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Organic & Biomolecular Chemistry
Page 2 of 5
DOI: 10.1039/C8OB01930D
COMMUNICATION
unprecedented photophysical properties. Interestingly, Scholl Table
Journal Name
1
Optimization
for
the
synthesis
of
cyclization has not been extensively explored for the synthesis tetramethoxytriphenylenea,b
of heteroaryl incorporated phenylenes, probably due to the
easydeactivation of the available catalyst in the presence of
heteroaryls. We ventured to explore Scholl cyclization using
simple and inexpensive one-electron oxidant and Lewis acid
catalyst for synthesizing polyaromatic hydrocarbons and
polyheteroaromatic compounds. Herein, we have explored the
use of cerium ammonium nitrate (CAN, [(NH4)2Ce(NO3)6,
which can act as an oxidant as well as a Lewis acid for the
Scholl’s cyclization. CAN is a simple, inexpensive environment-
friendly one-electron oxidant widely used in organic synthesis
for generation of radicals to form C-C and C-Heteroatom bond
in relatively milder conditions. The large reduction potential of
CAN along with its poor reactivity with radical quenchers like
oxygen makes it an attractive free radical generator in many
organic solvents.14 Our hypothesis is based on a study by
Parker and co-workers where they suggested the involvement
of cation radical intermediate in an efficient oxidative C-C
bond formation for biaryl synthesis via the Scholl reaction.15
Recently, the use of CAN as an effective promoter for the
oxidative addition reactions of electrophilic radicals have been
explored significantly.16
We commenced our optimization studies with tetramethoxy
substituted o-terphenyl 1a as a model substrate, treated with
aReaction conditions: 1a (35 mg, 0.1 mmol), CAN ( equiv),
additive ( equiv) taken in indicated solvent (2 ml), stirred at rt
for 2 h. b Isolated yield.
1 equiv ceric (IV) ammonium nitrate in dichloromethane at
room temperature. We observed intramolecular cyclization in
1a to form corresponding triphenylene 2a in 40% yield (Table
1, entry 1). With an encouraging preliminary lead, we
proceeded to find the best optimized condition for the
intramolecular oxidative coupling. Few important observations
are described in table 1. We decided to explore the effect of
additives on the yield of 2a. Screening of Bronsted acid such as
CH3SO3H and CF3COOH, Lewis acids such as BF3.OEt2 and AlCl3,
as an additive in corresponding solvents was realized to be
futile as no significant improvement in the product formation
was observed (table 1, entries 2-5). Introduction of a weak
base as an additive reduced the yield (table 1, entry 6).
Screening of other solvents such as acetonitrile, THF, Et2O, 1,4-
Dioxane and hexane was carried out, of which acetonitrile
offered best yield (table 1, entries 7-10). Additionally, it was
observed that the equivalent of oxidizing agent CAN was
affecting the reaction efficiency. Performing the oxidative
coupling using 2 equivalent of CAN in CH3CN gave better yield
(table 1, entry 11). On the other hand, exceeding CAN amount
to 3 equivalent resulted in decomposition of the reaction
mixture (table 1, entry 12). It was observed that even a slight
increment in the CAN equivalent from 2.0 to 2.1 led to drop in
conversion of oxidized product (table 1, entry 13). With these
optimized conditions (table 1, entry 11) in hand, we planned to
explore this protocol on different o-terphenyl such as 5, 6
diaryl N-protected benzimidazoles, their substituted analogues
and diarylquinoxalines/pyrazines. First, we explored the
substrate scope of this newly developed protocol for a variety
of o-terphenyls as Scholl precursors as highlighted in table 2. A
Miyaura coupling, by utilising corresponding 1,2-dihalo arenes
and 3,4-disubstituted phenyl boronic acids. The oxidation of
3,4,3’’,4’’-tetramethoxy-o-terphenyl 1a and 3,4,3’’,4’’-
tetramethoxy-3’,4’-dimethyl-o-terphenyl 1b gave 2,3,6,7-
tetramethoxytriphenylene 2a and 2,3,6,7-tetramethoxy-10,11-
dimethyltriphenylene 2b in very good yield (table 2). We
observed that due to the high oxidative power of the reagent
and the electron-rich nature of the substrate, the reaction was
very fast and completed 75-80% conversion in only 30
minutes. Further, if the 4 and 4’’ position of the o-terphenyls
(
1c
,
1d) are fluoro substituted, two methoxy groups were
2d, table 2).
sufficient for the cyclization in moderate yield (2c
,
However, the addition of two methoxy groups on the middle
aromatic ring of o-terphenyl with 4 and 4’’ position fluoro
substitution yielded very good cyclization (2e). In another
oxidative cyclization, where 3 and 3’’ position of the o-
terphenyl are methyl substituted with two methoxy groups
gave excellent yield for the cyclization (2f). Consequently, 3,
3’’-dimethyl 4, 3’, 4’, 4’’-tetramethoxymethoxy-o-terphenyl
gave moderate yield of corresponding triphenylene (2g).
Substitution of electron withdrawing group such as formyl and
fluoro group on the middle aryl ring of o-terphenyls with four
methoxy on the other two aryls did not change the yield
drastically and gave cyclized product in good yield (2h, 2i).
Attempts to oxidize o-terphenyl without –OMe substitution
did not lead to the corresponding cyclized product (see SI for
details). The versatility of CAN for the oxidative
cyclodehydrogenation was further explored for the synthesis
number of o-terphenyls and their substituted analogues 1a-i
,
were synthesized by following the well-established Suzuki-
2 | J. Name., 2012, 00, 1-3
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Gupta, Vijay
