Development of novel synthetic routes to bis(perfluoroalkyl)-substituted anthracene derivatives

Article abstract of DOI:10.1039/c3ra40974k

Commercially available anthraquinones were smoothly converted to either symmetrically or unsymmetrically substituted 9,10-bis(perfluoroalkyl)anthracene- 9,10-diols by way of bistrifluoromethylation or successive trifluoromethylation- nucleophilic perfluoroalkylation, respectively, and these diols can be easily aromatized to form bis(perfluoroalkyl)anthracene derivatives in good yields by treatment with a mixture of CBr₄ and PPh₃. Further cross-coupling reactions using halogen-containing anthracene derivatives realized a successful extension of the original π-conjugation systems.

Full text of DOI:10.1039/c3ra40974k

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Development of novel synthetic routes to
bis(perfluoroalkyl)-substituted anthracene derivatives3
Cite this: DOI: 10.1039/c3ra40974k
Shigeyuki Yamada,a Keita Kinoshita,a Shota Iwama,a Takashi Yamazaki,*a
Toshio Kubotab and Tomoko Yajimac
Received 26th February 2013,
Accepted 18th March 2013
DOI: 10.1039/c3ra40974k
www.rsc.org/advances
Commercially available anthraquinones were smoothly converted
to either symmetrically or unsymmetrically substituted 9,10-
bis(perfluoroalkyl)anthracene-9,10-diols by way of bistrifluoro-
methylation or successive trifluoromethylation-nucleophilic per-
fluoroalkylation, respectively, and these diols can be easily
aromatized to form bis(perfluoroalkyl)anthracene derivatives in
good yields by treatment with a mixture of CBr4 and PPh3. Further
cross-coupling reactions using halogen-containing anthracene
derivatives realized a successful extension of the original p-con-
jugation systems.
a new and effective approach to the preparation of various types of
Rf-containing anthracenes by less than 4 facile steps.
Our approach for this purpose consists of the following three
reaction steps: (1) nucleophilic addition of CF3SiMe3 to 9,10-
anthraquinones, followed by RfLi, (2) hydrolysis of the resultant
silyl ethers, and (3) reductive aromatization (Scheme 1).
Our study was initiated by the synthesis of symmetrical bis(tri-
fluoromethyl)anthracenes (3) with reference to the previously
reported conditions,5 using CF3SiEt3 as the CF3 source for the
reaction with anthraquinones (1) in the presence of K2CO3 as an
activator. In our instance, due to its ready availability, 3.0 equiv. of
Ruppert–Prakash reagent (CF3SiMe3)6 was subjected to a DMF
solution of 9,10-anthraquinone (1a) in the presence of 0.4 equiv. of
K2CO3 at room temperature, and after 15 h, the corresponding
bis(trifluoromethyl)adduct was obtained in 82% yield.7
Incorporation of other Rf groups such as C4F9 or C6F13 to 1a by
way of the corresponding lithium species was found unsuccessful,
possibly due to their low thermal stability and nucleophilicity
along with low solubility of 1a at the reaction temperature of 280
uC. This silylated adduct was easily hydrolysed by exposure to
concentrated hydrochloric acid, leading to the exclusive formation
of 9,10-bis(trifluoromethyl)anthracene-9,10-diol (2a) in 96% yield
with the anti configuration as the sole stereoisomer7 (71% yield in
2 steps from 1a). While the usual aromatization conditions, like
SnCl2 with HCl, did not work at all,8 smooth transformation of the
diol 2a was realized by treatment with a mixture of CBr4 and PPh3
(3.0 and 4.5 equiv., respectively) in CH2Cl2 at rt for 15 h to produce
the desired 9,10-bis(trifluoromethyl)anthracene (3a) in 66% yield
(entry 1, Table 1). As shown in entries 2–5, the above
Acenes, represented by anthracenes with linearly fused benzene
rings, are well-known as
a family of polycyclic aromatic
hydrocarbons (PAHs) which have been drawing enormous interest
as important materials for a variety of organic electronic devices1,2
by utilization of their characteristics, like light weight, flexibility,
ready structural modification, and so forth.3 Functionalization of
the anthracene backbone is one of the most straightforward and
facile methods to affect the original quality, and various elements
as well as groups have been introduced to this structure. Among
them, perfluoroalkyl (Rf) moieties are quite intriguing due to their
strong electron-withdrawing nature which would effectively lower
the HOMO and LUMO energy levels as well as affect good
alignment by steady intermolecular electrostatic interactions,
leading to the construction of a higher-ordered stacking structure
(Fig. 1). While Rf-substituted anthracenes have been synthesized
by a few groups,4 to the best of our knowledge no reports have
appeared thus far on their preparation with two different Rf
moieties at 9 and 10 positions. In this communication, we disclose
aDepartment of Applied Chemistry, Graduate School of Engineering, Tokyo University
of Agriculture and Technology, 2-24-16 Nakamachi, Koganei 184-8588, Japan.
E-mail: tyamazak@cc.tuat.ac.jp
bDepartment of Biomolecular Functional Engineering, Ibaraki University,
Nakanarusawa 4-12-1, Hitachi 316-8511, Japan. E-mail: t.kubota@mx.ibaraki.ac.jp
cDepartment of Chemistry, Faculty of Science, Ochanomizu University, Otsuka,
Bunkyo-ku, Tokyo 112-8610, Japan. E-mail: yajma.tomoko@ocha.ac.jp
Electronic supplementary information (ESI) available: Experimental details and
3
X-ray crystallographic data. CCDC 924504 for 3j, 924505 for 3l, 924506 for 3o, 924507
for 3q, 924508 for 6aB and 924509 for 6aC, see DOI: 10.1039/c3ra40974k
Fig. 1 Possible effects of perfluoroalkyl groups on anthracenes.
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Scheme 2 Preparation of mono-trifluoromethylated substrate 4a.
aid of RfLi met with difficulty, our strategy was to start from the
monotrifluoromethylation of 1, which would offer higher solubility
of the product due to the unsymmetrical substitution pattern,
rendering a better chance of acceptance to attack by these
nucleophiles, even at a low temperature.
Initially, incorporation of only one CF3 moiety to 1a was
conducted by the above bistrifluoromethylation procedure with
control over the reagent amount (Method A in Scheme 2), which
smoothly proceeded to form the desired adduct 4a in 43% yield,
together with 27% of bis(trifluoromethyl) adduct. After intensive
examination,9 the slow addition of a slight excess of CF3SiMe3 (1.2
equiv.) to a THF solution of 1a containing 0.10 equiv. of CsF was
found to be quite effective, and the following stirring at rt for 3 h
(Method B) furnished the desired mono-trifluoromethyl adduct 4a
in excellent 90% isolated yield.
To the obtained 4a, the nucleophilic addition of in situ
generated RfLi was then carried out by dropwise addition of a
MeLi–LiBr complex to an Et2O solution of 4a and perfluorobutyl
iodide at 280 uC.10 This reaction took place smoothly with stirring
for 2 h at the same temperature to afford the corresponding
adduct in 79% yield, which led to the formation of a differently-
substituted 9,10-diol 5aA in 79% yield (62% yield in 2 steps from
4a) after simple acidic hydrolysis in the same manner (entry 1,
Table 2). This diol, 5aA, was successfully converted to the
corresponding unsymmetrical 9,10-bis(perfluoroalkyl)anthracene
6aA in 93% yield via our reductive aromatization conditions (CBr4–
PPh3). As shown in entries 2–4, the representative mono-
trifluoromethyl adduct 4a successfully accepted nucleophilic
attack by such lithium species as C6F13Li, C8F17Li, and C10F21Li,
and further deprotection to 9,10-diols 5aB–D was realized in 42%–
57% yields by the same procedure. Their subsequent reductive
aromatization was also found to proceed well to provide the
unprecedented unsymmetrical anthracenes 6aB–D in good yields.
Fortunately, the unsymmetrically 9,10-perfluoroalkylated
anthracene 6aB furnished a single crystal appropriate for X-ray
crystallographic analysis, and the structure obtained is illustrated
in Fig. 2. It is interesting to note that one fluorine atom in the CF3
group in 6aB occupied the vertical position to the aromatic
backbone (F-C-C-C dihedral angle of 89.8u), which might bring
about a slight bend of the anthracene core, possibly for reducing
the undesired repulsive interaction between fluorine and hydro-
gen atoms at the peri position (Fig. 2a).11 A unit cell consisted of
four molecules, two of which were p-stacked so as to enable the
electrostatic interaction of the electron-deficient central ring with
Scheme 1 Outline of our approach to Rf-substituted anthracenes.
bistrifluoromethylation protocol was also examined towards
2-mono or 2,6-dihalogenated substrates 1b–e, prepared in good
yields by the well-known Sandmeyer reaction of the corresponding
commercially available NH2-possessing counterparts (52–80%).
The diols with two CF3 groups 2b–e were obtained by subjecting
1b–e to the similar nucleophilic trifluoromethylation conditions,
followed by hydrolysis. Conversion of the intermediary silyl ether
from 1e was the special case, not effectively giving the
corresponding diol 2e, while deprotection was facilitated by
tetrabutylammonium fluoride (TBAF), allowing isolation of 2e in
74% total yield from 1e. Aromatization of these products 2b–e with
halogen atoms was similarly operated to form the corresponding
anthracenes 3b–e in 52–94% yields.
At the next stage, our interest was focused on the synthesis of
hitherto unknown unsymmetrical bis(perfluoroalkyl)anthracenes.
As described above, since direct introduction of Rf groups with the
Table 1 Synthesis of 9,10-bis(trifluoromethyl)anthracenes 3 from 1
Entry
X, Y in 1
Yield of 2 (%)a
Yield of 3 (%)a
1
2
3
4
5
H, H (1a)
Br, H (1b)
I, H (1c)
Br, Br (1d)
I, I (1e)
71 (2a)
66 (3a)
94 (3b)
52 (3c)
73 (3d)
84 (3e)
Quant (2b)
Quant (2c)
85 (2d)
74b (2e)
a
b
Isolated yields. Tetrabutylammonium fluoride was used instead
of c-HCl aq.
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structure of 6aB shown in (c) in Fig. 2 clearly indicates the
presence of the fluorophilic effect between neighbouring C6F13-
chains, whose F–F distance (301 pm) is only 7 pm longer than the
sum of van der Waals radii.
Table 2 Synthesis of unsymmetrical 9,10-bis(perfluoroalkyl)anthracene deriva-
tives from mono-trifluoromethyl adduct 4a
For clarification of the usefulness of the ‘‘halogen handle’’ at
the benzene ring for assembly of the extended p-conjugate
systems, we attempted the palladium-catalyzed introduction of
substituents with sp2- or sp-carbon reaction sites as illustrated in
Scheme 3. Thus, 2-iodo- (3c) and 2,6-diiodo-9,10-bis(trifluoro-
methyl)anthracenes (3e) as the model compounds were subjected
to the well-accepted cross-coupling reactions with arylboronic
acids (Suzuki–Miyaura)14 or terminal alkynes (Sonogashira),15
leading to 2-aryl- (3f–i), 2-arylethynyl- (3j–k), 2,6-diaryl- (3l–o), and
2,6-bis(arylethynyl)-substituted anthracenes (3p–q) in good to
excellent yields.
Entry
Rf
Yield of 5a (%)a
Yield of 6a (%)a
1
2
3
4
C4F9
62 (5aA)
52 (5aB)
57 (5aC)
42 (5aD)
93 (6aA)
64 (6aB)
74 (6aC)
87 (6aD)
C6F13
C8F17
C10F21
Conclusions
In conclusion, we have developed a new synthetic pathway not
only to symmetrical bis(trifluoromethyl)anthracenes but also to
hitherto unknown unsymmetrically perfluoroalkyl-substituted
counterparts at the 9 and 10 positions, both of which were
formed from the corresponding anthraquinones in less than four
easy steps. Moreover, 2-iodinated and 2,6-diiodinated bis(trifluor-
omethyl)anthracenes as the representative examples were sub-
jected to Suzuki–Miyaura and Sonogashira cross-coupling
reactions, achieving the incorporation of various types of
substituents with p-conjugate systems. Crystallographic data of
a
Isolated yields.
the relatively electron-rich edge part where two C6F13 groups in
different molecules point towards opposite directions (Fig. 2b).
The other two molecules constituted a C–H p interaction with the
electron-deficient ring, constructing Rf-aggregation known as the
‘‘fluorophilic effect’’.12 Packing of these compounds was found to
be relatively tight, which was supported by the shortest C–C
(between two stacking anthracene rings) and C–H (between one
anthracene central ring carbon and the other anthracene
hydrogen) distances of 333 and 275 pm, respectively, both of
which are below the sum of the van der Waals radii.13 The
…
Scheme 3 Synthetic application of 2-iodo- (3c) or 2,6-diiodoanthracene deriva-
tives (3e) to CF3-containing p-conjugate systems.
Fig. 2 Crystal structure of 6aB.
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A. Nagl, Acta Pharmaceutica (Zagreb), 1995, 45, 37–43; (d) H. Sun,
US-Pat. WO2011022678.
6aB unambiguously clarified the effectiveness of our concept,
where Rf groups properly work for construction of a regular
arrangement of acene molecules. Further studies on the prepara-
tion and structural characterization of a variety of perfluoroalkyl-
substituted acenes are currently under investigation in our
laboratory.
Present results were obtained as a part of AGC Research
Collaboration Program. We thank Dr Kyoko Yamamoto at the
Research Center, Asahi Glass Co., Ltd. for her important technical
support.
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