Ring closure reactions of 2,6-diazaheptatrienyl metal compounds: Synthesis of 3-aminoindole derivatives and 14-membered macrocyclic dimers

Article abstract of DOI:10.1021/jo201521v

2,6-Diazaheptatrienyl metal compounds 6^-K⁺ are easily accessible from the corresponding diimines 6 by deprotonation using KO-t-Bu as base. According to quantum chemical calculations, they are, in comparison to other isomeric species

Full text of DOI:10.1021/jo201521v

Article
pubs.acs.org/joc
Ring Closure Reactions of 2,6-Diazaheptatrienyl Metal Compounds:
Synthesis of 3-Aminoindole Derivatives and 14-Membered
Macrocyclic Dimers
Benedikt Neue, Ralph Reiermann, Klaus Gerdes, Roland Frohlich, Birgit Wibbeling,
̈
and Ernst-Ulrich Wurthwein*
̈
Organisch-Chemisches Institut, Westfalische Wilhelms-Universitat, Corrensstrasse 40, 48149 Munster, Germany
̈
̈
̈
S
* Supporting Information
ABSTRACT: 2,6-Diazaheptatrienyl metal compounds 6−K+
are easily accessible from the corresponding diimines 6 by
deprotonation using KO-t-Bu as base. According to quantum
chemical calculations, they are, in comparison to other
isomeric species with nitrogen atoms in other positions, highly
reactive intermediates, which undergo in dilute solution at
50 °C ring closure reactions to form 3-aminoindole derivatives
8/10. In contrast, in more concentrated solution at room
temperature, the formation of 14-membered macrocyclces 13
as a result of formal dimerization is observed. The 3-
aminoindole derivatives obtained in this work possess rare substitution patterns, and the macrocyclic compounds are essentially
unknown. Two-fold vinylogous derivatives 7 give rise to tricyclic systems with δ-carboline backbone 12. The experimental results
are interpreted using high-level DFT calculations with regard to the possible reaction mechanism and the nature of the transition
state of the five-membered ring formation. The molecular structures in the solid state of all types of compounds were elucidated
by X-ray diffraction.
to predict that azaheptatrienyl metal compounds with nitrogen
atoms in even positions of the chain (position 2 in structure 1,
Scheme 1) are destabilized and therefore prone to undergo
thermodynamically favorable electrocyclic ring closure reactions
to form the respective heterocyclic anions (compound 2 in
Scheme 1). In contrast, anions with nitrogen atoms in odd
positions (1- or 3-position) are more stable and do not undergo
cyclization reactions.
The behavior of such nitrogen-substituted polyenyl metal
compounds in regioselective reactions with carbonyl com-
pounds and for the diastereoselective synthesis of alkyl-
substituted N-allylimines at low temperature to prevent
cyclization was also investigated in our group.5
INTRODUCTION
■
The tendency of 2-aza- and 2,4-diazapentadienyl metal
compounds to undergo electrocyclic ring closure reactions1 to
form five-membered heterocycles containing one or two
nitrogen atoms was reported first by Hunter et al.2 In
subsequent studies, we were able to explain this interesting
chemical behavior by mechanistic and quantum chemical
studies, to generalize its basic principles and to apply them in
various ring forming reactions for five-, six-, and seven-
membered ring systems3 (1, Scheme 1). Thus, we learned
Scheme 1. Reaction of 2-Azaheptatrienyl Metal Compounds
and Structure of Benzannulated 2,6-Diazaheptatrienyl Metal
Compounds
Various applications of these principles allowed easy and
straightforward access to a large number of N-heterocyclic
systems just by appropriate positioning of the nitrogen atom in
polyenylic anionic starting materials.6 Besides linear examples,
also benzannulated compounds react in the same manner.
In this study, we extend this concept to hitherto unknown
benzannulated 2,6-diazaheptatrienyl metal compounds (3). In
the following, we describe our motivation to study these special
systems, their preparation, and the use of these metal organic
compounds as easily accessible precursors for the efficient
that within the classes of such nitrogen-containing polyenyl
anions (metal compounds) and also of the corresponding
cations the ability to undergo ring closure reactions strongly
depends on the position of thein comparison to carbon
more electronegative nitrogen within the unsaturated chain.4
According to these findings (“ring closure rules”), we were able
Received: July 21, 2011
Published: October 11, 2011
© 2011 American Chemical Society
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Figure 1. Optimized conformers with relative energies of 3,4-benzannulated diazaheptatrienyl anions with the two nitrogen atoms in different
positions (energies in [kcal/mol], SCS-MP2/6-311+G(d,p)//B3LYP/6-311+G(d,p)+ZPE).
synthesis of various 3-aminoindole derivatives and novel
macrocyclic dimers.
Scheme 2. Calculated Cyclization Energies of Three Selected
Diphenyldiazaheptatrienyl Anions (SCS-MP2/6-311+G(d,p)//
B3LYP/6-31G(d)+ZPE [kcal/mol])
RESULTS AND DISCUSSION
■
Choice of the System. In order to identify benzannulated
diazaheptatrienyl anions (metal compounds) capable for ring
closure reactions, we have investigated by quantum chemical
methods a number of anionic benzoheptatrienyl systems with
the two nitrogen atoms in varying positions. On the SCS-MP2/
6-311+G(d,p)//B3LYP/6-311+G(d,p)7,8 level of theory (cor-
rected for zero-point energies, calculations without countercation),9
we determined the relative energies for the best conformers of
benzannulated diazaheptatrienyl anions as given in Figure 1
(numbering in analogy to the 3,4-benzoheptatrienyl anion).
In accordance with the rules mentioned above, anionic
compounds with both nitrogen atoms in odd positions of the
chain are low in energy.3 Here, the nitrogen atoms are located
in coefficient positions of the HOMO with high electron
density (5/7, 1/7, and 1/5, Scheme 2). Among these, the most
stable is the anion with nitrogen atoms in 5- and 7-positions
(0.0 kcal/mol). Changing the location of one of the two
nitrogen atoms to an even position results in elevated relative
energies for most of these compounds (examples 2/7, 1/6, and
2/5 in Scheme 2). In these anions, one heteroatom is
positioned in a less favorable nodal position of the HOMO,
which causes destabilization (for example structure 2/7, 17.7
kcal/mol). If both nitrogen atoms are located in even positions,
the system is most destabilized (structure 2/6, 34.9 kcal/mol).
Here both heteroatoms are located in electron-deficient nodal
positions of the HOMO causing high reactivity (e.g., for ring
forming reactions).
selected diphenyl-substituted diazaheptatrienyl metal com-
pounds with two nitrogen atoms in 5/7-, 2/5- and 2/6-
position (Scheme 2) (calculations peformed without metal
countercation).
The anion with both nitrogen atoms in odd positions with
high electron density (5/7) is low in energy and is not capable
of undergoing an electrocyclic ring closure reaction (+15.7
kcal/mol). Cyclization of the 2,5-compound (one nitrogen in
odd and one in even position) is approximately thermoneutral
(−1.0 kcal/mol). In contrast, due to the destabilization of the
open chain compound, the corresponding electrocyclic ring
closure reaction of the benzannulated 2,6-diazaheptatrienyl
anion is thermodynamically highly favored (−19.1 kcal/mol)
since after the cyclization one nitrogen atom is in a favorable
position with a large coefficient of the HOMO. Figure 2 shows
These relative energies are in excellent accordance with
calculated reaction energies for the respective ring closure
reactions to form five-membered ring systems. Hence, we
compared the tendencies for 1,5-electrocyclization of three
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Figure 2. HOMOs of the open chain (left) and of the cyclic anion (right) of the 1,7-diphenyl-2,6-diaza-4,5-benzoheptatrienyl system (B3LYP/
6-31G(d), isocontour value 0.04).
the electronic structures of the HOMO of the open chain and
the cyclic compound.
On the basis of these quantum chemical predictions, we have
chosen benzannulated 2,6-diazaheptatrienyl metal compounds
as starting points for our experimental and theoretical
investigation described in this work.
Configuration and conformation of diimine 6c was
determined by X-ray diffraction14 (Figure 3). Compound 6c
shows E-configurations for both iminic bonds.
It should be mentioned that anionic systems with adjacent
nitrogen atoms (not shown in Scheme 2) also show high
reactivity. We have investigated the reactions of such
hydrazone-derived compounds in another project.10
Synthesis of the Precursors. In previous studies, we had
learned that deprotonation reactions using strong, sterically
hindered bases are promising methods for the synthesis of such
nitrogen-containing polyenyl anions (metal compounds). Thus,
for the preparation of benzannulated diazaheptatrienyl anions
6−, the corresponding 2,6-diazaheptatrienes (diimines) 6 are
the starting materials of choice (Scheme 3).11
Figure 3. Molecular structure of compound 6c (Schakal plot15).
Scheme 3. Synthesis of Diaryldiazabenzoheptatrienes 6
To gain additional synthetic possibilities, the conjugated
system was elongated by introduction of further double bonds
to give the two-fold 1-azabutadiene derivatives 9, which turned
out to be thermolabile. For this reason, the distillation had to
be performed very carefully, preferably under low pressure by
using as low temperatures as possible (Scheme 4; see
The diimines 6 were synthesized from commercially available
2-aminobenzylamine 4 and various aromatic aldehydes 5, which
were used in at least four-fold excess, by a two-fold imine
condensation reaction (Scheme 3, Table 1) in the presence of
Scheme 4. Synthesis of Diaryldiazabenzoundecapentaenes 7
Table 1. Overview of the Synthesized Diazabenzoheptatrienes
6 and Isolated Yield
no.
R
yield (%)
no.
R
yield (%)
6a
6b
6c
6d
6e
6f
Ph
91
84
63
87
68
89
92
94
6i
2-pyridyl
99
95
99
86
88
56
80
4-Me-Ph
4-Cl-Ph
6j
2-NO2-Ph
4-CF3-Ph
6k
6l
experimental details). Subsequent recrystallization after dis-
tillation was necessary to isolate the pure compounds in
moderate to good yield.
The molecular structure of compound 7a was determined by
X-ray diffraction giving evidence for E-configurations for both
the iminic CN bonds as well as for the CC double bonds
(Figure 4).
Deprotonation Reactions, Formation of Monomeric
Products. After treatment of compounds 6 (0.5−2.0 mmol in
150 mL of THF) with base (KO-t-Bu, 1.1 equiv) for the
indicated period of time at elevated temperatures (50 °C),
subsequent addition of trimethyl acetyl chloride (pivaloyl
chloride, 4.0 equiv), and aqueous workup, 3-(N-acylamino)-
indoles 8 were obtained in one case in low, but mostly in
4-OMe-Ph
4-NEt2-Ph
thien-2-yl
4-t-Bu-Ph
4-CN-Ph
anthracene-9-yl
naphthalene-2-yl
4-Br-Ph
6m
6n
6o
6g
6h
2-Me-Ph
molecular sieves.12 After removal of the excess of aldehyde by
distillation and recrystallization, pure compounds 6 were
obtained in good to excellent yields. They are sensitive toward
moisture. Use of the aldehydes in less than 4.0 equiv resulted in
the formation of six-membered aminals as side products.13
Reactions of 4 with aliphatic aldehydes gave no satisfactory
results but inseparable mixtures of various compounds. Thus,
only aromatic aldehydes were used in this study.
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Table 3. Reaction Times and Isolated Yields for the
Conversion of Compounds 6 into 3-(N-Benzylamino)indoles
10 and 3-(N-Benzylideneamino)indoles 11
reaction
time
product diimine
R
yield 10
yield 11
10a/11a
11b
6c
6l
4-Cl-Ph
4 h
10a/55% 11a/47%
11b/50%
anthracen-9-yl
4-OMe-Ph
3 h
11c
6d
10 min
11c / 34%
Figure 4. Molecular structure of compound 7a (Schakal plot).
satisfying or good yield, respectively (Table 2, Scheme 5). In all
cases, the crude products were purified by recrystallization. The
formation of seven-membered heterocyclic compounds was not
observed (see below).
Table 2. Reaction Times and Yields for Conversion of
Diimines 6 into 3-(N-Pivaloylamino)indoles 8
Figure 5. Molecular structure of compound 8f (Schakal plot).
no.
diimine
R
reaction time
isolated yield (%)
8a
8b
8c
8d
8e
8f
6a
6b
6c
6d
6m
6f
Ph
3 h
62
64
74
86
47
47
14
41
4-Me-Ph
15 min
4 h
Scheme 6. Synthesis of Compound 9
4-Cl-Ph
4-OMe-Ph
naphthalen-2-yl
thien-2-yl
4-t-Bu-Ph
2-Me-Ph
10 min
4 h
4 h
8g
8h
6g
6o
1 h
2 h
Scheme 5. Deprotonation of Compounds 6, 1,5-Electrocyclic
Reaction, and Subsequent Reaction with Trimethyl Acetyl
Chloride To Form Compounds 8
As seen from Table 2, satisfactory yields were generally
achieved after a few hours of stirring at 50 °C (6a, 6c, 6m, and
6g) (TLC or NMR reaction control). As expected, significantly
shorter reaction times were observed for diimines with
electron-donating groups such as 4-Me-Ph (6b) and 4-MeO-
Ph (6d). In the cases of 6j (2-NO2-Ph), 6k (4-CF3-Ph), and 6e
(4-NEt2-Ph), no cyclization reactions took place or complex
mixtures were obtained. Compound 6l underwent an 1,5-
electrocyclization but did not react with trimethyl acetyl
chloride, but gave compound 11b (see below, Table 3) upon
aqueous workup. The molecular structure of compounds 8f was
determined by X-ray crystallographic analysis (Figure 5).
If the deprotonation of compound 6a (1.0 mmol) was
carried out using 2.0 equiv of KO-t-Bu in 150 mL of 1,4-
dioxane at 90 °C with stirring for 4 h, the doubly acylated N-
benzyl-N-(2-phenyl-1-pivaloyl-1H-indol-3-yl)pivalamide 9 was
obtained in 32% yield after treatment with 4.0 equiv of
Figure 6. Molecular structure of compound 9 (Schakal plot).
trimethyl acetyl chloride, aqueous workup, and recrystallization
(Scheme 6). The molecular structure of compound 9 was
determined by X-ray diffraction (Figure 6). Obviously, the two-
fold acylation reaction is the result of the harsh reaction
conditions and the larger excess of electrophile.
In a second series of experiments (0.5−1.0 mmol of 6, 65−
150 mL of THF, 1.1 equiv of KO-t-Bu), the reaction mixtures
were treated with water without any further electrophile after
the indicated time of stirring at 50 °C. In these experiments, 3-
(N-benzylamino)indole 10 and 3-(N-benzylideneamino)-
indoles 11 were obtained (Scheme 7, Table 3 for yields and
reaction times). Presumably, spontaneous oxidation by air
converted during the workup the 3-(N-benzylamino)indoles 10
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Scheme 7. Formation of Compounds 10 and 11
partially or completely to the 3-(N-benzylideneamino)indoles
11. In case of the 4-chlorophenyl derivative 10a/11a, the two
products could be separated by recycling GPC using toluene as
eluant. Spectroscopic analysis gave good evidence for the
formation of 10a, and the structure 11a was proven by X-ray
diffraction (Figure 7). The isolated compounds 10 and 11 are
sensitive toward oxidation and/or hydrolysis.
conversion was low, and it was not possible to isolate the
product 12a in pure form (Figure 7, Scheme 8). Similary,
Scheme 8. Synthesis of Compounds 12
indications for the formation of 12b in the reaction mixture
were obtained by NMR spectroscopy and mass spectrometry.
Reaction control experiments by NMR and GC revealed that
the starting materials 9 polymerize very fast under these
conditions. Reduction of temperature, variation of the
concentrations, and use of different bases decrease the
formation of polymers and also prevent the formation of the
anion and/or the cyclization. The observed substitution
patterns are hitherto unknown. δ-Carbolines are of biological
and pharmaceutical importance but are rare in nature.16,18,19
These additional examples underline the manifold possibilities
of diazapolyenyl metal compounds for the synthesis of
heterocyclic compounds to be studied in the future.
Formation of Dimers. During the optimization of the
synthesis of compounds 8-11, starting from 6, a second product
was found in some cases in the crude mixture. This compound
could be identified by X-ray crystallographic analysis as a
macrocyclic dimer with the racemic (all-R and all-S) structure
13 (Figure 9).
Figure 7. Molecular structure of compound 11a (Schakal plot).
Reactions with electrophiles other than trimethyl acetyl
chloride or water were studied, but the corresponding products
could not be isolated in pure form.
3-Aminoindole derivatives 8−11 are of interest in
pharmaceutical and medicinal chemistry.16 Compounds with
similar substitution patterns are rare in literature,17 and the
examples presented here are to our knowledge unknown.
Then, we used the diazabenzoundecapentaenes 7 to
investigate the scope of the cyclization reaction with respect
to this two-fold vinylogous system. Here, an anion might be
formed with the negative charge delocalized over 11 atoms.
After deprotonation of compound 7a with KO-t-Bu (1.1 equiv),
stirring for 4 h at 50 °C, and aqueous workup, compound 12a
was obtained. The X-ray diffraction study of 12a (Figure 8)
confirms the structure of a δ-carboline. Unfortunately,
Figure 9. X-ray structure of compound 13c.
We were able to modify the procedure to obtain compounds
Figure 8. Molecular structure of compound 12a (Schakal plot).
13 in higher yields. By use of a larger excess of base and more
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concentrated solutions (1.0−25.0 mmol of 6, 2.0 equiv of KO-t-
Bu, 60 mL of dry THF), stirring for 24−48 h at rt (see Table 4)
might be used as a new class of ligands in coordination
chemistry.
Mechanism. The formation of the observed 3-amino-
indolyl compounds 8/11, the macrocyclic compounds 13/14,
and also of the expected, but not observed, benzodiazepine
derivative 15 may be rationalized by the following mechanism
(Scheme 10).
Table 4. Yields of Tetraazadibenzocyclotetradecatetraenes
13/14
no.
diimine
R
isolated yield (%)
13a
13b
13c
13d
13e
14
6a
6c
6n
6i
Ph
38
50
99
49
14
21
We assume that, in the first step, the diimine 6 is
deprotonated by KO-t-Bu, forming the potassium compound
6−K+. The electrocyclization step may either lead to the seven-
membered intermediate 15−K+ or to the five-membered
intermediate 16−K+. In comparison to KO-t-Bu, these
potassium compounds themselves might be considered, on
the one hand, to be strong bases, which may also deprotonate
starting material 6, while being converted into the protonated
forms 15, 16, 17, and 10 (E = H). These, on the other hand,
with regard to the structure of the product obtained, may be the
subject of further tautomerization steps, triggered by the mutual
presence of excess KO-t-Bu, the basic potassium compounds, as
well as tert-butyl alcohol. With regard to these various
equilibria, taking place over the long period of time and
elevated temperature, the final quenching reaction with the
electrophile may eventually lead to the experimentally observed
3-aminoindole derivatives 8/10. These latter tautomerization
steps obviously benefit energetically greatly from the
aromaticity of the final product 8/10. This is indicated by a
very low calculated relative energy of about −19 kcal/mol of 10
in comparison to the various other protonated intermediates
including the not observed seven-membered ring system 15. Of
course, solvent and counterion effects may also influence the
reaction pathway. Finally, aqueous workup or reaction with
pivaloyl chloride leads to the observed products 8 and 10. Air
oxidation of 10 gives rise to the formation of compound 11.
We furthermore studied the nature of the ring forming
reaction starting from deprotonated 6− to give the five-
membered intermediate 16− via transition state TS-6−−16−.
Here, anions in the gas phase without counterions were
calculated (Scheme 11).
4-Cl-Ph
4-Br-Ph
2-pyridyl
thien-2-yl
4-CN-Ph
a
6f
6h
a
Mixture of diastereomers or configurational isomers.
and subsequent quenching with water, the tetraazadibenzocy-
clotetradecatetraenes 14 could be isolated in moderate to good
yields.
From compounds 6b, 6d, 6j, and 6k, the formation of
products 13 was not observed, and in the cases of 6b,d, the
indole derivatives 8b and 8d/11d were formed exclusively. In
the case of diimine 6l, a product of type 11 could be identified
in the crude mixture, but isolation was not possible. In the case
of compound 13e, which was isolated by column chromatog-
raphy, two sets of signals were seen in the NMR spectra.
Probably due to the purification method (the other compounds
were purified by crystallization or washing), an additional
diastereomer or configurational isomer was detected but could
not be separated.
The formation of the dimeric, macrocyclic compounds 13/
14 may possibly be explained by a template effect,20,21 exerted
by the potassium counterion (Scheme 9). During the reaction a
2,6-diazaheptatrienyl potassium compound (6−K+) might react
as a nucleophile with a molecule of 6, which acts as an
electrophile.
Interestingly, starting from compound 6h, an oxidative
process, probably by air, lead to compound 14. This compound
is poorly soluble but easy to purify by washing with DCM and
1
DMSO (Scheme 9). The H NMR and 13C NMR spectra of
Thus, the calculated structure of 6− and the transition
structure TS-6−−16− are in accordance with a disrotatory
cyclization mode, which is reasonable for an electrocyclization
involving 6π electrons (Figure 10).
compound 14f were found to be very similar to the ones of
compound 13a−d, except for the absence of the signals for the
four CH groups. The mass spectroscopic analysis also coincides
with the proposed structure.
For the almost planar 6π transition structure, a minimal
NICS value of −6.7 ppm (B3LYP/6-311G+(d,p); see
Supporting Information) was calculated along an axis
perpendicular to the center of the forming ring.24,25 Together
with the small charge separation of 0.16e (NBO,26 6-31+G(d)),
Macrocyclic compounds of type 13/14 are to the best of our
knowledge rare. We could only trace a few examples with
related structures in the literature.22 They show some analogy
to porphyrins,23 which makes these compounds, especially
compound 14 with its fully conjugated system, interesting for
further investigations. Obviously, these 14-membered ring
systems offer the preconditions for metal complexation and
the characteristics of a Huckel-type aromatic transition state of
̈
an electrocyclic reaction are given.
Scheme 9. Formation of Compounds 13a−e (Only One Enantiomer Shown) and Oxidation to Compound 14
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Scheme 10. Proposed Reaction Mechanism for the Formation of Five- and Seven-Membered Ring Compounds with Relative
Energies for the Protonated Species (E = H, R = Ph) ([kcal/mol], SCS-MP2/6-311+G(d,p)//B3LYP/6-31G(d)+ZPE)
intermediates, we now studied the generation and reactivity
of benzannulated 2,6-diazaheptatrienyl metal compounds. At
50 °C in dilute solution, 3-(N-acylamino)indoles 8 and their
oxidation products 3-(benzylideneamino)indoles 11 were
found to be the major products; the formation of seven-
membered ring systems was not observed. In contrast, reaction
in concentrated solution at room temperature leads to the
formation of macrocyclic dimers of type 13 with novel
substitution patterns. Such 14-membered heterocyclic systems
are promising as ligands for metal complexation. The elongated
systems 7 are shown to be useful precursors for the synthesis of
tricyclic compounds (12) with hitherto unknown structural
motifs. Quantum chemical calculations again came out to be
very valuable for the choice of the system under study and for
the interpretation of the experimental results with regard to the
reaction mechanism.
Scheme 11. Formation of the Five-Membered Ring
Compound 16−
EXPERIMENTAL SECTION
■
Melting points are uncorrected. 1H, 13C, 19F NMR spectroscopy: TMS
(1H) (0.00 ppm), CD2Cl2 (1H) (5.32 ppm), CDCl3 (1H) (7.26 ppm),
C6D6 (1H) (7.16 ppm), THF-d8 (1H) (1.72/3.58 ppm), CD2Cl2 (13C)
(53.8 ppm), CDCl3 (13C) (77.0 ppm), C6D6 (13C) (128.1 ppm),
THF-d8 (13C) (25.3/67.2 ppm), CFCl3 (19F) (0.0 ppm) were used as
external reference. NMR spectra of indoles were measured in CDCl3
containing one drop of TFA (trifluoroacetic acid). If necessary, the
experiments were carried out with complete exclusion of moisture.
Abbreviations: DE diethylether, EA ethyl acetate, TEA triethylamine,
DCM dichloromethane, DCE dichloroethane.
Figure 10. Calculated structures of compound 6− (left) and transition
structure TS-6−−16− (right) (B3LYP/6-31G(d)//B3LYP/6-31G(d)).
CONCLUSION
■
General Procedure for the Synthesis of 2,6-Diaza-4,5-
benzoheptatrienes (6a−o). The compounds were synthesized
using the molecular sieves method.12 In a Schlenk flask, 2-
aminobenzylamine (1 equiv) was dissolved in dry DCM. Sub-
sequently, the aldehyde (4 equiv) in pure or dissolved in dry DCM
was added to the mixture while stirring. The solution was stirred for
18 h and filtered through a pad of Celite which was washed three times
with DCM (3 × 50 mL). The solvent was removed under reduced
As shown by high-level quantum chemical calculations,
topology and relative electronegativity of nitrogen in
comparison to carbon are the principal properties in the
chemistry of isomeric cationic or anionic azapolyenyl
derivatives, which control the reactivity, for example, toward
ring closure reactions to form heterocyclic systems. In
continuation of our previous work on such charged
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pressure. In order to purify the diimine, the excess of aldehyde was
either removed by Kugelrohr distillation or the crude product was
purified by recrystallization.
6.96 (m, 1H), 7.18−7.22 (m, 3H), 7.79−7.82 (m, 2H), 7.91 (d, J = 9.0
Hz, 2H), 8.23 (s, 1H), 8.36 (s, 1H); 13C NMR (C6D6, 100 MHz) δ =
12.8 ppm, 44.3, 61.6, 111.4, 118.3, 125.2, 125.3, 125.4, 129.2, 130.4,
1,7-Diphenyl-2,6-diaza-4,5-benzo-1,4,6-heptatriene (6a): From
12.53 mL (124.09 mmol) of benzaldehyde and a solution of 3.79 g
(31.02 mmol) of 2-aminobenzylamine dissolved in 100 mL of dry
DCM. The excess of aldehyde was removed by distillation at 60 °C
(9.0 × 10−3 mbar): A yellowish oil was obtained which solidifies after
2 days of drying in vacuo to give a colorless solid: 8.42 g (28.22 mmol,
̃
131.23, 134.9, 149.5, 150.1, 152.0, 159.4, 161.7; IR (neat) ν = 1599
cm−1 (CN), 1584 (CN); HRMS (ESI) calcd for C29H36N4H
441.3013, found 441.3020.
1,7-Di(thien-2-yl)-2,6-diaza-4,5-benzo-1,4,6-heptatriene (6f): From
1.22 g (10.00 mmol) of 2-aminobenzylamine, dissolved in 100 mL
of dry DCM, and 3.74 mL (40.00 mmol) of 2-thiophenecarbaldehyde.
In order to purify the crude product, the excess of aldehyde was
removed by distillation in a Kugelrohr oven (120 °C, 2.2 × 10−2
mbar): 2.80 g (8.87 mmol, 89%) was obtained as a yellow-brown
1
91%), mp 48−49 °C; H NMR (CDCl3, 400 MHz) δ = 4.79 ppm (s,
2H), 6.45−7.50 (m, 14H), 7.73 (s, 1H), 7.86 (s, 1H); 13C NMR
(CDCl3, 100 MHz) δ = 61.4 ppm, 117.7, 126.0, 126.2, 126.6, 127.3,
128.1, 128.2, 128.5, 128.9, 129.0, 129.8, 130.6, 132.8, 136.3, 136.3,
1
oil; H NMR (C6D6, 400 MHz) δ = 5.01 ppm (s, 2H), 6.81−6.63
(m, 1H), 6.65−6.67 (m, 1H), 6.68−6.72 (m, 1H), 6.77 (dt, J = 5.2 Hz,
J = 1.2 Hz, 1H), 6.86 (dd, J = 3.6 Hz, J = 1.2 Hz, 1H), 6.89 (dt, J = 4.8
Hz, J = 1.2 Hz, 1H), 6.94 (dd, J = 3.6 Hz, J = 1.2 Hz, 1H), 7.06−7.11
(m, 2H), 7.56−7.60 (m, 1H), 8.00 (s, 1H), 8.22 (s, 1H); 13C NMR
(C6D6, 100 MHz) δ = 61.1 ppm, 118.0, 126.4, 127.1, 127.7, 128.8,
129.6, 130.1, 130.2, 134.0, 143.8, 143.9, 150.2, 152.6, 155.4; IR (neat)
150.5, 159.9, 162.4; IR (KBr) ν
̃
= 1641 (CN), 1634 (CN);
HRMS (ESI) calcd for C21H18N2H 299.1543, found 299.1545. Anal.
Calcd for C21H18N2 (298.38): C, 84.53; H, 6.08; N, 9.39. Found: C,
84.38; H, 6.10; N, 9.29.
1,7-Bis(4-methylphenyl)-2,6-diaza-4,5-benzo-1,4,6-heptatriene
(6b): From 27.66 mL (0.24 mol) of 4-methylbenzaldehyde and a
solution of 7.32 g (0.06 mol) of 2-aminobenzylamine in 100 mL of dry
DCM. The resulting diimine was purified by removing the aldehyde by
distillation at 70 °C (9.0 × 10−3 mbar): 16.45 g (0.05 mol, 84%) was
obtained as a yellow oil; 1H NMR (C6D6, 400 MHz) δ = 2.02 ppm (s,
3H), 2.06 (s, 3H), 5.12 (s, 2H), 6.92 (d, 2H, J = 7.6 Hz), 7.00 (d, 2H,
J = 7.6 Hz), 7.13−7.16 (m, 4H), 7.69 (d, 2H, J = 7.6 Hz), 7.76 (d, 2H,
J = 7.6 Hz), 8.08 (s, 1H), 8.20 (s, 1H); 13C NMR (C6D6, 100 MHz) δ
= 21.3 ppm, 21.4, 61.4, 118.0, 126.0, 127.1, 128.3, 128.6, 128.6, 129.2,
129.3, 129.3, 129.4, 129.5, 129.6, 134.1, 134.6, 134.7, 140.5, 141.5,
ν
̃
= 1630 cm−1 (CN), 1614 (CN); HRMS (ESI) calcd for
C17H14N2S2H 311.0671, found 311.0666. Anal. Calcd for C17H14N2S2
(310.44): C, 65.77; H, 4.55; N, 9.02. Found: C, 65.51; H, 4.81;
N, 9.19.
1,7-Bis(4-tert-butylphenyl)-2,6-diaza-4,5-benzo-1,4,6-heptatriene
(6g): From 6.69 mL (40.00 mmol) of 4-tert-butylbenzaldehyde,
dissolved in 50 mL of dry DCM, and 1.22 g (10.00 mmol) of 2-
aminobenzylamine, dissolved in 50 mL of dry DCM. The crude
product was purified by Kugelrohr distillation (120 °C, 6.0 × 10−2
1
= 1626 cm−1 (CN), 1609 (CN);
mbar): 3.79 g (9.23 mmol, 92%) was obtained as a brown oil; H
151.1, 159.6, 161.8; IR (neat) ν
̃
NMR (C6D6, 300 MHz) δ = 1.15 ppm (s, 9H), 1.20 (s, 9H), 5.18 (s,
2H), 6.79−6.85 (m, 1H), 7.12−7.18 (m, 2H), 7.23 (d, J = 8.4 Hz,
2H), 7.31 (d, J = 8.4 Hz, 2H), 7.65−7.68 (m, 1H), 7.76 (d, J = 8.4 Hz,
2H), 7.84 (d, J = 8.4 Hz, 2H), 8.14 (s, 1H), 8.27 (s, 1H); 13C NMR
(C6D6, 75 MHz) δ = 31.2 ppm, 34.8, 34.9, 61.6, 118.1, 125.7, 125.9,
126.1, 128.6, 129.2, 129.4, 134.1, 134.7, 134.8, 151.3, 153.6, 154.7,
HRMS (ESI) calcd for C23H22N2H 327.1856, found 327.1854. Anal.
Calcd for C23H22N2 (326.43): C, 84.63; H, 6.79; N, 8.58. Found: C,
84.39; H, 6.76; N, 8.49.
1,7-Bis(4-chlorophenyl)-2,6-diaza-4,5-benzo-1,4,6-heptatriene
(6c): From 3.67 g (30.00 mmol) of 2-aminobenzylamine, dissolved in
50 mL of dry DCM, and 14.42 g (120.00 mmol) of 4-
chlorobenzaldehyde, dissolved in 50 mL of dry DCM. The excess of
aldehyde was removed by distillation at 95 °C (9.0 × 10−3 mbar): 7.00
g (19.00 mmol, 63%), as a colorless solid; mp 102−103 °C; 1H NMR
(C6D6, 300 MHz) δ = 5.00 ppm (s, 2H), 6.71−7.55 (m, 12H), 7.84 (s,
1H), 7.94 (s, 1H); 13C NMR (C6D6, 75 MHz) δ = 61.3 ppm, 117.9,
126.5, 128.3, 129.0, 129.2, 129.5, 129.7, 130.2, 133.8, 135.3, 135.4,
159.8, 161.9; IR (neat) ν
(ESI) calcd for C29H34N2H 411.2795, found 411.2783.
̃
= 1641 cm−1 (CN), 1628 (CN); HRMS
1,7-Bis(4-cyanophenyl)-2,6-diaza-4,5-benzo-1,4,6-heptatriene
(6h): From 5.25 g (40.00 mmol) of 4-cyanobenzaldehyde, dissolved in
50 mL of dry DCM, and 1.22 g (10.00 mmol) of 2-aminobenzylamine,
dissolved in 50 mL of dry DCM. The product was purified by
Kugelrohr distillation (140 °C, 4.1 × 10−2 mbar): 3.28 g (9.42 mmol,
136.6, 137.4, 150.5, 158.3, 160.5; IR (KBr) ν
̃
= 1638 cm−1 (CN),
1
94%) was obtained as a yellow-brown solid; mp 139−140 °C; H
1626 (CN); HRMS (ESI) calcd for C21H16Cl2N2H 367.0763, found
367.0767. Anal. Calcd for C21H16Cl2N2 (367.27): C, 68.68; H, 4.39; N,
7.63. Found: C, 68.50; H, 4.25; N, 7.55. X-ray crystal structure data of
6c can be found in the Supporting Information.
NMR (C6D6, 300 MHz) δ = 5.05 ppm (s, 2H), 6.80 (m, 1H), 7.04 (d,
J = 8.4 Hz, 2H), 7.13 (d, J = 8.4 Hz, 2H), 7.24−7.27 (m, 4H), 7.38 (d,
J = 8.4 Hz, 2H), 7.47 (d, J = 8.4 Hz, 2H), 7.54−7.57 (m, 1H), 7.87 (s,
1H), 7.93 (s, 1H); 13C NMR (C6D6, 75 MHz) δ = 61.2 ppm, 114.3,
114.9, 117.7, 118.4, 118.5, 127.2, 128.5, 128.5, 129.0, 129.6, 132.3,
1,7-Bis(4-methoxyphenyl)-2,6-diaza-4,5-benzo-1,4,6-heptatriene
(6d): From 7.33 g (0.06 mol) of 2-aminobenzylamine, dissolved in
100 mL of dry DCM, and 26.98 mL (0.24 mol) of 4-
methoxybenzaldehyde. The crude product was purified by Kugelrohr
distillation (80 °C, 9.0 × 10−3 mbar): 18.65 g (0.05 mmol, 87%) of a
yellow oil was obtained; 1H NMR (C6D6, 300 MHz) δ = 3.19 ppm (s,
3H), 3.23 (s, 3H), 5.16 (s, 2H), 6.76 (d, J = 8.8 Hz, 2H), 6.83 (d, J =
8.8 Hz, 2H), 6.89−6.91 (m, 1H), 7.22−7.24 (m, 2H), 7.72−7.74 (m,
1H), 7.78 (d, J = 8.8 Hz, 2H), 7.85 (d, J = 8.8 Hz, 2H), 8.08 (s, 1H),
8.21 (s, 1H); 13C NMR (C6D6, 75 MHz) δ = 54.7 ppm, 54.9, 61.5,
114.0, 114.2, 114.4, 118.1, 125.9, 127.3, 128.0, 128.3, 129.4, 130.1,
132.4, 133.7, 149.8, 157.8, 160.2; IR (neat) ν
̃
= 1672 cm−1 (CN),
1649 (CN); HRMS (ESI) calcd for C23H16N4H 349.1448, found
349.1441. Anal. Calcd for C23H16N4 (348.40): C, 79.29; H, 4.63; N,
16.08. Found: C, 79.14; H, 4.32; N, 16.00.
1,7-Di(2-pyridyl)-2,6-diaza-4,5-benzo-1,4,6-heptatriene (6i): From
1.22 g (10.00 mmol) of 2-aminobenzylamine, dissolved in 100 mL dry
DCM, and 3.80 mL (40.00 mmol) of 2-pyridinecarbaldehyde. The
excess of aldehyde was removed by Kugelrohr distillation (60 °C, 2.3
× 10−2 mbar): 2.99 g (9.96 mmol, 99%) was obtained as a dark purple
oil; 1H NMR (C6D6, 400 MHz) δ = 5.06 ppm (s, 2H), 6.59 (m, 1H),
6.65 (m, 1H), 6.78 (d, J = 7.6 Hz, 1H), 6.97−7.14 (m, 4H), 7.44 (m,
1H), 8.15 (d, J = 8.0 Hz, 1H), 8.21 (d, J = 8.0 Hz, 1H), 8.44 (d, J = 4.8
Hz, 1H), 8.48 (d, J = 4.8 Hz, 1H), 8.69 (s, 1H), 8.71 (s, 1H); 13C
NMR (C6D6, 100 MHz) δ = 61.1 ppm, 117.9, 121.0, 121.5, 124.4,
124.9, 126.9, 129.5, 133.9, 136.0, 136.2, 149.5, 149.8, 149.8, 155.6,
̃
130.9, 131.8, 134.2, 151.3, 159.1, 161.9, 162.6, 161.2; IR (neat) ν =
1639 cm−1 (CN), 1607 (CN); HRMS (ESI) calcd for
C23H22N2O2H 359.1754, found 359.1752. Anal. Calcd for
C23H22N2O2 (358.43): C, 77.07; H, 6.19; N, 7.82. Found: C, 76.99;
H, 6.27; N, 7.78.
1,7-Bis(4-diethylaminophenyl)-2,6-diaza-4,5-benzo-1,4,6-hepta-
triene (6e): From 1.22 g (10.00 mmol) of 2-aminobenzylamine,
dissolved in 50 mL of dry DCM, and 7.09 g (40.00 mmol) of 4-
diethylaminobenzaldehyde, dissolved in 50 mL of dry DCM. The
excess of aldehyde was removed by distillation (139 °C, 1.4 × 10−2
155.8, 161.1, 163.7; IR (neat) ν
̃
= 1645 cm−1 (CN), 1630 (CN);
HRMS (ESI) calcd for C19H16N4H 301.1447, found 301.1435.
1,7-Bis(2-nitrophenyl)-2,6-diaza-4,5-benzo-1,4,6-heptatriene
(6j): From 6.83 g (45.20 mmol) of 2-nitrobenzaldehyde, dissolved in
50 mL of dry DCM, and 1.38 g (11.30 mmol) of 2-aminobenzylamine,
dissolved in 50 mL of dry DCM. The crude product was purified by
Kugelrohr distillation at 110 °C (7.3 × 10−2 mbar): 4.17 g (10.74 mmol, 95%)
1
mbar): 2.98 g (6.77 mmol, 68%) as a red-brown oil was obtained; H
NMR (C6D6, 300 MHz) δ = 0.81 ppm (q, J = 6.9 Hz, 12H), 2.83−
2.91 (m, J = 6.9 Hz, 8H) 5.23 (s, 2H), 6.48 (t, J = 9.0 Hz, 4H), 6.93−
8801
dx.doi.org/10.1021/jo201521v|J. Org. Chem. 2011, 76, 8794−8806

The Journal of Organic Chemistry
Article
was obtained as a yellow solid; mp 120−121 °C; 1H NMR (C6D6, 300
MHz) δ = 4.99 ppm (s, 1H, CH2), 6.61 ppm (t, J = 8.4 Hz, 1H), 6.70
(t, J = 8.4 Hz, 1H), 6.82 (t, J = 7.5 Hz, 1H), 6.89−6.92 (m, 1H), 7.01
(t, J = 7.5 Hz, 1H), 7.05−7.12 (m, 2H), 7.36 (d, J = 8.1 Hz, 1H),
7.41−7.46 (m, 2H), 8.00 (d, J = 7.9 Hz, 1H), 8.09 (d, J = 7.9 Hz, 1H),
8.63 (br s, 2H); 13C NMR (CDCl3, 75 MHz) δ = 61.0 ppm,
124.3, 124.8, 127.2, 128.7, 129.5, 129.9, 130.0, 130.8, 131.1, 131.3,
131.4, 132.8, 133.5, 133.7, 149.0, 149.4, 149.6, 155.8, 158.0; IR (neat)
126.0, 126.6, 129.5, 129.9, 130.4, 132.0, 132.2, 133.7, 135.7, 135.8,
150.5, 158.4, 160.6; IR (neat) ν
̃
= 1645 (CN), 1628 (CN);
HRMS (ESI) calcd for C21H16Br2N2H 456.9734, found 456.9732.
Anal. Calcd for C21H16Br2N2 (456.17): C, 55.29; H, 3.54; N, 6.14.
Found: C, 55.44; H, 3.52; N, 5.96.
1,7-Bis(2-methylphenyl)-2,6-diaza-4,5-benzo-1,4,6-heptatriene
(6o): From 5.00 g (40.90 mmol) of 2-aminobenzylamine, dissolved in
100 mL of dry DCM, and 18.90 mL (164.00 mmol) of 2-
methylbenzaldehyde. The excess of aldehyde was removed by
Kugelrohr distillation (75 °C, 1.5 × 10−2 mbar) to give 10.70 g
(32.78 mmol, 80%) of 6o as a yellow oil: 1H NMR (C6D6, 300 MHz)
δ = 2.19 ppm (s, 3H), 2.22 (s, 3H), 6.80 (s, 2H), 6.80−6.86 (m, 1H),
6.89−6.93 (m, 2H), 7.03−7.06 (m, 2H), 7.07−7.10 (m, 2H), 7.15−
7.21 (m, 2H), 7.64−7.69 (m, 1H), 8.10−8.16 (m, 1H), 8.16−8.22 (m,
1H), 8.48 (s, 1H), 8.56 (s, 1H); 13C NMR (C6D6, 75 MHz) δ = 19.5
ppm, 62.3, 118.1, 126.2, 126.3, 126.5, 128.2, 128.4, 128.7, 129.0, 129.4,
130.2, 131.0, 131.0, 131.3, 134.1, 134.8, 134.9, 138.0, 138.9, 151.7,
ν
̃
= 1641 cm−1 (CN), 1628 (CN); HRMS (ESI) calcd for
C21H16N4O4H 389.1244, found 389.1260. Anal. Calcd for C21H16N4O4
(388.38): C, 64.94; H, 4.15; N, 14.43. Found: C, 64.93; H, 3.83;
N, 14.45.
1,7-Bis(4-trifluoromethylphenyl)-2,6-diaza-4,5-benzo-1,4,6-hep-
tatriene (6k): From 1.22 g (10.00 mmol) of 2-aminobenzylamine,
dissolved in 100 mL of dry DCM, and 5.35 mL (40.00 mmol) of 4-
trifluoromethylbenzaldehyde. The excess of aldehyde was removed by
Kugelrohr distillation at 100 °C (2.2 × 10−2 mbar): 4.33 g (9.97 mmol,
1
99%) was obtained as a light yellow solid; mp 67−68 °C; H NMR
158.9, 160.7; IR (neat) ν
̃
= 1624 (CN), 1601 (CN); HRMS
(C6D6, 300 MHz) δ = 5.02 ppm (s, 2H), 6.72−6.75 (m, 1H), 7.18−
7.21 (m, 1H), 7.27 (d, J = 8.1 Hz, 2H), 7.36 (d, J = 8.1 Hz, 2H),
7.48−7.56 (m, 6H), 7.87 (s, 1H), 7.97 (s, 1H); 13C NMR (C6D6, 75
MHz) δ = 61.4 ppm, 117.9, 125.6, 125.7, 125.8, 125.8, 128.5, 128.6
129.2, 129.6, 133.7, 139.7, 139.8, 150.2, 158.2, 160.5; 19F NMR (C6D6,
(ESI) calcd for C23H22N2H 327.1856, found 327.1857. Anal. Calcd for
C23H22N2 (326.43): C, 84.63; H, 6.79; N, 8.58. Found: C, 84.42; H,
6.77; N, 8.35.
Synthesis of 4,8-Diaza-6,7-benzoundeca-1,3,6,8,10-pen-
taene (7a,b). The synthesis of compounds 7a,b was performed
analogously to compounds 6a−o.
300 MHz) δ = −62.43 ppm, −62.37; IR (neat) ν
̃
= 1647 cm−1 (C
N), 1632 (CN); HRMS (ESI) calcd for C23H16F6N2H 435.1290,
found 435.1298. Anal. Calcd for C23H16F6N2 (434.38): C, 63.60; H,
3.71; N, 6.45. Found: C, 63.23; H, 3.65; N, 6.26.
1,11-Diphenyl-4,8-diaza-6,7-benzoundeca-1,3,6,8,10-pentaene
(7a): From 3.05 g (25.00 mmol) of 2-aminobenzylamine, dissolved in
20 mL of dry DCM, and 12.59 mL (100.00 mmol) of trans-
cinnamylaldehyde. The solution was stirred for 18 h at rt. The excess
of aldehyde was removed by Kugelrohr distillation at 60 °C (1.5 ×
10−2 mbar), and the crude product was subsequently purified by
recrystallization from toluene: 4.80 g (13.70 mmol, 55%) was obtained
as colorless crystals; mp 113−114 °C; 1H NMR (C6D6, 300 MHz) δ =
5.16 ppm (s, 1H), 6.58 (d, J = 15.0 Hz, 1H.), 6.69 (d, J = 15.0 Hz,
1H), 6.85−6.88 (m, 1H), 6.99−7.08 (m, 7H), 7.11−7.22 (m, 7H),
7.65−7.68 (m, 1H), 7.94 (d, J = 8.7 Hz, 1H), 8.02 (d, J = 8.7 Hz, 1H);
13C NMR (C6D6, 75 MHz) δ = 61.6 ppm, 117.9, 126.3, 127.4, 127.7,
1,7-Di(anthracen-9-yl)-2,6-diaza-4,5-benzo-1,4,6-heptatriene
(6l): From 8.25 g (40.00 mmol) of anthracene-9-carbaldehyde,
dissolved in 50 mL of dry DCM, and 2.44 g (20.00 mmol) of 2-
aminobenzylamine, dissolved in 50 mL of dry DCM. The crude
product was recrystallized from DCE: 8.60 g (17.25 mmol, 86%) was
1
obtained as a yellow solid; mp 179−180 °C; H NMR (THF-d8, 400
MHz) δ = 5.38 ppm (s, 2H), 7.21−7.26 (m, 2H), 7.26−7.29 (m, 9 H),
7.69 (d, J = 7.6 Hz, 1H), 7.97 (d, J = 8.8 Hz, 2H), 8.07 (d, J = 7.6 Hz,
2H), 8.49 (s, 1H), 8.64 (s, 1H), 8.65 (d, J = 8.8 Hz, 2H), 8.99 (d, J =
8.8 Hz, 2H), 9.63 (s, 1H), 9.81 (s, 1H); 13C NMR (THF-d8, 100
MHz) δ = 63.8 ppm, 119.0, 126.0, 126.2, 126.3, 127.1, 127.3, 128.0,
128.4, 129.11 129.2, 129.6, 129.9, 130.2, 130.3, 131.4, 131.8, 132.0,
128.4, 128.9, 129.0, 129.4, 129.5, 134.3, 136.1, 136.4, 141.1, 143.4,
151.2, 161.4, 163.4; IR (neat) ν
̃
= 1630 cm−1 (CN), 1611 (CN);
HRMS (ESI) calcd for C25H22N2H 351.1856, found 351.1858. Anal.
Calcd for C25H22N2 (350.46): C, 85.68; H, 6.33; N, 7.99. Found: C,
85.56; H, 6.41; N, 7.71. X-ray crystal structure data of 7a can be found
in the Supporting Information.
132.5, 132.6, 134.8, 152.8, 160.8, 161.8; IR (neat) ν
̃
= 1624 cm−1 (C
N), 1593 (CN); HRMS (ESI) calcd for C37H26N2H 499.2169,
found 499.2167. Anal. Calcd for C37H26N2 (498.62): C, 89.13; H,
5.26; N, 5.62. Found: C, 89.16; H, 5.29; N, 5.63.
1,11-Bis(4-methoxyphenyl)-4,8-diaza-6,7-benzoundeca-
1,3,6,8,10-pentaene (7b): From 1.15 g (9.43 mmol) of 2-amino-
benzylamine, dissolved in 50 mL of dry DCM, and 6.12 g (37.72
mmol) of 4-methoxycinnamylaldehyde, dissolved in 50 mL of dry
DCM. The compound was purified by recrystallization from toluene/
DCM (1:1): 3.20 g (7.80 mmol, 83%) was obtained as a yellow solid;
1,7-Di(naphthalen-2-yl)-2,6-diaza-4,5-benzo-1,4,6-heptatriene
(6m): From 1.48 g (12.12 mmol) of 2-aminobenzylamine, dissolved in
50 mL of dry DCM, and 7.57 g (48.49 mmol) of naphthalene-2-
carbaldehyde, dissolved in 50 mL of dry DCM. The excess of aldehyde
was removed by distillation at 160 °C (4.5 × 10−2 mbar): 4.27 g
(10.72 mmol, 88%) was obtained as a light brown solid; mp 130−
131 °C; 1H NMR (CD2Cl2, 300 MHz) δ = 5.09 ppm (s, 1H), 7.10 (d,
J = 7.5 Hz, 1H), 7.27−7.64 (m, 7H), 7.71 (d, J = 7.5 Hz, 1H), 7.81−
7.85 (m, 3H), 7.91−8.03 (m, 4H), 8.18 (s, 1H), 8.28 (d, J = 8.4 Hz,
1H), 8.55 (s, 1H), 8.58 (s, 1H); 13C NMR (CD2Cl2, 75 MHz) δ =
61.8 ppm, 118.3, 124.2, 124.4, 126.5, 126.7, 127.2, 127.6, 128.2, 128.3,
128.4, 128.7, 128.8, 129.0, 129.1, 129.3, 129.7, 130.5, 131.9, 133.6,
133.6, 133.7, 134.7, 134.7 135.1, 135.6, 151.3, 160.6, 162.8; IR (neat)
1
mp 140−141 °C; H NMR (C6D6, 300 MHz) δ = 3.22 ppm (s. 3H),
3.24 (s, 3H), 5.21 (s, 2H), 6.56−6.78 (m, 6H), 6.89−6.92 (m, 1H),
7.05−7.24 (m, 8H), 7.69−7.72 (m, 1H), 8.00 (d, J = 9.0 Hz, 1H), 8.09
(d, J = 9.0 Hz, 1H); 13C NMR (C6D6, 75 MHz) δ = 54.8 ppm, 54.8,
114.5, 114.6, 127.4, 127.4, 117.9, 126.1, 128.4, 128.9, 129.0, 129.2,
129.3, 129.4, 134.4, 140.8, 143.3, 151.5, 160.7, 161.2, 161.6, 163.6; IR
(neat) ν
̃
= 1632 cm−1 (CN), 1620 (CN); HRMS (ESI) calcd for
= 1634 cm−1 (CN), 1618 (CN); HRMS (ESI) calcd for
C27H26N2O2H 411.2067, found 411.2049. Anal. Calcd for C27H26N2O2
(410.51): C, 79.00; H, 6.38; N, 6.82. Found: C, 78.82; H, 6.34;
N, 6.83.
ν
̃
C29H22N2H 399.1856, found 399.1846. Anal. Calcd for C29H22N2
(398.50): C, 87.41; H, 5.56; N, 7.03. Found: C, 87.04; H, 5.66;
N, 7.04.
General Procedure for the Synthesis of 3-(N-Acylamino)-
indoles (8a−h). In a Schlenk flask, a solution of KO-t-Bu (1.1 equiv,
1 M in THF or solid) in dry THF was heated to 50 °C. Then 1.0 equiv
of 6 in dry THF was added in portions within 15 min. An intense color
appeared. The reaction mixture was stirred at 50 °C for a definite
period of time. After addition of trimethyl acetyl chloride (2.0 equiv),
the solution immediately decolorized. Then the mixture was stirred for
15−30 min, 50 mL of DE was added, and the organic layer was washed
with saturated NaHCO3 solution (3 × 50 mL) and dried over
Mg2SO4. The solvent was removed in vacuo. The crude products were
purified by recrystallization.
1,7-Bis(4-bromophenyl)-2,6-diaza-4,5-benzo-1,4,6-heptatriene
(6n): From 3.67 g (30.00 mmol) of 2-aminobenzylamine, dissolved in
50 mL of dry DCM, and 22.20 g (120.00 mmol) of 4-
bromobenzaldehyde, dissolved in 50 mL of dry DCM. The excess of
aldehyde was removed by distillation in a Kugelrohr oven (95 °C, 1.4
× 10−2 mbar): 7.70 g (16.88 mmol, 56%) was obtained as a light
1
yellow solid; mp 117−118 °C; H NMR (C6D6, 300 MHz) δ = 4.98
ppm (s, 2H), 6.69−6.74 (m, 1H), 7.10−7.20 (m, 4H), 7.25−7.34 (m,
4H), 7.36−7.40 (m, 2H), 7.50−7.56 (m, 1H), 7.82 (s, 1H), 7.92
(s, 1H); 13C NMR (C6D6, 100 MHz) δ = 61.4 ppm, 117.9, 125.1,
8802
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Article
N-Benzyl-N-(2-phenyl-1H-indol-3-yl)pivalamide (8a): From 0.46
g (1.54 mmol) of 6a in 20 mL of dry THF, added to a stirred solution
of 0.19 g (1.69 mmol) of KO-t-Bu, dissolved in 130 mL of dry THF,
and after 3 h, 0.38 mL (3.08 mmol) of trimethyl acetyl chloride. The
crude product was purified by recrystallization from DCE: 0.37 g (0.95
mmol, 62%) of compound 8a was obtained as colorless crystals; mp
C28H30N2O3 (442.55): C, 75.99; H, 6.83; N, 6.33. Found: C, 75.69;
H, 6.82; N, 6.27. X-ray crystal structure data of 8d can be found in the
Supporting Information.
N-(2-(Naphthalen-2-yl)-1H-indol-3-yl)-N-(naphthalen-2-
ylmethyl)pivalamide (8e): A solution of 1.10 mL (1.10 mmol) of
KO-t-Bu (1 M solution in THF) in 130 mL of dry THF was warmed
to 50 °C. Subsequently, 0.40 g (1.00 mmol) of diimine 6m dissolved
in 20 mL of dry THF was added slowly. The color of the solution
changed to dark red. After 4 h at this temperature, 0.25 mL (2.00
mmol) of trimethyl acetyl chloride was added. The crude product was
purified by recrystallization from DCM: 0.23 g (0.47 mmol, 47%) of
compound 8e was obtained as a light brown solid; mp 237−238 °C;
1H NMR (CDCl3/TFA, 300 MHz) δ = 1.00 ppm (s, 9H), 4.99 (d, J =
1
260−261 °C; H NMR (CDCl3/TFA, 400 MHz) δ = 0.94 ppm (s,
9H), 4.51 (d, J = 13.5 Hz, 1H), 5.49 (d, J = 13.5 Hz, 1H), 6.90 (d, J =
8.0 Hz, 1H), 6.98 (t, J = 7.5 Hz, 1H), 7.12−7.21 (m, 6H), 7.34−7.38
(m, 2H), 7.40−7.46 (m, 4H), 8.36 (br s, 1H); 13C NMR (CDCl3/
TFA, 100 MHz) δ = 28.9 ppm, 41.4, 57.6, 110.3, 111.3, 113.2, 116.0,
117.1, 118.8, 119.3, 121.1, 123.7, 126.0, 126.7, 128.1, 128.4, 128.8,
̃
129.6, 130.1, 130.3, 131.9, 134.0, 136.5, 182.8; IR (neat) ν = 1601
cm−1 (CO); HRMS (ESI) calcd for C26H26N2ONa 405.1937, found
405.1945. Anal. Calcd for C26H26N2O (382.50): C, 81.64; H 6.85; N,
7.23. Found: C, 81.48; H, 6.71; N, 7.52. X-ray crystal structure data of
8a can be found in the Supporting Information.
13.5 Hz, 1H), 5.41 (d, J = 13.5 Hz, 1H), 6.96−7.08 (m, 2H), 7.19−
7.24 (m, 1H), 7.31−7.67 (m, 12H), 7.72−7.76 (m, 3H), 8.46 (br s,
1H); 13C NMR (CDCl3/TFA, 75 MHz) δ = 29.0 ppm, 41.8, 57.8,
108.8, 111.4, 112.6, 116.4, 119.1, 121.3, 123.2, 123.8, 125.4, 126.0,
126.1, 126.6, 127.0, 127.5, 127.5, 127.8, 128.0, 128.0, 128.4, 129.1,
129.6, 132.2, 132.9, 133.0, 133.2, 133.3, 133.7, 134.2, 182.9; IR (neat)
N-(4-Methylbenzyl)-N-(2-p-methylphenyl-1H-indol-3-yl)-pivala-
mide (8b): A solution of 0.55 mL (0.55 mmol) of KO-t-Bu (1 M
solution in THF) in 130 mL of dry THF was heated to 50 °C.
Subsequently, 0.16 g (0.50 mmol) of 6b, dissolved in 20 mL of dry
THF, was slowly added. The color of the solution immediately turned
to deep orange. After 10 min, the reaction mixture was quenched with
0.12 mL (1.00 mmol) of trimethyl acetyl chloride. The product was
recrystallized from DCE: 0.13 g (0.32 mmol, 64%) of compound 8b
ν
̃
= 1612 cm−1 (CO); HRMS (ESI) calcd for C34H30N2OH
483.2431, found 483.2438. Anal. Calcd for C34H30N2O (482.61): C,
84.61; H, 6.27; N, 5.80. Found: C, 84.28; H, 6.26; N, 5.71.
N-(2-(Thien-2-yl)-1H-indol-3-yl)-N-(thien-2-yl-methyl)-pivalamide
(8f): Diimine 6f (0.43 g, 1.39 mmol) was dissolved in 20 mL of dry
THF. Subsequently, the mixture was added slowly to a solution of KO-
t-Bu (1.53 mL, 1.53 mmol, 1 M solution in THF) in 130 mL of dry
THF at 50 °C. The solution immediately turned to dark purple. After
4 h, 0.34 mL (2.78 mmol) of trimethyl acetyl chloride was added: 0.25
g (0.64 mmol, 46%) of compound 8f was obtained as a light yellow
crystals; mp 218−219 °C; 1H NMR (CDCl3, 300 MHz) δ = 0.87 ppm
(s, 9H), 4.19 (d, J = 14.4 Hz, 1H), 5.61 (d, J = 14.4 Hz, 1H), 6.57−
6.58 (m, 1H), 6.64−6.68 (m, 2H), 6.84 (t, J = 7.8 Hz, 1H), 6.99−7.02
(m, 1H), 7.02−7.11 (m, 2H), 7.13−7.17 (m, 2H), 7.22−7.25 (m, 1H),
8.36 (br s, 1H); 13C NMR (CDCl3, 75 MHz) δ = 28.6 ppm, 41.3, 51.9,
111.1, 113.0, 116.5, 116.8, 119.0, 121.2, 123.7, 124.3, 126.3, 126.6,
1
was obtained as a yellow solid; mp 240−241 °C; H NMR (CDCl3/
TFA, 400 MHz) δ = 0.92 ppm (s, 9H), 2.26 (s, 3H), 2.37 (s, 3H), 4.32
(d, 1H, J = 15.0 Hz), 5.44 (d, 1H, J = 15.0 Hz), 6.88−6.95 (m, 4H),
7.10−7.19 (m, 5H), 7.33 (d, J = 8.0 Hz, 1H), 7.41 (d, J = 8.0 Hz, 1H),
8.44 (br s, 1H); 13C NMR (CDCl3/TFA, 100 MHz) δ = 20.1 ppm,
20.2, 29.0, 41.0, 56.1, 110.9, 118.0, 120.0, 120.3, 122.8, 125.7, 127.2,
127.9, 128.7, 129.8, 129.9, 131.7, 133.8, 135.1, 136.8, 138.1, 179.6; IR
(neat) ν
̃
= 1599 cm−1 (CO); HRMS (ESI) calcd for C28H30N2ONa
433.2250, found 433.2260. Anal. Calcd for C28H30N2O (410.55): C,
81.91; H, 7.37; N, 6.82. Found: C, 81.51; H, 7.06; N, 6.75.
N-(4-Chlorbenzyl)-N-(2-p-chlorphenyl-1H-indol-3-yl)-pivalamide
(8c): A solution of 2.08 mL (2.08 mmol) of KO-t-Bu (1 M solution in
THF) in 130 mL of dry THF was warmed to 50 °C. Subsequently,
0.69 g (1.89 mmol) of 6c dissolved in 20 mL dry THF was added
slowly to the stirred mixture. The color of the solution immediately
turned to dark red. After 4 h of stirring, 0.47 mL (3.78 mmol) of
trimethyl acetyl chloride was added. The crude product was purified by
recrystallization from DCE: 0.63 g (1.40 mmol, 74%) of compound 8c
126.7, 128.1, 128.8, 132.0, 134.0, 138.8, 182.1; IR (neat) ν̃ = 1601
cm−1 (CO); HRMS (ESI) calcd for C22H22N2OS2Na 417.1066,
found 417.1071. Anal. Calcd for C22H22N2OS2 (394.55): C, 66.97; H,
5.62; N, 7.10. Found: C, 66.77; H, 5.39; N, 6.99. X-ray crystal structure
data of 8f can be found in the Supporting Information.
N-(4-tert-Butylbenzyl)-N-(2-p-tert-butylphenyl-1H-indol-3-yl)-piv-
alamide (8g): A solution of 1.10 mL (1.10 mmol) of KO-t-Bu (1 M
solution in THF) in 130 mL of dry THF was prepared. Subsequently,
0.41 g (1.00 mmol) of 6g, dissolved in 20 mL of dry THF, was slowly
added to the stirred mixture. The color of the solution turned to dark
red. After 1 h at 50 °C, 0.25 mL (2.00 mmol) of trimethyl acetyl
chloride was added: 0.08 g (0.15 mmol, 15%) of compound 8g was
obtained as light yellow crystals from DE; mp 101−102 °C; 1H NMR
(CDCl3, 300 MHz) δ = 0.94 ppm (s, 9H), 1.26 (s, 9H), 1.33 (s, 9H),
4.37 (d, J = 15.0 Hz, 1H), 5.48 (d, J = 15.0 Hz, 1H), 6.79−6.82 (m,
1H), 6.89 (t, J = 6.0 Hz, 1H), 7.10−7.17 (m, 4H), 7.32−7.46 (m, 6H),
8.57 (br s, 1H); 13C NMR (CDCl3, 75 MHz) δ = 29.1 ppm, 31.3, 31.5,
34.5, 34.8, 41.2, 55.8, 110.9, 117.9, 119.6, 120.3, 122.8, 125.0, 125.7,
126.1, 127.4, 127.9, 129.9, 131.9, 134.0, 135.3 150.4, 151.3, 179.8; IR
1
was obtained as yellow crystals; mp 275−276 °C; H NMR (CDCl3/
TFA, 400 MHz) δ = 0.94 ppm (s, 9H), 4.45 (d, J = 14.0 Hz, 1H), 4.49
(d, J = 14.0 Hz, 1H), 6.95−7.38 (m, 12H), 8.15 (br s, 1H); 13C NMR
(CDCl3/TFA, 100 MHz) δ = 28.9 ppm, 41.7, 56.8, 108.8, 111.5,
112.6, 116.4, 119.0, 120.1, 121.6, 124.2, 127.1, 128.5, 129.8,
131.6,134.3, 134.6, 134.9, 183.0; IR (KBr) ν
̃
= 1593 cm−1 (CO);
HRMS (ESI) calcd for C26H24Cl2N2ONa 473.1158, found 473.1159.
Anal. Calcd for C26H24Cl2N2O (451.39): C, 69.18; H, 5.36; N, 6.21.
Found: C, 69.34; H, 4.99; N, 5.99.
N-(4-Methoxybenzyl)-N-(2-p-methoxyphenyl-1H-indol-3-yl)-piva-
lamide (8d): A solution of 2.03 mL (2.03 mmol) of KO-t-Bu (1 M
solution in THF) in 130 mL of dry THF was heated to 50 °C: 0.66 g
(1.85 mmol) of diimine 6d, dissolved in 20 mL of dry THF, was added
slowly to the stirred mixture. The color of the solution turned to dark
red. The anionic intermediates were quenched with 0.46 mL (3.70
mmol) of trimethyl acetyl chloride. Recrystallization from DCE
afforded the product: 0.70 g (1.59 mmol, 86%) of compound 8d was
obtained as light yellow crystals; mp 224−225 °C; 1H NMR (CDCl3/
TFA, 400 MHz) δ = 0.93 ppm (s, 9H), 3.73 (s, 3H), 3.83 (s, 3H), 4.39
(d, J = 13.2 Hz, 1H), 5.33 (d, J = 13.2 Hz, 1H), 6.64 (d, J = 8.7 Hz,
2H), 6.88 (d, J = 9.0 Hz, 3H), 6.96 (t, J = 7.9 Hz, 1H), 7.12 (d, J = 8.5
Hz, 3H), 7.31 (d, J = 8.1 Hz, 1H), 7.41 (d, J = 8.9 Hz, 2H), 8.40 (br s,
1H); 13C NMR (CDCl3/TFA, 100 MHz) δ = 29.0 ppm, 41.0, 55.2,
55.3, 55.6, 110.8, 113.3, 114.5, 117.3, 119.3, 120.3, 122.6, 123.3, 127.2,
(neat) ν
̃
= 1599 cm −1 (CO); HRMS (ESI) calcd for C34H42N2OH
495.3370, found 495.3366. Anal. Calcd for C34H42N2O (494.71): C,
82.55; H, 8.56; N, 5.66. Found: C, 82.00; H, 8.71; N, 5.57.
N-(2-Methylbenzyl)-N-(2-o-methylphenyl-1H-indol-3-yl)-pivala-
mide (8h): A solution of 1.10 mL (1.10 mmol) of KO-t-Bu (1 M
solution in THF) in 130 mL dry THF was warmed to 50 °C.
Subsequently, 0.33 g (1.00 mmol) of 6o, dissolved in 20 mL dry THF,
was added slowly. The color of the solution changed to dark red. After
2 h at this temperature, 0.25 mL (2.00 mmol) of trimethyl acetyl
chloride was added. The crude product was purified by recrystalliza-
tion from DE: 0.17 g (0.41 mmol, 41%) of compound 8h was obtained
as a colorless solid; mp 102−103 °C; 1H NMR (CDCl3, 300 MHz) δ =
0.98 ppm (s, 9H), 1.95 (s, 3H), 2.20 (s, 3H), 4.75−4.99 (m, 2H),
6.86−6.92 (m, 2H), 6.97−7.04 (m, 3H), 7.08−7.17 (m, 5H), 7.20−
7.29 (m, 2H), 8.21 (br s, 1H); 13C NMR (CDCl3, 75 MHz) δ = 19.2
ppm, 21.0, 29.3, 41.3, 53.7, 111.1, 119.0, 119.5, 120.5, 122.8, 125.7,
̃
127.2, 130.4, 131.3, 131.7, 133.8, 158.9, 159.4, 179.68; IR (KBr) ν =
3217 cm−1 (NH), 1612 (CO); HRMS (ESI) calcd for
C28H30N2O3Na 465.2149, found 465.2149. Anal. Calcd for
8803
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1
126.1, 126.3, 126.9, 128.9, 130.0, 130.3, 130.4, 131.3, 132.9, 133.8,
ammonium chloride (yellow crystals): mp 239−240 °C; H NMR
(CD2Cl2, 300 MHz) δ = 1.34 ppm (t, J = 7.3 Hz, 9H), 3.03 (q, J = 7.3
Hz, 6H), 7.10−7.16 (m, 2H), 7.31−7.61 (m, 9H), 7.88 (d, J = 8.4 Hz,
2H), 8.01 (t, J = 9.1 Hz, 4H), 8.15 (d, J = 8.4 Hz, 2H), 8.27−8.30 (m,
1H), 8.34 (s, 1H), 8.64 (br s, 1H), 8.71 (s, 1H), 9.67 (s, 1H); 13C
NMR (CD2Cl2, 100 MHz) δ = 9.0 ppm, 46.3, 112.1, 120.2, 121.6,
123.7, 125.6, 126.2, 126.8, 127.0, 127.3, 129.2, 129.8, 130.5, 131.8,
136.1, 136.2, 136.6, 180.0; IR (neat) ν
̃
= 1630 cm−1 (CO); HRMS
(ESI) calcd for C28H30N2ONa 433.2250, found 433.2248.
N-Benzyl-N-(2-phenyl-1-pivaloyl-1H-indol-3-yl)pivalamide (9): KO-
t-Bu (0.22 g, 2.00 mmol) was dissolved in 130 mL of 1,4-dioxane and
heated to 90 °C. Then, 0.29 g (1.00 mmol) of diimine 6a in 20 mL
of 1,4-dioxane was added slowly. The color of the reaction mixture
turned to dark red. After 4 h at 90 °C, 0.49 mL (4.00 mmol) of
trimethyl acetyl chloride was added. The workup was performed
analogously to the synthesis of compounds 8. The crude product was
recrystallized from 1,4-dioxane: 0.15 g (0.32 mmol, 32%) of
compound 9 was obtained as colorless crystals; mp 148−149 °C;
1H NMR (CDCl3, 300 MHz) δ = 0.90 ppm (s, 9H), 0.92 (s, 9H), 4.52
(d, J = 12.0 Hz, 1H), 5.23 (d, J = 12.0 Hz, 1H), 7.00−7.08 (m, 2H),
7.13−7.25 (m, 8H), 7.29−7.33 (m, 1H), 7.31−7.38 (m, 3H); 13C
NMR (CDCl3, 100 MHz) δ = 28.1 ppm, 29.2, 41.3, 45.1, 56.6, 111.4,
119.4, 121.2, 122.0, 124.5, 126.0, 127.7, 128.3, 128.8, 128.9, 129.4,
132.1, 132.3, 156.5; IR (neat) ν
̃
= 1603 cm−1 (CN); HRMS (ESI)
calcd for C37H24N2H 497.2012, found 497.2015. X-ray crystal structure
data of 11b can be found in the Supporting Information.
(E)-N-(4-Methoxybenzylidene)-2-(4-methoxyphenyl)-1H-indol-3-
amine (11c): For the synthesis of compound 6d, 0.36 g (1.00 mmol)
of diimine 6d was dissolved in 20 mL of dry THF. The solution was
slowly added to a mixture of 1.10 mL (1.10 mmol) of KO-t-Bu (1.0 M
in THF) in 130 mL of dry THF. After stirring for 2 h at 50 °C, 10 mL
of distilled H2O was added to quench the reactive intermediates. The
product was purified by recycling GPC (toluene) and subsequent
recrystallization from toluene: 0.12 g (0.34 mmol, 34%) of compound
11c was obtained as a yellow solid; mp 156−157 °C; 1H NMR (C6D6,
400 MHz) δ = 3.20−3.27 ppm (m, 1H), 3.30 (s, 3H), 3.31 (s, 3H),
6.26 (d, J = 12.0 Hz, 1H), 6.45−6.51 (m, 2H), 6.77−6.81 (m, 4H),
6.94−7.00 (m, 1H), 7.35−7.40 (m, 2H), 7.69−7.75 (m, 2H), 8.38 (s,
1H); 13C NMR (C6D6, 100 MHz) δ = 54.7 ppm, 54.8, 114.1, 114.3,
115.8, 116.1, 117.0, 118.0, 129.2, 130.6, 131.2, 132.1, 132.8, 134.9,
̃
130.1, 131.6, 133.5, 134.5, 137.9, 179.6, 186.6; IR (neat) ν = 1713
cm−1 (CO), 1638 (CO); HRMS (ESI) calcd for C31H34N2O2Na
489.2512, found 489.2519. Anal. Calcd for C31H34N2O2 (466.61): C,
79.79; H, 7.34; N, 6.00. Found: C, 79.36; H, 7.46; N, 5.92. X-ray
crystal structure data of 9 can be found in the Supporting Information.
General Procedure for the Synthesis of 3-Aminoindole
Derivatives (10a/11a−c). A solution of 1.1 equiv of KO-t-Bu (1.0
M in THF or solid) in dry THF was prepared and heated to 50 °C.
Then, 1.0 equiv of diimine 6, dissolved in dry THF, was added slowly.
Immediately an intense color appeared, and the solution was stirred
for a definite period of time. The reactive anionic intermediates were
quenched by addition of 10 mL of distilled water. Immediately, the
intense color of the solution faded. The organic phase was washed
with saturated NaCl solution and dried over MgSO4. Afterward, the
solvent was removed in vacuo and the product was purified by column
chromatography, recycling GPC (in toluene), and/or recrystallization.
N-(4-Chlorobenzyl)-2-(4-chlorophenyl)-1H-indol-3-amine (10a): Dii-
mine 6c (0.37 g, 1.00 mmol) was dissolved in 20 mL of dry THF and
added slowly to a stirred mixture of 1.10 mL (1.10 mmol) of KO-t-Bu
(1.0 M in THF) in 130 mL of dry THF at 50 °C. The reaction mixture
was stirred for 4 h and subsequently quenched with distilled water.
The color of the solution turned to yellow. The crude product was
purified by recycling GPC (toluene) to give 0.20 g (0.55 mmol, 55%)
as a yellow solid: mp 147−148 °C; 1H NMR (C6D6, 400 MHz)
δ = 3.51 ppm (s, 1H), 3.89 (s, 2H), 6.68 (br s, 1H), 6.73 (d, J =
7.6 Hz, 1H), 6.80 (d, 3J = 7.2 Hz, 2H), 6.96−7.07 (m, 4H), 7.17−7.18
(m, 2H), 7.22−7.26 (m, 1H), 7.43−7.48 (m, 2H); 13C NMR (C6D6,
100 MHz) δ = 53.1 ppm, 111.6, 118.7, 119.9, 123.2, 124.2, 125.2,
125.6, 127.9, 128.2, 128.7, 129.0, 129.0, 129.1, 130.1, 131.1, 131.2,
148.4, 149.7, 158.9, 160.0, 166.6; IR (neat) ν
̃
= 1605 cm−1 (CN)
HRMS (ESI) calcd for C23H20N2O2H 357.1598, found 357.1578. Anal.
Calcd for C23H20N2O2 (356.42): C, 77.51; H, 5.66; N, 7.84. Found: C,
77.54; H, 5.31; N, 7.66.
Procedure for the Synthesis of 2-Phenethyl-3-phenyl-5H-
pyrido[3,2-b]indole (12a). Following the procedure for the syn-
thesis of compounds 8a−h, 0.35 g (1.00 mmol) of compound 7a was
dissolved in 20 mL of dry THF. The mixture was added slowly to a
stirring mixture of 0.12 g (1.10 mmol) of KO-t-Bu in 80 mL of dry
THF and heated to 50 °C. Immediately, the colorless to light yellow
solution turned to dark red. The crude product was recrystallized from
DCM/PE: 0.07 g (0.20 mmol, 20%) of compound 12a was obtained
as a brown oil which was not pure; 1H NMR (CD2Cl2, 300 MHz) δ =
3.01−3.07 ppm (m, 2H), 3.19−3.24 (m, 2H), 6.99−7.59 (m, 14H),
7.54 (s, 1H), 8.38 (m, 1H), 8.98 (br s, 1H); HRMS (ESI) calcd for
C25H20N2H 349.1699, found 349.1690. X-ray crystal structure data of
12a can be found in the Supporting Information.
General Procedure for the Synthesis of Tetraazadibenzocy-
clotetradecaenes (13/14). Under an inert argon atmosphere, a
Schlenk flask was charged with KO-t-Bu (1.0 M solution in THF or
solid) and dry THF. At room temperature, a solution of the diimine 6
in dry THF was slowly added over a period of 30 min. The solution
immediately adopted an intense color. The mixture was stirred for 48 h.
Subsequently, 10 mL of distilled water was added, and the color of the
solution faded within seconds. Fifty milliliters of DE was added, and the
organic phase was washed with distilled water (3 × 50 mL). The solvent
was removed in vacuo, and the product was purified by column
chromatography or recrystallization.
131.5, 133.1, 135.5, 139.2; IR (neat) ν
̃
= 3063 cm−1 (NH); HRMS
(ESI) calcd for C21H16Cl2N2H 367.0763, found 367.0762.
(E)-N-(4-Chlorobenzylidene)-2-(4-chlorophenyl)-1H-indol-3-
amine (11a): Obtained in a mixture with compound 10a and could
be separated by recycling GPC (toluene) and subsequent recrystalliza-
tion from 1,4-dioxane to give 0.17 g (0.47 mmol, 47%) of compound
11a as yellow crystals: mp 159−160 °C; 1H NMR (CD2Cl2, 400
MHz) δ = 7.19−7.23 ppm (m, 1H), 7.26−7.30 (m, 1H), 7.44−7.50
(m, 5H), 8.47 (br s, 1H), 9.12 (s, 1H); 13C NMR (CD2Cl2, 75 MHz)
δ = 112.2 ppm, 120.4, 121.8, 122.1, 124.0, 126.3, 129.3, 129.5, 129.6,
(R,R,R,R)- and (S,S,S,S)-2,3,9,10-Tetraphenyldibenzo[e,l]-1,4,8,11-
tetraazacyclotetradeca-4,6,11,13-tetraene (13a): A solution of
25.48 mL (25.48 mmol) of KO-t-Bu (1.0 M solution in THF) in 40 mL
of dry THF was prepared. The solution immediately turned deep red
when 3.80 g (12.74 mmol) of diimine 6a, dissolved in 20 mL of dry
THF, was added slowly at rt. The mixture was stirred for 24 h.
Distilled water was added to quench the reactive intermediates, and
the solution immediately turned yellow. The crude product was
purified by recrystallization from DE: 1.45 g (2,43 mmol, 38%) was
̃
129.8, 130.8, 132.1, 134.1, 136.2, 136.5, 137.0, 155.3; IR (neat) ν =
1622 cm−1 (CN); HRMS (ESI) calcd for C21H14Cl2N2Na 387.0426,
found 387.0432. Anal. Calcd for C21H14Cl2N2 (365.26): C, 69.05; H,
3.86; N, 7.67. Found: C, 68.69; H, 4.00; N, 7.40. X-ray crystal structure
data of 11a can be found in the Supporting Information.
1
obtained as light yellow crystals; mp 286−287 °C; H NMR (C6D6,
(E)-2-(Anthracen-9-yl)-N-(anthracen-9-yl-methylene)-1H-indol-3-
amine (11b): Diimine 6l (0.25 g, 0.50 mmol) was dissolved in 10 mL
of dry THF and added slowly to a stirring mixture of 0.55 mL (0.55
mmol) of KO-t-Bu in 65 mL of dry THF at 50 °C. Immediately a dark
red color appeared. The reaction mixture was stirred for 4 h and
subsequently quenched with distilled water. The color of the solution
turned to yellow. After addition of TEA, the yellow solid precipitate
was purified by recrystallization from DCM/DE to give 0.12 g (0.25
mmol, 50%) of compound 11b, cocrystallizing with triethyl
400 MHz) δ = 4.56 ppm (s, 2H), 5.32 (d, J = 7.2 Hz, 2H), 6.33 (td, J =
7.2 Hz, J = 0.8 Hz, 2H), 6.44 (d, J = 8.0 Hz, 2H), 6.71 (dd, J = 7.6 Hz,
J = 1.6 Hz, 2H), 6.08−6.85 (m, 2H), 6.97−7.01 (m, 2H), 7.11−7.20
(m, 10H), 7.43 (d, J = 7.6 Hz, 4H), 7.67 (d, J = 7.2 Hz, 4H), 7.81 (s,
2H), 11.52 (d, J = 7.2 Hz, 2H); 13C NMR (C6D6, 100 MHz) δ = 63.0
ppm, 80.3, 112.1, 115.0, 118.0, 127.4, 127.5, 127.7, 128.4, 128.8, 128.9,
132.0, 134.9, 142.7, 143.3, 148.9, 165.9; IR (neat) ν
̃
= 1626 cm−1 (C
N); HRMS (ESI) calcd for C42H36N4H 597.3013, found 597.3016.
8804
dx.doi.org/10.1021/jo201521v|J. Org. Chem. 2011, 76, 8794−8806

The Journal of Organic Chemistry
Article
Anal. Calcd for C42H36N4 (596.76): C, 84.53; H, 6.08; N, 9.39. Found:
C, 84.56; H, 6.05; N, 9.38. X-ray crystal structure data of 13a can be
found in the Supporting Information.
were obtained which could not be separated by column chromatog-
raphy: 0.05 g (0.08 mmol, 14%) of compound 13e was obtained as a
light yellow solid; mp 227−228 °C; 1H NMR (CD2Cl2, 400 MHz) δ =
4.96 ppm (s, 2H, Dia1), 5.12 (s, 2H, Dia2), 5.50 (d, J = 7.6 Hz, 2H,
Dia1+Dia2), 6.56−6.72 (m, 4H, Dia1+Dia2), 6.86−6.94 (m, 4H,
Dia1+Dia2), 7.01−7.09 (m, 4H, Dia1+Dia2), 7.12−7.26 (m, 8H,
Dia1+Dia2), 8.30 (s, 2H, Dia1), 8.39 (s, 2H, Dia2), 11.08 (d, J = 7.6
Hz, 2H, Dia1+Dia2); 13C NMR (CD2Cl2, 100 MHz) δ = 58.7 ppm,
59.3, 74.9, 76.0, 111.1, 111.7, 115.7, 115.8, 118.0, 118.0, 124.9, 125.0,
125.2, 125.4, 125.5, 125.7, 126.6, 126.9, 127.1, 127.2, 128.7, 129.5,
132.6, 132.7, 135.2, 135.3, 145.4, 146.0, 146.6, 146.9, 148.7, 149.1,
(R,R,R,R)- and (S,S,S,S)-2,3,9,10-Tetrakis-(4-chlorophenyl)-
dibenzo[e,l]-1,4,8,11-tetraazacyclotetradeca-4,6,11,13-tetraene
(13b): A solution of 0.89 g (8.00 mmol) of KO-t-Bu in 40 mL of dry
THF was prepared. Subsequently, 1.47 g (4.00 mmol) of compound
6c, dissolved in 20 mL of dry THF, was added slowly. The color of the
solution immediately turned dark purple and changed to yellow after
quenching with distilled water. The crude product was purified by
recrystallization from DCE: 0.52 g (0.72 mmol, 36%) of compound
1
166.9, 167.3; IR (neat) ν
for C34H28N4S4H 621.1270, found 621.1274.
̃
= 1605 cm−1 (CN); HRMS (ESI) calcd
13b was obtained as colorless crystals; mp 230−231 °C; H NMR
(CDCl3, 600 MHz) δ = 4.57 ppm (br s, 2H), 5.19 (d, J = 7.2 Hz, 2H),
6.33 (d, J = 8.4 Hz, 2H), 6.53 (t, J = 7.8 Hz, 2H), 7.04 (t, J = 8.4 Hz,
2H), 7.07 (d, J = 7.8 Hz, 2H.), 7.19−7.23 (m, 4H), 7.26−7.29 (m,
8H), 7.43 (d, J = 8.4 Hz, 4H), 8.09 (br s, 2H), 11.02 (d, J = 7.2 Hz,
2H); 13C NMR (CDCl3, 150 MHz) δ = 61.8 ppm, 78.9, 111.7, 115.3,
117.3, 128.4, 128.5, 128.7, 129.0, 132.2, 133.2, 133.4, 134.8, 140.2,
2,3,9,10-Tetrakis-(4-cyanophenyl)-dibenzo[e,l]-1,4,8,11-tetraaza-
cyclotetradeca-2,4,6,9,11,13-hexaene (14): A solution of 1.39 g
(4.00 mmol) of compound 6h in 20 mL of dry THF was prepared.
The solution was added slowly to a stirred mixture of 8.00 mL (8.00
mmol) of KO-t-Bu (1.0 M solution in THF) in 40 mL of dry THF.
After 24 h, 10 mL of distilled water was added and the dark purple
color of the solution changed to red. The resulting orange solid was
washed with DCM and toluene: 0.29 g (0.41 mmol, 21%) of
140.7, 148.0, 166.1; IR (neat) ν
̃
= 1622 cm−1 (CN); HRMS (ESI)
calcd for C42H32Cl4N4Na 755.1273, found 755.1293. Anal. Calcd for
C42H32Cl4N4 (734.54): C, 68.68; H, 4.39; N, 7.63. Found: C, 68.53;
H, 4.23; N, 7.49. X-ray crystal structure data of 13b can be found in the
Supporting Information.
1
compound 14 was obtained; mp 301−302 °C; H NMR (DMSO-d6,
400 MHz) δ = 7.19 ppm (t, J = 6.8 Hz, 2H), 7.29 (t, J = 7.2 Hz, 2H),
7.50 (d, J = 8.0 Hz, 2H), 7.95−8.00 (m, 8H), 8.12−8.16 (m, 6H),
8.27−8.30 (m, 4H), 9.26 (s, 2H), 12.03 (br s, 2H); 13C NMR ppm
(DMSO-d6, 100 MHz) δ = 109.6 ppm, 111.9, 112.4, 118.9, 119.0,
120.3, 120.6, 121.3, 123.9 126.1, 128.3, 128.6, 131.9, 132.3, 132.7,
(R,R,R,R)- and (S,S,S,S)-2,3,9,10-Tetrakis-(4-bromophenyl)-
dibenzo[e,l]-1,4,8,11- tetraazacyclotetradeca-4,6,11,13-tetraene
(13c): A solution of 7.63 mL (7.63 mmol) of KO-t-Bu (1.0 M
solution in THF) in 40 mL of dry THF was prepared. Then, 1.74 g
(3.81 mmol) of compound 6n in 20 mL of dry THF was added slowly.
Recrystallization from DCM afforded 1.74 g (1.91 mmol, 99%) of the
135.9, 136.3, 141.7, 153.7; IR (neat) ν
̃
= 2236 (CN), 1603 cm−1
(CN); HRMS (ESI) calcd for C46H28N8Na 715.2329, found
1
715.2337.
product as yellow crystals: mp 291−292 °C; H NMR (CD2Cl2, 300
MHz) δ = 4.63 ppm (d, J = 0.9 Hz, 2H), 5.23 (d, J = 7.8 Hz, 2H), 6.36
(d, J = 8.4 Hz, 2H), 6.55 (td, J = 7.5 Hz, J = 0.9 Hz, 2H), 7.03−7.08
(m, 2H), 7.11 (dd, J = 7.8 Hz, J = 1.50, 2H), 7.26−7.29 (m, 4H),
7.40−7.44 (m, 8H), 7.46−7.49 (m, 4H), 8.14 (s, 1H), 11.03 (d, J =
7.8 Hz, 2H); 13C NMR (CD2Cl2, 75 MHz) δ = 62.1 ppm, 79.0, 112.0,
115.8, 117.9, 121.6, 121.7, 129.3, 129.4, 132.0, 132.2, 132.6, 135.3,
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C spectra for the new compounds; optimized
Cartesian coordinates (B3LYP/6-31G(d,p) and SCS-MP2/
6-311+G(d,p)//B3LYP/6-31G(d,p)+ZPE energies for the
calculated structures; graphics of the crystal structures showing
thermal ellipsoids with 50% probability. This material is
available free of charge via the Internet at http://pubs.acs.org.
141.2, 141.8, 148.5, 166.8; IR (neat) ν
̃
= 1622 cm−1 (CN); HRMS
(ESI) calcd for C42H32Br4N4Na 934.9212, found 934.91291. Anal.
Calcd for C42H32Br4N4 (912.35): C, 55.29; H, 3.54; N, 6.14. Found:
C, 55.44; H, 3.61; N, 6.01. X-ray crystal structure data of 13c can be
found in the Supporting Information.
(R,R,R,R)- and (S,S,S,S)-2,3,9,10-Tetra-(2-pyridyl)-dibenzo[e,l]-
1,4,8,11-tetraazacyclotetradeca-4,6,11,13-tetraene (13d): KO-t-Bu
(2.74 mL, 2.74 mmol, 1.0 M solution in THF) was dissolved in 40 mL
of dry THF. Subsequently, 0.41 g (1.37 mmol) of diimine 6i in 20 mL
of dry THF was added slowly to the stirred mixture. The reaction
mixture was stirred overnight at room temperature. Distilled water was
added to quench the reactive anionic species. After adding EA, a
yellow solid precipitate was washed with EA: 0.20 g (0.34 mmol, 49%)
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: wurthwe@uni-muenster.de. Fax: +49-251-83-39772.
Dedication
Dedicated to Prof. Dr. Gerhard Erker at the occasion of his
65th birthday.
1
of compound 13d was obtained as a yellow solid; mp >350 °C; H
NMR (CD2Cl2, 300 MHz) δ = 5.13 ppm (s, 2H), 5.89 (d, J = 8.4 Hz,
2H), 6.49 (t, J = 8.4 Hz, 4H), 7.00−7.06 (m, 4H), 7.11−7.17 (m, 4H),
7.22−7.26 (m, 2H), 7.38 (d, J = 7.7, 2H), 7.53 (td, J = 7.7 Hz, J = 1.7
Hz, 2H), 7.61 (td, J = 7.7 Hz, J = 1.7 Hz, 2H), 8.14 (s, 2H), 8.69 (d,
J = 4.1 Hz, 4H.), 11.07 (d, J = 8.4 Hz, 2H); 13C NMR (CD2Cl2, 100
MHz) δ = 63.4 ppm, 79.4, 112.1 115.4, 117.9, 121.5, 122.5, 122.6,
122.8, 132.5, 135.1, 136.5, 136.6, 149.3, 149.8, 150.4, 161.7, 161.8,
ACKNOWLEDGMENTS
■
This work was supported by the IRTG 1143 Munster-Nagoya
(Deutsche Forschungsgemeinschaft (DFG, Bad Godesberg))
and the Fonds der Chemischen Industrie (Frankfurt).
̈
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167.6; IR (neat) ν
̃
= 1626 cm−1 (CN); HRMS (ESI) calcd for
■
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