Polyaniline-Induced Arylation with Arenediazonium Salts Derived from Anilines

Article abstract of DOI:10.1002/chem.201700630

A catalytic amount of a reduced form of polyaniline (a redox-active π-conjugated polymer) was found to induce C?H direct arylation of (hetero)arenes with arenediazonium salts prepared from anilines with methanesulfonic acid (MeSO₃H) and tert-butyl nitrite (tBuONO). The difficult part of this method is the coexistence of an oxidant and a reductant in this sequential diazotization and arylation system; diazotization requires weak oxidants such as alkyl nitrites, whereas the arylation is induced by a reductant. This was achieved by the careful control of the amount of tBuONO (1.0 equivalent) for the diazotization step, and sequential arylation using 5 mol % of the polyaniline. The reaction took place under mild conditions without any metals or strong bases at room temperature, and the amino group is a formal leaving group. The scope of the substrates demonstrates the versatility in the combination of anilines with a variety of functional groups and several (hetero)arenes. Two-directional arylation for the synthesis of an unsymmetrical 1,4-diarylated (furyl and pyrrolyl groups) benzene was achieved, using mono-Boc-protected 1,4-phenylenediamine as a substrate. This shows potential for the synthesis of more complicated oligoarene compounds.

Full text of DOI:10.1002/chem.201700630

A Journal of
Accepted Article
Title: Polyaniline-induced Arylation with Arenediazonium Salts Derived
from Anilines
Authors: Dai Hata, Toshiyuki Moriuchi, Toshikazu Hirao, and Toru
Amaya
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Polyaniline-induced Arylation with Arenediazonium Salts Derived
from Anilines
Dai Hata,[a] Toshiyuki Moriuchi,[a] Toshikazu Hirao,+[a] and Toru Amaya*[a]
Abstract: A catalytic amount of a reduced form of polyaniline, redox-
active π-conjugated polymer, induced C-H direct arylation of
(hetero)arenes with arenediazonium salts prepared from anilines with
methanesulfonic acid (MeSO3H) and tert-butyl nitrite (t-BuONO). The
difficult point is the coexistence of an oxidant and a reductant in this
sequential diazotization and arylation system; the diazotization
reagents such as alkyl nitrites are weak oxidants and the arylation is
induced by a reductant. It was achieved by the careful control of the
amount of t-BuONO (1.0 equivalent) for the diazotization step and the
sequential arylation using 5 mol% of the polyaniline. The reaction took
place under mild conditions without any metals and strong bases at
room temperature, where the amino group is a formal leaving group.
The scope of the substrates demonstrated the versatility in the
combination of anilines with a variety of functional groups and several
(Scheme 1c).[4] Due to the low reduction potential (E1/2
=
+0.14~0.45 V vs SCE[5]) of arenediazonium salts 1, the radical
initiation and propagation steps can be performed under mild
conditions. Recently, various reductants such as organic
reductants, low-valent metals, and photocatalyst under light, have
been reported for this type of reaction.[6-8] As an example for the
reactions under metal-free conditions, a photocatalyst eosin Y
was demonstrated for the C-H arylation of arenes with
arenediazonium salts by König et al.[7b]
For all that, arenediazonium salts 1 are hard to be preserved
and the commercial source is limited due to their unhandy
character. Alternatively, the arylation with anilines 4 via in-situ
preparation of arenediazonium salts 1 is attractive, which can not
only overcome the preservation problem but become
complementary method of arylation with arylhalides because an
amino group is a formal leaving group here. It is also advantage
that various anilines 4 can be available from commercial sources.
However, there is difficulty due to the coexistence of an oxidant
and a reductant in this sequential diazotization and arylation
system; the diazotization reagents such as alkyl nitrites are weak
oxidants and the arylation is induced by a reductant (Scheme 1e).
Therefore, the examples have been limited.[8] Recently, transition-
metal-free conditions have been reported.[8e,i-k] For examples,
ascorbic acid and gallic acid-initiated C-H arylation of arenes were
demonstrated by Carrillo and coworkers.[8e,k] Light-induced and
catalyst-free method was also described by de Frutos, Kappe et
al, where diazo anhydride intermediate was suggested.[8j]
On the other hand, polyaniline is a redox-active π-conjugated
polymer. We have constructed redox-reaction systems based on
polyanilines.[9] Its reduced form 5 (Scheme 1d) is a suitable single-
electron donor for the reduction of arenediazonium salts in terms
of the redox potentials (the oxidation potential is reported to be
E1/2 = +0.13 V vs SCE[10]). Moreover, the formed radical cation of
polyaniline is stabilized by its π-conjugated system. Polyaniline is
also able to be removed easily from the reaction mixture. In this
regard, we have achieved the arylation of (hetero)arenes using
arenediazonium salts induced by a catalytic amount of the
reduced form of polyaniline 5 (Scheme 1d).[11] In this context, this
study was conducted to develop the sequential diazotization and
arylation (Scheme 1e). Development of such mehod leads to
iterative and polydirectional arylation if some amino-groups can
be differentiated using protecting groups.[12] Herein, we report the
polyaniline-induced arylation with arenediazonium salts 1 derived
from anilines 4 without the use of any metal additives, strong
bases, and light (Scheme 1e-I). We also demonstrate the two-
directional arylation strategy using Boc-protected 1,4-
phenylenediamine 6 to synthesize the arene 7 with furyl and
pyrrolyl groups (Scheme 1e-II).
(hetero)arenes.
Exploiting
mono-Boc-protected
1,4-
phenylenediamine, two-directional arylation for the synthesis of the
unsymmetrically 1,4-diarylated (furyl and pyrrolyl groups) benzene
was achieved, which shows a potential for the synthesis of more
complicated oligoarene compounds.
Introduction
Biaryls are commonly found in natural compounds, medicines,
and other functional organic materials. Transition-metal-catalyzed
cross-coupling reactions made it possible to get the biaryls
directly (Scheme 1a).[1] In terms of environmental aspects,
however, the alternative method to access biaryl moieties under
transition-metal-free conditions is required. One of such
[2]
strategies is homolytic aromatic substitution (HAS),
which is
consisted of the addition of an aryl radical to an arene and the
subsequent aromatization (Scheme 1b). Recently, significant
improvements of HAS have been achieved with arylhalides as
radical precursors and alkali metal t-butoxide as a base, where
radical chain mechanism is suggested.[3]
Arenediazonium salts 1 have a diazonio group as a desirable
leaving group for this reaction, and readily accept one electron to
yield aryl radicals. The cross-coupling reaction of 1 with an arene
2 to give a biaryl 3 is known as the Gomberg-Bachmann reaction
[a]
[+]
D. Hata, Dr. T. Moriuchi, Prof. Dr. T. Hirao, Dr. T. Amaya
Department of Applied Chemistry
Graduate School of Engineering, Osaka University
Yamada-oka, Suita, Osaka 565-0871 (Japan)
E-mail: amaya@chem.eng.osaka-u.ac.jp
Present address is described below.
The Institute of Scientific and Industrial Research, Osaka University,
Mihoga-oka, Ibaraki, Osaka 567-0047, (Japan).
Supporting information for this article is given via a link at the end of
the document.
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arenediazonium salt 1a to the equivalents of t-BuONO and
reaction time (supplementary investigation is also shown in Table
S1-S4). In the following optimization, the reactions were
performed with an internal standard (1,3,5-tribromobenzene), and
the yield was determined by the integral ratio in the 1H NMR
spectrum after sampling and dilution with [D6]DMSO. Under the
conditions with 1.5 equivalents of t-BuONO and 0.5 h reaction
time, the desired product 3aa was obtained in 12% (Table 1, entry
1). The reaction required 8.5 h until the yield of 3aa reached a
maximum yield of 36% with the trace amounts of 1a (Table 1,
entry 2). In the reaction, the diazotization step seems to be
incomplete judging from the 1H NMR spectra of the reaction
mixture. Methanesulfonic acid (MeSO3H) dramatically promoted
the formation of the corresponding arenediazonium salts 1a
(87%), but the yield of 3aa remains low (10%; Table 1, entry 3).
The foremost concern is the deactivation of 5 by t-BuONO under
the acidic conditions, which was demonstrated using N,N’-
diphenylphenylenediamine as a model compound of 5 (Scheme
S1).
Table 1. One-pot synthesis of 3aa based on in-situ diazotization of 4a and
its arylation with 2a induced by polyaniline 5.
Yield [%][a]
t-BuONO
x [equiv.]
Time
[h]
Entry
Arylated furan
Arenediazonium
3aa
salt 1a
1
2
1.5
0.5
8.5
12
36
trace
17
1.5
1.5
3
0.5
10
87
(with MeSO3H)[b]
[a] Yield was determined by 1H NMR analysis of the reaction mixture based
on 1,3,5-tribromobenzene as an internal standard. [b] Reaction was
performed with 1.0 equivalent of MeSO3H.
With these results in hand, increasing of the amount of
polyaniline 5 and the careful investigation on the amount of t-
BuONO were conducted as shown in Table 2 (Supplementary
investigation of nitrites and solvents is also shown in Table S4),
where the dropwise procedure was employed. As expected, use
of 5 mol% of 5 and 1.0 equivalent of t-BuONO gave 3aa in 73%
yield (Table 3, optimized conditions, entry 1) with 11% of
diarylated furan 8aa. Slight increase of the amount of t-BuONO
(1.1 equivalents) significantly lowered the conversion of the
arenediazonium salt 1a (Table 2, entry 2), which supports the
hypothesis of the deactivation of polyaniline 5 by t-BuONO.
However, further increasing of 5 to 10 mol% gave rise to lower the
yield of 3aa (66% and 64%, Table 3, entries 3 and 4, respectively).
Scheme 1. (a) Transition-metal-catalyzed biaryl synthesis, (b) alternative biaryl
synthesis via homolytic aromatic substitution, (c) Gomberg-Backmann reaction,
(d) previous work, and (e) this work, I: sequential diazotization and arylation,
and II: two-directional arylation strategy.
Results and Discussion
One-pot reaction was examined as an initial investigation, where
tert-butyl nitrite (t-BuONO) as a diazotization reagent was added
to the [D6]DMSO solution of 4-bromoaniline 4a, 10 equivalents of
furan 2a, and 1 mol% of a reduced form of polyaniline 5 (mole of
5 was calculated based on aniline tetramer). Table 1 summarizes
the yields of 2-(4-bromophenyl)furan (3aa) and the corresponding
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These results indicate that the arylation of polyaniline 5 took place
competitively (IR spectroscopy revealed the competitive reaction,
see Supporting Information, Figure S1). Without polyaniline 5, the
arylation did not proceed and the arenediazonium salt 1a
remained in 92% yield (Table 3, entry 5). Using the optimized
amounts of the substrates and reagents, they are jumbled and
mixed together to get 3aa in a less yield of 57% (Table 3, entry 6,
one-pot procedure). As described in our previous study, [11] the
arylation induced by 5 was found to be affected by the order and
speed for the addition of the substrate. The steady low-kept
concentration of the aryl radical by dropwise addition is
considered to be a key point in the arylation, which can lead to the
situation that an aryl radical is surrounded by large excess of
arenes.
Table 2. Investigation of the amounts of t-BuONO and polyaniline 5 in the
cross-coupling reaction under the conditions with a dropwise addition of the
solution of the prepared arenediazonium salt 1a from 4a to the mixture of 5
and 2a
Yield [%][a]
Polyaniline
t-BuONO
x [equiv.]
di-
arylated
furan
8aa
Entry
5
Mono-
arylated
furan 3aa
Arene
diazonium
salt 1a
y [mol%]
1
2
1.0
1.1
1.0
1.1
1.0
1.0
5
5
73
22
66
64
-
11
1
-
63
-
3
10
10
0
12
9
4
-
5
-
92
-
6[b]
5
57
7
[a] Yield was determined by 1H NMR analysis of the reaction mixture based
on 1,3,5-tribromobenzene as an internal standard. [b] One-pot procedure
was employed instead of the dropwise one.
Under the optimized reaction conditions, the scope and
limitation of the arylation of heteroarenes (furan 2a, thiophene 2b,
and N-Boc-pyrrole 2c) and an arene 2d were investigated
(Scheme 2). In the case of the reaction using 4b-4k with furan 2a,
mono-arylated furans 3ba-3ka were obtained in moderate to good
yields (51 to 86%) regardless of the electronic state of the aniline
derivatives 4b-4k. Large family of functional groups were
tolerated in the arylation, such as chloro, bromo, iodo, nitro, cyano,
acetyl, and methoxy groups. Moreover, the aniline 4l with ethynyl
group can be used for the reaction to give the biaryl 3la in 39%.
Scheme 2. Scope and limitation of the sequential diazotization of anilines 4 and
the arylation with arenes 2 induced by polyaniline 5. Yield was determined by
1H NMR analysis based on 1,2,4,5-tetrabromobenzene as an internal standard.
The reaction was conducted using 0.2 mmol of 4. In some cases, the reaction
was conducted in DMSO instead of [D6]DMSO (see experimental section). [a]
Isolated yield. [b] 1.0 mmol of 4 was used. [c] 2.0 mmol of 4 was used. [d]
Isolated yield of the coupling products at the C2 and C3 positions (91:9 for 3eb,
90:10 for 3fb, 95:5 for 3gb).
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The reaction employing the substrate 4m bearing quinone moiety Conclusions
also took place to afford 3ma in 43% yield. The arylation of
thiophene 2b was conducted with 4d-4g to give the corresponding
products 3db-3gb in moderate yields (32 to 50%). In the case of
thiophene, the coupling product at the C-3 position of thiophene
was also observed as a minor product (ca. 5-10%) in 1H NMR and
GC-MS. Boc-protected pyrrole 2c was also available with this
arylation, where Boc-protecting group remained intact (80% NMR
yield in 0.2 mmol scale and 71% isolated yield in 2.0 mmol scale
for 3ec). m-Nitroaniline 4f is less reactive to give the products 3fa
and 3fb to result in 15 to 20% less than those of p- and o-
nitroanilines 4e and 4g. Mesitylene 2d was demonstrated as a
six-membered arene to provide 3ed in moderate yields.
As N-Boc amino group was tolerated through the reaction
as demonstrated in the synthesis of 3ec in Scheme 3, it motivated
us further investigation of the potential of our methodology. That
is, the synthesis of arene 7 with furyl and pyrrolyl groups using N-
Boc-phenylenediamine 4n was carried out. This two-directional
arylation strategy is attractive because it is able to prepare a
variety of hetero-substituted benzene. First, 4n was diazotized
and the resulting arenediazonium salt cross-coupled with 2a in
the presense of 5 mol% of 5 to give the corresponding
heterobiaryl 3na in 76% yield, where Boc group was intact.
In summary, a catalytic amount of polyaniline 5-induced C-H
arylation of arenes 2 with arenediazonium salts 1 prepared by the
preceding diazotization of anilines 4 has been developed, where
the amino group in anilines 4 is a formal leaving group. This
sequential reaction proceeds under mild conditions without any
metals and strong bases at room temperature to yield biaryls.
Although there is difficulty in the coexistence of diazotization of
amino group and the arylation induced by one-electron reduction,
it can be achieved by the careful control of the amount of t-
BuONO (1.0 equivalent) for the diazotization step and the
sequential arylation using 5 mol% of polyaniline 5. Employing the
developed arylation, the two-directional arylation strategy using
N-Boc-phenylenediamine 4n was demonstrated by the synthesis
of 1,4-disubstituted benzene 7 with furyl and pyrrolyl groups. This
strategy may be applied to the synthesis of more complicated
oligoarenes. Further investigation and application are now in
progress.
Experimental Section
Deprotection
of
Boc
group
was
performed
in
General. NMR spectra were recorded on a JEOL JNM-ECP 400
spectrometer. Chemical shifts in CDCl3 were reported in ppm on the 
scale relative to a residual solvent ( 7.26 for 1H NMR and 77.16 ppm for
13C NMR) as an internal standard. Infrared spectra were recorded as KBr
pellets on a JASCO FT/IR-480plus. Mass spectra were measured on a
JEOL JMS-DX-303 spectrometer using fast atom bombardment (FAB)
mode, a BRUKER AUTOFLEX III (MALDI−TOF) mass spectrometer, or
SHIMADZU GC-2010 PARVUM2 100V (GC-MS, EI). Reaction under
microwave irradiation was performed on a Biotage initiator 2.5. Silica gel
column chromatography was performed on a Yamazen EPCLC-W-Prep
2XY A-Type with an ULTRA PACKTM cartridge.
hexafluoroisopropanol at 150 °C under microwave irradiation for
75 min to give the corresponding aniline.[13] After the evaporation
of hexafluoroisopropanol, the reaction mixture was used for the
next reaction without purification. Finally, the second sequential
diazotization and arylation with 2c induced by polyaniline 5 was
demonstrated to afford the desired oligoarene 7 in 46% yield
based on 3na.
Materials. A reduced form of polyaniline 5 was prepared according to the
reported method.[11] Anilines 4a-n, arenes 2a-d, t-BuONO, MeSO3H,
DMSO, [D6]DMSO, and hexafluoroisopropanol were purchased from the
commercial sources, and used without further purification unless otherwise
mentioned.
Polyaniline-induced arylation with arenediazonium salts via in-situ
diazotization: synthesis of 3ia. In an oven-dried 30 mL two-necked flask
with a stirring tip, aniline 4i (169 mg, 1.25 mmol) was dissolved in 9.5 mL
of DMSO under a nitrogen atmosphere. To the solution were added
MeSO3H (81 μL, 1.25 mmol) and t-BuONO (165 μL, 1.25 mmol). Then, the
reaction mixture was stirred at room temperature for 30 min, 80 volume %
of which was dropwise added by using a syringe pump (60 mL/h) to the 2
mL DMSO solution of polyaniline 5 (18 mg, 50 μmol, based on aniline
tetramer) and arene 2a (730 μL, 10 mmol) in another oven-dried 30 mL
two-necked flask with a stirring tip. After the reaction for 30 minutes, the
reaction mixture was poured into the mixture of Et2O and water. The
resulting black solid of the polyaniline 5 was filtered through silica gel
before the liquid-liquid separating operation. The aqueous layer was
extracted with Et2O three times. The combined organic layer was washed
with water and brine, then dried with Na2SO4, and concentrated in vacuo.
The residue was purified by silica gel column chromatography
(hexane/ethyl acetate = 9/1) to give the product 4fa (132 mg, 0.71 mmol,
71%). The reactions for 2 mmol scale synthesis were also carried out with
the same procedure. In the synthesis of 3ha, aniline 4h (295 mg, 2.5 mmol),
MeSO3H (81 μL, 1.25 mmol) and t-BuONO (165 μL, 1.25 mmol),
Scheme 4. Synthesis of the 1,4-disubstituted benzene 7 with furyl and pyrrolyl
groups based on two-directional arylation strategy using N-Boc-
phenylenediamine 4n. [a] Yield was determined by 1H NMR analysis of the
reaction mixture based on 1,3,5-tribromobenzene as an internal standard. [b]
Isolated yield.
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polyaniline 5 (36 mg, 100 μmol, based on aniline tetramer), and arene 2a
(1.45 mL, 20 mmol) were used. The speed of dropwise addition of
diazotization reaction mixture was 120 mL/h. After purification by silica gel
column chromatography (hexane/ethyl acetate = 9/1), the product 3ha
(240 mg, 1.42 mmol, 71%) was obtained.
Spectral data for the new compounds.
1
2-(4-Ethynylphenyl)furan (3la): H NMR (400 MHz, CDCl3) δ = 7.61-7.65
(m, 2H), 7.53-7.46 (m, 3H), 6.69 (d, J = 3.7 Hz, 1H), 6.49 (dd, J = 3.7 Hz,
1.8 Hz, 1H), 3.12 (s, 1H) ppm; 13C NMR (100 MHz, CDCl3) δ = 153.37,
142.75, 132.64, 131.21, 123.69, 120.87, 112.02, 106.25, 83.80, 77.95
ppm; IR(KBr) 3285, 3126, 2926, 2105, 1921, 1612, 1509, 1475, 1417,
1376, 1281, 1221, 1157, 1112, 1042, 1010, 903, 885, 842, 807, 738, 665,
620, 595, 540 cm-1; HRMS (FAB) (m/z): [M]+ calcd for C12H8O, 168.0575;
found, 168.0576.
General procedure for the optimization and the substrate scope
investigation of the sequential diazotization and arylation. In an oven-
dried 10 mL two-necked flask with stirring tip, aniline 4 (0.2 mmol) were
reacted with arene 2 (2.0 mmol) as described above (synthesis of 3ia) in
the presence of an internal standard (ca. 0.10 mmol). The speed of
dropwise addition of diazotization reaction mixture was 25.4 mL/h. A
sample was taken from the reaction mixture after a certain time and diluted
ten times with [D6]DMSO to be measured by NMR spectroscopy. The yield
of products 3 was calculated based on the integral ratio in the 1H NMR
spectrum. The reactions conducted with DMSO as a solvent were carried
out similarly (3ea, 3eb, 3ec, 3fa, 3fb, 3ga, 3gb, 3la, 3ma). The yield was
determined by 1H NMR analysis of the crude mixture based on 1,3,5-
tribromobenzene as an internal standard after the similar work-up as
described in the synthesis of 3ia.
tert-Butyl (4-(furan-2-yl)phenyl)carbamate (3na): 1H NMR (400 MHz,
CDCl3) δ = 7.58-7.62 (m, 2H), 7.43 (d, J = 1.8 Hz, 2H), 7.38 (d, J = 8.7 Hz,
2H), 6.56 (d, J = 3.5 Hz, 3H), 6.49 (br, 1H), 6.45 (dd, J = 3.5 Hz, 1.8 Hz,
1H), 1.53 (s, 9H) ppm; 13C NMR (100 MHz, CDCl3) δ = 154.00, 152.74,
141.77, 137.71, 126.16, 124.73, 118.71, 111.73, 104.13, 80.84, 28.51
ppm; IR(KBr) 3367, 3006, 2985, 2933, 1700, 1614, 1594, 1577, 1523,
1509, 1484, 1462, 1446, 1415, 1393, 1368, 1315, 1297, 1265, 1236, 1160,
1117, 1079, 1058, 1017, 1008, 903, 884, 838, 805, 770, 733, 663, 648,
628, 594, 518 cm-1; HRMS (FAB) (m/z): [M]+ calcd for C15H17NO3,
259.1208; found, 259.1208.
tert-Butyl 2-(4-(furan-2-yl)phenyl)-1H-pyrrole-1-carboxylate (7): 1H NMR
(400 MHz, CDCl3) δ = 7.63-7.67 (m, 2H), 7.48 (dd, J = 1.8 Hz, 0.9 Hz, 1H),
7.39-7.34 (m, 3H), 6.60 (dd, J = 3.7 Hz, 0.9 Hz, 1H), 6.48 (dd, J = 3.7 Hz,
1.8 Hz, 1H), 6.26-6.20 (m, 2H) ppm; 13C NMR (100 MHz, CDCl3) δ =
154.10, 149.54, 142.21, 134.89, 133.47, 129.82, 129.56, 123.16, 122.94,
114.70, 111.83, 110.81, 105.15, 83.90, 27.84 ppm; IR(KBr) 3147, 3118,
3003, 2981, 2930, 2850, 1733, 1515, 1469, 1455, 1416, 1394, 1370, 1338,
1316, 1257, 1221, 1149, 1075, 1010, 975, 903, 882, 849, 817, 805, 773,
749, 725, 670, 598 cm-1; HRMS (FAB) (m/z): [M]+ calcd for C19H19NO4,
309.1365; found, 309.1368.
Identification of the products 3 was conducted by comparison with the data
reported previously except for new compounds after isolation of the
product by preparative TLC or silica gel chromatography, see supporting
information: 2-(4-bromophenyl)furan (3aa)[7b]
(3ba)[7b], 2-(4-iodophenyl)furan (3ca)[14], 2-(2-bromophenyl)furan (3da)[15]
, 2-(4-chlorophenyl)furan
,
2-(2-bromophenyl)thiophene (3db)[16], 2-(4-nitrophenyl)furan (3ea)[7b], 2-
(4-nitrophenyl)thiophene (3eb)[7b], tert-butyl 2-(4-nitrophenyl)-1H-pyrrole-
1-carboxylate
(3ec)[7b]
,
2-(3-nitrophenyl)furan
,
(3fa)[8j]
,
2-(3-
2-(2-
nitrophenyl)thiophene (3fb)[8j]
2-(2-nitrophenyl)furan (3ga)[8j]
,
nitrophenyl)thiophene (3gb)[8j], 4-(furan-2-yl)benzonitrile (3ha)[7b], 1-(4-
(furan-2-yl)phenyl)ethanone (3ia)[17], 2-(4-methoxyphenyl)furan (3ja)[7b], 2-
phenylfuran
(3ma)[8d]
bromophenyl)furan (8aa)[19]
(3ka)[7b]
2,4,6-trimethyl-4'-nitro-1,1'-biphenyl (3ed)[18]
,
2-(furan-2-yl)-dihydroanthracene-9,10-dione
2,5-bis(4-
,
,
Acknowledgements
.
This work was supported by a Grant-in-Aid for Scientific Research
on Innovative Areas “Advanced Molecular Transformations by
Organocatalysts” from The Ministry of Education, Culture, Sports,
Science and Technology, Japan (26105736).
Two-directional arylation: synthesis of 7. The mono-arylated furan 3na
was synthesized following the procedure mentioned above. The yield was
determined by 1H NMR analysis of the crude mixture based on 1,3,5-
tribromobenzene as an internal standard (76%). The crude mixture was
purified by silica gel column chromatography (hexane/ethyl acetate =
10/0→9/1) to give the product 3na (124 mg, 0.48 mmol, 48%), where the
isolated yield decreased from the 1H NMR yield because the separation of
the product 3na from the by-product N-Boc aniline was difficult. Microwave
vial for 2-5 mL was charged with 3na (130 mg, 0.5 mmol) and
hexafluoroisopropanol (5.0 mL) under the flow of nitrogen, and sealed with
the special cap. Then the suspension of 3na was treated under the
irradiation of microwave at 150 °C for 75 min, then evaporated. In an oven-
dried 10 mL two-necked flask with a stirring tip, the resulting solid was
dissolved in 3.8 mL of DMSO under a nitrogen atmosphere. When
MeSO3H (32 μL, 0.5 mmol) and t-BuONO (66 μL, 0.5 mmol) were added
to the solution, 80 volume % of the reaction mixture dropwise added
immediately by syringe to the DMSO solution of polyaniline 5 (7.0 mg, 20
μmol, based on aniline tetramer) and arene 2c (670 μL, 4 mmol) in another
oven-dried 10 mL two-necked flask with a stirring tip. After the reaction for
30 minutes, the reaction mixture was poured into the mixture of Et2O and
water. The aqueous layer was extracted with Et2O three times. The
combined organic layer was washed with water and brine, then dried with
Na2SO4, and concentrated in vacuo. The black solid of polyaniline was
filtered during the liquid-liquid separating operation. The yield was
determined by 1H NMR analysis of the crude mixture based on 1,3,5-
tribromobenzene as an internal standard (46%).The crude mixture was
purified by preparative thin layer chromatography (hexane/ethyl acetate =
85/15) to give the product 7 (48 mg, 0.16 mmol, 39%).
Keywords: C-C coupling • Gomberg-Bachmann reaction •
Radical reactions • Polyaniline • In-situ diazotization
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A catalytic amount of a reduced form of
polyaniline induced C-H direct arylation
of (hetero)arenes with arenediazonium
salts prepared from anilines with
methanesulfonic acid (MeSO3H) and
tert-butyl nitrite (t-BuONO). Exploiting
Dai Hata, Toshiyuki Moriuchi, Toshikazu
Hirao, and Toru Amaya*
Page No. – Page No.
Polyaniline-induced Arylation with
Arenediazonium Salts Derived from
Anilines
mono-Boc-protected
phenylenediamine,
1,4-
two-directional
arylation for the synthesis of the
unsymmetrically 1,4-diarylated (furyl
and pyrrolyl groups) benzene was also
achieved.
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