One-Pot, High-Yielding, Oxidative Cyclodehydrogenation Route for N-Doped Nanographene Synthesis

Article abstract of DOI:10.1021/acs.orglett.5b03312

An intramolecular oxidative cyclodehydrogenation via a one-pot process is described, which induces selective C-C bond formation and bromine functionalization. The application of this new route gives rise to a novel family of partially fused, selectively b

Full text of DOI:10.1021/acs.orglett.5b03312

Letter
pubs.acs.org/OrgLett
One-Pot, High-Yielding, Oxidative Cyclodehydrogenation Route for
N‑Doped Nanographene Synthesis
†
†
,†,‡
Colm Delaney,†,‡ Gearoid M. O Maille, Brendan Twamley, and Sylvia M. Draper*
́
́
́
‡
†School of Chemistry and Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), Trinity College Dublin,
College Green, Dublin 2, Ireland
S
* Supporting Information
ABSTRACT: An intramolecular oxidative cyclodehydrogenation via
a one-pot process is described, which induces selective C−C bond
formation and bromine functionalization. The application of this new
route gives rise to a novel family of partially fused, selectively
brominated N-doped pyrimidine graphenes.
nterest in the synthesis of N-containing polycyclic hydro-
carbons (PAHs), particularly from a materials chemistry
Using elemental bromine under controlled conditions, this
new work demonstrates that it is possible to induce intra-
molecular bond formation at the pyrimidine rings in diaza-
substituted polyphenylenes. Furthermore, it shows that con-
trolled bromination is achievable at the para positions of pendant
unsubstituted phenyl rings, giving a range of brominated
pyrimidine-fused PAHs. Figure 1 shows the mass spectrum of
the reaction mixture, comprising 1-pyrimidyl-2,3,4,5,6-penta-
phenylbenzene (1) and elemental bromine after 10 min. At room
I
perspective, is growing exponentially.1 The realization of
multiple inter- and intramolecular bond fusions in halogenated
polyphenylenes, catalyzed by Au(111),2 Pt(111),3 and Cu(111)4
surfaces,5−7 has prompted this revived research attention. Such
processes offer low-energy routes to N-doped graphene
nanoribbons and nanofragments, via single-source precur-
sors.5,6,8 Synthetic work is required, however, to improve the
yield and purity of the N-doped halogenated precursors and to
optimize the selectivity of their coupling reactions.
Oxidative cyclodehydrogenation in solution (the Scholl
reaction) is understood to require a Lewis acid and oxidant
and to occur either by a radical cation (electron transfer) or by an
arenium cation (proton transfer) mechanism.9,10 In N-
containing materials, the extent of ring fusion is highly catalyst-
and dopant- dependent. For one polyphenylene precursor, 1,2-
dipyrimidyl-3,4,5,6-tetra(4-tert-butylphenyl)benzene, fully fused
materials were previously obtained using AlCl3/CuCl2 as Lewis
acid and oxidant, whereas a variety of incomplete ring closures
are produced when FeCl3 is used.11,12 Increasing the number of
N dopant atoms causes a decrease in reactivity, even in the
presence of resonance-stabilizing methoxy substituents.13 Such a
lack of specificity and control has given rise to the search for
alternative catalytic reagents.
The authors have an established interest in the bottom-up
fabrication of N-doped graphene fragments.12,14,15 Prompted by
this and the drive to develop and test new routes to N-doped
fused and partially fused materials, they decided to revisit the
earlier findings of Gourdon et al. into the cyclodehydrogenation
of diaza-substituted polyphenylenes.16 This work had shown that
cyclodehydrogenations using AlCl3/CuCl2 or MoCl5 gave rise to
insoluble polychlorinated products and had led the authors to
conclude that para unsubstituted pendant phenyl rings promote
uncontrolled oligomerization.
Figure 1. Mass spectrum of a sample of the reaction mixture of 1-
pyrimidyl-2,3,4,5,6-pentaphenylbenzene polyphenylene (1) and bro-
mine after 10 min in an open vessel at room temperature.
Received: November 17, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.5b03312
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
temperature, no remaining uncyclized polyphenylene is observed
after a reaction time of 10 min. By controlling the time and
temperature of the reaction, the degree of substitution can be
optimized to yield 8,9,10-tris(4-bromophenyl)-
tribenzoperimidine (3) and 5,13-dibromo-8,9,10-tris(4-
bromophenyl)tribenzoperimidine (4) in 80 and 50% yields,
respectively.
Inspired by the one-pot reaction conditions employed by
Rathore to generate hexakis(4-bromophenyl)benzene,17 we used
a 1 × 10−8 M solution of polyphenylene 1 in CDCl3, with 100
equiv of reagent grade bromine. Despite the fact that the excess
bromine would cause significant shifting of the NMR signals of
the products, a study of the crude reaction mixture was
1
undertaken, using in situ H NMR spectroscopy. From this, it
was possible to gain an insight into the time scale of each step of
the reaction as it proceeded. The spectroscopic study, over the
course of 25 min, documented the almost instantaneous nature
of the cyclization between the pyrimidine ring and its
neighboring phenyl rings, the stepwise bromination of the
pendant phenyl rings, and finally the bromination of the fused
pyrimidine core. The information garnered from the resulting 1H
NMR spectra (S15) suggested how we might vary the reaction
conditions (reaction time, temperature, solvent, vessel con-
ditions (open or closed)) to separately optimize the formation of
each of the products.
Figure 2. 1H NMR spectra of 1 and the isolated products 2, 3, and 4 in
CDCl3 (solvent signal marked with an asterisk).
Initially, 1 was reacted in neat bromine at room temperature
for varying reaction times (5 min to 5 h) to yield different
proportions of 2, 3, and 4. Column chromatography using
dichloromethane as eluent, followed by recrystallization from
dichloromethane/methanol, allowed the isolation of each highly
pure fraction. Subsequently, more direct routes to two of the
major products were successfully obtained. Changing to pressure
tube conditions in toluene resulted in the formation of only 2 in
quantitative yields. The pure product could be crystallized
directly from the reaction mixture without the need for any
additional purification. Refluxing in chloroform was successful in
driving the reaction to higher yields of the pentabrominated 4.
The evolution of HBr was observed in all cases. Figure 2 presents
the individual spectra of the isolated materials.
measurements. The molecule crystallized in the P1 space
̅
group with two molecules per unit cell. Solvent molecules
found in the voids could not be modeled to an acceptable level,
and therefore, SQUEEZE was applied.
As a result of the ring closure, the fused phenyl and pyrimidine
rings now form part of a significantly curved bowl-like structure.
The strained nature of this pyrimidine section results in a curve of
20° at the extremities, relative to the plane of the central ring. The
molecules pack in a head-to-tail fashion, with π−π interactions
between the aromatic cores resulting in intermolecular distances
of 3.538 Å. Analysis of the single-crystal X-ray structure of the
tribrominated 3 shows that the bromine atoms present result in
only minimal changes to the molecular structure. The dimeric
lateral overlap of the fused aromatic portions, however, was very
much enhanced in 3, possibly due to the presence of two
dichloromethane molecules in the void, as seen in Figure 3b.
1H NMR spectroscopy was the primary tool for characterizing
the new products. A comparison of the spectra is presented in
Figure 2. Taking the spectrum of the starting material as a
reference, the most dramatic change occurs upon the initial
cyclization to give 2, whereupon the resonance of proton (H1) in
the pyrimidine ring of 1 shifts from 8.6 ppm to a peak at 9.8 ppm.
Once this ring is fused (as in 2, 3, and 4), the chemical shift of this
signal remains essentially constant. The signal at 8.2 ppm (H2) in
the starting material (corresponding to both protons, α to
nitrogen) is now absent. From the in situ experiment, a plot was
generated of the integrations of the pyrimidyl signals (e.g., H1
and H2) and their variation with reaction time. The plot is
consistent with the rapid formation of the C−C intramolecular
bonds (complete within 4 min). Fusion results in the significant
deshielding of protons (H4) (from the multiplet at 6.9 ppm in 1)
to a doublet at 9.4 ppm in the 1H NMR spectra of 2 and 3 (Figure
2). This doublet then becomes a singlet in 4 after the final
bromination takes place.
Fortunately, single-crystal X-ray diffraction was possible for
most of the isolated products and gave data that were consistent
with those arising through spectral characterization techniques.
Diffusion of 5-(4′,5′,6′-triphenyl-[1,1′:2′,1″-terphenyl]-3′-yl)-
pyrimidine into toluene solutions allowed the growth of single
crystals of 2, suitable for single-crystal X-ray diffraction
Figure 3. (a) Asymmetric unit and packing motif of 2; (b) asymmetric
unit and packing motif of 3. Displacement ellipsoids shown at 50%.
Hydrogen atoms omitted for clarity.
B
DOI: 10.1021/acs.orglett.5b03312
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Organic Letters
Letter
At this point, it was decided to explore the generality of the
new method and to apply it to the more challenging 4N-
containing polyphenylene 1,2-dipyrimidyl-3,6-bis(4-tert-butyl-
phenyl)-4,5-bis(4-bromophenyl)benzene 5. This precursor was
chosen for comparison with a system previously studied by
Draper et al.15 The difference in this case is that two t-butyl
groups are present to block two of the para positions on the
pendant phenyls. On heating dipyrimidyl polyphenylene
precursor 5 in toluene with Br2 for 45 min, the half-cyclized
product 6 was isolated in 70% yield (Figure 4). This was a
positive improvement on the reported yields of similar half-
cyclized analogues that were generated by the traditional FeCl3
route (e.g., 32%).12
phenyl rings bearing electron-withdrawing substituents, such as
Br. This new work supports the general consensus that for bond
formation to occur, via electrophilic attack, a sufficiently electron-
rich contiguous ring is required.
In summary, a gateway reaction has been demonstrated that
offers an unprecedented and one-step process to partially fused
and bromo-functionalized N-doped polyaromatics. These are
suitable for chemical functionalization and/or further aromatiza-
tion using existing routes. The work impacts recent publications
that mark the point of convergence between top-down and
bottom-up synthetic routes to doped nanoribbons. The arrival of
an alternative reagent to brominated precursors with precise
substitution patterning will provide new opportunities for the
control of the symmetry and edge characteristics of graphene
materials and the broadening of their potential application in
electronic devices. Under the right conditions, such materials can
be intermolecularly stitched to form a patchwork holey graphene
sheet or nanoribbon. The new selective fusion and bromination
of highly aromatic di- and tetra-aza PAHs also introduces a high-
yielding methodology to deliver novel ligands. The systems
isolated to date are relevant to making orthometalated or N-
coordinated transition metal complexes with interesting photo-
physical applications.
Figure 4. Schematic of the reaction to generate a fused dipyrimidyl
analogue (6) from polyphenylene precursor (5): (i) Br2, toluene, 90 °C,
1 h.
ASSOCIATED CONTENT
* Supporting Information
■
S
Recrystallization of 6 from CH2Cl2/MeOH yielded the
product as a crystalline yellow solid. After filtering, no further
purification was necessary, and on diffusing the product in a
methanol solution, twinned crystals suitable for X-ray diffraction
studies were genereated. The data were refined as a two-
component twin using PLATON and HKLF 5 and were
successfully integrated using a triclinic unit cell. The unit cell
contains 6 H2O molecules, which were treated as a diffuse
contribution to the overall scattering without specific atom
positions by SQUEEZE/PLATON. The packing motif (Figure
5) shows the head-to-tail stacking between alternating molecules,
with very small interplanar distances of 3.365 and 3.349 Å.
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.5b03312.
Additional experimental details and figures (PDF)
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: smdraper@tcd.ie.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This publication has emanated from research conducted with the
financial support of Science Foundation Ireland (SFI) under the
Grants 14/TIDA/2330 and 10/IN.1/I2974.
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