An efficient and facile synthesis of highly substituted 2,6-dicyanoanilines

Article abstract of DOI:10.1021/jo800260b

(Chemical Equation Presented) A one-pot procedure for the synthesis of substituted 2,6-dicyanoanilines starting from readily available ynones and malononitrile has been developed. For instance, penta-1,4-diyn-3-one is converted into the acetylene-substituted aniline derivative 1 in good yield. Upon photoexcitation, this chromophore shows a strong blue emission with a high quantum yield. The ground- and the excited-state geometries, charge distributions, and excitation energies of 1 have been evaluated by ab initio calculations.

Full text of DOI:10.1021/jo800260b

methods for the synthesis of polysubstituted and functionalized
benzenes starting from simple acyclic substrates, and a number
of procedures have been developed with use of a variety of
protocols.5 However, the control of both regio- and chemose-
lectivity remains a great challenge to organic chemists.6
Recently, Deng et al. reported on the one-pot tandem reaction
of alkylidienemalononitriles with nitroolefins in the presence
of a base to yield polysubstituted benzenes.7
2,6-Dicyanoanilines are best prepared from 1-arylethyliden-
emalononitrile and arylidenemalononitrile and by a three-
component reaction of aldehydes, ketones, and malononitrile.8
The reaction of malononitrile with R,ꢀ-unsaturated aldehydes
or ketones is also reported to give 2,6-dicyanoanilines but the
yields are low.9 To the best of our knowledge, although
diversifications at positions C3, C4, and C5 of the 2,6-
dicyanoaniline core have produced a large number of compound
libraries,8–10 up to now there are no examples with the acetylenic
functionality. This is presumably due to the lack of a suitable
synthetic method since an alkynyl residue is expected to be
problematic during the three-component coupling method as it
opens many pathways for side reactions. Moreover, despite their
attractiveness, only a few papers on the optical properties of
2,6-dicyanoanilines have been published so far.11
An Efficient and Facile Synthesis of Highly
Substituted 2,6-Dicyanoanilines
Chenyi Yi, Carmen Blum, Shi-Xia Liu,* Gabriela Frei,
Antonia Neels, Philippe Renaud, Samuel Leutwyler, and
Silvio Decurtins
Departement für Chemie und Biochemie, UniVersität Bern,
Freiestrasse 3, CH-3012 Bern, Switzerland, and Institut de
Microtechnique, UniVersité de Neuchâtel, Rue Jaquet Droz
1, CH-2002 Neuchâtel, Switzerland
liu@iac.unibe.ch
ReceiVed February 01, 2008
We present here a facile way to prepare 2,6-dicyanoaniline
derivatives 1-6 (Scheme 1) under mild reaction conditions from
A one-pot procedure for the synthesis of substituted 2,6-
dicyanoanilines starting from readily available ynones and
malononitrile has been developed. For instance, penta-1,4-
diyn-3-one is converted into the acetylene-substituted aniline
derivative 1 in good yield. Upon photoexcitation, this
chromophore shows a strong blue emission with a high
quantum yield. The ground- and the excited-state geometries,
charge distributions, and excitation energies of 1 have been
evaluated by ab initio calculations.
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Introduction
Multifunctionalized benzenes with electron donor (D) and/
or acceptor (A) moieties such as 2,6-dicyanoaniline derivatives
are of considerable interest; they are not only key constituents
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synthetically occurring,1 but are also useful as versatile precur-
sors for asymmetric syntheses,2 as important substrates for
nonlinear optical materials3 and molecular electronic devices.4
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3596 J. Org. Chem. 2008, 73, 3596–3599
10.1021/jo800260b CCC: $40.75 2008 American Chemical Society
Published on Web 03/15/2008

SCHEME 1. Reactions of Ynones with Malononitrile
FIGURE 1. X-ray crystal structure of 1 (ORTEP, thermal ellipsoids
set at the 50% probability level). Selected bond lengths [Å]: C1-C2
1.391(2), C2-C3 1.395(2), C3-C4 1.410(2), C4-C5 1.409(2), C5-C6
1.414(2), C6-C1 1.407(2), C1-C8 1.438(2), C8-C9 1.120(2), C9-Si1
1.853(1), C3-Si2 1.906(2), C5-N3 1.360(2), C7-N1 1.147(2),
C16-N2 1.148(2). Hydrogen atoms are partially omitted for clarity.
SCHEME 2. Most Plausible Mechanism for the Formation
of Substituted 2,6-Dicyanoanilines 1–6
malononitrile.10c The first step of this process involves either a
Knoevenagel condensation leading to the alkylidenemalononi-
trile A,13 or a conjugate addition leading to B. Reaction of A
or B with a second equivalent of malononitrile affords the
tautomeric intermediates C and C′ that could undergo a second
conjugate addition with a third molecule of malononitrile leading
to D. Two consecutive Thorpe-Ziegler cyclizations afford
intermediates E and F. Finally, intermediate F is unstable under
basic conditions and evolves to 1-6 by a fragmentation process
with elimination of the 1,1,1-tricyanomethyl anion. This mech-
anism is supported by the fact that best yields are obtained when
at least 3 equiv of malononitrile are used.
Interestingly, the enone method according to Victory’s
mechanism gives a cyclohexadiene intermediate that has to be
oxidized, presumably by air, to afford a stable aromatic
derivative. In contrast to that method, the ynone method leads
directly to an aromatic derivative. This may explain why it takes
place under mild conditions and is high yielding.
Rod-like crystals of 1 were obtained by slow evaporation of
a dichloromethane solution. The compound crystallizes in the
j
triclinic crystal system, space group P1, with one molecule per
asymmetric unit (Figure 1). With the exception of the methyl
groups, the molecule is planar; the largest deviation from the
least-squares plane (from all non-methyl atoms) is 0.164(1) Å
for atom Si1.
In the crystal structure of 1, two molecules related by an
inversion center are arranged in close proximity to each other,
so that they form a pair of N-H· · ·NC hydrogen bonds (see
the Supporting Information). Due to the bulky trimethylsilyl
groups in meta-positions, the structure lacks π-stacking
interactions.
The chromophore 1 strongly absorbs in the violet as
evidenced by its yellow color. The UV–vis spectrum recorded
in dichloromethane shows strong absorption bands around 370
nm and between 300 and 200 nm with extinction coefficients ε
in the order of 1 × 104 to 4 × 104 L mol-1 cm-1 (Figure 2).
Upon UV excitation, the chromophore shows an intense blue
the corresponding ynones and malononitrile. We report also the
single-crystal X-ray structure analysis, the photophysical proper-
ties, and a theoretical investigation of the electronic structure
of the 3-acetylenic-2,6-dicyanoaniline 1.
The reaction of 1,5-bis(trimethylsilyl)penta-1,4-diyn-3-one12
with 3 equiv of malononitrile in the presence of Et3N (1 equiv)
in refluxing toluene gives the tetrasubstituted aniline 1 in 70%
yield (Scheme 1). This transformation under the same conditions
has been tested with success on other ynones. The detailed
experimental procedures and full spectroscopic characterizations
of all new compounds are available in the Supporting Informa-
tion.
A plausible reaction mechanism is depicted in Scheme 2. This
mechanism is closely related to the one proposed by Victory et
al. for the formation of 2,6-dicyanoanilines from enones and
(13) It has been demonstrated that the reaction of the corresponding vinyl
malononitrile with malononitrile in CH2Cl2 in the presence of triethylamine gave
1 in 55% yield.
(12) Bowling, N. P.; Mcmahon, R. J. J. Org. Chem. 2006, 71, 5841–5847.
J. Org. Chem. Vol. 73, No. 9, 2008 3597

FIGURE 2. Electronic absorption (solid line) and emission fluorescence
(dash line) spectra of 1 in deaerated dichloromethane solution; λex
)
365 nm, λem ) 405 nm, at room temperature, together with the
calculated oscillator strength.
fluorescence with emission maximum at 405 nm and a high
quantum yield of 25% (using 9,10-diphenylanthracene as
FIGURE 3. Molecular orbitals of 1 that are involved in the S0 f S1
(HOMO to LUMO) and S0 f S2 transitions (HOMO-1 to LUMO).
standard) while the Stokes shift amounts to 1900 cm-1
.
Furthermore, the fluorescence–excitation spectrum (measured
at 430 nm emission wavelength) agrees well with the corre-
sponding absorption profile. The photophysical properties and
high fluorescence quantum yield are in line with a recent study
on dicyanoanilines.14 Compared to the 2,6-dicyanoaniline chro-
mophore, both the absorption and emission of 1 are shifted about
20 nm to longer wavelengths.
and intensity are in very good agreement with the longest-
wavelength absorption (370 nm), for which the 320–410 nm
energy-integrated absorption yields an oscillator strength f )
0.16. The S0 f S2 excitation is predicted to be a π f π*
transition at 290 nm, with an oscillator strength of f ) 0.34.
This is in excellent agreement with the second UV absorption
band observed at 291 nm with intensity similar to the S0 f S1
band. The transition is polarized along the direction of the
acetylene substituent.
To understand the ground- and excited-state electronic
properties of chromophore 1, density functional theory (DFT)
as well as time-dependent DFT (TD-DFT) calculations were
performed with the B3LYP functional and the TZVP (valence
triple-ꢁ plus polarization) basis set, using the Turbomole 5.9
program.15 The minimum-energy geometry is calculated to have
Cs symmetry and the central dicyanoaniline framework is planar
in both ground and excited states. A planar geometry has
previously been found for 2,6-dicyanoaniline itself and was
rationalized by intramolecular hydrogen bonding between the
amino and the cyano groups.16 We have checked this point (see
the Supporting Information) by comparing the angles at the
amino group in 2,6-dicyanoaniline to that in p-cyanoaniline
(which has no N-H· · ·cyano contact). If the N lone pair
donation into the electron-deficient 2,6-dicyano aromatic ring
is the important mechanism, the amino group should be
calculated planar or near-planar also in p-cyanoaniline. However,
this is not the case. We conclude that the “side-on” N-H· · ·cyano
hydrogen bonds are indeed responsible for the amino group
planarity.
According to the TD-DFT calculation, the S0 f S1 electronic
excitation is dominated by the HOMO f LUMO contribution
(93%). As Figure 3 shows, this corresponds partially to a
π-electron flow from the amino N atom toward the benzene
ring, where electron density spreads toward the two cyano and
the acetylene substituents. The small Stokes shift indicates that
the emission occurs from the locally excited S1 π f π* state.
Adiabatic excited-state relaxation to a twisted intramolecular
charge-transfer (TICT) state (as is characteristic for the TICT
states of m- and p-cyanoanilines) is absent in this compound.
The S0 f S2 transition is dominated by the one-electron
excitation from HOMO-1 to the LUMO (90%). This transition
moves π-electron density from the Ct C bonding π orbital into
the benzene ring.
In our study we developed a convenient and brief synthetic
route to polysubstituted benzenes, highly functionalized with
an amino group flanked by two carbonitrile substituents, and
particularly in the cases of 1 and 2, with ethynyl groups.
Remarkably, this efficient one-pot procedure provides a new
and straightforward entry to the regioselective formation of
polysubstituted benzenes. Moreover, it is noteworthy that 1 has
a promising topology and functionality as a useful substrate for
Sonogashira coupling reactions and conjugate additions,17
thereby further generating molecular diversity and functionality.
The vertical TD-DFT calculation predicts the S0 f S1
excitation to be an intense (f ) 0.21) π f π* transition at 352
nm (3.52 eV) as shown with the stick spectrum in Figure 2.
The transition is polarized within the molecular plane and
approximately perpendicular to the amino substituent, in line
1
with a benzenic Lb-type transition. Both the transition energy
(14) Oshima, J.; Yoshihara, T.; Tobita, S. Chem. Phys. Lett. 2006, 423, 306–
311.
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Lett. 1989, 162, 165–169. (b) Treutler, O.; Ahlrichs, R. J. Chem. Phys. 1995,
102, 346–354. (c) Bauernschmitt, R.; Ahlrichs, R. Chem. Phys. Lett. 1996, 256,
454–464. (d) Hättig, C.; Weigend, F. J. Chem. Phys. 2000, 113, 5154–5161.
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285, 55–72.
(17) Yi, C.; Blum, C.; Liu, S.-X.; Ran, Y.; Frei, G.; Neels, A.; Stoeckli-
Evans, H.; Calzaferri, G.; Leutwyler, S.; Decurtins, S. Cryst. Growth Des. 2008.
Submitted for publication.
3598 J. Org. Chem. Vol. 73, No. 9, 2008

1062, 946, 845, 759, 671; HRMS, ESI (positive) calcd for
C16H21N3NaSi2 334.1172, found 334.1171.
Experimental Section
General Procedure for the Preparation of 1–6. A mixture of
the respective ynone (0.5 mmol), malononitrile (100 mg, 1.5 mmol),
and triethylamine (50 mg, 0.5 mmol) in toluene (3.0 mL) was
refluxed with stirring at 120 °C for 2 h. The solvent was removed
under reduced pressure. Purification of the brownish oily residue
by column chromatography on silica gel eluting with CH2Cl2 gave
the desired compound as a light yellow solid.
Acknowledgment. This work was supported by the Swiss
National Science Foundation (grant No. 200020-116003 and
COST Action D31).
Supporting Information Available: General experimental
details and characterization data for the prepared compounds
1-6 as well as the precursors 6-methyl-1-(trimethylsilyl)hepta-
6-en-1,4-diyn-3-ol (2a) and 6-methyl-1-(trimethylsilyl)hepta-
Data for 2-Amino-4-(trimethylsilyl)-6-(trimethylsilylethyn-
yl)isophthalonitrile (1) as an Example. Yield 110.5 mg (70%);
mp 122–124 °C; 1H NMR (300 MHz, CDCl3) δ 6.97 (s, 1H), 5.15
(s, 2H), 0.41 (s, 9H), 0.30 (s, 9H); 13C NMR (75.5 MHz, CDCl3)
δ 152.93, 152.90, 131.81, 128.13, 118.34, 116.43, 107.34, 102.31,
102.20, 102.08, 1.22, 0.002; selected IR data (cm-1, KBr pellet)
3479, 3362, 2959, 2924, 2218, 2160, 1735, 1637, 1538, 1403, 1253,
1
6-en-1,4-diyn-3-one (2b); copies of the H and 13C spectra of
all new compounds; CIF file for 1 (CCDC 656928) as well as
the crystal packing and computational studies of 1. This material
is available free of charge via the Internet at http://pubs.acs.org.
JO800260B
J. Org. Chem. Vol. 73, No. 9, 2008 3599