A Strategy towards the Multigram Synthesis of Uncommon Hexaarylbenzenes
Abstract
A novel rational synthetic pathway—the “functionalization of para-nitroaniline”(FpNA)—provides substituted hexaarylbenzenes (HABs) with uncommon
symmetries that bear up to five different substituents, fully avoiding
regioisomeric product distributions during the reactions. 4-Nitroaniline
is functionalized by a cascade of electrophilic halogenations,
Sandmeyer brominations, and Suzuki cross-coupling reactions, leading to
26 substitution geometries, of which 18 structures are not available by
the current established techniques. Furthermore, we demonstrate that
this method is applicable to the bulk production of such systems on a
multigram scale. Regarding optoelectronic properties, we demonstrate how
highly functionalized HABs can show strong luminescent behavior, making
these molecules very attractive to organic electronic devices.
These compounds with star-like substitution patterns represent
extraordinary building blocks in large light-harvesting architectures,[4] and they proved to be versatile backbones for catalytic scaffolds.[5, 6]
The literature provides a plethora of further examples in which HABs
and HBCs have been introduced into highly sophisticated molecules or
molecular assemblies. Interestingly, until quite recently, only HABs and
HBCs with a rather small variety of symmetries were available—the most
prominent being the fully symmetrical A6 HAB, the monosubstituted A5B, and the ortho and para disubstituted HABs with A4B2 and (A2B)2 patterns (compare structures #1, #2, #3, and #5 in Figure 1).
Regrettably, the controlled formation of HABs with specific
substitution patterns from unsymmetrical starting materials via standard
techniques, such as the [2+2+2] cyclotrimerization of tolans and the
Diels–Alder reactions of perarylated cyclopentadienones and acetylenes,
is limited. Very often, instead of only one product, mixtures of
regioisomers are obtained.[7]
As recently as 2015, a spectacular route consisting of a variety of
palladium-catalyzed arylation reactions led to the first HAB bearing six
different substituents.[8]
Despite the great achievement, this eight-step methodology suffers from
low overall yields, is not applicable for bulk synthesis, and the final
statistical Diels–Alder reaction leading to two regioisomers.
Nevertheless, engineering the arylated periphery of benzene results in
compounds displaying properties of fundamental importance, for example
an outstanding blue emission in organic light-emitting diodes (OLEDs)[9] and detection of H2S in living cells[10] and of explosives like picric acid and TNT.[11]
Importantly, toroidal π-delocalization in HABs, for a long time
underestimated, can be fine-tuned by the nature of aryl substituents,
strongly suggesting that HABs are candidates for organic electronics.[12] However, HABs with substitution patterns such as those in compounds 1–4 have hardly been investigated. In this context, the facile access to larger amounts of these materials is of utmost importance.
Here,
we present our own wet-chemical approach, which is quite different to
the established methods. Importantly, we wanted this procedure to be
simple and applicable towards the preparation of bulk material, without
involving highly sophisticated techniques or purification difficulties
due to the formation of regioisomers.
Our method, the functionalization of para-nitroaniline (FpNA), utilizes 5 as a cheap and commercially available starting material, which leads selectively to 26 substitution patterns (Figure 1). Depending on the desired structure, the first step involves the conversion of 5 to bromo species 6, 7, or 8 (see Figure 2), which can be conducted on a multiple-hundred-gram scale.[13-15] In this way the pattern of the upper—“northern” hemisphere is determined. As described in Scheme 1, an A3 hemisphere is generated by the threefold Suzuki cross-coupling reaction of 8 with three equivalents of arylboronic acid in a microwave reactor,[16] or under conventional conditions.[17] An ABA hemisphere is derived from 7 by coupling two equivalents of aryl moieties A, followed by halogenation of the mid position and a final coupling reaction with aryl moiety B. Similarly, an ABC hemisphere requires, after the first cross-coupling reaction of 6 with aryl moiety A, an aromatic halogenation ortho to the amine functionality, followed by the same procedure as described for the ABA
hemisphere. After the completion of this “northern” hemisphere, the
design of the “southern” hemisphere can be addressed. Thus,
triarylnitrobenzene is activated by reductive conversion of the nitro
moiety to the amine by using either SnCl2 or H2
and Pd/C. Halogenating agents can be either iodine monochloride or
bromine, yielding diodo- and dibromoaniline, respectively. Following the
“northern” hemisphere strategy, the halogenated aniline can be
transformed into the pentaarylaniline. Finally, the amine is converted
into a bromide and the hexaarylbenzene synthesis concludes with
arylation. All synthetic details can be extracted from the Supporting
Information. Following this method, HABs with up to five different
substituents can be constructed, avoiding statistical regioisomeric
product distributions and concomitant difficulties in purification. Most
importantly, the beauty of this strategy lies in its simplicity and the
fact that all reaction steps rely on very well-known and
well-established reaction procedures.
possible substitution patterns of HABs that can be prepared by the
herein reported method; CT=also available by cyclotrimerization, DA=also
available by Diels–Alder reaction. The structures are classified as
obtainable by the methods, if no regioisomers are formed during the
reaction.
the 36 possible substitution geometries of hexaarylbenzene (Scheme S3
in the Supporting Information), we are able to prepare 26 structures,
from which we enlarge the family of HAB substitution geometries by 18
novel structures. These were, to the best of our knowledge, previously
unknown or only very difficult to obtain by the common techniques.
We
examined the properties of the HABs with uncommon geometries. We
observed an outstanding emission behavior of HABs that bear a quadrupole
or octupole substitution pattern. In Figure 3, we show synthesized examples (compounds 9–12)
and their emission—ranging from dark to bright blue—in solution and
more importantly, in the solid state. Their application in
light-emitting devices is currently under investigation. Consequently,
we are convinced that the toroidal π-delocalization of hexaarylbenzenes,
which is responsible for charge delocalization of nonconjugated, but
parallel proximate π-systems, will prove to be a potent tool in
materials chemistry and the design of functional molecules.[12]
are depicted as ORTEP models with 50 % thermal ellipsoids; hydrogen
atoms are omitted for clarity. Further crystallographic depictions can
be extracted from the Supporting Information in Figures S2 and S3.
system on a decagram scale, in order to show that this method opens the
gate towards uncommon HAB motifs in bulk quantities (Scheme 2).[18, 19] Therefore, we cross-coupled 10 g of 8 with 4-tert-butylphenyl boronic acid, using Pd(dppf)Cl2 as the catalyst; we obtained 13 in 89 % yield after purification by precipitation from methanol. Compound 13 was subsequently reduced and the resulting amine was precipitated from methanol and halogenated with 2.5 equiv of Br2, providing dibromoaniline 14 in 81 % yield over two steps. Next, a twofold Suzuki cross-coupling with phenylboronic acid gave pentaarylaniline 15
in 92 % yield, after purification by precipitation from hexanes and
methanol. The final and critical Sandmeyer halogenation was carried out
using isoamyl nitrite in CHBr3 at 100 °C, which served as excellent solvent and reactant at the same time.[20] Compound 16 was obtained in 75 % yield after a short silica gel plug filtration and precipitation from CH2Cl2
and methanol. Importantly, conventional Sandmeyer halogenations yielded
only little product, or failed completely. Hence, bromoform played the
pivotal role as solvent and reagent, leading to the successful
bromination of highly arylated and sterically crowded anilines. Lastly,
despite the large steric hindrance of the di-ortho-substituted bromobenzene 16, the terminal Suzuki coupling with 4-formylphenylboronic acid under standard conditions generated the desired “uncommon” A3BCB-substituted HAB in 80 % yield (the overall yield, starting from 8 was 40 %).
is depicted as an ORTEP model with 50 % thermal ellipsoids; hydrogen
atoms are omitted for clarity. Further crystallographic depictions can
be extracted from the Supporting Information in Figure S4.
CHO) were successfully introduced to HABs and their precursors
(Scheme S1 and Table S1). However, in the case of substituents that are
labile under the reaction conditions, a powerful alternative is offered
by the postfunctionalization of the readily prepared HAB core. Several
protocols for the sixfold halogenation of hexaphenylbenzene are
available, which can be modified to halogenate only the available para-positions of the otherwise unsubstituted phenyl moiety (compare compound 4 in Figure 2 and S36–S39 in Scheme S2).[21]
Overall we demonstrated a novel rational pathway—the functionalization of para-nitroaniline (FpNA)—to
substituted hexaarylbenzenes with uncommon symmetries, avoiding
regioisomeric product distributions during the reaction. This was made
possible by utilizing 4-nitroaniline (5), a cheap and
commercially available starting material, and by applying a cascade of
electrophilic halogenations, and Suzuki cross-coupling reactions. A
successfully mastered obstacle was the Sandmeyer-like bromination of
highly crowded pentaarylanilines. Due to the simple and well-established
synthetic protocols, we proved that this method is applicable to the
bulk production of the final products. Further we demonstrated that
these highly functional and complex molecules do not need highly
sophisticated synthetic methods, but rather a sophisticated synthetic
plan. With this novel tool in hand, we are convinced that the now open
gate to the family of new HAB architectures—in total 18 geometries—will
lead to a manifold of interesting findings based on HABs, which will be
particularly attractive to the fields of molecular materials,
nano-electronics and medicine. We are convinced that a new era in
materials chemistry of HABs with “uncommon” symmetries and their
derivatives is currently evolving, guiding the research community to new
and highly exciting results.
Acknowledgements
Wegratefully acknowledge the funding by the German Research Council (DFG)
through the Collaborative Research Center SFB 953 (Synthetic Carbon
Allotropes). D.L. and D.R. thank the Graduate School Molecular Science
(GSMS) for financial support.
0 件のコメント:
コメントを投稿