1,3,5-Triazapentadienes by Nucleophilic Addition to 1,3- and 1,4-Dinitriles - Sterically Constrained Examples by Incorporation into Cyclic Peripheries: Synthesis, Aggregation, and Photophysical Properties

Article abstract of DOI:10.1021/acs.joc.6b00126

1,3,5-Triazapentadienes usually show U- or twisted S-shaped conformations along the N-C-N-C-N skeleton due to dominating n/π? interactions. If, however, the 1,3,5-triazapentadiene unit is part of a ring, its W conformation might be restricted to the plane

Full text of DOI:10.1021/acs.joc.6b00126

Article
pubs.acs.org/joc
1,3,5-Triazapentadienes by Nucleophilic Addition to 1,3- and 1,4-
DinitrilesSterically Constrained Examples by Incorporation into
Cyclic Peripheries: Synthesis, Aggregation, and Photophysical
Properties
Agnes Johanna Wrobel, Ralph Lucchesi, Birgit Wibbeling, Constantin-Gabriel Daniliuc, Roland Frohlich,
̈
and Ernst-Ulrich Wurthwein*
̈
Organisch-Chemisches Institut der Universitat Munster, Corrensstrasse 40, D-48149 Munster, Germany
̈
̈
̈
S
* Supporting Information
ABSTRACT: 1,3,5-Triazapentadienes usually show U- or
twisted S-shaped conformations along the N−C−N−C−N
skeleton due to dominating n/π* interactions. If, however, the
1,3,5-triazapentadiene unit is part of a ring, its W conformation
might be restricted to the plane. Here, we describe the
synthesis of 13 new 1,3,5-triazapentadienes 10−12, which are
sterically restrained by incorporation into six- or seven-
membered ring systems, by addition of a lithiated primary
amine or hydrazine 5 to a dinitrile 7, 8, or 9 with the two
cyano groups in 1,3 or 1,4 distance. These novel compounds
show very strong tendency for aggregation due to hydrogen
bonding, especially to form homodimers as seen from X-ray data in the solid state. Additional hydrogen bonding generates also
linear chains in the crystal. Several of the new compounds show fluorescence in solution. Quantum chemical DFT calculations
were used for evaluation of the dimerization energies and for interpretation of the photophysical properties.
The aim of the present work is the synthesis of 1,3,5-
triazapentadienes with novel cyclic and aromatic backbones by
integrating the N−C−N− motive of the triazapentadiene into a
six- or seven-membered ring (Scheme 2). These hitherto
unknown compounds are new types of heterocycles, which
promise to be efficient donors and acceptors for hydrogen
bonding, e.g., to form very stable homodimers as well as to
function as excellent ligands for the coordination of metal ions,8
which in the case of Zn(II) complexes are useful catalysts for
lactide polymerization and in the case of Pd(II) complexes for
cross-coupling reactions.
In this study we show that this goal can be achieved by
reaction of deprotonated amines 5 with dinitriles having the
two nitrile groups in a 1,3- or 1,4-distance of an alicyclic or
aromatic backbone. Thus, novel functionalized bi- and tricyclic
heterocycles incorporating 1,3,5-triazapentadiene moieties
became accessible. As alicyclic and aromatic dinitriles, three
different starting materials have been studied: 1,8-dicyanonaph-
thalene 7, 2,2′-dicyanobiphenyl 8, and substituted o-cyanome-
thylbenzonitriles 9a,b as dinitriles with a mixed aliphatic−
aromatic (benzylic) spacer. An additional aspect of this study is
the first use of lithiated hydrazines 5 as nucleophiles in the
reaction with dicyano compounds. This method allows
INTRODUCTION
■
The class of 1,3,5-triazapentadienes 3 has been known for more
than a century.1 These interesting nitrogen-containing
conjugated ligands with an open chain backbone like 3 tend
to prefer U- and twisted S-shaped conformations, the latter due
to n/π* interactions dominating over π /π* interactions, which
would lead to planar structures.2 They are easily prepared by
reaction of imidoyl chlorides 1 and amidines 2 (Scheme 1).1a
However, in a conformationally restricted W-shaped 1,3,5-
triazapentadiene chain, the two n-orbitals at the imino nitrogen
atoms point into the same direction, giving rise to new
possibilities for hydrogen bonding and coordination chemistry.
In this context, 1,3,5-triazapentadienes 6,6′, where the three
central C−N−C atoms are part of a five-membered
dihydropyrrole ring, have been studied previously in our
group (Scheme 2).3,4 These derivatives 6,6′ were synthesized
by reaction of lithiated amines 5 with tetramethylsuccinonitrile
4.5,6 The deprotonated amine attacks one of the two
electrophilic nitrile carbon atoms forming an amidinate center
that itself reacts with the second nitrile group. Thus, a 1,3,5-
triazapentadiene anion is formed which is protonated during
aqueous workup. If a primary amine is used, in some cases an
additional proton shift leads to the tautomer 6′ shown in
Scheme 2. A 3-fold application of this cyclization procedure to
give fused tricyclic heterosystems was recently published by
Gorman et al.7
Received: January 19, 2016
© XXXX American Chemical Society
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Scheme 1. 1,3,5-Triazapentadienes from Imidoylchlorides and Amidines1a
2,2′-Dicyanobiphenyl 8 was prepared in a partially optimized
way from 9,10-phenanthrenequinone and sulfamide and
subsequent pyrolysis at 600 °C (Scheme 4).10 In the solid
state the two aryl moieties of 8 are twisted by 135.5° with
respect to the central single bond (for X-ray details see SI).
Scheme 2. 1,3,5-Triazapentadienes, Incorporated into
a
Five-,3,4 Six-, and Seven-Membered Rings
Scheme 4. Synthesis of Dinitrile 8 from 9,10-
Phenanthrenequinone
a
Spacer = 1,3- or 1,4-aromatic (7,8) and 1,3-benzylic-aromatic (9)
backbones.
Compounds 9a,b were prepared in 69% and 83% yield by
double alkylation at the benzylic position of 2-cyanomethyl-
benzonitrile using either ethyl iodide or 1,4-dibromobutane in
the presence of aqueous sodium hydroxide solution following a
literature phase transfer procedure (see Scheme 5).13 It should
introduction of a further nitrogen atom into the unsaturated
chain.
Depending on the chemical distance of the two cyano groups
either six-membered heterocycles (from 7 and 9) or seven-
membered systems (from 8) were expected.9 The tricyclic
triazapentadienes obtained from 7 and 8 consist only of sp2-
hybridized carbon and nitrogen atoms and contain formally 12
Scheme 5. Synthesis of the Dinitriles 9a,b from 2-
Cyanomethylbenzonitrile
π electrons, indicating anti-Huckel-aromatic behavior. In
̈
contrast, the ring-forming reactions starting from 9b lead to
the generation of novel bicyclic spiro systems.
In addition to the synthesis, the structural properties in the
solid state with special regard to hydrogen bonding as well as
the UV−vis spectroscopic properties of these conjugated
heterosystems were the subject of this investigation. Quantum
chemical DFT calculations were used for evaluation of
dimerization energies and for interpretation of the UV−vis
spectra.
be mentioned that 2-cyanomethylbenzonitrile itself does not
yield 1,3,5-triazapentadienes upon treatment with lithiated
amines but is, as expected, deprotonated at the benzylic
position.
RESULTS AND DISCUSSION
Cyclization Reaction of Dinitriles 7−9. Treatment of
lithiated primary amines or hydrazines 5 with dinitriles 7, 8, and
9 first at −78 °C and then at room temperature or 45 °C in dry
THF allowed the synthesis of various 1,3,5-triazapentadienes
and 1,2,4,6-tetrazahexatrienes (1-amino-1,3,5-triazapenta-
dienes) with a naphthalene backbone 10a−e (Type A), a
biphenyl backbone (11a−c Type B), or an isoquinoline
backbone (12a−e Type C or D) after aqueous workup.
Scheme 6 and Table 1 summarize the products 10−12
obtained from the dinitriles 7−9 and various nucleophiles 5.
Thus, from dinitrile 7 (1,8-dicyanonaphthalene) and lithiated
primary aromatic amines three triazapentadienes 10a−c of the
benz[de]isoquinoline (or 2-azaphenylene) type A were
synthesized in satisfactory yield; nonaromatic amines only
reacted in traces with this dinitrile. Lithiated N,N-dimethyl
hydrazine and N-methyl-N-phenyl hydrazine reacted with 1,8-
■
Starting Materials. 1,8-Dicyanonaphthalene 7 was pre-
pared from acenaphthenequinone and sulfamide (H2N−SO2−
NH2) to form acenaphtho[1,2-c-]-1,2,5-thiadiazol-1,2-dioxide
and subsequent thermolysis at 150 °C according to literature
procedures (Scheme 3).10−12
Scheme 3. Synthesis of Dinitrile 7 from
Acenaphthenequinone
B
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Scheme 6. Overview over the Synthetic Routes Leading to 1,3,5-Triazapentadienes 10−12 with Aromatic or Benzylic Backbones
by Reaction of Lithiated Primary Amines and Hydrazines 5 with Dinitriles 7−9 (see Table 1)
Table 1. Substitution Pattern, Structural Type, and Yields for
1,3,5-Triazapentadienes 10−12
Scheme 7. Site of the Nucleophilic Attack at Substituted 2-
Cyanomethyl Benzonitriles and Resulting Products of Type
C and D
product
type
R
R1, R2
yield [%]
10a
10b
10c
10d
10e
11a
11b
11c
12a
12b
12c
12d
12e
A
A
A
A
A
B
B
B
C
C
C
C
D
ph
64
48
50
94
97
26
14
47
45
97
46
42
45
ptol
2-pyridyl
−N(Me)2
−N(Me)Ph
ptol
2-pyridyl
−N(Me)2
ptol
reaction pathway. In addition to 12e, an impure hydrolysis
product 13 could be isolated in 5% yield and characterized by
X-ray diffraction (Scheme 8).
Et
Et
−N(Me)2
ptol
−(CH2)4−
−(CH2)4−
−(CH2)4−
NMePh
2-pyridyl
Scheme 8. Synthesis of the 1,3,5-Triazapentadienes 12e by
Reaction of Lithiated Primary Amines with the Benzylic
Dinitrile 9b and Hydrolysis To Give Product 13
dicyanonaphthalene 7 to give 1,2,4,6-tetraazahexatetraenes
10d,e in excellent yields (Scheme 6, Table 1).
2,2′-Dicyanobiphenyl 8 reacts in a similar manner with
deprotonated primary amines or hydrazines 5 to give the seven-
membered heterocyclic compounds 11a−c of the dibenz[c,e]-
azepine type B, although mostly in modest yield (Scheme 6,
Table 1).
In contrast to the symmetrical dinitriles 7 and 8, compound
9 contains two chemically different cyano groups: one of them
is attached to an aromatic moiety and the other to a benzylic
quarternary carbon atom; thus, the formation of two
regioisomeric 3,4-dihydroisoquinolin-1-amines (type C) and
1,4-dihydroisoquinolin-3-amines (type D) may be expected
(Scheme 7).
Lithiated primary amines attack in the first step preferentially
the cyano group at the aromatic moiety of 9a or 9b before the
intramolecular ring closure reaction by nucleophilic addition to
the benzylic cyano group takes place as seen in the isoquinoline
derivatives 12a−d, which all show structural type C (Scheme 6,
Table 1). In contrast, use of the lithiated 2-aminopyridine as
nucleophile leads in a 45% yield to product 12e of structural
type D with an intramolecular hydrogen bond, resulting from
initial attack at the benzylic cyano group (for X-ray see below).
Possibly, the two coordination sites for the lithium counterion
of the attacking nucleophile may have an influence on the
The carbon atom of a cyano group bound to a sp3 carbon
atom is supposed to be more electrophilic compared to the
corresponding carbon atom bound to a sp2-hybridized carbon
atom of an aromatic ring, as the latter interacts electronically by
conjugation with the π-system of the aromatic ring. This is well
in line with NBO charges14 of 9b based on a geometry
optimization at the DFT level M062x/6-311++G(d,p)//
M062x/6-311++G(d,p).15,16 According to these calculations
C
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Scheme 9. Synthesis of the 1,3,5-Triazapentadienes 12f,g by Reaction of Lithiated Secondary Amines with the Benzylic
Dinitriles 9a,b and Hydrolysis to N-Acylamidine 14
the nitrile carbon atom attached to the aromatic moiety has a
positive natural charge of +0.279 e and the one bound to the
spiro cycle a slightly higher charge of +0.295e. In comparison,
the calculated NBO charges at the nitrogen atoms of typical
nitrogen nucleophiles like N-deprotonated aniline (−0.892 e)
and 2-aminopyridine (amine anion −0.870 e, pyridyl −0.625 e,
calculated without counterions) indicate similar nucleophilic-
ities for both reagents at the deprotonated amine groups.
Furthermore, two secondary lithiated amines were examined
in reactions with dinitrile 9. Whereas product 12f (from
lithiated pyrrolidine) could be obtained in 48% yield after
aqueous workup, the corresponding product 12g (from
lithiated piperidine) could not be isolated but was obtained
as hydrolysis product (N-acylamidine) 14 after aqueous workup
in 58% yield. Both examples confirm again the preferred attack
of the nucleophile at the cyano group bound to the aromatic
ring (Scheme 9). In general, N-acylamidines have found
Figure 1. Homodimeric structure of 10b in the solid state (Schakal
plot).
manifold applications in metal coordination.17
Structural Properties. Due to their conjugated multiple π-
bonds all 1,3,5-triazapentadienes reported here are highly
potent hydrogen bond donor and acceptor molecules, thus
being typical examples for the concept of resonance-assisted
hydrogen bonding.18 This is convincingly seen in the solid state
X-ray diffraction structures we were able to obtain from several
of these novel compounds. In most cases, homodimers with
strong 2-fold hydrogen bridges were found; in some cases,
cocrystallizing solvent (water or acetone) led to chain
structures. 2-Pyridyl substituents as in 10c favor strong
intramolecular hydrogen bonding; here, a monomer with
additional intermolecular contacts was obtained. Of special
interest is also compound 11c, where a chain structure of
enantiomers of conformer 11c-B with additional peripheral
enantiomeric conformers 11c-A is observed.
Derivatives with a Naphthyl Backbone 10a−e. X-ray
analyses of 10a and 10b show the formation of homodimers in
the form of eight-membered rings involving two N−C−N
subunits in the solid state with N−N distances in 10a of 3.02 Å
and in 10b of 3.12 Å; for comparison, the sum of the van der
Waals radii of two N atoms amounts to 3.10 Å19 (Figure 1 for
the X-ray structure of 10b), thus indicating quite strong
hydrogen bonding. The gas-phase dimerization energy of 10b
calculated by the DFT functional M062x using the 6-311+
+G(d,p) basis set and the Grimme GD3 dispersion correction20
amounts to −29.13 kcal/mol (complete geometry optimization
including zero-point energy; Gaussian 0915). This value is
significantly larger compared, for example, to the aggregation
energy of the adenine−thymine nucleobase pair (−14.14 kcal/
mol) at the same level of theory and is in a similar range as the
guanine−cytosine base pair (−27.57 kcal/mol) which shows
three hydrogen bridges.21
Triazapentadiene 10c shows another tautomeric form in the
solid phase compared to triazapentadienes 10a and 10b (see
Figure 2) due to strong intramolecular hydrogen bonding
caused by the proton attached to N2 and the nitrogen atom of
the pyridine substituent. The respective intramolecular N−N
bond distance amounts to 2.62 Å. In addition to the
intramolecular hydrogen bond, also intermolecular hydrogen
bonding is observed, leading to a network of molecules as
shown in Figure 2. The intermolecular N−N distances amount
to 3.09 Å. As anticipated, triazapentadienes 10a−c show almost
planar triazapentadiene chains with dihedral angles along the
backbone close to 180°, in contrast to noncyclic examples2
(10a: N1−C2−N2−C6 −175.21°, C2−N2−C6−N3 −
178.64°; 10b: N1−C2−N2−C6 −174.53°, C2−N2−C6−N3
179.85°; 10c: N1−C2−N2−C6 179.31°, C2−N2−C6−N3
179.22°).
Formally, the 1H-benz[de]isoquinoline or 2-aza-phenalenyl
compounds 10a−c accommodate each of the 12 π-electrons in
the tricyclic system, which, according to the Huckel definition,
̈
means that these molecules have to be considered to be
antiaromatic in character. Indeed, X-ray analyses show quite
long bond lengths for the C2−C3 and C5−C6 bonds of 1.48
(10b) and 1.47 Å (10c) (see Figure 2). These values are very
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Figure 2. Intra- and intermolecular hydrogen bonding in the solid state structure of 10c shown from two perspectives (Schakal and XP plots).
close to those of nonconjugated Csp2−Csp2 single bonds (1.48
Å) and much longer than aromatic Csp2−Csp2 bonds (1.39 Å in
benzene).22 Hence, electronic interaction of the 1,3,5-
triazapentadiene chain with the naphthalene backbone is
substantially reduced by pushing the triazapentadiene subunit
away in order to avoid the unfavorable antiaromatic character,
thus achieving two electronically better separated π-systems.23
Derivatives with a Biphenyl Backbone 11. The X-ray
structure of 2-pyridyl derivative 11b also shows the formation
of homodimers from two monomeric enantiomers and one
molecule of water. The molecules are connected via two NH−
N hydrogen bonds (N1−N2′ and N2−N1′ 3.03 Å) involving
two of the three 1,3,5-triazapentadiene nitrogen atoms and bind
additionally to two molecules of water (N1−O1 and N1′−O2
2.90 Å, N4−O2 and N4′−O1 2.88 Å; see Figure 3) with the
pyridyl nitrogen atoms as hydrogen bond acceptors. In 11b and
in the tetrazahexatetraene 11c the phenyl moieties of the
biphenyl system are twisted by about 40° relative to each other.
Consequently, the triazapentadiene chain is also bent out of
plain (11b: N(H2)−C−N−C 166.7°, C−N−C−N(py)
−141.1°). Similarly, as in compounds 10, here also the 1,3,5-
triazpentadiene subunit is quite distant from the biphenyl
Figure 3. Homodimeric structure of 11b in the solid state (Schakal
plot).
moiety (C−C bond lengths: C4−C5 1.487 Å and C1−C6
1.493 Å), indicating the absence of strong aromatic interactions
between both subunits.
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Figure 4. Linear arrangement of 11b (XP plot).
Figure 5. Linear arrangement of enantiomeric molecules 11c-B with neighboring molecules of type 11c-A bonded by 2-fold hydrogen bonds in the
solid state. Furthermore, acetone molecules are hold by hydrogen bonding to 11c-A (XP plot).
Furthermore, for 11b chain-like structures are observed.
These are formed by intermolecular hydrogen bonds from N1−
H to an oxygen atom of water followed by a hydrogen bond
from OH to N1 as acceptor (N−O 2.90 Å). Each molecule has
a parallel adjustment to its next but one neighbor (see Figure
4).
Characteristic for the solid state structure of 11c is the
presence of crystallographically independent molecules 11c-A
and 11c-B. Thus, enantiomeric molecules of structural type
11c-B form by alternating arrangement of linear chains based
on intermolecular hydrogen bonding (N2B−N3B 3.083 Å)
(Figures 5 and 6). Each of the chain molecules 11c-B is also
part of a homodimer formed by 2-fold hydrogen bonding
(N1B−N2A 3.072 Å, N1A−N2B 3.075 Å) to the respective
enantiomer of conformer 11c-A with slightly different structural
properties compared to 11c-B as best seen from the torsional
angles. Furthermore, one molecule of acetone (from the
recrystallization) cocrystallizes per dimer via hydrogen bonding
using the second NH of N2A. Thus, all available NH moieties
are subject to hydrogen bonding.
The calculated gas-phase dimerization energy for the
Figure 6. Packing of 11c as determined by X-ray analysis involving
formation of a homodimer of 11c amounts to −15.34 kcal/
mol. This is about 14 kcal/mol less in comparison to the
dimerization energy of the six-membered system 10b, probably
due to conformational ring strain exerted by the seven-
membered ring with regard to the hydrogen bonding ability.
also hydrogen bonding to acetone molecules. View along the c axis
(XP plot).
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6-311++G(d,p)+GD3+ZPE level.15,24 Transition state structure
11c-TS was localized by scanning the rotation about the
biphenyl axis as well as using the QST2 approach25 and verified
by IRC calculations.26 It is characterized by a relatively planar
triazapentadienyl subunit and a substantially twisted biphenyl
torsional angle (Figure 7). Thus, at room temperature in
solution an equilibrium between both enantiomers is expected.
Derivatives with an Isoquinoline Backbone 12. The
compounds with isoquinoline substructures 12a−d and 12f
form also homodimers in the solid state (see Supporting
Information). As a structural example the X-ray structure of 12a
(type C, Scheme 6) is shown in Figure 8. The triazapentadiene
chain is almost planar (N1−C1−N2−C2 171.10°, C1−N2−
C2−N3 173.02°). The formation of the homodimeric structure
is based on 2-fold intermolecular hydrogen bonding (NH−N
3.01 Å).
Figure 7. Calculated structures, biphenyl torsional angles of atoms
C3−C4−C5−C6 (for atom numbering see Figure 5), and relative
energies of 11c and transition structure 11c-TS (M062x/6-311+
+G(d,p)//M062x/6-311++G(d,p)+GD3+ZPE) (Gaussview plot).
In derivative 12e (structural type D, Scheme 6) a linear
arrangement of molecules is formed due to intermolecular
hydrogen bonding (N−N distance amounts to 2.98 Å, see
Figure 9). To each molecule of 12e one molecule of acetone,
which was used for crystallization, is attached by N−O
hydrogen bonding with a N−O distance of 2.99 Å. The
triazapentadiene chain is twisted, which is visualized by dihedral
angles of −172.54° for the N1−C1−N2−C2 chain and
−160.10° for the C1−N2−C2−N3 chain (see Figure 9).
N-Acylamidine 13 is a hydrolysis product of 12e. 13 forms
stable dimers with its tautomer bonded by 3-fold hydrogen
bonding in the solid state (see Figure 10). The calculated gas-
phase dimerization energy (M062x/6-311++G(d,p)+gd3+zpe)
amounts to −20.04 kcal/mol (with respect to the sum of both
tautomers).
For the homodimeric tetraazatetraenes 12b,d the structure of
12b is shown here as an example (Figure 11). Besides the
“normal” hydrogen bonding as seen in the other examples
(N1−N2′; N−N distance 3.01 Å), here also bifurcated
hydrogen bonding involving the tertiary hydrazine nitrogen
atom is found, with the NH2 group (N1) acting as hydrogen
bond donor and the nitrogen atoms N2 and N4 acting as
hydrogen bond acceptors (N1−N4′; N−N distance 3.06 Å).
For 12d, the corresponding hydrogen bond parameters amount
to 2.94 and 2.933 Å, indicating a stronger interaction compared
to 12b. The triazapentadiene chains are slightly twisted as
shown by the dihedral angles (12b: N1−C1−N2−C2 178.49°,
C1−N2−C2−N3: 172.51°, N2−C3−N3−N4 −3.27°; 12d:
Figure 8. Homodimeric structure of 12a in the solid state (Schakal
plot).
This observation is supported by the relatively long measured
N−N distances.
By rotation about the central biphenyl C−C single bond,
conformer 11c can be converted into its enantiomer by passing
a significantly less twisted (about 22°) transition state 11c-TS
with a relative energy of 18.2 kcal/mol according to quantum
chemical calculations at the M062x//6-311++G(d,p)//M062x/
Figure 9. X-ray structure of 12e with intermolecular hydrogen bonds (Schakal plot).
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substituted imines (aza-vinylogous amidines) as seen by their
UV−vis absorption properties. Furthermore, the three 1,3,5-
triazapentadienes 10a−c and the tetraazahexadienes 10e show
fluorescence (at relatively high concentrations of about 10−4
mol/L) in dichloromethane solution. The tetraazahexadiene
12d shows a more intense fluorescence in solution (at 10−5
mol/L). In contrast, 10d does not show any fluorescence, and
10e exhibits only very weak emission. Table 2 summarizes
characteristic values of the absorption and emission spectra
(including the irradiation wavelength for the fluorescence) as
well as the TD-DFT results for the calculated absorption
properties. The Stokes shifts amount to approximately 90−150
nm (5000−8600 cm−1).
In order to interpret the spectroscopic absorption data TD-
DFT (CAM-B3LYP/6-311+G(d,p)//CAM-B3LYP/6-311+G-
(d,p) including dichloromethane as solvent (IEF-PCM))
calculations were performed for the monomeric compound
10c as well as for the monomer and homodimers of
compounds 10a,b and 12d. In general, the calculated shapes
of the spectra match reasonably well with the experimental
curves. The deviations between experimental and calculated
longest wavelength maxima amount to 0.09−0.49 eV. The
calculated maxima and the assignment for the respective
transitions are shown in Table 2.
Figure 10. X-ray structure of 13 with N−O and N−N hydrogen bond
distances (Schakal plot).
As expected, compounds 10a and 10b exhibit similar UV−vis
properties (10b: Figure 12, for spectra of 10a see SI) with the
typical two-band pattern. The emission at about 500 nm leads
to a Stokes shift of 149 nm (8570 cm −1) with the almost
perpendiculary placed N-substituent not taking extensively part
in conjugation to the triazapentadienyl moiety. We assume the
presence of dimeric structures of 10a,b also in solution as found
in the solid state. The quantum-chemical calculations for 10b
indicate a blue shift of about 19 nm due to dimerization. The
calculated longest absorption maximum for 10b deviates from
the experimental value by 9 nm (0.09 eV) for the dimer and 19
nm (0.27 eV) for the monomer. The main transitions are
assigned to HOMO → LUMO, HOMO−1 → LUMO, and
HOMO → LUMO+1 transitions (Figure 13). Interestingly, the
occupied orbitals HOMO and HOMO−1 show large
coefficients both at the central moiety and also at the N-
substituent, whereas LUMO and LUMO−1 only have large
coefficients at the main part of the molecule, indicating the
possibility of intramolecular charge transfer (ICT).
Figure 11. Derivative 12b as homodimer in the solid state (Schakal
plot).
N1−C1−N2−C2 −175.88°, C1−N2−C2−N3: −170.53°,
N2−C3−N3−N4 5.10°).
For 12b the calculated gas-phase dimerization energy
(M062x/6-311++G(d,p)+GD3+ZPE) amounts to −24.09
kcal/mol and that for 12d −31.26 kcal/mol, which is well in
line with shorter measured and calculated hydrogen bond
distances of 12d.
Photophysical Properties of 1,3,5-Triazapentadienes.
In general, compounds 10−12 are mostly yellow (12) or red
(10) solids, indicating their dyestuff nature as donor−acceptor-
The UV−vis absorption and emission spectra of the
monomeric derivative 10c, which is expected to be planar in
Table 2. Characteristic Experimental Absorption and Emissions Data (measured in dichloromethane, c = 1.0 × 10−4 mol/L) and
Calculated Absorption Spectra (dichloromethane, TD-CAM-B3LYP/6-311+G(d,p)/6-311+G(d,p)) of the Derivatives 10b, 10c,
and 12d (see SI for details)
absorption maxima [nm]
calculated longest wavelength absorption maxima [nm],
emission maxima [nm]
(irradiation wavelength)
compound
(ε [L·M−1·cm−1])
oscillator strength f, assignment
10b
349 nm (16 085)
243 nm (35 238)
monomer: 377.6, f = 0.470, HOMO → LUMO
498 (350)
monomer: 320.8, f = 0.129, HOMO−1 → LUMO
dimer: 358.0, f = 0.797, HOMO−1 → LUMO, HOMO → LUMO+1
dimer: 315.5, f = 0.241, HOMO−3 → LUMO+1, HOMO−2 → LUMO
342.3, f = 0.767, HOMO → LUMO)
10c
12d
365 nm (31 554)
249 nm (44 820)
506 (350)
471 (415)
301.7, f = 0.089, HOMO−1 → LUMO
monomer: 334.8, f = 0.269, HOMO → LUMO
a
378 (7902)
a
256 (38 757)
monomer: 268.6, f = 0.104, HOMO → LUMO+3
dimer: 330.8, f = 0.594, HOMO → LUMO+1, HOMO−1 → LUMO
a
c = 1.0 × 10−5 mol/L
H
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Figure 13. Four frontier orbitals from HOMO−1 to LUMO+1
(orbital numbers 74−77) (CAM-B3LYP/6-311+G(d,p)//CAM-
B3LYP/6-311+G(d,p) calculated including dichloromethane as
solvent (IEF-PCM)) and Lewis formula (top left) of 10b (Gaussview
plot).
Figure 12. Absorption spectrum (normalized and molar extinction,
solid line) and emission spectrum (normalized emission, dashed line,
irradiation at 350 nm) measured in dichloromethane (top) and
calculated absorption spectra for the monomeric form (solid line) and
the dimer (dashed line) (bottom, CAM-B3LYP/6-311+G(d,p)//
CAM-B3LYP/6-311+G(d,p) including dichloromethane as solvent
(IEF-PCM)) of 10b.
solution due to the intramolecular hydrogen bridge, are shown
in Figure 14. The UV−vis spectrum is characterized by a broad
longest wavelength absorption at 365 nm and a typical aromatic
band at about 250 nm. The red shift of the longest wavelength
absorption in comparison to 10a,b may be taken as a hint for
their nonplanar structures (see Figure 1). The emission
spectrum shows a single, broad band at about 500 nm,
resulting in a Stokes shift of about 140 nm (7630 cm−1).
According to TD-DFT calculations we assign the longest
wavelength absorption maximum of 10c (calculated at 342 nm,
deviation 23 nm = 0.22 eV) to a HOMO → LUMO transition
(see Figure 15). Both the HOMO and the LUMO show
coefficients all over the molecule with characteristic nodal
patterns along the 1,3,5-triazapentadienyl subunit.
For 12d absorption maxima are detected in the UV spectrum
at 256 and 378 nm, thus red-shifted compared to 10b,c (Figure
16). In contrast to compounds 10 and 11 the triazapentadienyl
moiety of compound 12 is not involved in thorough cyclic
conjugation. Relatively strong emission is observed at 471 nm,
resulting in a small Stokes shift of 5224 cm−1. TD-DFT
calculations give two maxima (238 and 334 nm, see SI) in less
satisfactory agreement with the measured values (deviation of
0.42 and 0.46 eV). On the basis of the calculations excitation of
an electron from the HOMO to the LUMO is assigned to the
maximum at 335 nm, while the transition from HOMO−1 to
LUMO contributes to the maximum at 238 nm (Figure 17).
HOMO−1 and the HOMO have large coefficients at the
triazapentadienyl subunit and at the N-substituent. The LUMO
has large coefficients at the backbone but not at the N-
Figure 14. Absorption spectrum (normalized and molar extinction,
solid line) and emission spectrum (normalized emission, dashed line,
irradiation at 350 nm) measured in dichloromethane (top) and
calculated absorption spectrum (bottom, CAM-B3LYP/6-311+G-
(d,p)//CAM-B3LYP/6-311+G(d,p) calculated including dichloro-
methane as solvent (IEF-PCM)) of 10c.
I
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Article
Figure 16. Absorption spectrum (normalized and molar extinction,
solid line) and emission spectrum (normalized emission, dashed line,
irradiation at 415 nm) measured in dichloromethane (top) and
calculated absorption spectra for the monomeric form (solid line) and
the dimer (dashed line) (bottom, CAM-B3LYP/6-311+G (d,p)//
CAM-B3LYP/6-311+G(d,p) including dichloromethane as solvent
(IEF-PCM)) of 12d.
Figure 15. Four frontier orbitals from HOMO−1 to LUMO+1
(orbital numbers 70−73) (CAM-B3LYP/6-311+G(d,p)//CAM-
B3LYP/6-311+G(d,p) calculated including dichloromethane as
solvent (IEF-PCM)) and Lewis formula (top left) of 10c (Gaussview
plot).
substituent, indicating internal charge transfer (ICT) (Figure
17).
CONCLUSION
■
Starting from three different types of dinitriles 7−9 (featuring
1,3- or 1,4-nitrile distances) three novel types of sterically
constrained 1,3,5-triazapenta-1,3-dienes (and 1,2,4,6-tetraaza-
hexa-2,4-dienes) 10−12 were synthesized by nucleophilic
addition of lithiated amines or hydrazines 5 and subsequent
protonation by aqueous workup. According to X-ray diffraction
studies the resulting polycyclic heterocyclic compounds show
strong tendencies to aggregation, either by homodimerization
due to 2-fold hydrogen bridging or by formation of infinite
chains or a combination of both in the solid state. This
aggregation behavior suggests the use of these novel ligands
also for metal coordination. The yellow to red 1,3,5-
triazapentadienyl compounds 10−12 have the chromophore
of an aza-vinylogous amidine, which is well recognized from the
UV−vis spectra. High-level TD-DFT calculations including the
dichloromethane solvent sphere were used to evaluate the
dimerization energies and to assign the electronic transitions.
Some of the new compounds show fluorescence upon
irradiation with UV light.
EXPERIMENTAL SELECTION
■
Figure 17. Four frontier orbitals from HOMO−1 to LUMO+1
(orbital numbers 84−87) (CAM-B3LYP/6-311+G(d,p)//CAM-
B3LYP/6-311+G(d,p) calculated including dichloromethane as
solvent (IEF-PCM)) and Lewis formula (top left) of 12d (Gaussview
plot).
General. All solvents were dried by standard methods. When
necessary, the experiments were carried out with complete exclusion of
moisture using argon, septum and syringe technique, and glassware,
which was thoroughly dried by heating under vacuum and subsequent
1
venting with argon. NMR spectra were recorded at 298 K: H 300.13
J
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MHz and 13C 75.48 MHz; 1H 400.03 and 13C 100.59 MHz; 1H 499.85
2-(1-Cyano-cyclopentyl)-benzonitrile (9b). In analogy to the
literature procedure by Snow et al.13 sodium hydroxide (19.78 g, 0.5
mol) was dissolved in water (150 mL). 2-Cyanophenyl cyanomethane
(3.58 g, 25.2 mmol), tetrabutylammonium bromide (0.48 g, 1.5
mmol), and 1,4-dibromobutane (6.52 g, 30.0 mmol) were added. The
reaction mixture was stirred for 3 days, poured onto ice, and extracted
three times with ethyl acetate. The combined organic layers were dried
with sodium sulfate, and the solvent was removed under reduced
pressure. The crude product was purified by column chromatography
(pentane/ethyl acetate, 15:1 → 10:1); 4.14 g (21.1 mmol, 83%) of 9b
was obtained as colorless oil. Rf = 0.32 (pentane/ethyl acetate = 15:1).
1
MHz and 13C 125.67 MHz; H 599.79 MHz and 13C 150.83 MHz.
Assignments of the resonances were supported by 2D experiments and
referenced internally to residual solvent resonances (chemical shift
data in δ). 13C NMR spectra were all proton decoupled. IR spectra
were recorded as Nujol mull between CsI plates or with an ATR
sampling system. Electron impact (EI) mass and electrospray
ionization (ESI) spectra were recorded. Elemental analyses were
determined by the microanalytic laboratory in our institute. Melting
points are uncorrected.
1,8-Dicyanonaphthaline 7 was prepared according to literature
procedures.10−12
̃
IR: ν = 610 (s), 633 (vs), 654 (s), 667 (s), 677 (s), 764 (s), 827 (w),
2,2′-Dicyanobiphenyl (8). In our work, an optimized pathway for
the synthesis of compound 8 was adapted from a literature
procedure10 as follows: 10.2 g (38 mmol) of phenanthro[9,10-
c][1,2, 5]thiadiazole, 2,2-dioxide10,27 was divided into 5 portions of
about 2 g. Each of them was dissolved in little dry acetone and put into
a 100 mL Schlenk flask. This solution was freed from the solvent using
a rotatory evaporator, resulting in a thin film at the flask. This flask was
then equipped with a foam brake and a reflux condenser filled with
glass wool. Under a weak argon stream the flask was heated to about
630 °C using a heat gun. The resulting product 8 precipitated in the
foam brake, reflux condenser, and at the glass wool, from which it was
washed off using dichloromethane. This procedure was repeated for
each of the portions. The resulting solutions of the raw products were
brought together, freed from the solvent in vacuo, and dissolved in a
minimal amount of boiling dry chloroform. After cooling to room
temperature and filtering off the insoluble residue, the yellow solution
was freed from the solvent in vacuo. Product 8 was obtained as yellow
solid (mp 173 °C, 173 °C10) in a yield of 3.5 g (17 mmol, 45%, lit.:10
80%). C14H8N2 (204.23): HRMS (ESI) m/z: [M + Na]+ Calcd for
C14H8N2Na 227.0577. Found 227.0580. The other analytical data are
in coincidence with literature data.28 For X-ray crystal structure data
see the Supporting Information.
2-(1-Cyano-1-ethyl-propyl)-benzonitrile (9a). This compound was
prepared in analogy to a procedure by Snow et al.13 To a solution of
sodium hydroxide (7.5 g, 0.19 mol) in 70 mL of water 2-cyanomethyl
benzonitrile (1.4 g, 10 mmol), tetrabutylammonium bromide (0.2 g,
0.6 mmol) and ethyl iodide (4.7 g, 30 mmol) were added. The
reaction mixture was stirred for 2 days and poured onto ice. The
aqueous layer was extracted with ethyl acetate three times. The
combined organic layers were dried with magnesium sulfate.
Subsequent purification by flash chromatography (pentane/ethyl
acetate =10:1) gave 1.4 g (6.9 mmol, 69%) of 3a as colorless oil. Rf
957 (vw), 1169 (vw), 1194 (vw), 1233 (vw), 1287 (vw), 1323 (vw),
1445 (s), 1483 (s), 1597 (m), 2226 (vs), 2322 (w), 2342 (w), 2361
(m), 2878 (m), 2918 (w), 2961 (s), 3076 (vw) cm−1. 1H NMR
(300.13 MHz, CDCl3): δ = 2.00−2.18 (m, 4 H, CH2), 2.27−2.42 (m,
3
4
2 H, CH2), 2.63−2.76 (m, 2 H, CH2), 7.46 (td, J = 7.5 Hz, J = 1.4
3
3
4
Hz, 1 H, CHar), 7.46 (td, J = 7.7 Hz, J = 8.1 Hz, J = 1.5 Hz, 1 H,
3
4
4
CHar), 7.77 (ddd, J = 7.6 Hz, J = 0.5 Hz, J = 1.5 Hz, 1 H, CHar)
ppm. 13C NMR (75.47 MHz, CDCl3): δ = 24.6 (CH2), 39.4 (CH2),
47.8 (Cq), 111.2, 118.0, 122.8 (2 CN, i-Car), 127.8 (CHar), 128.6
(CHar), 133.3 (CHar), 135.7 (CHar), 142.3 (i-Car) ppm. HRMS (ESI)
m/z: [M + Na]+ Calcd for C13H12N2Na 219.0893. Found 219.0888.
Anal. Calcd for C13H12N2 (196.27): C, 79.56; H, 6.16; N, 14.27.
Found: C, 79.28; H, 6.06; N, 14.26.
General Procedure for the Synthesis of 1,3,5-Triazapenta-
1,3-dienes and 1,2,4,6-Tetraazahexa-2,4-dienes. In analogy to
the literature procedure by Wurthwein et al.3 a secondary or primary
̈
amine or a hydrazine was dissolved in dry tetrahydrofuran and cooled
to −78 °C. One equivalent of n-butyllithium (1.6 M solution in n-
hexane) was added dropwise. The reaction mixture was stirred at −78
°C for 30 min or the specified time and at room temperature for 1 h or
the time stated, before it was cooled to −78 °C again. A solution of the
respective dinitrile 7−9 in tetrahydrofuran was added, and the solution
was slowly warmed to room temperature and stirred at room
temperature or 45 °C overnight. The reaction was quenched by
addition of water, and the aqueous layer was extracted with diethyl
ether three times. The combined organic layers were dried with
magnesium sulfate, and the solvent was removed under reduced
pressure.
3-Phenylimino-3H-benzo[de]isoquinolin-1-ylamine (10a). 10a
was obtained from a solution of aniline (0.56 g, 6.0 mmol) in 10
mL of tetrahydrofuran, n-butyllithium (3.75 mL, 6.0 mmol) and a
solution of 7 (0.53 g, 3.0 mmol) in 100 mL of tetrahydrofuran
according to the general procedure. Subsequent crystallization from
acetone gave 0.52 mg (1.92 mmol, 64%) of 10a as red solid (mp 120
̃
= 0.32 (pentane/ethyl acetate = 10:1). IR: ν = 617 (m), 667 (w), 741
(w), 750 (w), 768 (vs), 791 (s), 895 (m), 934 (w), 962 (vw), 997
(vw), 1026 (m), 1038 (w), 1084 (m), 1124 (vw), 1167 (w), 1194
(vw), 1207 (vw), 1260 (vw), 1285 (vw), 1325 (m), 1348 (m), 1383
(m), 1414 (vw), 1441 (vs), 1460 (s), 1470 (vs), 1481 (vs), 1503 (vw),
1514 (vw), 1530 (w), 1551 (w), 1574 (w), 1597 (s), 1612 (w), 1620
(w), 1632 (w), 1641 (w), 1649 (w), 1659 (w), 1666 (w), 1680 (vw),
1692 (vw), 1836 (vw), 1958 (vw), 1992 (vw), 2222 (vs), 2237 (w),
2326 (vw), 2342 (vw), 2357 (vw), 2880 (w), 2938 (w), 2959 (m),
2968 (s), 2978 (s), 3071 (vw), 3605 (vw), 3624 (vw), 3638 (vw),
3665 (vw), 3684 (vw), 3705 (vw), 3717 (vw), 3740 (vw), 3748 (vw),
3790 (w), 3811 (w), 3829 (vw), 3848 (w), 3860 (w), 3877 (vw), 3896
(vw), 3912 (vw) cm−1. 1H NMR (400.13 MHz, CDCl3): δ = 0.93 (t, 3J
̃
°C, decomp.). IR: ν = 669 (m), 683 (s), 702 (vs), 766 (vs), 799 (w),
826 (w), 839 (s), 907 (w), 926 (w), 934 (w), 972 (w), 1024 (w), 1032
(vw), 1057 (w), 1065 (w), 1076 (w), 1117 (m), 1152 (m), 1167 (w),
1194 (w), 1231 (s), 1246 (w), 1306 (s), 1352 (m), 1387 (s), 1441 (s),
1485 (vs), 1497 (vs), 1526 (vs), 1570 (vs), 1585 (m), 1611 (s), 1655
(vs), 1715 (vw), 1749 (vw), 1809 (vw), 1877 (vw), 1944 (vw), 2720
(vw), 2776 (vw), 2889 (vw), 3053 (m, br), 3325 (w), 3456 (s) cm−1.
UV−vis (DCM): λAbs (ν
̃
, ε) = 240 nm (41 666 cm−1, 25 683 L M−1
cm−1), 349 nm (28 653 cm−1, 9081 L M−1 cm−1). Fluorescence
(DCM, 10−4 mol/L, λIrradiation = 380 nm): λEm (ν
̃
) = 498 nm (20 080
cm−1), 513 nm (19 493 cm−1). 1H NMR (300 MHz, CDCl3): δ = 1.61
(s, 1 H, CH3), 7.12−7.04 (m, 2H, CHar), 7.18 (dd, J = 10.4, 4J = 4.3
3
2
= 7.4 Hz, 6 H, CH3), 2.19 (dq, J = 17.7 Hz, 3J = 7.4 Hz, 2 H, CH2),
Hz, 1 H, CHar), 7.47−7.38 (m, 2 H, CHar), 7.60 (d, 3J = 5.2 Hz, 2 H,
2.54 (dq, 2J = 17.7 Hz, 3J = 7.4 Hz, 2 H, CH2), 7.46 (dt, 3J = 7.6 Hz, 4J
= 1.1 Hz, 1 H, NCCipsoCHarCHar), 7.65 (dt, 3J = 7.8 Hz, 4J = 1.5 Hz, 1
H, CqCipsoCHarCHar), 7.77 (dd, 3J = 7.6 Hz, 4J = 1.1 Hz, 1 H,
3
3
4
CHar), 7.68 (dd, J = 8.1, 7.5 Hz, 1 H, CHar), 8.00 (dd, J = 8.2, J =
0.9 Hz, 1 H, CHar), 8.10−8.04 (m, 1 H, CHar), 8.70 (dd, 3J = 7.4, 4J =
1.1 Hz, 1 H, CHar). 13C NMR (100.62 MHz, (CD3)2SO): δ = 119.6
(Cipso,naph), 121.7 (p-CHph), 122.9 (CHph), 124.5, 126.1, 126.5, 126.9
(CHnaph), 127.2 (Cipso,naph), 128.1 (CHph), 129.0 (Cipso,naph), 130.0
(CHnaph), 131.8 (Cipso,naph), 132.3 (CHnaph), 151.6 (Cipso,ph), 154.2,
159.9 (CN) ppm. HRMS (ESI) m/z: [M + H]+ Calcd for C18H14N3
272.1182. Found 272.1191. Anal. Calcd for C18H13N3 (271.32): C,
79.68; H, 4.83; N, 15.49. Found: C, 79.43; H, 4.52; N, 15.41. For X-
ray crystal structure data see the Supporting Information.
3
4
NCCipsoCHar), 7.85 (dd, J = 8.0 Hz, J = 0.7 Hz, 1 H, CqCipsoCHar)
ppm. 13C NMR (100.62 MHz, CDCl3): δ = 10.2 (CH3), 31.7 (CH2),
51.9 (Cq), 108.9 (CipsoCN), 118.5 (CipsoCN), 121.4 (CqCN), 128.5
(CNCipsoCHarCHar), 130.7 (CqCipsoCHar), 133.4 (CqCipsoCCHarCHar),
136.3 (CNCipsoCHar), 140.6 (CHarCipso) ppm. HRMS (ESI) m/z: [M
+ Na]+ Calcd for C13H14N2Na 221.1049. Found 221.1041.
Anal. Calcd for C13H14N2 (198.27): C, 78.75; H, 7.12; N, 14.13.
Found: C, 78.53; H, 7.24; N, 14.05.
K
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[3-Amino-benzo[de]isoquinolin-(1Z)-yliden]-p-tolyl-amine (10b).
10b was obtained from a solution of p-toluidine (0.10 g, 1.0 mmol) in
5 mL of tetrahydrofuran and n-butyllithium (0.63 mL, 1.0 mmol)
according to the general procedure. 7 (0.12 mg, 1.0 mmol) was
however dissolved in 15 mL of bromobenzene and added to the
reaction mixture. The solution was stirred for 2 h before it was
quenched. Subsequent crystallization from toluene gave 0.13 g (0.5
(vs), 837 (vs), 926 (m), 989 (vs), 1016 (w), 1038 (vw), 1078 (vw),
1126 (w), 1225 (w), 1317 (m), 1352 (vw), 1364 (vw), 1381 (w), 1418
(w), 1437 (m), 1466 (w), 1501 (m), 1528 (vs), 1585 (vw), 1603 (vw),
1636 (s), 1734 (vw), 1987 (vw), 2021 (vw), 2052 (vw), 2168 (vw),
2191 (vw), 2222 (vw), 2326 (vw), 2361 (vw), 2770 (vw), 2814 (vw),
2853 (w), 2951 (vw), 3057 (vw), 3146 (vw), 3157 (vw), 3167 (vw),
1
3310 (vw), 3319 (vw), 3329 (vw) cm−1. H NMR (300.13 MHz,
CDCl3): δ = 2.70 (s, 6 H, CH3), 7.54−7.60 (m, 2 H, CHar), 7.92 (dd,
̃
mmol, 46%) of 10b as red solid (mp 239−240 °C). IR: ν = 653 (m),
4
682 (m), 715 (m), 725 (w), 773 (vs), 785 (w), 810 (m), 840 (m), 856
(m), 881 (vw), 933 (w), 964 (vw), 974 (vw), 1016 (vw), 1029 (w),
1056 (vw), 1074 (vw), 1105 (w), 1116 (w), 1161 (w), 1192 (vw),
1207 (vw), 1230 (w), 1242 (vw), 1307 (m), 1350 (w), 1386 (m),
1435 (m), 1498 (vs), 1527 (vs), 1570 (s), 1585 (w), 1608 (s), 1652
(vs), 1894 (vw), 1951 (vw), 2027 (vw), 2036 (vw), 2085 (vw), 2094
(vw), 2139 (vw), 2162 (vw), 2185 (vw), 2248 (vw), 2360 (vw), 2717
(vw), 2918 (vw), 3018 (w), 3319 (w), 3072 (w), 3055 (w), 3450 (s)
3J = 8.2 Hz, J = 1.0 Hz, 1 H, CHar), 7.98−8.06 (m, 2 H, CHar), 8.49
(dd, 3J = 7.4 Hz, 4J = 1.1 Hz, 1 H, CHar) ppm. 13C NMR (75.48 MHz,
CDCl3): δ = 47.5 (CH3), 121.8 (Cipso), 124.0 (123.96, CHar), 124.0
(123.99, CHar), 124.8 (Cipso), 125.9, 126.8 (CHar), 128.5 (Cipso), 129.7,
131.9 (CHar), 132.6 (Cipso), 150.0, 155.8 (CN) ppm. HRMS (ESI)
m/z: [M + H]+ Calcd for C14H15N4 239.1290. Found 239.1291.
3-(Methyl-phenyl-hydrazono)-3H-benzo[de]isoquinolin-1-yl-
amine (10e). 10e was obtained from a solution of N-methyl-N-
phenylhydrazine (0.96 g, 7.9 mmol) in 20 mL of tetrahydrofuran, n-
butyllithium (4.9 mL, 7.8 mmol), and a solution of 7 (0.90 g, 5.1
mmol) in 130 mL of tetrahydrofuran according to the general
procedure. In this case, the solution of the dinitrile was cooled to −78
°C and the solution of the deprotonated hydrazine was added. The
crude product was purified with flash chromatography (dichloro-
methane/triethylamine, 10:1) twice. The product was solved in
toluene and filtered over Celite. The Celite was washed thoroughly
with toluene; 1.46 g (4.9 mmol, 97%) of 10e as dark purple solid was
obtained (mp 162 °C, decomp.). Rf = 0.51 (dichloromethane/
cm−1. UV−vis (DCM): λAbs (ν
̃
, ε) = 243 nm (41 152 cm−1, 35 238 L
M
−1 cm−1), 349 nm (28 653 cm−1, 16 085 L M−1 cm−1). Fluorescence
(DCM, 10−4 mol/L, λIrradiation = 350 nm): λEm (ν
̃
) = 498 nm (20 080
1
cm−1). H NMR (300.13 MHz, (CD3)2SO): δ = 2.28 (s, 3H, CH3),
6.98−7.09 (m, 4H, CHar), 7.64−7.73 (m, 2H, CHar), 7.45−8.05 (br,
3
4
3
2H, NH2), 8.12 (dd, J = 8.15 Hz, J = 0.8 Hz, 1H), 8.20 (d, J = 8.1
Hz, 1H) 8.28 (d, 3J = 6.8 Hz, 1H), 8.56 (dd, 3J = 7.4, 4J = 1.1 Hz, 1H)
ppm. 13C NMR (75.48 MHz, (CD3)2SO): δ = 20.6 (CH3), 119.6
(Cipso), 123.0 (CHph), 124.4, 126.1, 126.3, 126.9 (CHnaph), 127.3
(Cipso), 128.6 (CHph), 129.0 (Cipso), 129.8 (CHnaph), 130.5 (Cipso),
131.8 (Cipso), 132.3(CHnaph), 154.0, 159.7 (CN) ppm. HRMS (ESI)
m/z: [M + H]+ Calcd for C19H16N3 286.1339. Found 286.1340. Anal.
Calcd for C19H15N3 (M = 285.34): C, 79.98; H, 5.30; N, 14.73. Found:
C, 79.73; H, 5.07; N, 14.49. For X-ray crystal structure data see the
Supporting Information.
̃
triethylamine = 10:1). IR: ν = 615 (m), 665 (w), 691 (vs), 708 (m),
721 (vw), 750 (vs), 764 (vs), 773 (s), 785 (vs), 799 (vw), 837 (m),
856 (vw), 872 (w), 901 (m), 957 (w), 964 (w), 991 (m), 1026 (m),
1080 (w), 1097 (s), 1155 (vw), 1184 (w), 1202 (vw), 1233 (w), 1290
(s), 1310 (vs), 1350 (w), 1385 (w), 1416 (w), 1435 (m), 1458 (w),
1487 (vs), 1528 (s), 1591 (s), 1641 (vs), 2874 (vw), 2909 (vw), 3046
(1Z)-1-(Pyridin-2-ylimino)-1H-benzo[de]isoquinolin-3-amine
(10c). 10c was obtained from a solution of 2-aminopyridine (1.04 g,
11.0 mmol) in 15 mL of tetrahydrofuran, n-butyllithium (6.9 mL, 11.0
mmol), and a solution of 7 (1.78 g, 10.0 mmol) in 200 mL of
tetrahydrofuran according to the general procedure. The reaction
mixture was refluxed for 5 h and quenched afterward. The crude
product was crystallized twice from toluene, giving 0.27 g (1.5 mmol,
(w, br), 3285 (vw), 3482 (w) cm−1. UV−vis (DCM): λAbs (ν
̃
, ε) = 469
nm (21 322 cm−1, 29 742 L M−1 cm−1). Fluorescence (DCM, 10−4
1
mol/L, λIrradiation = 480 nm): λEm (ν
̃
) = 595 nm (16805 cm−1). H
NMR (300 MHz, CDCl3) δ = 3.36 (s, 3 H, CH3), 6.89 (t, 3J = 7.2 Hz,
1 H, CHar), 7.11−7.20 (m, 2 H, CHar), 7.22−7.34 (m, 2 H, CHar),
7.58 (dd, 3J = 8.2, 7.5 Hz, 1 H, CHar), 7.60−7.67 (m, 1 H, CHar), 7.92
(d, 3J = 7.2 Hz, 1 H, CHar), 7.96 (dd, 3J = 8.2, 4J = 0.8 Hz, 1 H, CHar),
̃
50%) of 10c as red solid (mp 166 °C, decomp.). IR: ν = 617 (w), 679
3
3
4
8.03 (d, J = 7.9 Hz, 1 H, CHar), 8.71 (dd, J = 7.5, J = 1.1 Hz, 1 H,
CHar). 13C NMR (75.47 MHz, (CD3)2SO): δ = 41.0 (CH3), 113.7
(CHph), 117.8 (CHar), 119.9 (Cipso), 123.2 (CHar), 123.5 (CHar), 126.1
(CHar), 126.8 (CHar), 127.1 (Cipso), 127.8 (CHar), 128.5 (CHph), 128.9
(Cipso), 131.5 (CHar), 132.2 (Cipso), 148.7, 151.2, 156.2 (N-Cipso, C
N, CN) ppm. HRMS (ESI) m/z: [M + H]+ Calcd for C19H17N4
301.1448. Found 301.1452. Anal. Calcd for C19H16N4 (300.36): C,
75.98; H, 5.37; N, 18.65. Found: C, 76.00; H, 5.35; N, 18.63.
(vw), 700 (s), 714 (vw), 733 (vs), 770 (vs), 843 (s), 870 (s), 916 (w),
932 (w), 941 (w), 974 (w), 993 (s), 1028 (w), 1049 (w), 1078 (w),
1097 (w), 1128 (m), 1146 (w), 1155 (m), 1165 (w), 1200 (m), 1236
(vs), 1256 (s), 1267 (s), 1279 (m), 1287 (m), 1323 (vs), 1356 (s),
1369 (w), 1387 (m), 1418 (s), 1447 (s), 1464 (vs), 1491 (s), 1522
(vs), 1547 (s), 1566 (s), 1587 (s), 1603 (w), 1626 (m), 1672 (vs),
1711 (vw), 1771 (vw), 3003 (s), 3038 (s), 3225 (w), 3358 (vw) cm−1.
UV−vis (DCM): λAbs (ν
cm−1), 365 nm (27 397 cm−1, 31 554 L M−1 cm−1). Fluorescence
(DCM, 10−4 mol/L, λirradiation = 350 nm): λEm (ν
) = 506 nm (broad,
̃
, ε) = 249 nm (40 160 cm−1, 44 820 L M−1
5-(p-Tolylimino)-5H-dibenzo[c,e]azepin-7-amine (11a). 11a was
obtained from a solution of p-toluidine (0.32 g, 3.0 mmol) in 30 mL of
tetrahydrofuran, n-butyllithium (1.9 mL, 3.0 mmol), and a solution of
8 (0.61 g, 3.0 mmol) in 15 mL of tetrahydrofuran according to the
general procedure. The crude product was crystallized from toluene.
Some unreacted 2,2′-dicyanobiphenyl (8) could be separated from the
filtrate. The residue was purified by flash chromatography (tert-
butylmethyl ether + 5% triethylamine). Subsequent crystallization
from acetonitrile/dichloromethane gave 0.24 g (0.8 mmol, 26%) of
11a as yellow solid (mp 197−199 °C). Rf = 0.43 (tert-butylmethyl
̃
1
3
19763 cm−1). H NMR (400.13 MHz, (CD3)2SO): δ = 6.95 (t, J =
6.1, 2 H, CHar), 7.64 (dt, 3J = 6.8, 4J = 1.7, 1 H, CHar), 7.67−7.79 (m,
2 H, CHar), 8.19 (dd, 3J = 8.1, 4J = 0.8, 1 H, CHar), 8.25 (d, 3J = 8.1, 1
H, CHar), 8.35 (t, 3J = 6.5, 1 H, CHar), 8.59 (dd, 3J = 6.6, 3J = 0.9, 1 H,
CHar) ppm. 13C NMR (100.62 MHz, (CD3)2SO): δ = 117.4 (CHar),
117.7 (Cipso), 119.5 (Cipso), 125.1, 126.2 (CHar), 126.4 (Cipso), 127.0
(126.98), 127.0 (127.01) (CHar), 128.8 (Cipso), 130.7 (CHar), 131.8
(CHar), 132.6 (CHar), 136.6 (CHar), 148.0 (CHar), 155.1, 160.0, 164.2
(CN) ppm. HRMS (ESI) m/z: [M + H]+ Calcd for C17H13N4
273.1135. Found 273.1133. Anal. Calcd for C17H12N4 (272.30): C,
74.98; H, 4.44; N, 20.58. Found: C, 74.61; H, 4.43; N, 20.18. For X-
ray crystal structure data see the Supporting Information.
̃
ether + 5% triethylamine). IR: ν = 615 (w), 669 (m), 687 (m), 712
(vw), 743 (vs), 764 (w), 775 (s), 808 (vs), 841 (vw), 864 (w), 937
(vw), 953 (vw), 986 (vw), 1018 (w), 1034 (w), 1055 (w), 1065 (vw),
1111 (w), 1136 (vw), 1165 (vw), 1179 (vw), 1227 (m), 1261 (w),
1319 (vs), 1379 (w), 1404 (vs), 1437 (m), 1504 (s), 1570 (vs), 1587
(vs), 1628 (s), 1709 (vw), 2336 (vw), 2359 (vw), 2864 (vw), 2916
(vw), 3022 (vw), 3051 (vw), 3063 (vw), 3136 (w), 3258 (vw), 3296
3-(Dimethyl-hydrazono)-3H-benzo[d,e]isoquinolin-1-ylamine
(10d). 10d was obtained from a solution of N,N-dimethylhydrazine
(0.35 mL, 0.27 mg, 4.5 mmol) in 10 mL of tetrahydrofuran, n-
butyllithium (2.80 mL, 4.5 mmol), and a solution of 7 (0.53 g, 3.0
mmol) in 40 mL of tetrahydrofuran according to the general
procedure. The mixture was warmed to 50 °C overnight; 0.39 mg
(2.83 mmol, 94%) of 10d was obtained as red resin. Further
purification was not possible due to the sensitivity of the compound.
1
(vw), 3445 (w) cm−1. H NMR (300.13 MHz, (CD3)2SO): δ = 2.24
(s, 3 H, CH3), 6.72 (d, 3J = 8.1 Hz, 2 H, CHar), 7.03 (d, 3J = 8.1 Hz, 2
H, CHar), 7.15 (s, br, 2 H, NHar), 7.47−7.60 (m, 3 H, CHar), 7.60−
7.71 (m, 2 H, CHar), 7.71−7.81 (m, 3 H, CHar) ppm. 13C NMR (75.47
MHz, CDCl3): δ = 20.5 (CH3), 109.6, 122.6, 127.2, 127.5, 127.9,
128.0, 128.1, 128.6, 129.0, 129.7, 130.7 (CHar), 131.5, 133.0, 134.9,
̃
IR: ν = 613 (vs), 644 (s), 667 (vw), 719 (vw), 770 (vs), 799 (w), 824
L
DOI: 10.1021/acs.joc.6b00126
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
137.5, 142.3, 147.3 (Cipso), 157.6, 158.9 (CN) ppm. HRMS (ESI)
m/z: [M + H]+ Calcd for C21H18N3 312.1495. Found 312.1493. Anal.
Calcd for C21H17N3 (311.38): C, 81.00; H, 5.50; N, 13.49. Found: C,
80.94; H, 5.62; N, 13.11.
[7-Amino-dibenzo[c,e]acepin-(5Z)-yliden]-pyridin-2-ylamine
(11b). 11b was obtained from a solution of 2-aminopyridine (0.28 g,
3.0 mmol) in 10 mL of tetrahydrofuran, n-butyllithium (1.9 mL, 3.0
mmol), and a solution of 8 (0.41 g, 2.0 mmol) in 20 mL of
tetrahydrofuran according to the general procedure. However, in this
case, the solution of the dinitrile was cooled to −78 °C and the
solution of the deprotonated amine was added. Subsequent
crystallization from toluene and dichloromethane gave 0.14 mg (0.4
3126 (w), 3319 (vw), 3462 (m) cm−1. 1H NMR (400.13 MHz,
3
CDCl3) δ = 0.53 (t, 6 H, J = 7.3, CH2CH3), 1.54−1.63 (m, CH2),
1.89−1.98 (m, CH2), 2.39 (s, 3 H, CH3), 6.84 (d, 3J = 8.1, 2 H, CHar),
3
3
7.15 (d, J = 8.0, 2 H, CHar), 7.25 (d, J = 9.2, 1 H, CqCipsoCHar),
3
4
7.30−7.34 (m, 1 H, CimCHarCHar), 7.45 (dt, J = 8.0, J = 1.4, 1 H,
CHar), 8.38 (dd, 3J = 7.9, 4J = 1.2, 1 H, CHar) ppm. 13C NMR (100.62
MHz, CDCl3): δ = 9.2 (CH2CH3), 21.3 (CarCH3), 35.7 (CH2), 47.7
(Cq), 122.4 (CHar), 124.0 (CqCipsoCHar), 126.7, 126.8 (CimCipsoCHar,
CimCipsoCHarCHar), 128.7 (CqCipso), 129.3 (CHar), 130.9
(CqCipsoCHarCHar), 130.9 (CH3Cipso), 139.3 (CimCipso), 149.8
(NCipso), 153.3 (CipsoN−CN), 170.9 (NC−NH2) ppm. HRMS
(ESI) m/z: [M + H]+ Calcd for C20H24N3 306.1965. Found 306.1963.
Anal. Calcd for C20H23N3 (305.42): C, 78.65; H, 7.59; N, 13.76.
Found: C, 78.50; H, 7.76; N, 13.49. For X-ray crystal structure data see
the Supporting Information.
̃
mmol, 14%) of 11b as colorless solid (mp 157−158 °C). IR: ν = 613
(vs), 642 (s), 689 (m), 735 (vs), 770 (s), 775 (vs), 791 (w), 864 (w),
878 (vw), 959 (w), 995 (m), 1034 (m), 1051 (w), 1061 (w), 1096
(vw), 1123 (w), 1150 (w), 1163 (vw), 1179 (w), 1244 (m), 1265 (s),
1287 (w), 1325 (vs), 1423 (vs), 1437 (vw), 1466 (s), 1485 (vw), 1497
(vw), 1553 (vs), 1570 (m), 1585 (s), 1595 (m), 1655 (m), 1674 (w),
(1Z)-1-(Dimethylhydrazinylidene)-4,4-diethyl-1,4-dihydroisoqui-
nolin-3-amine (12b). 12b was obtained from a solution of N,N-
dimethylhydrazine (0.73 mL, 0.57 g, 9.5 mmol) in 20 mL of
tetrahydrofuran, n-butyllithium (5.96 mL, 9.5 mmol), and a solution of
9a (1.71 g, 8.6 mmol) in 20 mL tetrahydrofuran according to the
general procedure; 2.12 g (8.4 mmol, 97%) of 12b was obtained as
1
3003 (vw), 3065 (w), 3107 (w), 3335 (vw) cm−1. H NMR (300.13
MHz, (CD3)2SO): δ = 6.65 (d, 3J = 7.0 Hz, 1 H, CHar), 6.95 (dd, 3J =
3
6.4, J = 5.0, 1 H, CHar), 7.32 (s, br, 2 H, NH2), 7.50−7.71 (m, 5 H,
CHar), 7.71−7.86 (m, 4 H, CHar), 8.29 (dd, 3J = 4.8, 4J = 1.0 Hz, 1 H,
CHar) ppm. 13C NMR (75.47 MHz, (CD3)2SO): δ = 116.8 (CHar),
118.2 (CHar), 127.5 (CHar), 127.8 (CHar), 128.0 (CHar), 128.2 (CHar),
128.3 (CHar), 129.4 (CHar), 129.7 (CHar), 130.8 (CHar), 132.8 (Cipso),
134.9 (Cipso), 136.9 (CHar), 137.3 (Cipso), 141.6 (Cipso), 148.3 (CHar),
158. Nine (CN), 160.6 (CN), 162.8 (CN) ppm. HRMS (ESI)
m/z: [M + H]+ Calcd for C19H15N4 299.1291. Found 299.1280. Anal.
Calcd for C19H14N4 (298.34), C19H14N4·H2O: C, 72.13; H, 5.10; N,
17.71. Found: C, 72.27; H, 5.19; N, 17.57. For X-ray crystal structure
data see the Supporting Information.
̃
yellow solid without further purification (mp 140 °C). IR: ν = 664
(w), 687 (vs), 716 (w), 758 (s), 777 (s), 814 (w), 849 (m), 903 (w),
945 (w), 961 (m), 974 (vs), 1011 (m), 1036 (w), 1088 (vw), 1125
(vw), 1155 (s), 1171 (w), 1206 (w), 1223 (w), 1258 (vw), 1308 (m),
1339 (vs), 1377 (w), 1393 (w), 1402 (w), 1425 (w), 1439 (s), 1452
(s), 1470 (w), 1483 (m), 1539 (vs), 1591 (m), 1609 (m), 1636 (m),
2776 (w), 2816 (w), 2860 (w), 2876 (w), 2943 (w), 2968 (m), 3030
1
(vw), 3073 (w), 3279 (vw), 3505 (s) cm−1. H NMR (400.13 MHz,
CDCl3): δ = 0.60 (t, 3J = 7.3 Hz, 6 H, CH2CH3), 1.98 (q, 3J = 7.3 Hz,
4 H, CH2), 2.62 (s, 6 H, N(CH3)2), 6.45−7.21 (br, 2 H, NH2), 7.26−
7.32 (m, 2 H, CHar), 7.40−7.48 (m, 2 H, CHar), 8.24 (dd, 3J = 8.4 Hz,
4J = 1.5 Hz, 1 H, CHar) ppm. 13C NMR (100.62 MHz, CDCl3): δ =
7-(Dimethyl-hydrazono)-7H-dibenzo[c,e]-azepin-5-ylamine
(11c). 11c was obtained from a solution of N,N-dimethylhydrazine
(0.37 mL, 288 mg, 4.8 mmol) in 10 mL of tetrahydrofuran, n-
butyllithium (3.0 mL, 4.8 mmol), and a solution of 8 (817 mg, 4.0
mmol) in 20 mL of tetrahydrofuran according to the general
procedure. Subsequent crystallization from toluene gave 1.51 g (5.0
9.1 (CH2CH3), 36.4 (CH2), 47.4 (N(CH3)2), 49.0 (Cq), 124.5 (CHar),
124.7 (CHar), 126.5 (CHar), 128.3 (i-Car), 130.7 (CHar), 138.5 (i-Car),
149.8 (Cim), 165.9 (Cim) ppm. HRMS (ESI) m/z: [M + H]+ Calcd for
C15H23N4 259.1917. Found 295.1916. Anal. Calcd for C15H22N4
(258.36): C, 69.73; H, 8.58; N, 21.69. Found: C, 69.69; H, 8.18; N,
21.57. For X-ray crystal structure data see the Supporting Information.
3-Amino-(1Z)-ylidene-p-tolyl-amin-spiro[cyclopentan-1′,4-4H-
isoquinoline] (12c). 12c was obtained from a solution of p-toluidine
(1.39 g, 12.9 mmol) in 10 mL of tetrahydrofuran, n-butyllithium (8.1
mL, 13.0 mmol), and a solution of 9b (2.11 g, 11.8 mmol) in 10 mL of
tetrahydrofuran according to the general procedure. Subsequent
crystallization from toluene gave 1.51 g (5.0 mmol, 46%) of 12c as
̃
mmol, 46%) of 11c as colorless solid (mp 179−180 °C). IR: ν = 615
(w), 664 (vs), 679 (s), 737 (vs), 768 (vs), 835 (w), 866 (m), 874 (m),
955 (w), 988 (vs), 1018 (s), 1034 (m), 1055 (w), 1123 (w), 1144 (w),
1169 (vw), 1179 (vw), 1217 (w), 1231 (w), 1261 (w), 1321 (s), 1389
(m), 1398 (w), 1435 (w), 1443 (w), 1468 (w), 1483 (w), 1497 (vw),
1537 (vw), 1557 (m), 1572 (vs), 1589 (vs), 1607 (s), 1649 (vs), 2768
(w), 2810 (m), 2849 (w), 2955 (vw), 3065 (vw), 3165 (w), 3316
(vw), 3372 (vw) cm−1. 1H NMR (300 MHz, CDCl3): δ = 2.52 (s, 6 H,
CH3), 7.35−7.47 (m, 3 H, CHar), 7.50−7.59 (m, 2 H, CHar), 7.60−
̃
yellow solid (mp 225 °C). IR: ν = 673 (w), 686 (s), 698 (s), 721 (m),
3
4
7.66 (m, 2 H, CHar), 7.69 (dd, J = 7.8, J = 1.2 Hz, 1 H, CHar). 13C
NMR (75 MHz, CDCl3): δ = 48.1 (CH3), 126.5 (CHar), 127.8 (CHar),
128.1 (CHar), 128.2 (CHar), 128.6 (CHar), 129.0 (CHar), 130.5 (CHar),
131.0 (CHar), 132.1 (Cipso), 135.9 (Cipso), 139.3 (Cipso), 140.3 (Cipso),
155.8 (Cim), 156.2 (Cim). HRMS (ESI) m/z: [M + H]+ Calcd for
C16H17N4 265.1448. Found 265.1432. Anal. Calcd for C16H16N4
(264.33): C, 72.70; H, 6.10; N, 21.20. Found: C, 72.90; H, 6.09; N,
21.23. For X-ray crystal structure data see the Supporting Information.
[3-Amino-4,4-diethyl-4H-isoquinoliline-(1Z)-yliden]-p-tolyl-amin
(12a). 12a was obtained from a solution of p-toluidine (0.43 g, 4.0
mmol) in 10 mL of tetrahydrofuran, n-butyllithium (2.5 mL, 4.0
mmol), and a solution of 9a (0.40 g, 2.0 mmol) in 15 mL of
tetrahydrofuran according to the general procedure. Column
chromatography (pentane/tert-butylmethyl ether = 2:1 + 3% triethyl-
amine) and subsequent crystallization from n-heptane gave 0.55 g (1.8
mmol, 45%) of 12a as yellow solid (mp 252−254 °C). Rf = 0.47
750 (vs), 777 (w), 798 (s), 821 (s), 831 (m), 844 (w), 867 (m), 904
(vw), 939 (w), 954 (m),981 (w), 1016 (m), 1035 (m), 1049 (vw),
1101 (w), 1118 (w), 1157 (m), 1170 (w), 1207 (vw), 1238 (m), 1246
(m), 1271 (m), 1288 (m), 1307 (m), 1328 (vs), 1411 (m), 1452 (s),
1479 (s), 1500 (vs), 1533 (vs), 1593 (s), 1610 (s), 1656 (vs), 2870
(w), 2914 (w), 2956 (m), 2972 (w), 3024 (w), 3327 (vw), 3466 (s)
1
cm−1. H NMR (400.13 MHz, (CD3)2SO): δ = 1.87 − 2.03 (m, 6 H,
3
CH2), 2.16−2.26 (m, 5 H, CH3, CqCH2), 6.86 (d, J = 8,0 Hz, 2 H,
CHph), 6.97 (br, 1 H, NH), 7.03 (d, 3J = 8.0 Hz, 2 H, CHph), 7.32 (t, 3J
= 7.4 Hz, 1 H, CimCipsoCHCH), 7.38 (d, 3J = 7.4 Hz, 1 H, CqCipsoCH),
7.42−7.50 (m, 1 H, CqCipsoCHCH), 8.17 (dd, 3J = 7.8 Hz, 4J = 1.3 Hz,
1 H, CimCipsoCH) ppm. 13C NMR (100.62 MHz, (CD3)2SO): δ = 20.5
(CH3), 26.4 (CH2), 41.5 (CH2), 47.7 (Cq), 122.7 (CHph), 128.4
(CHph), 129.2 (CimCipsoCq), 124.6 (CHar), 125.6 (CHar), 125.9 (CHar),
130.0 (CHar), 130.1 (p-Cph), 144.8 (CqCipsoCq), 148.9 (N-Cph), 154.0
(CN), 174.0 (CimNH2) ppm. HRMS (ESI) m/z: [M + H]+ Calcd
for C20H22N3 304.1808. Found 304.1804. Anal. Calcd for C20H21N3
(303.40): C, 79.17; H, 6.98; N, 13.85. Found: C, 78.96; H, 6.94; N,
13.87. For X-ray crystal structure data see the Supporting Information.
(1′Z)-1′-(2-Methyl-2-phenylhydrazinylidene)-1′H-spiro-
[cyclopentane-1,4′-isoquinolin]-3′-amine (12d). 12d was obtained
from a solution of N,N-methylphenylhydrazine (0.61 g, 5.0 mmol) in
10 mL of tetrahydrofuran, n-butyllithium (3.1 mL, 5.0 mmol), and a
solution of 9b (1.04 g, 5.3 mmol) in 10 mL of tetrahydrofuran
̃
(pentane/tert-butylmethyl ether = 2:1 + 3% triethylamine). IR: ν =
665 (vw), 678 (s), 692 (vs), 715 (s), 758 (vs), 775 (m), 806 (s), 831
(w), 852 (s), 877 (w), 906 (w), 929 (w), 947 (vw), 962 (vw), 991 (w),
1014 (vw), 1035 (w), 1055 (vw), 1080 (vw), 1105 (m), 1118 (w),
1155 (m), 1172 (w), 1209 (w), 1246 (s), 1257 (w), 1313 (s), 1330
(vs), 1382 (w), 1409 (w), 1452 (s), 1481 (s), 1498 (vs), 1531 (vs),
1597 (s), 1612 (s), 1649 (vs), 1138 (vw), 1884 (vw), 1950 (vw), 1977
(vw), 2875 (w), 2918 (w), 2933 (w), 2966 (m), 3012 (w), 3057 (w),
M
DOI: 10.1021/acs.joc.6b00126
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The Journal of Organic Chemistry
Article
3
according to the general procedure. Subsequent crystallization from
toluene gave 0.66 g (2.1 mmol, 42%) of 12d as orange solid (mp 194
MHz, CDCl3) δ = 0.70 (t, 6 H, J = 7.3, CH3), 1.79−1.92 (m, 2 H,
CH2), 1.92−2.01 (m, 6 H, CH2CH3, NCH2CH2), 2.13−2.25 (m, 2 H,
3
°C). IR: ν
̃
= 650 (w), 689 (vs), 704 (m), 723 (w), 748 (vs), 772 (s),
CH2CH3), 3.80 (t, J = 6.6, 4 H, NCH2), 7.24−7.32 (m, 2 H, CHar),
7.42−7.52 (m, 2 H, CHar), 7.71 (d, J = 7.8, 1 H, CHar) ppm. 13C
3
829 (w), 868 (m), 878 (w), 935 (m), 955 (vw), 991 (m), 1026 (m),
1038 (w), 1105 (s), 1159 (w), 1192 (m), 1269 (w), 1283 (w), 1302
(w), 1325 (s), 1354 (vs), 1412 (w), 1420 (w), 1454 (m), 1476 (m),
1495 (s), 1537 (vs), 1564 (vw), 1589 (s), 1607 (w), 1643 (vs), 2344
(vw), 2361 (vw), 2799 (vw), 2859 (w), 2893 (vw), 2959 (w), 3022
NMR (75.47 MHz, CDCl3) δ = 9.7 (CH3), 25.9 (CH2), 34.2
(NCH2CH2), 49.2, 50.9 (NCH2, Cq), 125.2, 126.3, 126.5, 126.6, 130.9,
145.9 (CHar, Cipso), 159.3, 173.8 (NCN) ppm. HRMS (ESI) m/z: [M
+ H]+ Calcd for C17H24N3 270.1965. Found 270.1957. Anal. Calcd for
C17H23N3 (269.38): C, 75.80; H, 8.61; N, 15.60. Found: C, 75.81; H,
8.84; N, 15.32.
(vw), 3059 (vw), 3296 (vw), 3472 (m) cm−1. UV/vis (DCM): λAbs (ν
̃
,
ε) = 256 nm (39 063 cm−1, 38 757 L M−1 cm−1), 378 nm (26 455
cm−1, 7902 L M−1 cm−1). Fluorescence (DCM, 10−5 mol/L, λIrradiation
1-Amino-4-spiro[cyclopentan]-4H-isoquinolin]-3-on (13). During
the purification of 12e a side product, generated by hydrolysis, was
observed, which could be enriched by crystallization from acetone/
water. The impure compound could be characterized by X-ray
diffraction to be 13. Yield: 0.21 g (1.0 mmol, 5%), colorless solid,
impure. HRMS (ESI) m/z: [M + CH3]+ Calcd for C14H17N2O
229.1336. Found 229.1338. For X-ray crystal structure data see the
Supporting Information.
1-Piperidyl-spiro[cyclopentane-1′,4-4H-isoquinolin]-3-one (14).
14 was obtained from a solution of piperidine (0.59 mL, 0.51 g, 6.0
mmol) in 10 mL of tetrahydrofuran, n-butyllithium (3.80 mL, 6.0
mmol), and a solution of 9b (1.08 g, 5.0 mmol) in 5 mL of
tetrahydrofuran according to the general procedure. Instead of the
usual workup, the reaction was quenched by adding 1 equiv of water
(0.33 mL, 0.33 mg, 6.0 mmol) and filtered over Celite. Subsequent
flash chromatography (pentane/ethyl acetate = 3:1 + 10% triethyl-
amine) gave 0.83 g (2.9 mmol, 58%) of 14 as a colorless oil. Rf = 0.17
= 415 nm): λEm (ν
̃
) = 471 nm (broad, 21186 cm−1). 1H NMR (400.13
MHz, CDCl3): δ = 1.66 − 1.78 (m, 2 H, CH2), 1.85−2.00 (m, 2 H,
CH2), 2.00−2.18 (m, 4 H, CH2), 3.14 (s, 3 H, CH3), 6.83 (t, 3J = 7.3
Hz, 1 H, CHar), 6.99 (dd, 3J = 8.8, 4J = 1.0 Hz, 2 H, CHar), 7.23−7.32
(m, 4 H, CHar), 7.38−7.44 (m, 1H, CHar), 8.35 (dd, 3J = 8.2, 4J = 1.4
Hz, 1 H, CH2). 13C NMR (100.62 MHz, CDCl3): δ = 27.0 (CH2),
41.1 (CH3), 42.1 (CH2), 49.6 (Cq), 114.1 (CHar), 116.0 (Cipso), 118.8
(CHar), 124.5 (CHar), 125.3 (CHar), 126.6 (CHar), 129.0 (Cipso), 129.1
(CHar), 130.6 (CHar), 143.4 (Cipso), 151.3 (Cim), 155.4 (Cim). HRMS
(ESI) m/z: [M + H]+ Calcd for C20H23N4 319.1917. Found 319.1919.
Anal. Calcd for C20H22N4 (318.42): C, 75.44; H, 6.96; N, 17.60.
Found: C, 75.64; H, 6.97; N, 17.44. For X-ray crystal structure data see
the Supporting Information.
(3′Z)-3′-(Pyridin-2-ylimino)-3′H-spiro[cyclopentane-1,4′-isoqui-
noline]-1′-amine (12e). 12e was obtained from a solution of 1-
aminopyridine (2.40 g, 25.6 mmol) in 20 mL of tetrahydrofuran, n-
butyllithium (15.6 mL, 25.6 mmol), and a solution of 9b (4.09 g, 20.8
mmol) in 15 mL of tetrahydrofuran according to the general
procedure. Subsequent repeated crystallization from acetone gave
1.30 g (4.5 mmol, 22%) of 12e as yellow solid (mp 174 °C). As a side
product, hydrolysis product 13 could be separated in a small amount
̃
(pentane/ethyl acetate = 3:1 + 10% triethylamine). IR: ν = 671 (vw),
689 (m), 733 (vw), 760 (vs), 795 (vw), 829 (vw), 853 (w), 885 (w),
908 (vw), 951 (vw), 1005 (m), 1022 (m), 1078 (vw), 1113 (m), 1136
(vw), 1159 (m), 1211 (w), 1258 (m), 1279 (vs), 1304 (s), 1368 (w),
1433 (vs), 1468 (s), 1514 (vs), 1582 (s), 1599 (m), 1665 (s), 1695
(w), 2857 (w), 2938 (m) cm−1. 1H NMR (300.13 MHz, CDCl3): δ =
1.65−1.96 (m, 12 H, CH2), 2.40−2.60 (m, 2 H, CH2), 3.81−4.00 (m,
4 H, NCH2), 7.22−7.32 (m, 1 H, CHar), 7.37−7.66 (m, 3 H, CHar)
ppm. 13C NMR (75.47 MHz, CDCl3): δ = 24.7, 25.4, 26.6, 37.1
(CH2), 49.2 (Cq), 55.6 (NCH2), 124.3 (CHar), 125.5 (CHar, Cipso),
126.9 (CHar), 131.0 (CHar), 148.3 (Cipso), 167.2 (CN), 187.0 (C
O) ppm. HRMS (ESI) m/z: [M + H]+ Calcd for C18H23N2O
283.1805. Found 283.1800. Anal. Calcd for C18H22N2O (282.38): C,
76.56; H, 7.85; N, 9.92. Found: C, 76.90; H, 7.91; N, 9.69
̃
from the reaction mixture in impure form (see below). IR: ν = 619
(vw), 658 (s), 675 (s), 689 (m), 694 (m), 739 (vw), 760 (vw), 781
(s), 806 (vw), 835 (w), 853 (m), 876 (w), 908 (vw), 947 (w), 964
(vw), 989 (m), 1049 (m), 1069 (vw), 1096 (vw), 1115 (vw), 1146
(m), 1177 (w), 1240 (s), 1256 (s), 1277 (s), 1287 (s), 1302 (s), 1333
(m), 1420 (vw), 1435 (s), 1447 (s), 1464 (vw), 1520 (vw), 1558 (w),
1582 (vw), 1616 (w), 1636 (vw), 1665 (vw), 2332 (w), 2342 (w),
2359 (w), 2776 (vw), 2830 (vw), 2870 (w), 2938 (m), 2947 (m),
2978 (w), 3007 (m), 3063 (m), 3171 (vw), 3337 (vw), 3383 (vw),
3426 (w) cm−1. 1H NMR (400.13 MHz, CDCl3): δ = 1.92−2.15 (m, 6
3
3
ASSOCIATED CONTENT
H, CH2), 2.51−2.58 (m, 2 H, CH2), 7.06 (ddd, J = 7.4 Hz, J = 5.0
■
Hz, 4J = 1.1 Hz, 1 H, CHar), 7.35−7.40 (m, 3 H, CHar), 7.52−7.56 (m,
1 H, CHar), 7.74 (ddd, J = 8.1 Hz, J = 7.4 Hz, J = 2.0 Hz, 1 H,
CHar), 8.43 (ddd, J = 5.0 Hz, J = 2.0 Hz, J = 0.8 Hz, 1 H, CHar),
S
* Supporting Information
3
3
4
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.6b00126.
3
4
4
3
4
8.50 (dd, J = 8.2 Hz, J = 1.4 Hz, 1 H, CHar), 13.57 (s, 1 H, NH)
ppm. 13C NMR (100.62 MHz, CDCl3): δ = 28.0 (CH2), 43.2 (CH2),
52.6 (Cq), 119.8 (CHar), 123.9 (CHar), 125.8 (CHar), 126.1 (i-Car),
126.5 (CHar), 126.8 (CHar), 132.5 (CHar), 138.2 (CHar), 146.4 (i-Car),
146.5 (CHar), 146.9 (i-Car), 160.6 (i-Car−NH2), 177.3 (CqCim) ppm.
HRMS (ESI) m/z: [M + H]+ Calcd for C18H19N4 291.1604. Found
291.1594. Anal. Calcd for C18H18N4 (290.36): C, 74.46; H, 6.25; N,
19.30. Found: C, 74.48; H, 6.18; N, 19.62. For X-ray crystal structure
data see the Supporting Information.
Crystallographic data for 8 (CIF)
Crystallographic data for 10a (CIF)
Crystallographic data for 10b (CIF)
Crystallographic data for 10c (CIF)
Crystallographic data for 11b (CIF)
Crystallographic data for 11c (CIF)
Crystallographic data for 12a (CIF)
Crystallographic data for 12b (CIF)
Crystallographic data for 12c (CIF)
Crystallographic data for 12d (CIF)
Crystallographic data for 12e (CIF)
Crystallographic data for 12f (CIF)
Crystallographic data for 13 (CIF)
Experimental details (NMR spectra and detailed X-ray
data) and quantum chemical DFT results (PDF)
4,4-Diethyl-1-pyrrolidin-1-yl-4H-isoquinoline-(3Z)-ylidenamine
(12f). 12f was obtained from a solution of pyrrolidine (0.3 mL, 0.33 g,
4.0 mmol), 15 mL of tetrahydrofuran, n-butyllithium (2.5 mL, 4.0
mmol), and a solution of 9a (0.79 g, 4.0 mmol) in 5 mL of
tetrahydrofuran according to the general procedure. Subsequent
crystallization from n-heptane gave 0.52 g (1.9 mmol, 48%) of 12f
̃
as yellow solid (mp 101 °C). IR: ν = 680 (vs), 704 (vs), 734 (m), 758
(vs), 783 (vs), 794 (m), 815 (w), 848 (w), 875 (vs), 891 (s), 906 (w),
923 (m), 945 (w), 979 (w), 1037 (m), 1051 (m), 1074 (m), 1082
(m), 1101 (w), 1120 (w), 1155 (m), 1163 (m), 1182 (m), 1219 (m),
1232 (m), 1257 (m), 1303 (s), 1313 (s), 1332 (vs), 1340 (vs), 1365
(m), 1377 (m), 1436 (vs), 1481 (m), 1516 (vs), 1579 (s), 1620 (m),
1629 (m), 1674 (w), 1842 (vw), 1975 (vw), 2004 (vw), 2015 (vw),
2025 (vw), 2160 (vw), 2341 (w), 2362 (w), 2873 (m), 2935 (m),
AUTHOR INFORMATION
■
Corresponding Author
1
2968 (s), 3016 (w), 3176 (vw), 3315 (m) cm−1. H NMR (300.13
*E-mail: wurthwe@uni-muenster.de
N
DOI: 10.1021/acs.joc.6b00126
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin,
K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.;
Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega,
N.; Millam, M. J.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.;
Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.;
Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.;
Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.;
Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, O.;
Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09,
Revision D.01; Gaussian, Inc.: Wallingford, CT, 2009.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support from the Deutsche Forschungsgemeinschaft
(SFB 858) is gratefully acknowledged. We thank very cordially
Prof. Dr. J. Neugebauer for helpful discussions concerning the
DFT calculations and Prof. Dr. B. J. Ravoo and his research
̈
group, Dr. S. Janich and Dr. F. Hohn (Institute for
Biochemistry) for their help with the UV−vis measurements.
̈
(17) (a) Clodt, J. I.; Frohlich, R.; Eul, M.; Wurthwein, E.-U. Eur. J.
̈
̈
Inorg. Chem. 2012, 2012, 1210−1217. (b) Wigbers, C.; Prigge, J.; Mu,
Z.; Frohlich, R.; Chi, L.; Wurthwein, E.-U. Eur. J. Org. Chem. 2011,
2011, 861−877. (c) Hellmann, J.; Rhotert, I.; Westenberg, H.;
Frohlich, R.; Wibbeling, B.; Uhl, W.; Wurthwein, E.-U. Eur. J. Org.
̈
̈
DEDICATION
■
Dedicated to Prof. Dr. Gunter Haufe at the occasion of his 65th
birthday.
̈
̈
̈
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