4.649
4.390
4.413
4.753
4.511
310
311
310
311
311
312
310
311
310
310
312
4.569
4.764
4.684
4.700
4.648
4.629
4.633
4.335
4.381
4.716
4.496
379
380
378
379
382
382
380
381
379
380
383
4.381
4.568
4.500
4.519
4.471
4.413
4.488
4.184
4.232
4.575
4.245
402
403
402
402
407
407
404
404
402
402
407
23
23
24
23
25
25
24
23
23
22
24
42
37
39
39
33
31
35
34
44
47
34
Figure 9. Normalized absorption and emission spectra of 5 measured in acetonitrile. Emission spectra were recorded at an excitation of
360 nm.
eton. The LUMO+1 and LUMO+2 orbitals, on the other bands at approximately 400 nm. The Stokes shifts are in the
hand, have isodensities mostly located on the N-phenyl sub- range of 20 nm. The UV/Vis and fluorescence spectra show
stituents. They are situated approximately 0.36 and 0.66 eV a similar pattern, but the quantum yields vary, depending
higher in energy, respectively, than the corresponding on the type of substituent. Derivatives 5j and 5k show the
LUMO.
largest Stokes shifts but the lowest quantum yields. Com-
pounds 5o and 5p, which contain either a fluoro or tri-
fluoromethyl substituent, showed the highest quantum
yields of 44 and 47%, respectively.
Absorption and Fluorescence Properties
The optical properties were examined by UV/Vis and
fluorescence spectroscopy in acetonitrile, and the data are
sumarized in Table 6. The UV/Vis spectra of various deriva-
tives of 5 as the main chromophore are shown in Figure 9.
Conclusions
We successfully synthesized a new series of N-heteropen-
The UV/Vis spectra contain two absorption bands at ap- tacenes (5,7-dihydropyrido[3,2-b:5,6-bЈ]diindoles) by using
proximately 290–310 and 380 nm. The substituent located a Pd-catalyzed site-selective Suzuki reaction and a twofold
at the nitrogen atom did not have a strong influence. The C–N coupling annulation. During the optimization of the
spectra of compounds 5j, 5k, and 5t, which contain ali- reaction conditions, the use of bidentate ligands proved to
phatic subtituents, are slightly redshifted, presumably be- be important. The electrochemical and optical properties
caue of the positive inductive effect of the alkyl group. The of the products were studied in detail. The results of DFT
absorption bands of those compounds that contain elec- calculations and an experimental study indicate that N-
tron-withdrawing groups, such as derivative 5d, are shifted phenyl-substituted derivatives have smaller band gaps than
somewhat to shorter wavelengths.
the N-alkyl-substituted derivatives. The smallest band gaps
The fluorescence spectra were measured in acetonitrile were observed for compound 5g. The optical results exhib-
(excitation at 360 nm) by using a standard quinine hemi- ited very high quantum yields for all derivatives 5a–5t (Φfluo
sulfate salt monohydrate in 0.05 m H2SO4, which has a = 31–47%). The values of the Stokes shifts of 5a–5t are not
fluorescence yield of 52%.[21] The spectra showed emission dependent on the substituents (variation in the range of
8
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Synthesis and Properties of 5,7-Dihydropyrido[3,2-b:5,6-bЈ]diindoles
residue was partitioned between water and dichloromethane and
then extracted with dichloromethane. The organic layer was dried
with MgSO4 and filtered, and the solvent was evaporated in vacuo.
The yellow residue was purified by column chromatography (silica
gel; heptanes/ethyl acetate, 10:1) to yield 3,5-dibromo-2,6-bis(2-
bromophenyl)pyridine (3; 1.1 g, 80%) as a white solid; m.p. 174–
only 22–25 nm). In addition to this new and interesting syn-
thesis strategy, the electronic, optical, and electrochemical
properties reported herein might be used as an attractive
starting point for further applications.
1
175 °C. H NMR (300 MHz, CDCl3): δ = 8.24 (s, 1 H), 7.58 (d, J
Experimental Section
= 8.0 Hz, 2 H), 7.37–7.25 (m, 4 H), 7.20 (dd, J = 8.4, 7.3 Hz, 2 H)
ppm. 13C NMR (63 MHz, CDCl3): δ = 156.75 (s), 143.78 (s),
139.78 (s), 132.75 (s), 130.33 (s), 127.37 (s), 122.50 (s), 120.43 (s)
General Methods: Chemicals were purchased from Alfa Aesar and
Sigma Aldrich and were used without further purification. The
NMR spectroscopic data were recorded with Bruker AV 300 and
250 MHz instruments. IR spectra were recorded with a Perkin–
Elmer FTIR 1600 spectrometer [attenuated total reflectance
(ATR)]. Mass spectra were obtained with a Hewlett–Packard
HPGC–MS 5890/5972 instrument (EI, 70 eV) by using a GC inlet
or with an MX-1321 instrument (EI, 70 eV) by using a direct inlet.
Column chromatography was performed on silica gel (200 mesh,
Merck), and silica gel Merck 60 F254 plates were used for TLC.
Commercially available solvents were distilled for column
chromatography. All other solvents were purified and dried by stan-
dard methods. Crystallographic data were deposited with the
CCDC.[22]
ppm. IR (ATR): ν = 2922 (m), 2850 (m), 1562 (m), 1529 (m), 1477
˜
(m), 1470 (m), 1441 (m), 1427 (m), 1406 (s), 1348 (m), 1329 (m),
1284 (m), 1275 (w), 1265 (m), 1240 (m), 1194 (m), 1117 (m), 1041
(s), 1024 (s), 1005 (s), 984 (m), 951 (m), 889 (s), 870 (m), 850 (m),
756 (vs), 725 (s), 692 (s), 683 (s), 660 (m), 646 (m), 631 (s), 596 (m),
532 (m) cm–1. GC–MS (EI, 70 eV): m/z (%) = 547 (21), 468 (73),
227 (100), 193 (10), 113 (13), 75 (11). HRMS (EI): calcd. for
C17H9NBr4 [M]+ 542.74630, found 542.74628; calcd. for
C17H9NBr381Br [M]+ 544.74425, found 544.74445; calcd. for
C17H9NBr281Br2 [M]+ 546.74221, found 546.74277; calcd. for
C17H9NBr81Br3 [M]+ 548.74016, found 548.74086; calcd. for
C17H9N81Br4 [M]+ 550.73811, found 550.73897.
General Procedure A for Double C–N Coupling with Aniline Deriva-
tives as Exemplified by the Preparation of 5,7-Diphenyl-5,7-di-
hydropyrido[3,2-b:5,6-bЈ]diindole (5a): Aniline (0.1 mL, 1.09 mmol)
was added to a pressure tube that was charged with 3 (100 mg,
0.18 mmol), Pd2(dba)3 (8 mg, 9 μmol), dppf (10 mg, 18 μmol), and
sodium tert-butoxide (105 mg, 1.09 mmol) under argon. The tube
was backfilled with argon several times. The mixture was dissolved
in anhydrous toluene (10 mL) and then heated at 100 °C for 7 h.
After cooling, the reaction mixture was diluted with dichlorometh-
ane (20 mL), and the resulting mixture was filtered through a pad
of Celite, which was washed with dichloromethane (40 mL). The
filtrate was concentrated in vacuo. The crude product was purified
by flash chromatography (silica gel; heptanes/dichloromethane/
ethyl acetate, 10:1:1) to yield 5a (62 mg, 83%) as a white solid; m.p.
General Procedure for the Preparation of 2,3,5,6-Tetrabromopyridine
(1): To a solution of pyridine-2,6-diamine (10.9 g, 100 mmol) in
glacial acetic acid (200 mL) was added dropwise bromine (11.4 mL,
220 mmol) at 0 °C. The temperature was then increased to room
temperature, and the mixture was stirred for 5 h. The reaction mix-
ture was treated with aqueous Na2SO3 solution to remove the resid-
ual bromine. The solvent was removed in vacuo. Water was added
to the mixture, which was neutralized by the addition of NaOH to
pH = 8–9. Upon filtration, a brown solid (22 g, 83%) was obtained,
which was washed with water and dried in vacuo. To a solution of
the 3,5-dibromopyridine-2,6-diamine (10 g, 37.5 mmol) in 48%
HBr (30 mL) was added dropwise a saturated aqueous solution of
NaNO2 (20.7 g, 300 mmol) at –3 °C. The resulting mixture was
stirred at the same temperature for 2 h, and the temperature was
then increased to room temperature and maintained at that tem-
perature for an additional 2 h. The pH of the solution was adjusted
to 8–9 by the addition of NaOH, and the resulting mixture was
extracted with ethyl acetate. The organic layer was collected, dried
with MgSO4, filtered, and concentrated in vacuo. The mixture was
separated by column chromatography (silica gel; heptanes/dichloro-
methane, 5:1) to yield 2,3,5,6-tetrabromopyridine (1; 3 g, 20%) as
1
298–300 °C. H NMR (300 MHz, CDCl3): δ = 8.69 (d, J = 7.2 Hz,
2 H), 7.58 (dt, J = 8.9, 4.3 Hz, 9 H), 7.50–7.38 (m, 8 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 142.35, 137.85, 137.31, 134.32,
130.26, 129.08, 127.86, 127.15, 127.09, 126.71, 122.55, 121.08,
120.78, 109.80, 96.93 ppm. IR (ATR): ν = 3036 (m), 2926 (w), 2852
˜
(w), 1591 (s), 1497 (s), 1479 (m), 1454 (s), 1435 (m), 1404 (s), 1387
(s), 1313 (m), 1242 (s), 1205 (m), 1188 (s), 1178 (s), 1155 (m), 1144
(m), 1103 (m), 1074 (m), 1039 (m), 1028 (m), 1011 (m), 939 (m),
924 (m), 847 (m), 829 (m), 760 (m), 739 (s), 729 (s), 692 (vs), 667
(m), 638 (s), 623 (m), 615 (s), 582 (s), 567 (m), 536 (s) cm–1. GC–
MS (EI, 70 eV): m/z (%) = 409 (100), 332 (8), 204 (14). HRMS
(ESI): calcd. for C29H20N3 [M + H]+ 410.16517, found 41016512;
calcd. for C29H20N3Na [M + Na]+ 432.14712, found 432.14744.
1
white crystals; m.p. 172–174 °C. H NMR (300 MHz, CDCl3): δ =
7.99 (s, 1 H) ppm. 13C NMR (63 MHz, CDCl3): δ = 145.32 (s),
140.60 (s), 123.01 (s) ppm. IR (ATR): ν = 3084 (m), 3036 (m), 1529
˜
(m), 1502 (s), 1362 (vs), 1352 (vs), 1288 (s), 1277 (s), 1238 (m), 1213
(m), 1149 (vs), 1136 (s), 1016 (vs), 945 (m), 931 (m), 897 (vs), 833
(m), 806 (m), 798 (m), 781 (m), 704 (s), 656 (s), 648 (s) cm–1. GC–
MS (EI, 70 eV): m/z (%) = 395 (100), 314 (42), 235 (26), 154 (13),
75 (42). HRMS (EI): calcd. for C5HNBr381Br [M]+ 392.6815, found
392.68185; calcd. for C5HNBr281Br2 [M]+ 394.67961, found
394.67983; calcd. for C5HNBr81Br3 [M]+ 396.67756, found
396.67761.
5,7-Bis[4-(tert-butyl)phenyl]-5,7-dihydropyrido[3,2-b:5,6-bЈ]diindole
(5b): Following general procedure A and using compound 3
(100 mg, 0.18 mmol) and 4-(tert-butyl)aniline (118 mg, 1.09 mmol)
gave a crude product, which was purified by flash chromatography
(silica gel; heptanes/dichloromethane/ethyl acetate, 8:1:1) to yield
General Procedure for the Preparation of 3,5-Dibromo-2,6-bis(2- 5b (80 mg, 84 %) as a white solid; m.p. 317–319 °C. 1H NMR
bromophenyl)pyridine (3): 2,3,5,6-tetrabromopyridine (1; 1 g,
2.5 mmol), 2-bromophenylboronic acid (2; 1.1 g, 5.5 mmol),
Pd(PPh3)4 (73 mg, 63 μmol), and sodium hydroxide (608 mg,
15.2 mmol) were added to a Schlenk flask (500 mL), which was
(300 MHz, CDCl3): δ = 8.64 (d, J = 7.5 Hz, 2 H), 7.68–7.59 (m, 5
H), 7.56–7.35 (m, 10 H), 1.42 (s, 18 H) ppm. 13C NMR (63 MHz,
CDCl3): δ = 150.65, 142.37, 138.00, 134.61, 134.27, 126.96, 126.72,
126.46, 122.68, 120.65, 120.37, 109.76, 96.77, 34.80, 31.39 ppm. IR
backfilled several times with argon. To the mixture were added (ATR): ν = 2958 (m), 2902 (w), 2866 (w), 1591 (m), 1518 (m), 1479
˜
THF (70 mL) and distilled water (10 mL), and the flask was then
backfilled several times with argon. The reaction mixture was 1309 (m), 1290 (w), 1261 (m), 1242 (s), 1207 (m), 1188 (m), 1169
heated at 70 °C for 4 h. The solvent was evaporated in vacuo. The (m), 1153 (m), 1147 (m), 1105 (m), 1036 (m), 1011 (m), 951 (w),
(w), 1456 (s), 1408 (m), 1392 (m), 1363 (m), 1350 (w), 1325 (w),
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T. T. Dang, P. Langer et al.
FULL PAPER
937 (w), 928 (w), 893 (w), 850 (m), 841 (m), 822 (m), 800 (m), 785 5,7-Bis(4-methoxyphenyl)-5,7-dihydropyrido[3,2-b:5,6-bЈ]diindole
(m), 741 (vs), 729 (vs), 706 (m), 660 (m), 640 (m), 625 (m), 592 (w), (5f): Following general procedure A and using compound 3
561 (s) cm–1. GC–MS (EI, 70 eV): m/z (%) = 521 (100), 491 (9), (100 mg, 0.18 mmol) and p-anisidine (135 mg, 1.09 mmol) gave a
253 (15), 217 (93), 172 (21). HRMS (EI): calcd. for C37H35N3
crude product, which was purified by flash chromatography (silica
gel; heptanes/dichloromethane/ethyl acetate, 5:1:1) to yield 5f
(80 mg, 93 %) as a white solid; m.p. 300–302 °C. 1H NMR
(300 MHz, CDCl3): δ = 8.67–8.58 (m, 1 H), 7.49–7.30 (m, 6 H),
7.14–7.04 (m, 2 H), 3.90 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 159.19, 142.89, 138.11, 134.99, 130.05, 128.70, 126.91, 122.84,
[M]+ 521.28255, found 521.28186.
5,7-Bis(3,5-dimethylphenyl)-5,7-dihydropyrido[3,2-b:5,6-bЈ]diindole
(5c): Following general procedure A and using compound 3
(100 mg, 0.18 mmol) and 3,5-dimethylaniline (175 μL, 1.09 mmol)
gave a crude product, which was purified by flash chromatography
(silica gel; heptanes/dichloromethane/ethyl acetate, 8:1:1) to yield
5c (72 mg, 85 %) as a white solid; m.p. 306–308 °C. 1H NMR
(300 MHz, CDCl3): δ = 8.53 (d, J = 7.6 Hz, 4 H), 7.48 (s, 2 H),
7.41–7.26 (m, 13 H), 7.11 (s, 8 H), 7.00 (s, 4 H), 2.32 (s, 25 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 142.23, 139.85, 138.03, 137.20,
134.29, 129.32, 126.73, 124.49, 122.76, 120.70, 120.38, 109.80,
120.81, 120.47, 115.51, 109.78, 96.35, 55.80 ppm. IR (ATR): ν =
˜
3047 (m), 2951 (m), 2924 (m), 2835 (m), 1614 (w), 1589 (m), 1510
(s), 1477 (m), 1456 (s), 1441 (s), 1408 (s), 1392 (m), 1315 (m), 1298
(m), 1279 (m), 1242 (vs), 1211 (m), 1190 (s), 1180 (s), 1144 (s), 1113
(m), 1103 (s), 1032 (s), 1007 (m), 953 (m), 928 (m), 887 (m), 835
(s), 825 (s), 810 (m), 793 (m), 742 (vs), 733 (s), 727 (s), 671 (m),
660 (m), 642 (m), 619 (m), 584 (s), 575 (s), 542 (s) cm–1. GC–MS
(EI, 70 eV): m/z (%) = 469 (100), 291 (27), 43 (57). HRMS (EI):
calcd. for C31H23O2N3 [M]+ 469.17848, found 469.17813.
96.90, 21.37 ppm. IR (ATR): ν = 3045 (w), 2914 (m), 2854 (w),
˜
1589 (s), 1470 (s), 1456 (s), 1435 (m), 1417 (m), 1404 (s), 1387 (m),
1373 (m), 1311 (m), 1298 (m), 1242 (s), 1190 (s), 1153 (m), 1138
(m), 1105 (m), 1011 (m), 916 (m), 864 (m), 843 (s), 785 (m), 741 5,7-Bis(3,5-dimethoxyphenyl)-5,7-dihydropyrido[3,2-b:5,6-bЈ]diindole
(vs), 725 (vs), 708 (s), 698 (s), 631 (m), 588 (m), 575 (m), 557 (m) (5g):[22] Following general procedure A and using compound 3
cm–1. GC–MS (EI, 70 eV): m/z (%) = 465 (100), 233 (12), 79 (7). (100 mg, 0.18 mmol) and 3,5-dimethoxyaniline (168 mg,
HRMS (EI): calcd. for C33H27N3 [M]+ 465.21995, found
465.21908.
1.09 mmol) gave a crude product, which was purified by flash
chromatography (silica gel; heptanes/dichloromethane/ethyl acet-
ate, 4:1:1) to yield 5f (92 mg, 95%) as a white solid; m.p. 230–
231 °C. 1H NMR (300 MHz, CDCl3): δ = 8.66 (d, J = 6.6 Hz, 2
H), 7.74 (s, 1 H), 7.46 (dd, J = 26.3, 6.9 Hz, 6 H), 6.75 (d, J =
1.9 Hz, 4 H), 6.57 (s, 2 H), 3.84 (s, 12 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 161.94, 142.13, 134.11, 127.38, 121.43, 120.89, 110.03,
5,7-Bis(4-fluorophenyl)-5,7-dihydropyrido[3,2-b:5,6-bЈ]diindole (5d):
Following general procedure A and using compound 3 (100 mg,
0.18 mmol) and 4-fluoroaniline (104 μL, 1.09 mmol) gave a crude
product, which was purified by flash chromatography (silica gel;
heptanes/dichloromethane/ethyl acetate, 8:1:1) to yield 5d (54 mg,
66 %) as a white solid; m.p. 338–340 °C. 1H NMR (300 MHz,
CDCl3): δ = 8.53 (d, J = 7.3 Hz, 2 H), 7.48–7.28 (m, 9 H), 7.27–
7.17 (m, 6 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 162.03 (d, J
= 248.1 Hz), 142.62, 138.39, 134.62, 133.36 (d, J = 3.1 Hz), 129.20
(d, J = 8.6 Hz), 127.24, 122.94, 121.00, 120.96, 117.44 (d, J =
105.08, 100.05, 55.67 ppm. IR (ATR): ν = 3066 (w), 2999 (w), 2935
˜
(w), 2841 (w), 1740 (w), 1595 (vs), 1477 (s), 1462 (s), 1446 (m),
1423 (m), 1404 (m), 1346 (m), 1311 (m), 1300 (m), 1292 (s), 1234
(s), 1201 (vs), 1190 (s), 1151 (vs), 1142 (s), 1065 (s), 1055 (m), 827
(s), 741 (s), 733 (s), 708 (m), 690 (s), 579 (w) cm–1. GC–MS (EI,
70 eV): m/z (%) = 529 (100), 471 (10), 207 (6). HRMS (EI): calcd.
for C33H27O4N3 [M]+ 529.19961, found 529.19898.
22.8 Hz), 109.69, 96.18 ppm. IR (ATR): ν = 3053 (w), 2918 (w),
˜
2848 (w), 1591 (m), 1506 (vs), 1481 (m), 1456 (s), 1406 (s), 1390
(m), 1311 (s), 1244 (s), 1221 (s), 1192 (s), 1173 (s), 1155 (s), 1113 5,7-Bis[4-(diethylamino)phenyl]-5,7-dihydropyrido[3,2-b:5,6-bЈ]di-
(m), 1101 (s), 1041 (m), 1011 (m), 935 (m), 889 (m), 835 (s), 812 indole (5h): Following general procedure A and using compound 3
(s), 800 (m), 744 (vs), 723 (vs), 700 (m), 671 (m), 661 (m), 640 (m), (100 mg, 0.18 mmol) and N1,N1-diethylbenzene-1,4-diamine
619 (m), 573 (s), 565 (s), 536 (s) cm–1. GC–MS (EI, 70 eV): m/z (%) (182 μL, 1.09 mmol) gave a crude product, which was purified by
= 445 (100), 222 (10), 95 (8). HRMS (EI): calcd. for C29H17N3F2 flash chromatography (silica gel; heptane/dichloromethane/ethyl
[M]+ 445.13851, found 445.13827.
acetate, 5:1:1) to yield 5h (70 mg, 69%) as a brown solid; m.p. 290–
291 °C. H NMR (300 MHz, CDCl3): δ = 8.58–8.49 (m, 2 H), 7.29
1
5,7-Bis[3-(trifluoromethyl)phenyl]-5,7-dihydropyrido[3,2-b:5,6-bЈ]di-
indole (5e): Following general procedure A and using compound 3
(100 mg, 0.18 mmol) and 3-(trifluoromethyl)aniline (137 μL,
1.09 mmol) gave a crude product, which was purified by flash
chromatography (silica gel; heptanes/dichloromethane/ethyl acet-
ate, 8:1:1) to yield 5e (70 mg, 70%) as a white solid; m.p. 268–
269 °C. 1H NMR (300 MHz, CDCl3): δ = 8.49 (d, J = 7.7 Hz, 2
H), 7.81 (s, 2 H), 7.67 (ddd, J = 13.0, 4.7, 1.7 Hz, 6 H), 7.47–7.26
(m, 7 H) ppm. 19F NMR (282 MHz, CDCl3): δ = –62.78 ppm. 13C
NMR (63 MHz, CDCl3): δ = 141.71, 138.69, 137.91, 133.61, 132.80
(q, J = 33.2 Hz), 130.85, 129.97, 127.30, 124.35 (q, J = 3.6 Hz),
123.65 (q, J = 3.9 Hz), 123.53 (q, J = 272.7 Hz), 123.01, 121.25,
(dddd, J = 6.7, 6.2, 5.2, 4.4 Hz, 12 H), 6.72 (d, J = 9.0 Hz, 4 H),
3.35 (q, J = 7.0 Hz, 8 H), 1.15 (t, J = 7.1 Hz, 12 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 147.30, 143.08, 137.58, 135.22, 128.41,
126.38, 124.72, 122.48, 120.44, 119.79, 112.29, 109.75, 96.57, 44.50,
12.67 ppm. IR (ATR): ν = 3043 (w), 2968 (m), 2929 (m), 2897 (w),
˜
2864 (w), 1732 (w), 1606 (m), 1591 (m), 1520 (vs), 1477 (m), 1460
(s), 1448 (m), 1394 (m), 1373 (m), 1354 (s), 1323 (m), 1309 (s), 1269
(s), 1240 (s), 1192 (s), 1149 (s), 1140 (s), 1119 (m), 1109 (m), 1097
(m), 1074 (m), 1047 (m), 1032 (m), 1007 (m), 930 (m), 922 (m), 885
(m), 841 (m), 823 (m), 812 (s), 793 (m), 785 (m), 750 (vs), 742 (s),
731 (vs), 725 (s), 696 (m), 656 (m), 640 (m), 621 (m), 561 (s), 536
(s) cm–1. GC–MS (EI, 70 eV): m/z (%) = 551 (100), 507 (15), 463
(13), 268 (7), 69 (20), 44 (59). HRMS (ESI): calcd. for C37H37N5
[M + H]+ 552.31217, found 552.31208; calcd. for C37H37N5Na [M
+ Na]+ 574.29412, found 574.2944.
120.92, 109.38, 96.01 ppm. IR (ATR): ν = 3061 (w), 2928 (w), 2854
˜
(w), 1591 (m), 1495 (m), 1485 (m), 1460 (s), 1404 (s), 1387 (m),
1354 (m), 1344 (m), 1323 (s), 1309 (s), 1279 (m), 1271 (m), 1244
(s), 1182 (s), 1173 (s), 1155 (s), 1115 (vs), 1097 (s), 1070 (s), 1041
(m), 1012 (m), 1003 (m), 962 (m), 931 (w), 918 (m), 904 (m), 854
(m), 849 (m), 800 (s), 746 (s), 727 (s), 708 (vs), 700 (vs), 669 (m),
General Procedure B for Double C–N Coupling with Chain Amine
Derivatives as Exemplified by the Preparation of 5,7-Diheptyl-5,7-
661 (s), 646 (m), 609 (w), 582 (m), 538 (m) cm–1. GC–MS (EI, dihydropyrido[3,2-b:5,6-bЈ]diindole (5i): A pressure tube was
70 eV): m/z (%) = 545 (100), 273 (22). HRMS (EI): calcd. for charged with 3 (100 mg, 0.18 mmol), Pd2(dba)3 (8 mg, 9 μmol),
C31H17N3 [M]+ 545.13212, found 545.13199.
DPEPhos (10 mg, 18 μmol), and sodium tert-butoxide (105 mg,
10
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Job/Unit: O43035
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Date: 20-12-14 13:01:46
Pages: 14
Synthesis and Properties of 5,7-Dihydropyrido[3,2-b:5,6-bЈ]diindoles
1.09 mmol) under argon. The tube was backfilled with argon sev-
eral times and then dissolved in anhydrous toluene (10 mL). n-
Heptylamine (0.2 mL, 1.09 mmol) was added, and the resulting
mixture was heated at 100 °C for 7 h. After cooling, the reaction
purified by flash chromatography (silica gel; heptanes/dichloro-
methane/ethyl acetate, 5:1:1) to yield 5l (52 mg, 84%) as a white
1
solid; m.p. 156–158 °C. H NMR (300 MHz, CDCl3): δ = 8.49 (d,
J = 7.2 Hz, 2 H), 7.44 (m, 2 H), 7.28 (m, 6 H), 6.02–5.86 (m, 2 H),
mixture was diluted with dichloromethane (20 mL), and filtered 5.04 (dd, J = 18.2, 13.7 Hz, 4 H), 4.88–4.75 (m, 4 H) ppm. 13C
through a pad of Celite, which was washed with dichloromethane
(40 mL). The filtrate was reduced in vacuo. The crude product was
purified by flash chromatography (silica gel; heptanes/dichloro-
NMR (63 MHz, CDCl3): δ = 141.45, 133.62, 131.87, 126.46,
120.63, 119.65, 117.03, 108.59, 94.67, 45.31 ppm. IR (ATR): ν =
˜
3057 (w), 2999 (w), 1616 (w), 1597 (m), 1514 (w), 1464 (s), 1435
methane/ethyl acetate, 5:1:1) to yield 5i (66 mg, 80%) as a white (m), 1408 (m), 1385 (m), 1358 (m), 1336 (m), 1317 (s), 1284 (m),
1
solid; m.p. 162–164 °C. H NMR (300 MHz, CDCl3): δ = 9.21 (d,
J = 7.6 Hz, 2 H), 8.12 (t, J = 7.3 Hz, 2 H), 8.06–7.60 (m, 15 H),
1254 (s), 1223 (m), 1213 (m), 1203 (m), 1184 (m), 1149 (m), 1138
(m), 1126 (m), 1113 (m), 1090 (m), 1068 (m), 1039 (m), 1026 (w),
4.92 (t, J = 6.9 Hz, 4 H), 3.66 (t, J = 6.9 Hz, 4 H) ppm. 13C NMR 1011 (m), 997 (m), 933 (s), 916 (m), 901 (m), 839 (m), 825 (s), 783
(63 MHz, CDCl3): δ = 141.13, 138.95, 136.22, 133.59, 128.99,
128.72, 126.80, 126.55, 122.10, 120.83, 119.62, 108.48, 94.63, 44.90,
(w), 766 (w), 741 (s), 721 (vs), 714 (vs), 683 (m), 656 (m), 633 (m),
609 (m), 586 (m), 557 (m), 548 (m) cm–1. GC–MS (EI, 70 eV): m/z
(%) = 337 (100), 296 (70), 255 (28), 127 (16), 43 (37). HRMS (EI):
calcd. for C23H19N3 [M]+ 337.15735, found 337.15705.
35.08 ppm. IR (ATR): ν = 3061 (w), 3020 (w), 2953 (w), 2933 (w),
˜
2877 (w), 2852 (w), 1595 (s), 1466 (s), 1454 (m), 1441 (m), 1410
(m), 1390 (m), 1352 (s), 1319 (s), 1257 (s), 1227 (m), 1203 (m), 1171
(s), 1124 (m), 1111 (m), 1080 (m), 1068 (m), 1012 (m), 827 (m), 742
(vs), 729 (vs), 698 (vs), 687 (s), 648 (m), 594 (m), 579 (m), 563 (m),
544 (s) cm–1. GC–MS (EI, 70 eV): m/z (%) = 453 (100), 368 (40),
282 (12), 269 (25). HRMS (EI): calcd. for C31H39N3 [M]+
453.31385, found 453.31353.
5,7-Dibenzyl-5,7-dihydropyrido[3,2-b:5,6-bЈ]diindole (5m): Follow-
ing general procedure B and using compound 3 (100 mg,
0.18 mmol) and benzylamine (120 μL, 1.09 mmol) gave a crude
product, which was purified by flash chromatography (silica gel;
heptanes/dichloromethane/ethyl acetate, 5:1:1) to yield 5m (56 mg,
70 %) as a white solid; m.p. 278–280 °C. 1H NMR (300 MHz,
CDCl3): δ = 8.51 (d, J = 7.6 Hz, 2 H), 7.42–6.94 (m, 18 H), 5.28
(s, 4 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 141.75, 137.33,
136.56, 133.91, 128.86, 127.61, 126.67, 126.46, 122.58, 120.71,
5,7-Dipropyl-5,7-dihydropyrido[3,2-b:5,6-bЈ]diindole (5j):[22] Follow-
ing general procedure B and using compound 3 (100 mg,
0.18 mmol) and n-propylamine (90 μL, 1.09 mmol) gave a crude
product, which was purified by flash chromatography (silica gel;
heptanes/dichloromethane/ethyl acetate, 5:1:1) to yield 5j (54 mg,
119.88, 108.79, 95.08, 46.62 ppm. IR (ATR): ν = 3028 (w), 2922
˜
(w), 2852 (w), 1616 (w), 1597 (m), 1510 (w), 1495 (m), 1483 (w),
86 %) as a white solid; m.p. 168–170 °C. 1H NMR (300 MHz, 1464 (s), 1450 (m), 1441 (m), 1408 (m), 1387 (m), 1350 (m), 1315
CDCl3): δ = 8.48 (d, J = 7.7 Hz, 2 H), 7.42 (ddd, J = 8.2, 7.1, (s), 1298 (m), 1277 (w), 1250 (s), 1221 (m), 1211 (m), 1203 (m),
1.2 Hz, 2 H), 7.32–7.20 (m, 5 H), 4.09 (t, J = 7.1 Hz, 4 H), 1.90– 1176 (s), 1155 (m), 1124 (m), 1111 (m), 1078 (m), 1065 (m), 1030
1.73 (m, 4 H), 0.88 (t, J = 7.4 Hz, 6 H) ppm. 13C NMR (63 MHz, (m), 1011 (m), 1003 (m), 985 (m), 970 (m), 945 (m), 930 (m), 903
CDCl3): δ = 141.48, 136.73, 133.72, 126.24, 122.31, 120.57, 119.26, (m), 895 (m), 839 (m), 822 (s), 796 (m), 741 (s), 725 (vs), 708 (s),
108.50, 94.09, 44.52, 22.09, 11.85 ppm. IR (ATR): ν = 2958 (m), 690 (vs), 665 (s), 634 (m), 623 (s), 615 (s), 604 (m), 582 (s), 563 (s),
˜
2929 (m), 2872 (m), 1593 (m), 1574 (m), 1520 (w), 1464 (s), 1408 555 (s), 532 (s) cm–1. GC–MS (EI, 70 eV): m/z (%) = 437 (100), 346
(m), 1385 (m), 1365 (m), 1358 (m), 1335 (w), 1315 (s), 1294 (m), (61), 255 (12), 91 (60), 65 (8). HRMS (EI): calcd. for C31H23N3
1248 (s), 1225 (m), 1207 (m), 1188 (m), 1151 (m), 1132 (m), 1122 [M]+ 437.18865, found 437.18850.
(m), 1111 (m), 1070 (m), 1024 (w), 1011 (m), 984 (w), 968 (m), 957
5,7-Bis(4-methoxybenzyl)-5,7-dihydropyrido[3,2-b:5,6-bЈ]diindole
(5n): Following general procedure B and using compound 3
(100 mg, 0.18 mmol) and 4-methoxybenzylamine (143 μL,
(w), 935 (m), 922 (m), 893 (m), 847 (w), 837 (m), 823 (s), 741 (s),
721 (vs), 704 (s), 667 (m), 623 (m), 596 (m), 579 (s), 569 (m) cm–1.
GC–MS (EI, 70 eV): m/z (%) = 341 (100), 312 (89), 269 (39), 171
1.09 mmol) gave a crude product, which was purified by flash
(6), 141 (20). HRMS (EI): calcd. for C23H23N3 [M]+ 341.18865,
chromatography (silica gel; heptanes/dichloromethane/ethyl acet-
found 341.18864.
ate, 3:1:1) to yield 5n (55 mg, 60%) as a white solid; m.p. 217–
5,7-Didodecyl-5,7-dihydropyrido[3,2-b:5,6-bЈ]diindole (5k): Follow-
ing general procedure B and using compound 3 (100 mg,
0.18 mmol) and n-dodecylamine (203 mg, 1.09 mmol) gave a crude
product, which was purified by flash chromatography (silica gel;
heptanes/dichloromethane/ethyl acetate, 5:1:1) to yield 5k (77 mg,
71%) as a white solid; m.p. 91–93 °C. 1H NMR (300 MHz, CDCl3):
219 °C. 1H NMR (250 MHz, CDCl3): δ = 8.53 (d, J = 7.7 Hz, 2
H), 7.44–7.36 (m, 2 H), 7.31–7.21 (m, 6 H), 7.01–6.88 (m, 4 H),
6.76–6.59 (m, 4 H), 5.23 (s, 4 H), 3.64 (s, 6 H) ppm. 13C NMR
(63 MHz, CDCl3): δ = 159.02, 141.67, 133.70, 131.97, 128.48,
127.77, 126.67, 120.79, 119.75, 114.17, 108.72, 95.43, 55.18,
46.10 ppm. IR (ATR): ν = 2955 (w), 2939 (w), 2839 (w), 1608 (m),
˜
δ = 8.57 (d, J = 7.5 Hz, 2 H), 7.52 (ddd, J = 8.2, 7.1, 1.2 Hz, 2 H), 1595 (m), 1510 (s), 1464 (s), 1443 (m), 1408 (m), 1389 (m), 1352
7.42–7.29 (m, 5 H), 4.43–4.15 (m, 4 H), 2.05–1.75 (m, 4 H), 1.56–
(m), 1333 (m), 1321 (m), 1313 (s), 1304 (m), 1282 (m), 1254 (vs),
1.07 (m, 36 H), 0.87 (t, J = 6.7 Hz, 6 H) ppm. 13C NMR (63 MHz, 1244 (vs), 1223 (m), 1205 (m), 1174 (vs), 1157 (m), 1151 (m), 1124
CDCl3): δ = 141.42, 136.78, 133.68, 126.28, 122.33, 120.63, 119.28, (m), 1111 (m), 1028 (s), 1012 (m), 1001 (m), 924 (m), 843 (m), 829
108.44, 94.10, 43.06, 31.88, 29.61, 29.59, 29.51, 29.42, 29.31, 28.74,
(s), 816 (s), 756 (m), 748 (s), 741 (s), 727 (vs), 687 (s), 636 (m), 619
27.36, 22.66, 14.08 ppm. IR (ATR): ν = 2918 (s), 2848 (s), 1597 (m), 606 (m), 582 (m), 569 (m), 538 (s) cm–1. GC–MS (EI, 70 eV):
˜
(m), 1466 (s), 1412 (m), 1350 (m), 1321 (s), 1257 (m), 1246 (m), m/z (%) = 497 (81), 207 (8), 121 (100), 77 (11). HRMS (EI): calcd.
1209 (m), 1190 (m), 1117 (m), 1076 (w), 1009 (w), 876 (w), 829 (m), for C33H27O2N3 [M]+ 497.20978, found 497.20946.
742 (s), 723 (vs) cm–1. GC–MS (EI, 70 eV): m/z (%) = 593 (100),
5,7-Bis(4-fluorobenzyl)-5,7-dihydropyrido[3,2-b:5,6-bЈ]diindole (5o):
Following general procedure B and using compound 3 (100 mg,
0.18 mmol) and 4-fluorobenzylamine (125 μL, 1.09 mmol) gave the
438 (45), 270 (16), 44 (21). HRMS (EI): calcd. for C41H59N3 [M]+
593.47035, found 593.47119.
5,7-Diallyl-5,7-dihydropyrido[3,2-b:5,6-bЈ]diindole (5l): Following crude product, which was purified by flash chromatography (silica
general procedure B and using compound 3 (100 mg, 0.18 mmol)
and allylamine (82 μL, 1.09 mmol) gave a crude product, which was
gel; heptanes/dichloromethane/ethyl acetate, 5:1:1) to yield 5o
(46 mg, 53 %) as a white solid; m.p. 220–221 °C. 1H NMR
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
11

Job/Unit: O43035
/KAP1
Date: 20-12-14 13:01:46
Pages: 14
T. T. Dang, P. Langer et al.
FULL PAPER
(300 MHz, CDCl3): δ = 8.51 (d, J = 7.6 Hz, 3 H), 7.45–7.37 (m, 3
(m, 2 H), 7.28–7.16 (m, 4 H), 6.72–6.50 (m, 5 H), 6.19 (s, 2 H),
H), 7.34–7.25 (m, 3 H), 7.25–7.16 (m, 4 H), 7.02–6.74 (m, 14 H),
4.29 (d, J = 6.4 Hz, 4 H), 3.60 (s, 6 H), 3.39 (s, 6 H), 2.92 (s, 4 H)
5.16 (s, 6 H) ppm. 19F NMR (282 MHz, CDCl3): δ = –114.56 (s) ppm. 13C NMR (75 MHz, CDCl3): δ = 148.94, 147.90, 141.20,
ppm. 13C NMR (75 MHz, CDCl3): δ = 162.16 (d, J = 246.3 Hz),
141.54 (s), 137.38 (s), 133.54 (s), 132.13 (d, J = 3.3 Hz), 128.02 (d,
133.51, 131.47, 126.39, 120.71, 120.56, 119.55, 112.48, 111.26,
108.52, 94.37, 55.78, 55.67, 45.07, 34.52 ppm. IR (ATR): ν = 2955
˜
J = 8.2 Hz), 126.73 (s), 122.60 (s), 120.71 (s), 119.99 (s), 115.73 (d, (w), 2937 (w), 2916 (w), 2833 (w), 1597 (m), 1516 (s), 1464 (m),
J = 21.7 Hz), 108.66 (s), 94.84 (s), 45.84 (s) ppm. IR (ATR): ν = 1454 (m), 1441 (w), 1435 (w), 1414 (m), 1387 (w), 1354 (m), 1327
˜
3047 (w), 1595 (m), 1506 (s), 1464 (s), 1443 (m), 1406 (m), 1385 (m), 1317 (m), 1261 (vs), 1236 (s), 1228 (s), 1211 (m), 1198 (m),
(m), 1348 (m), 1317 (s), 1254 (s), 1225 (s), 1215 (s), 1178 (s), 1155
1190 (m), 1157 (s), 1136 (s), 1122 (m), 1041 (w), 1030 (m), 1018 (s),
(s), 1124 (m), 1113 (m), 1095 (m), 1063 (m), 1009 (m), 922 (m), 837 860 (m), 808 (m), 764 (m), 742 (vs), 727 (vs), 683 (m), 644 (m), 557
(s), 808 (m), 741 (vs), 725 (vs), 700 (m), 692 (m), 665 (m), 638 (m), (m) cm–1. GC–MS (EI, 70 eV): m/z (%) = 585 (45), 434 (100), 284
621 (m), 613 (m), 596 (m), 579 (m), 567 (m) cm–1. GC–MS (EI, (27). HRMS (ESI): calcd. for C37H35N3O4 [M + H]+ 586.26276,
70 eV): m/z (%) = 473 (94), 364 (70), 255 (16), 127 (12), 109 (100). found 586.2700.
HRMS (ESI): calcd. for C31H21F2N3 [M + H]+ 474.17763, found
474.17793.
5,7-Bis(3-phenylpropyl)-5,7-dihydropyrido[3,2-b:5,6-bЈ]diindole (5s):
Following general procedure B and using compound 3 (100 mg,
5,7-Bis[3-(trifluoromethyl)benzyl]-5,7-dihydropyrido[3,2-b:5,6-bЈ]di- 0.18 mmol) and 3-phenylpropylamine (156 μL, 1.09 mmol) gave a
indole (5p): Following general procedure B and using compound 3
(100 mg, 0.18 mmol) and 3-(trifluoromethyl)benzylamine (157 μL,
1.09 mmol) gave a crude product, which was purified by flash
chromatography (silica gel; heptanes/dichloromethane/ethyl acet-
ate, 5:1:1) to yield 5p (54 mg, 52%) as a white solid; m.p. 229–
231 °C. 1H NMR (300 MHz, CDCl3): δ = 8.53 (d, J = 7.6 Hz, 2
H), 7.52–7.28 (m, 9 H), 7.18 (t, J = 6.9 Hz, 3 H), 6.96 (d, J =
crude product, which was purified by flash chromatography (silica
gel; heptanes/dichloromethane/ethyl acetate, 5:1:1) to yield 5s
(61 mg, 68%) as a white solid; m.p. 194–196 °C. 1H NMR
(300 MHz, CDCl3): δ = 8.46 (d, J = 7.6 Hz, 2 H), 7.39 (ddd, J =
8.3, 7.3, 1.2 Hz, 2 H), 7.28–6.97 (m, 16 H), 4.05 (t, J = 7.3 Hz, 4
H), 2.58 (t, J = 7.5 Hz, 4 H), 2.19–1.99 (m, 4 H) ppm. 13C NMR
(63 MHz, CDCl3): δ = 141.30, 140.90, 136.80, 133.47, 128.54,
8.7 Hz, 3 H), 5.24 (s, 4 H) ppm. 19F NMR (282 MHz, CDCl3): δ 128.39, 126.34, 126.22, 122.38, 120.61, 119.41, 108.45, 93.98, 42.10,
= –62.70 (s) ppm. 13C NMR (75 MHz, CDCl3): δ = 141.50 (s),
33.11, 29.72 ppm. IR (ATR): ν = 3024 (w), 2924 (w), 1593 (s), 1497
˜
137.49 (s), 133.54 (s), 131.24 (q, J = 32.5 Hz), 129.46 (s), 129.42 (m), 1464 (s), 1452 (s), 1435 (m), 1408 (m), 1387 (m), 1356 (m),
(s), 126.95 (s), 124.55 (q, J = 3.4 Hz), 123.81 (q, J = 272.5 Hz), 1315 (s), 1250 (s), 1227 (m), 1207 (m), 1194 (m), 1174 (m), 1163
123.12 (q, J = 3.7 Hz), 122.63 (s), 120.81 (s), 120.28 (s), 108.59 (s), (m), 1149 (m), 1124 (m), 1111 (m), 1088 (m), 1070 (m), 1028 (m),
94.52 (s), 46.11 (s) ppm. IR (ATR): ν = 3047 (w), 2926 (w), 1595 1016 (m), 1009 (m), 928 (w), 831 (m), 768 (m), 742 (vs), 729 (vs),
˜
(m), 1466 (m), 1443 (m), 1410 (m), 1327 (vs), 1315 (vs), 1254 (s), 694 (vs), 615 (m), 584 (m), 575 (m), 557 (m) cm–1. GC–MS (EI,
1223 (m), 1182 (s), 1167 (s), 1111 (vs), 1097 (vs), 1070 (vs), 1007 70 eV): m/z (%) = 493 (100), 388 (48), 269 (18), 69 (23), 44 (38).
(m), 968 (m), 949 (m), 937 (m), 930 (m), 916 (m), 881 (m), 862 (m), HRMS (ESI): calcd. for C35H31N3 [M + H]+ 494.25907, found
823 (m), 804 (m), 789 (s), 744 (vs), 733 (s), 714 (m), 696 (vs), 661 494.25922; calcd. for C35H31N3Na [M + Na]+ 516.24102, found
(s), 634 (m), 615 (m), 602 (m), 582 (m), 565 (s) cm–1. GC–MS (EI,
70 eV): m/z (%) = 573 (100), 414 (42), 255 (30), 159 (10). HRMS
(EI): calcd. for C33H21N3F6 [M]+ 573.16342, found 573.16519.
516.2405.
5,7-Dicyclohexyl-5,7-dihydropyrido[3,2-b:5,6-bЈ]diindole (5t): Fol-
lowing general procedure B and using compound 3 (100 mg,
5,7-Diphenethyl-5,7-dihydropyrido[3,2-b:5,6-bЈ]diindole (5q): Fol- 0.18 mmol) and cyclohexylamine (127 μL, 1.09 mmol) gave a crude
lowing general procedure B and using compound 3 (100 mg,
0.18 mmol) and phenylethylamine (138 μL, 1.09 mmol) gave the
crude product, which was purified by flash chromatography (silica
gel; heptanes/dichloromethane/ethyl acetate, 5:1:1) to yield 5q
product, which was purified by flash chromatography (silica gel;
heptanes/dichloromethane/ethyl acetate, 5:1:1) to yield 5t (42 mg,
55%) as a white solid; m.p. 277–279 °C. 1H NMR (300 MHz,
CDCl3): δ = 8.50 (d, J = 7.7 Hz, 2 H), 7.58 (s, 2 H), 7.47–7.36 (m,
(64 mg, 75 %) as a white solid; m.p. 124–126 °C. 1H NMR 4 H), 7.23 (ddd, J = 7.9, 6.0, 2.1 Hz, 2 H), 5.19–5.03 (m, 2 H),
(300 MHz, CDCl3): δ = 8.47 (d, J = 7.6 Hz, 2 H), 7.38 (t, J = 2.42–1.63 (m, 18 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 140.81,
7.3 Hz, 2 H), 7.30–6.79 (m, 16 H), 4.19 (t, J = 6.9 Hz, 4 H), 2.93 137.05, 132.62, 126.12, 122.85, 120.83, 119.21, 109.65, 96.35, 55.93,
(t, J = 6.9 Hz, 4 H) ppm. 13C NMR (63 MHz, CDCl3): δ = 141.00,
28.96, 25.48 ppm. IR (ATR): ν = 2928 (m), 2854 (m), 1591 (m),
˜
138.83, 133.46, 128.87, 128.59, 126.68, 126.43, 120.70, 119.50, 1485 (m), 1454 (m), 1416 (m), 1404 (m), 1377 (m), 1344 (m), 1327
108.35, 94.50, 44.77, 34.96 ppm. IR (ATR): ν = 2951 (m), 2928 (m), 1304 (m), 1250 (m), 1225 (s), 1188 (s), 1155 (m), 1142 (m),
˜
(m), 2874 (m), 2856 (m), 2845 (m), 1591 (s), 1481 (m), 1470 (s), 1126 (m), 1117 (m), 1072 (m), 1057 (m), 1028 (m), 1012 (m), 968
1464 (s), 1412 (m), 1387 (m), 1371 (m), 1354 (m), 1319 (s), 1250 (m), 893 (m), 837 (m), 742 (s), 729 (vs), 700 (m), 658 (m), 594 (m),
(s), 1230 (s), 1215 (m), 1201 (m), 1186 (m), 1174 (m), 1144 (s), 1124 577 (s), 532 (m) cm–1. GC–MS (EI, 70 eV): m/z (%) = 421 (100),
(m), 1113 (s), 1070 (m), 1024 (w), 1011 (m), 903 (m), 847 (m), 744 256 (31), 55 (22). HRMS (EI): calcd. for C29H31N3 [M]+ 421.25125,
(s), 725 (vs), 706 (s), 696 (m), 673 (m), 596 (m), 577 (m), 565 (m) found 421.25089.
cm–1. GC–MS (EI, 70 eV): m/z (%) = 465 (35), 374 (100), 282 (42).
Computational Methods: All calculations were carried out by using
HRMS (EI): calcd. for C33H27N3 [M]+ 465.21995; found
Gaussian 09, Revision C.01.[23] The geometry of the 5,7-dihydro-
465.21945.
pyrido[3,2-b:5,6-bЈ]diindoles was optimized without any symmetry
5,7-Bis(3,4-dimethoxyphenethyl)-5,7-dihydropyrido[3,2-b:5,6-bЈ]di-
indole (5r): Following general procedure B and using compound 3
(100 mg, 0.18 mmol) and (3,4-dimethoxyphenyl)ethylamine
(185 μL, 1.09 mmol) gave the crude product, which was purified by
flash chromatography (silica gel; heptanes/dichloromethane/ethyl
constraints at the B3LYP/6-31G* level of theory.[24] The optimized
geometry of each was confirmed as minima by frequency calcula-
tions at the same level (zero imaginary frequency). The B3LYP
method consists of the three hybrid exchange functional of
Becke[25] combined with the correlation function of Lee, Yang, and
Parr (LYP),[26] and it provides a nice balance between cost and
acetate, 3:1:1) to yield 5r (60 mg, 56%) as a white solid; m.p. 164–
1
165 °C. H NMR (300 MHz, CDCl3): δ = 8.45 (s, 2 H), 7.42–7.34 accuracy. The B3LYP/6-31G* level of theory was applied to the
12
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Synthesis and Properties of 5,7-Dihydropyrido[3,2-b:5,6-bЈ]diindoles
study of the geometric and electronic properties of neutral[19] and
charged systems,[27] which includes simple molecular to large poly-
meric structures.[28] The molecular orbitals were also simulated at
the B3LYP/6-31G* level of theory.
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Received: August 5, 2014
Published Online: ᭿
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Job/Unit: O43035
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Date: 20-12-14 13:01:46
Pages: 14
T. T. Dang, P. Langer et al.
FULL PAPER
Carbolines
T. Q. Hung, N. N. Thang, D. H. Hoang,
T. T. Dang,* K. Ayub, A. Villinger,
S. Lochbrunner, G.-U. Flechsig,
P. Langer* ....................................... 1–14
Synthesis and Properties of 5,7-Dihydro-
pyrido[3,2-b:5,6-bЈ]diindoles
5,7-Dihydropyrido[3,2-b:5,6-bЈ]diindoles
were prepared by a highly efficient two-step
synthesis that involved a site-selective Su-
zuki coupling reaction of 2,3,5,6-tetra-
bromopyridine and a subsequent Pd-cata-
lyzed cyclization that proceeded through a
twofold C–N coupling reaction with aro-
matic and aliphatic amines. R = n-C3H7.
Keywords: Nitrogen heterocycles / Cross-
coupling / Cyclization / Electrochemistry /
UV/Vis spectroscopy / Fluorescence spec-
troscopy
14
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