Synthesis of fused-ring aza-dipyrromethenes from aromatic nitriles

Article abstract of DOI:10.1039/c8cc04658a

Aza-dipyrromethenes are ligands for a number of useful fluorescent dyes and electronic materials. They have high absorption in the red and NIR range. Fused-ring aza-dipyrromethenes cannot be synthesized through the same methods used to make aza-dipyrromet

Full text of DOI:10.1039/c8cc04658a

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Synthesis of fused-ring aza-dipyrromethenes from
aromatic nitriles†
Cite this:DOI: 10.1039/c8cc04658a
George R. Mckeown, Joseph G. Manion, Alan J. Lough and Dwight S. Seferos
*
Received 11th June 2018,
Accepted 18th July 2018
DOI: 10.1039/c8cc04658a
rsc.li/chemcomm
Aza-dipyrromethenes are ligands for a number of useful fluorescent wavelengths past 900 nm with high quantum yields.3 They have
dyes and electronic materials. They have high absorption in the red been less explored due to their reduced solubility and the
and NIR range. Fused-ring aza-dipyrromethenes cannot be synthesized difficulty by which they are prepared.
through the same methods used to make aza-dipyrromethenes, which are
Because of their limited derivatization, aza-BODIPYs have been
common commercial dyes. The current synthesis is limited to treating a mostly used as p-type materials.4,5 p-type materials are relatively
phthalonitrile-based electrophile with a Grignard reagent followed by well-developed, with aza-BODIPYs having more potential application
reduction with formamide at high temperature. In this work, we introduce if more n-type derivatives could be synthesized. Aza-dipyrromethenes
a new fused-ring aza-dipyrromethene synthesis from ortho-lithiated have also seen promising applications outside of their boron-
aromatic nitriles. This method allows for a much wider range of functional coordinated complexes, especially as complexes of Zn(II), which
groups, less complicated starting materials, and yields that are consistent have successfully been incorporated as active components in
with the highest reported for aza-dipyrromethenes of any kind.
organic photovoltaics (OPVs).6–8
Aza-dipyrromethenes are most commonly synthesized from
Dipyrromethene is a versatile monoanionic bidentate ligand that 4-nitro-1,3-diarylbutan-1-ones in one step by heating with an
coordinates main group elements as well as transition metals. Its ammonia source.9,10 The reaction pathway is very complex, but
most common use is as a boron coordinated complex referred to as yields of 35% can be routinely achieved with simple purification.11
boron dipyrromethene1 (BODIPY), many examples of which are However, the reaction is limited to derivatives which are functiona-
commercially available. Aza-dipyrromethenes (A in Fig. 1) are a class lized only on the 2 and 4 positions of each pyrrole unit. Access to
of ligands that are identical to dipyrromethene, where the methene expanded fused-ring systems through this method requires further
bridge is replaced by a nitrogen atom. Aza-dipyrromethenes are modification of the aza-dipyrromethene core by adding aromatic
useful for reaching peak absorbance and emission at wavelengths groups to the 3-positions and oxidizing.12 Because the carbon
greater than 700 nm when coordinated with boron (aza-BODIPYs). atoms flanking the nitrogen bridge are quite electrophilic, aza-
Fused-ring aza-dipyrromethenes (B in Fig. 1) have been used in dipyrromethenes are sensitive to harsh conditions which limits
complexes with even lower bandgaps than aza-dipyrromethenes.2 the scope of how they can be derivatized.
Recent examples have been able to reach peak emission
Fused-ring aza-dipyrromethenes were exclusively synthesized
from Grignard reagents and phthalonitrile derivatives,13–15 until
recently when Zheng et al. reported a synthesis of asymmetric
aza-diisoindolmethines from phthalonitrile derivatives and a
potassium tert-butoxide.16 Although Zheng’s synthesis is a sig-
nificant improvement, it is limited to asymmetric derivatives
bearing a pendant aryl group on one side only. While fused-ring
aza-dipyrromethenes ligands have the potential to be a useful
class of optoelectronic materials, the existing synthetic options
leave very little room for derivatization.
Fig. 1 Structures of aza-dipyrromethenes (A) and fused-ring aza-
dipyrromethenes (B), as synthesized.
In the present work, we report the discovery that fused-ring
aza-dipyrromethenes can be synthesized from ortho-lithiated
aromatic nitriles. The fused-ring is not limited to phenyl rings,
as demonstrated by compound 1c in Fig. 3. Fig. 2 compares the
mechanism of the electrophilic nitrile cascade of phthalonitrile
Department of Chemistry, University of Toronto, 80 St. George Street, Toronto,
Ontario M5S 3H6, Canada. E-mail: dseferos@chem.utoronto.ca
† Electronic supplementary information (ESI) available: Experimental, NMR, MS,
X-ray, UV-Vis. CCDC 1841502. For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/c8cc04658a
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Fig. 2 New synthesis of aza-diisoindolmethines from aromatic nitriles.
in previous work to the same nitrile cascade between nitriles aza-diisoindolmethines, including aza-dipyrromethenes fused to
originating from two different molecules in this work. They key heterocycles such as thiophene (1c).
difference is that two different benzonitriles can be incorporated into
This reaction is not limited to benzonitrile derivatives. Hetero-
the reaction cascade allowing R1 and R2 to be varied independently. cycles, such as 3-thiophenecarbonitrile, can also undergo the same
We were also able to use a much broader library of benzonitriles. The process after being metallated in the 2-position. Because 3-thio-
five-membered ring is formed by an intramolecular reaction between phenecarbonitrile is more acidic than benzonitriles, it can be
an anionic imine and a nitrile ortho to it on an aromatic framework. deprotonated using a Grignard reagent. As the mechanism of this
The dimeric intermediate at the end of the cascade is identical to reaction is identical, any base works for this reaction so long as it is
that formed in the phthalonitrile reaction, but the original reactant able to quantitatively deprotonate the aromatic nitrile while avoiding
can include any aromatic compound that can be quantitatively nucleophilic attack on the cyano groups present. For this reason,
lithiated ortho to the nitrile.
n-butyllithium is unsuitable to use in these reactions.
Many aromatic nitriles can be quantitatively lithiated by
With the exception of the previously reported aza-diiso-
lithium diisopropylamide (LDA) in a position ortho to the cyano indolmethine 1d, none of the other compound synthesized
group. Most notable are 1,3-dicyanobenzene and 1,4-dicyano- could be made from phthalonitrile derivatives. The currently
benzene (at À98 1C in THF), and they can react with electrophiles in existing method requires that the phthalonitrile is symmetric
high yields.17 They will also form the intermediate shown in Fig. 2,
which can condense on itself after reductive amination with
formamide. Benzonitrile and 3-thiophenecarbonitrile can also be
lithiated in the same fashion, though benzonitrile requires lithium
2,2,6,6-tetramethylpiperidine (LiTMP) as a base, as LDA is not
selective at the 2-position.18
ortho-Lithiated nitriles can similarly be prepared from the
reaction of n-BuLi with ortho-brominated nitriles at low temperature,
but we have found this method to be inferior because it is very
difficult to separate partially brominated derivatives from the desired
product. Furthermore, ortho-brominated functional benzonitrile
compounds are not as easily accessible as those which can be
lithiated by deprotonation.
The synthetic scheme in Fig. 2 depicts both the homocoupling
reaction (R1 = R2) and the heterocoupling reaction (R1 a R2). In the
first case, the dimeric intermediate is generated simply by lithiating
half of the nitrile in solution at low temperature. In the latter, the
initial nitrile is lithiated with a full equivalent of base before
transferring the cold mixture by cannula into a room temperature
solution of the nitrile bearing R2. In this case, it is not necessary that
the second nitrile can be quantitatively lithiated in any position, as
it does not act as a carbon nucleophile at any point. Between the
two reactions, it is possible to generate a very large variety of Fig. 3 Products of homocoupling (1a–d) and heterocoupling (2a–b) reactions.
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Table 1 Synthetic results of aza-diisoindolmethines
Product
Nitrile 1
Nitrile 2
—
Base
LDA
Temperature
Scale (g)
10
Yield (%)
50
1a
À98 1C
1b
1c
1d
—
—
—
LDA
RT
10
1
50
2
LDA or CH3MgCl
LiTMP
À98 1C
À98 1C
1
10
2a
2b
LDA
LDA
À98 1C
À98 1C
5
5
47
4
across the plane between the two nitriles, as there is no control preferentially attack nitriles that are not lithiated, but it is
over which nitrile group is added to first. The structure of 1c impossible to avoid these reactions if the nitrile is not soluble
determined by X-ray crystallography shows that the thiophene at low temperature.
units fused to the aza-dipyrromethene structure are oriented in
one direction (Fig. 4).
The workup and purification of the aza-diisoindolmethines
varies depending on the solubility of the product. 1d and 2b are
The second step (Fig. 2) requires that only one nitrile is ortho soluble in common organic solvents, which allows them to be
to the imine anion. For example, if the same reaction is done with purified on a silica column. The solubility of 1a–c and 2a are
1,2-dicyanobenzene, the intermediate is asymmetric and also very low in most organic solvents (with the exception of DMF
has two cyano groups it can attack. For this reason, derivatives of and DMSO), which makes them unable to be purified on a silica
phthalonitrile are incompatible with these reaction conditions.
column. However, these reactions only produce small amounts
Each of the compounds synthesized are shown in Fig. 3. of higher molecular weight compounds, which allows them to
Table 1 lists the conditions and yield for each reaction. Because be purified by trituration with methanol, acetone and dichloro-
the solubility of 1,4-dicyanobenzene in cold THF is so low, the methane sequentially.
more soluble lithiated compounds react with each other to
When compared with examples like 1a and 2a, the yield of 1c and
generate a complex and inseparable mixture. However, all four 2b are very low. This likely has to do with the reduction step. For 1c,
protons of 1,4-dicyanobenzene are identical, which allows room the reaction produces an intense sulfur smell, indicating the decom-
temperature lithiation to generate a single product. An essential position of individual thiophene rings in the harsh conditions.
requirement for this reaction is that the lithiated compounds Greasy compounds like 2b tend to phase separate from formamide
at high temperature, which greatly reduces the efficiency of the
reaction. Further optimization of the reductive amination (e.g. using
mild conditions) is required to improve the synthesis of the low-yield
compounds. In contrast, the yield of 1d suffers from low selectivity
during lithiation, as the 2-lithium species is not quantitatively made.
The alkylated aza-diisoindolmethine is the sole compound with
solubility greater than B20 mg mLÀ1 in common organic solvents.
Because the borylated compounds are even less soluble, purifica-
tion is a major issue in the synthesis of aza-BODIPYs from these
compounds. The corresponding aza-BODIPY from compound 2b
was successfully purified and characterized, but the others were
unable to be separated from impurities generated during the
reaction. In contrast, the Zn(II) complexes of most of the aza-
diisoindolmethines are much more soluble than the ligands
themselves and can be purified in small quantities by column
Fig. 4 The molecular structure of 1c protonated with TFA. Displacement
ellipsoids are shown at the 30% probability level.
chromatography. The insoluble Zn(II) complex 1a-Zn was successfully
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Table 2 Optical and electrochemical properties in DCM
While the aza-isoindolmethines appear to strongly absorb
through one major transition (Fig. 5), their Zn(II) complexes
show two strong absorbance peaks between 600 and 800 nm
(Fig. S40, ESI†). The relative strengths of these transitions vary
depending on the specific ligand. Finally, we made a test OPV
device using P3HT as a donor and 2b-Zn as an acceptor. While
aggregation of 2b-Zn limited the current, the device shows that
these new aza-dipyrromethene compounds can accept electrons
from p-type materials (Fig. S42, ESI†).
In conclusion, we have developed a novel synthetic procedure for
the production of aza-diisoindolmethines. The technique has three
main benefits over existing syntheses. Firstly, the aromatic nitrile
does not have to be symmetric, which allows for the selective
synthesis of regioregular products. The second benefit is that the
reaction produces aza-diisoindolmethines with nitrile groups, some-
thing that would not have been possible with the existing syntheses.
Finally, aromatic nitriles are much more readily available than ortho-
dicyano compounds, which provides access to a much larger
product scope from less expensive materials. Further research
is required to learn more about the device properties of the
newly-accessible aza-diisoindolmethines and their complexes.
Aza-dipyrromethene
Zn(II)
ox
1/2
a
red a
1/2
lmax (nm)
E
(V)
E
(V)
lmax (nm)
1a
1b
1c
1d
2a
2b
621
648
640
653
624
632
0.6
—
—
0.1
0.5
—
À0.9
—
—
À1.3
À1.0
—
659
647
—
631
658
641
a
Half-wave potentials were measured in CH2Cl2/TBAPF6 (0.1 M) vs.
Ag/Ag+, scan rate 100 mV sÀ1, using Fc/Fc+ as an internal standard.
Conflicts of interest
There are no conflicts to declare.
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