Mild-Base-Promoted Arylation of (Hetero)Arenes with Anilines

Article abstract of DOI:10.1002/asia.201701585

Transition metal-free radical arylation of heteroarenes is achieved at room temperature by simply adding aqueous sodium carbonate to a solution of the corresponding heteroarene and arenediazonium salt, which can even be formed in situ. Such an easy, inexpensive and mild methodology has been optimized and applied to the expeditious modification of interesting molecular cores like naphthylimide or bisthienylcyclopentenes.

Full text of DOI:10.1002/asia.201701585

CHEMISTRY
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Accepted Article
Title: Mild-Base-Promoted Arylation of (Hetero)Arenes with Anilines
Authors: Diego Manuel Monzón, Tanausú Santos, Fernando Pinacho-
Crisóstomo, Víctor Sotero Martín, and Romen Carrillo
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10.1002/asia.201701585
Chemistry - An Asian Journal
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Mild-Base-Promoted Arylation of (Hetero)Arenes with Anilines
Diego M. Monzón,[a]† Tanausú Santos,[a]† F. Pinacho-Crisóstomo,[a] Víctor S. Martín,[a] and Romen
Carrillo*[a][b]
Dedication ((optional))
Abstract: Transition metal-free radical arylation of heteroarenes is
achieved at room temperature by simply adding aqueous sodium
carbonate to a solution of the corresponding heteroarene and
arenediazonium salt, which can even be formed in situ. Such an
easy, inexpensive and mild methodology has been optimized and
applied to the expeditious modification of interesting molecular cores
like naphthylimide or bisthienylcyclopentenes.
Actually, Gomberg and Bachmann detected arylations back in
1924, when diazo anhydrides were solved in aromatic solvents.9
However, yields of the Gomberg–Bachmann reaction are usually
very poor.10 There are, though, a few interesting precedents
reporting reasonable yields, such as the recent work by de
Frutos, Kappe and coworkers;11 or by Gokel and coworkers
longer ago.12 Yet in both cases successful reactions are only
achieved by irradiation or after the addition of a phase transfer
catalyst and very large amounts of reagent. And in both cases
pre-formed diazonium salts are employed.
Introduction
a)
Radical Arylation
X
R2
or
R2
R2
Biaryl compounds are truly privileged structures: Plenty of
molecules with applicability in fields ranging from materials
science to biomedicine display a carbon-carbon bond between
aromatic rings. Therefore, the development of selective and mild
arylation reactions is a critical goal in chemistry.1 Traditional
cross-coupling strategies based on transition metal catalysis
have been very fruitful, and yet there is a growing demand of
arylation reactions which do not require expensive or scarce
metals.2 In fact, there are stricter environmental laws, an
increasing social awareness, and the issue of trace metal
contamination. Indeed, it is well known that the level of heavy
metals is limited by strict guidelines in pharmaceutically active
compounds;3 less known is that metal traces may also be
devastating for the performance and properties of organic
materials and devices.4 Radical arylations have recently arisen
as an optimal alternative to traditional coupling methods.5 Such
kind of reaction must always start by the convenient generation
of an aryl radical (Scheme 1a), which then undergoes an
addition to an arene that does not need to be functionalized.
Considering what has been said above, a mild and metal-free
method to generate the aryl radical would be optimal.6 Herein we
will take advantage of the long known diazo anhydrides
(Scheme 1b),7 not only because they are easily synthesized
from the corresponding diazonium salt with mild bases, but also
because they are prone to decompose into aryl radicals.8
X
G
R2
or
R1
R1
Initiation
R1
(radical generation)
R1
b)
This work
X
R2
NH2
N
N
O
or
N
N
2
R1
R1
Products
i) Diazotization
ii) Na2CO3
in water
and other
Diazo anhydride
decomposition
compounds
R2
(Postulated intermediate)
Scheme 1. (a) General scheme of a radical arylation. (b)
Optimized Gomberg-Bachmann reaction.
Still, other arylations promoted by weak bases,13,14 made us
think that it could be feasible to optimize the Gomberg-
Bachmann arylation without the requirement of any other
additive than a mild base. Herein, the arylation of (hetero)arenes
with anilines promoted by weak bases has been explored and
optimized. Heteroarenes are very important for two reasons: On
one hand, they are usually more effective radical acceptors than
substituted benzenes and with better regioselectivity,15 therefore
higher yields are expected; on the other hand, heteroarene
derivatives are common scaffolds in drugs and organic
semiconductors, thus this methodology could be applied to the
development of high added value compounds for the
pharmaceutical or the organic electronics industries, without the
concern of transition metal traces.
[a]
Mr. D. M. Monzón, Mr. T. Santos, Dr. F. Pinacho-Crisóstomo, Prof.
V. S. Martín, Dr. R. Carrillo
Departamento de Química Orgánica
Instituto Universitario de Bio-Orgánica "Antonio González" (IUBO),
Universidad de La Laguna
Avda. Astrofísico Fco. Sánchez 2, Apdo. Correos 456, 38200 - La
Laguna, S/C. de Tenerife, Spain
E-mail: rocarril@ull.es
Results and Discussion
An
initial
attempt
with
4-chlorobenzenediazonium
tetrafluoroborate and furan in acetonitrile (Scheme 2), adding
just 2 equivalents of sodium carbonate as a 1M aqueous
solution, led only to traces of 2-(4-chlorophenyl)-furan (2a) after
1 hour. Instead, lactol 1 was isolated in a reasonable yield (67%).
Although 1 was not the expected product, this compound is a
valuable intermediate since it could be easily dehydrated and re-
aromatized to the desired product under acidic conditions.16
[b]
†
Dr. R. Carrillo
Instituto de Productos Naturales y Agrobiología,
Consejo Superior de Investigaciones Científicas (IPNA-CSIC)
Avda. Astrofísico Fco. Sánchez 3, 38206 - La Laguna, S/C. de
Tenerife, Spain.
These authors contributed equally to this work
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
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Indeed, by simply working up the reaction with a slight excess of
HCl 1M, then 70% yield of the desired compound is obtained.
was observed when the reaction was set up in the dark (entry
16), thus precluding any relevant effect of the light in this
reaction.
+
(1M)
BF4
HCl (1M)
N2
Na
2CO3
The one pot process, starting directly from the aniline is by far
more appealing, and thus it was also explored and optimized
(Table 2). tert-Butyl nitrite was chosen as diazotization agent,
and left for 15 minutes before adding furan and sodium
carbonate. However, the yield was poor (entry 1). It is well
known that the addition of acid enhances the diazotization step.
Therefore, a few acids were tested by adding them right after the
tert-butyl nitrite. All of them increased the yield, particularly
methanesulfonic acid (entry 5). Curiously, when more base was
added, yield drops down (entry 6). Worth to mention, exhaustive
control experiments were performed, and only a very low yield
was obtained when no base was added.17
OH
O
O
1
Work up
CH3CN
Cl
O
Cl
Cl
2a
70%
Scheme 2. Initial Experiment.
Several bases were tested to optimize this reaction, but all of
them gave lower yields (Table 1, entries 2-8). Nor increasing or
decreasing the amount of sodium carbonate drove to a better
yield (entries 9 and 10). Worth to mention, no final product was
isolated when no base but just water was added to the reaction
mixture (entry 11).
-
N2+BF4
Base, Solvent
O
O
Cl
Cl
t-BuONO, Acid
2a
Then work up:
HCl 1N
NH2
(1M)
Na
2CO3
O
Cl
O
Cl
2a
CH3CN
Table
1. Optimization of the coupling reaction between 4-
chlorobenzenediazonium tetrafluoroborate and furan.[a]
Then work up:
HCl 1N
Entry
1
Base[b]
Na2CO3
K2CO3
Li2CO3
Cs2CO3
CaCO3
AcONa
K3PO4
NaOH
Solvent
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
Acetone
MeOH
Yield[c]
70
60
59
57
13
10
65
5
Table 2. Optimization of the one-pot coupling reaction between 4-chloroaniline
and furan.[a]
Entry
Base
-
p-TsOH
AcOH
Yield[b]
30
45
2
1
2
3
3
10
4
5
6[c]
BF3·Et2O
CH3SO3H
CH3SO3H
67
70
42
4
5[d]
6
[a] Reaction conditions: To 4-chloroaniline (0.5 mmol) in acetonitrile (5 ml)
under argon, were added t-BuONO (0.75 mmol) and the acid (0.6 mmol). The
reaction mixture was left 15 minutes stirring and then, furan (5 mmol) and
finally 1 ml of 1M aqueous solution of Na2CO3 (1mmol) were added. The
reaction was left stirring 1h at room temperature, and then 2ml of HCl 1M was
added and left stirring for another hour. [b] Isolated yield. [c] 1.6 mmol of
Na2CO3 were added.
7
8
9[e]
10[f]
11
12
13
14
15[g]
16[h]
Na2CO3
Na2CO3
-
67
59
-
Once the conditions of both methods were optimized, the scope
of the reaction was explored (Tables 3 and 4). The process
starting from the diazonium salt (Method A) and the one pot
methodology from the aniline (Method B) are compared
throughout Tables 3 and 4. It is clearly seen that acceptor
substituted anilines (or diazonium salts) give higher yields. Also,
as a general trend, furan and pyrrole-Boc lead to better results.
Despite method A gives better yields in almost all cases, method
B has the advantage of avoiding pre-formation and manipulation
of diazonium salts, which can be convenient in sensitive and/or
expensive substrates.
In Table 3, several different functional groups were tested with
furan and reaction conditions probed to be compatible with a
good range of moieties, such as azides (2l), alkynes (2m),
esters (2f), halogens (2a-c), ketones (2n), trifluoromethyl (2j),
etc. Worth to mention, the substitution pattern slightly affects the
reaction: para, meta and ortho-nitroaniline (2d, 2h, 2i
respectively) led to similar outcomes, being the meta substitution
the highest in yield. However, 3,5-di-tert-butyl aniline led to very
poor yields (2k). Larger scale did not affect substantially the
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
62
40
17
72
71
Water
CH3CN
CH3CN
[a] Reaction conditions: To 4-chlorobenzenediazonium tetrafluoroborate (0.5
mmol) in the solvent (5ml) was added furan (5 mmol) and finally 1 ml of 1M
aqueous solution of base (1mmol). After 1h at room temperature, 2ml of HCl
1M was added and left stirring for another hour. b] 1ml of 1M aqueous solution
except otherwise stated. [c] Isolated yield. [d] 1 ml of saturated solution of
CaCO3. [e] 0.75 mmol of carbonate. [f] 2.5 mmol of carbonate. [g] Under
argon. [h] In the dark.
And regarding the organic solvent, acetonitrile proved to be the
best one. Finally, the reaction under inert atmosphere increased
slightly the yield (72%, entry 15), but no significant modification
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outcome of the reaction (2a, 2e). Additionally, respectable yields
of arylation (2o-2s) were also obtained with thiophene and
pyrrole protected as Boc. And regarding the last one, it is worth
mentioning that the acidic work up led to no deprotection of tert-
butyl carbamate.
better obtained following Gokel‘s procedure, which reinforces
the assumption that our procedures is specially indicated for the
arylation of heteroarenes.
Table 4. Arylation of benzene and some derivatives.
Method A:[a]
(1M),
Table 3. Scope of the reaction.
Na2CO3
CH3CN, r.t.
R2
A
then 1N HCl
Method A:[a]
R2
(1M),
R1
Method B:[b]
Na2CO3
R1
CH3CN, r.t.
A
(Method A)
(4Method B)
t-
H
BuONO, MeSO
(1M),CH 3
X
then 1N HCl
A=N2BF
A=NH2
R1
Na2CO3
3CN
R1
X
Method B:[a]
r.t.,
then 1N HCl
(for Method A)
A=N2BF
A=NH2
t-
H
BuONO, MeSO
(4for Method B)
(1M),CH 3
X= O, S, NBoc
X= O, S, NBoc
Na2CO3
3CN
r.t.,
then 1N HCl
O
2a
O
O
O
2w
2t
2u
2v
Cl
NC
O2N
MeO2C
2b
2c
2d
Cl
Br
I
O2N
O2N
Method A: 37%
Method B: 24%
Method A: 41%
Method B: 24%
Method A: 39%
Method B: 27%
Method B: 13%
72%
Method A:[a]
Method B:[b]
Method A: 41%
Method B: 40%
Method A: 54%
Method B: 33%
Method A: 66%
Method B: 65%
70% (69%)[c]
O
O
2aa
2z
O
2y
O
NO2
MeO
2x
Br
2h
2e
2f
2g
MeO2C
NC
MeO
Method B: 13%
Method B: n.d.[c]
Method B: n.d.[c]
Method B: 6%
Method A: 78% (75%)[c] Method A: 70%
Method A: 23%
Method B: 17%
Method B: 47%
Method B: 68%
Method B: 64%
O
O
O
O
2ab
Cl
Cl
2ac
2i
2k
2l
2j
N3
Method B: 19%
F3C
NO2
Method B: 20%
Method B:31%
Method B: 55%
Method B: 61%
Method B: 2%
[a] For detailed conditions of method A or method B, see the Experimental
Section. [c] n.d.=not detected
O
S
O
2m
O
2o
Cl
2n
TMS
Method A: 73%
Method B: 39%
Method B: 57%
Method B: 54%
Table 5. Comparing our methodology with Gokel’s (ref. 12)
N
S
S
N
Boc
Boc
O
O
O
MeO2C
2s
2p
NC
MeO2C
2q
2r
NC
2b
66%
2d
2a
72%
O2N
This work:[a]
Cl
This work:[a]
Gokel: 75%
Br
This work:[a]
Gokel: 55%
Method A: 56%
Method B: 45%
Method A: 45%
Method B: 75%
Method A: 34%
Method B: 37%
Method A: 60%
Method B: 57%
54%
Gokel: 30%
[a] For detailed conditions of method A or [b] method B, see the Experimental
Section. [c] 2mmol scale
S
2x
2t
2o
73%
Cl
Br
Cl
37%
13%
The scope of the present methodology was also tested with the
arylation of benzene, as expected lower yields were found
(Table 4). As expected lower yields were found than those
compared to furan, thiophene and pyrrole.
This work:[a]
Gokel: 62%
This work:[a]
Gokel: 80%
This work:[b]
Gokel: 81%
It is very interesting to compare the present methodology with
the previously described by Gokel,12 via phase transfer catalysis
(Table 5). Regarding furan and thiophene, results obtained with
our methodology are better than those reported by Gokel. It is
worth to mention that Gokel must employ a huge excess of furan
or thiophene (above 100 equivalents) and more drastic
conditions. Actually, Heinrich reproduced Gokel conditions, but
employing 10 equivalents of furan,14c and the yields were much
lower, and considerably worse than ours. On the other hand,
arylations of benzene or its derivatives with anilines are usually
2w
Cl
2ac
2aa
O2N
NO2
13%
6%
19%
This work:[b]
Gokel: 85%
This work:[b]
Gokel: 38%
This work:[b]
Gokel: 55%
[a] method A [b] method B, see the Experimental Section.
As a further proof of the synthetic potential of this methodology,
the arylation of a few interesting heteroarene molecular cores
was tested (Scheme 3). For instance, menadione and its
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derivatives have been applied from anticancer treatments18 to
green chemistry.19 As it is seen in Scheme 3a, menadione was
derivatized in one step by method B in good yield.
3c). Compounds like 5 are really interesting, because they are
just one reaction away from efficient non-fullerene acceptors for
organic solar cells.20 Even when 41% yield in the synthesis of 5
may seem mediocre, it is much better than the reported 2-step
procedure employing tin and palladium.21 Finally, diarylethenes
are also a very attractive molecular core, due to their potential
applications in photo-switching materials.22 In Scheme 3d, it is
shown a preliminary result of the selective monoarylation of
dithienylethene in a similar yield to that reported previously by
Itami and coworkers using palladium chemistry.23 Curiously, this
reaction always leave unreacted starting material, even if an
excess of diazonium salt is employed. This result remains
unchanged no matter if the reaction is set up in the dark or
under UV irradiation. Further studies about such an intriguing
behavior are under progress in our lab.
NH2
a)
O
O
O
CN
Method B
3
O
CN
64%
Bu-n
b)
To shed some light on
a plausible mechanism, some
Bu-n
O
N
O
experiments were performed. Firstly, when the reaction between
4-chlorobenzenediazonium tetrafluoroborate and furan was set
up under the method A conditions but at higher temperature
(70oC), the yield was lower (30%), which seems to discard the
thermal initiation of the reaction. Additionally, the aryl radical
was trapped with TEMPO and the adduct was isolated in 50%
yield. Moreover, the formation of lactol 1 (Scheme 2), must imply
that the radical addition to furan, is followed by a SET step,
losing one electron and leaving a cation which is attacked by
water. Considering these evidences and some precedents in the
literature, 11,13a a tentative mechanism is suggested (Scheme 4).
O
N
O
O
O
NH2
4
Method B
62%
Bu-n
c)
Bu-n
O
N
O
O
N
O
X-
NH2
N
t-BuONO
N
S
A
NH2
MeSO3H
CN
OH-
N
S
5
Method B
41%
OH
N
O
N
N
NC
N
N
B
-
D
N2+BF4
d)
OH-
N
O
F
F
N
O
N
N
F
F
F
F
F
N
N
F
C
CN
20%
(39% BRSM)[a]
F
F
F
F
E
F
SET
Method A
O
(2 eq of
diazonium)
S
S
S
S
CN
6
O
O
O
H
OH-
Scheme 3. Miscellaneous arylations. [a] BRSM=Based on Recovered Starting
G
G'
Material
Naphthylimides are a recurrent scaffold in fluorescent sensors
and organic semiconductors. Herein we coupled in just one step
the 4-amino-N-butyl-1,8-naphthalimide with furan (Scheme 3b),
yielding the fluorescent compound 4 in a considerable yield.
OH
Acidic work up
O
O
I
J
More interestingly,
a
similar reaction but using 2-
Scheme 4. Suggested mechanism
thiopheneacetonitrile instead of furan, also worked well (Scheme
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The corresponding aniline (10 mmol) was dissolved in a mixture of 4 mL
of distilled water and 3.4 mL of 50% hydrofluoroboric acid. After cooling
the reaction mixture to 0°C, sodium nitrite (0.69 g) dissolved in 1.5 mL of
water, was added dropwise. The resulting mixture was stirred for 1h and
the precipitate was collected by filtration, washed with water and re-
dissolved in minimum amount of acetone. Diethyl ether was added until
precipitation of the corresponding diazonium tetrafluoroborate, which is
filtered, washed several times with diethyl ether and dried under vacuum.
In the one pot methodology, the first step is the diazotization.
Once the diazonium salt (A) is formed, the mild basic aqueous
environment favors the formation of the corresponding diazo
anhydride (D),9b which is prone to decompose homolytically into
aryl radical (E), nitrogen and diazenyloxyl radical (F). The aryl
radical undergoes an addition to the heteroarene, giving radical
G/G’, which transfers one electron to the diazenyloxyl radical (F).
This SET process generates cation H and diazotate C, which
regenerates the diazo anhydride by addition to the diazonium
salt. Another plausible pathway could be an electron transfer
from radical G' directly to D (dashed arrow), which is a
reasonably stable compound and therefore it is likely to be
present in higher concentration in the reaction mixture than
short-lived radical F. In any case, cation H is attacked by one
hydroxyl anion giving lactol I. Finally, by acidic dehydration
during the work up, the final product is obtained.
Synthesis of N-(tert-butoxycarbonyl)-pyrrole.
Based on a literature procedure,24 DMAP (0.12 g, 1 mmol) and di-t-butyl
dicarbonate (2.62 g, 12 mmol) were added to a solution of pyrrole (0.69
mL, 10 mmol) in acetonitrile (10 mL) and the solution was stirred at room
temperature for 24 hours. The reaction mixture was diluted with Et2O and
washed with NaHCO3 and then brine. The organic layer was then dried
over MgSO4, filtered, and concentrated under reduced pressure. The
crude product was purified by flash column chromatography Hex/AcOEt
(99:1), yielding the title compound (1.44 g, 86%) as a colorless oil.
Conclusions
Synthesis of 4-amino-N-butyl-1,8-naphthalimide.
Following a reported procedure,25 a mixture of 4-amino-1,8-naphthalic
anhydride (400 mg, 1.88 mmol) and 1-butanamine (411.7 mg, 3.01
mmol) in ethanol (25 mL) in a single necked flask and was heated to
reflux under argon for 4 hours. After cooling to room temperature, the
solvent was removed under reduced pressure and purification by flash
column chromatography Hex/AcOEt (70:30), giving an orange solid (438
mg, 87% yield).
In conclusion, a radical arylation of heteroarenes with anilines
has been developed. Such a transition-metal free method is
induced by aqueous sodium carbonate at room temperature. In
such a way, Gomberg-Bachmann arylation has been optimized
and updated, with no irradiation, phase-transfer catalyst or very
large amounts of reagents required. Additionally, arylation of
interesting molecular cores such as naphthylimide or
bisthienylcyclopentenes has been achieved. Therefore, this mild,
inexpensive and operationally simple method might well become
part of the synthetic toolbox for material sciences and organic
electronics.
Synthesis of 4-azidoaniline.
Following a reported procedure,26 4-bromoaniline (555 mg, 3.22 mmol,
1.0 equiv) was taken in a mixture of EtOH-H2O (7:3, 10 mL) and sodium
ascorbate (27.5 mg, 0.16 mmol, 0.05 equiv), CuI (63.3 mg, 0.32 mmol,
0.1 equiv), N,N’-dimethylethylenediamine (52 µL, 0.48 mmol, 0.15 equiv)
were added and stirred for 10 min. Sodium azide (350 mg, 6.44 mmol,
2.0 equiv) was added to the reaction mixture and allowed to stir for 3 h at
reflux under argon atmosphere. After complete consumption according to
TLC analysis, the reaction was cooled, concentrated under vacuum and
the crude product was purified by flash chromatography using hexane-
ethyl acetate (95:5) mixture to give the desired azide (397.4 mg, 92%) as
a brown solid.
Experimental Section
Materials and Methods
1H NMR spectra were recorded at 600 MHz, 500MHz and 400 MHz; and
13C NMR spectra were recorded at 150 MHz. 125 MHz and 100 MHz.
Chemical shifts were reported in units (ppm) by assigning TMS
resonance in the 1H NMR spectrum as 0.00 ppm (chloroform, 7.26 ppm).
Data were reported as follows: chemical shift, multiplicity (s = singlet, d =
doublet, dd = double doublet, m =multiplet and br = broad), coupling
constant (J values) in Hz and integration. Chemical shifts for 13C NMR
spectra were recorded in ppm from tetramethylsilane using the central
peak of CDCl3 (77.00 ppm) as the internal standard. Accurate mass
(HRMS) were determined by electrospray ionization (ESI-TOF) or
electronic impact (EI-TOF). Flash column chromatography was
performed using silica gel, 60 Å and 0.2-0.5 mm with the indicated
solvent system according to standard techniques. Compounds were
visualized on TLC plates by use of UV light, or vanillin with acetic and
sulfuric acid in ethanol with heating. Anilines were purchased from
commercial suppliers and used without further purification. All the
solvents were treated according to general methods. Anhydrous
magnesium sulfate was used for drying solutions.
Synthesis of 4-((trimethylsilyl)ethynyl)aniline.
Following a reported procedure,27 4-Iodoaniline (547 mg, 2.5 mmol, 1.00
eq.), copper(I) iodide (10 mg, 0.05 mmol, 2.0 mol%),
bis(triphenylphosphine)palladium(II) chloride (70 mg, 0.10 mmol, 4.0
mol%) were added to dry NEt3 (4 mL, 0.6 M). The mixture was stirred for
5 min. Trimethylsilylacetylene (319 mg, 3.25 mmol, 1.30 eq.) was added
under argon to this mixture and the mixture was stirred overnight at room
temperature. CH2Cl2 (10 mL) was added, the organic layer was washed
with water (10 mL) and saturated aqueous ammonium chloride solution
(10 mL) and dried over sodium sulfate. The solvent was evaporated
under reduced pressure. Purification by column chromatography
(hexane/CH2Cl2, 7:3) gave 4-((trimethylsilyl)ethynyl)aniline (341 mg, 1.80
mmol) as an orange solid in 72% yield.
General Procedures
Synthesis of diazonium tetrafluoroborate salts.
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Synthesis
methylthiophene).
of
3,3’-(Perfluorocyclopent-1-ene-1,2-diyl)bis(2-
A 25 mL round bottom flask with a teflon-coated stirrer bar was charged
with the corresponding aniline (0.5 mmol). Then, 5ml of acetonitrile was
added by syringe under an atmosphere of dry argon, followed by the
addition of tert-butyl nitrite (90%, 0.75 mmol) and methanesulfonic acid
(0.04ml, 0.6 mmol). The reaction mixture was left stirring for 15 minutes,
and then the corresponding arene (5 mmol) was added. Finally, 1ml of a
1M aqueous solution of sodium carbonate was added. The reaction
mixture turns light orange and a fine bubbling starts thereafter. The
reaction mixture was stirred at ambient temperature for 1 h. Then the
reaction was worked up with 2ml of 1N solution of HCl and left stirring for
1 hour. The reaction mixture was extracted three times with ethyl acetate
(10ml). The organic layers were combined and dried with magnesium
sulphate and filtered. The crude was adsorbed in silica gel, and purified
by flash chromatography (SiO2, hexane/ethyl acetate), yielding the
corresponding (hetero)biaryl.
2-Methylthiophene was brominated with N-Bromosuccinimide in acetic
acid following a previously reported procedure,28 yielding the 2, 4-
dibromo-5-methylthiophene as an oil (84%). Then, it was subsequently
lithiated selectively at position 2, and reacted with water: A Schlenk tube
equipped with a magnetic stirring bar and capped with a rubber septum
was charged with 2, 4-dibromo-5-methylthiophene (4.0 g, 15.6 mmol, 1
equiv.) followed by the addition of dry THF (80 mL). The solution was
cooled to –78 °C. At that temperature, a hexane solution of nBuLi (1.6 m,
9.8 mL, 17.2 mmol, 1.1 equiv.) was added dropwise with stirring. After 1
h at low temperature, the reaction was quenched by carefully adding
water, followed by an extraction with Et2O. The organics were combined,
dried with anhydrous magnesium sulfate and filtered, and the solvents
were removed under reduced pressure. The crude material was
subjected to silica gel column chromatography using hexane as the
eluent, to obtain 3-bromo-2-methylthiophene (which is also commercially
available) as a colorless solid in 62% yield.
Characterization of Compounds.
All compounds were purified by flash chromatography on SiO2. All
compounds are amorphous solids, except from 2i, 2n, 2r and 22, which
are oils.
A flame-dried round bottom flask equipped with a magnetic stirring bar
was charged with 3-bromo-2-methylthiophene (1 g, 5.6 mmol, 2.2 equiv.)
under a flux of nitrogen before dry THF (20 mL) was added. The solution
was cooled to -78 °C before a hexane solution of nBuLi (1.6 M, 3.5 mL,
5.6 mmol, 2.2 equiv.) was added dropwise with stirring. Stirring was
maintained over 1 h at low temperature. Perfluorocyclopentene is a low
boiling temperature liquid, so it was transferred by tubing from the bottle
where it is sold, to a Schlenk tube at -78ºC under argon, and kept in the
freezer at -20ºC. A portion from such a flask was quickly added (340 μL,
2.6 mmol, 1.0 equiv.), and the mixture was allowed to slowly warm to
room temperature. The reaction was quenched by addition of water. The
biphasic system was extracted by adding Et2O. The organics were
washed several times with water, dried with anhydrous magnesium
sulfate, filtered, and the solvents were evaporated under reduced
1
2-(4-chlorophenyl)-furan (2a). H NMR (600 MHz, CDCl3, 298 K): δ ppm
7.60 (d, J = 8.6 Hz, 2H), 7.48 (br, 1H), 7.36 (d, J = 8.6 Hz, 2H), 6.64 (d, J
= 3.3 Hz, 1H), 6.48 (dd, J = 1.7, 3.2 Hz, 1H); 13C NMR (150 MHz, CDCl3,
298 K): δ ppm 152.9, 142.3, 132.9, 129.3, 128.8, 125.0, 111.7, 105.4;
HRMS (EI): m/z: calc for C10H7O35Cl [M+]: 178.0185, found: 178.0185 /
calc for C10H7O37Cl [M+]: 180.0156, found: 180.0155; Column
Chromatography: 98:2 (Hex-AcOEt)
1
2-(4-bromophenyl)-furan (2b). H NMR (600 MHz, CDCl3, 298 K): δ ppm
7.54 (d, J = 8.7 Hz, 2H), 7.50 (d, J = 8.7 Hz, 2H), 7.47 (d, J = 1.0 Hz, 1H),
6.65 (d, J = 3.3 Hz, 1H), 6.48 (dd, J = 1.8, 3.3 Hz, 1H); 13C NMR (150
MHz, CDCl3, 298 K): δ ppm 152.9, 142.3, 131.8, 129.8, 125.3, 121.0,
111.8, 105.5; HRMS (EI): m/z: calc for C10H7O81Br [M+]: 223.9660, found:
223.9666 / calc for C10H7O79Br [M+]: 221.9680, found: 221.9684; Column
Chromatography: 95:5 (Hex-AcOEt)
pressure. The crude product was purified by
chromatography using hexane as eluent, to afford a colorless solid
(642mg, 67% yield).
a silica column
1H NMR (600 MHz, CDCl3, 298 K): δ ppm 7.16 (d, J = 5.6 Hz, 2H), 7.06
(d, J = 4.9 Hz, 2H), 1.88 (s, 6H); 13C NMR (150 MHz, CDCl3, 298 K): δ
ppm 141.7, 136.2, 127.1, 124.9, 123.5, 116.2, 111.1, 14.0; HRMS (ESI-
negative): m/z: calc for C16H22N2ONa [M-H+]: 367.0050, found: 367.0045;
Column Chromatography: Hexane.
2-(4-iodophenyl)-furan (2c). 1H NMR (600 MHz, CDCl3, 298 K): δ ppm
7.71 (d, J = 8.4 Hz, 2H), 7.47 (d, J = 1.3 Hz, 1H), 7.41 (d, J = 8.4 Hz, 2H),
6.66 (d, J = 3.3 Hz, 1H), 6.48 (dd, J = 1.7, 3.2 Hz, 1H); 13C NMR (150
MHz, CDCl3, 298 K): δ ppm 153.0, 142.4, 137.7, 130.3, 125.4, 111.8,
105.6, 92.4; HRMS (EI): m/z: calc for C10H7OI [M+]: 269.9542, found:
269.9534; Column Chromatography: Hexane
General procedure for coupling from the diazonium salt (Method A).
2-(4-nitrophenyl)-furan (2d). 1H NMR (600 MHz, CDCl3, 298 K): δ ppm
8.22 (d, J = 8.8 Hz, 2H), 7.77 (d, J = 8.8 Hz, 2H), 7.56 (d, J = 1.2 Hz, 1H),
6.86 (d, J = 3.3 Hz, 1H), 6.54 (dd, J = 1.7, 3.3 Hz, 1H); 13C NMR (150
MHz, CDCl3, 298 K): δ ppm 151.7, 146.3, 144.1, 136.4, 124.2, 123.9,
112.4, 108.9; HRMS (EI): m/z: calc for C10H7NO3 [M+]: 189.0426, found:
189.0421; Column Chromatography: 95:5 (Hex-AcOEt)
A 25 mL round bottom flask with a teflon-coated stirrer bar was charged
with the corresponding arenediazonium tetrafluoroborate (0.5 mmol).
Then, 5ml of acetonitrile was added by syringe under an atmosphere of
dry argon, followed by the addition of the corresponding arene (5 mmol).
Finally, 1ml of a 1M aqueous solution of sodium carbonate was added.
The reaction mixture turns light orange and a fine bubbling starts
thereafter. The reaction mixture was stirred at ambient temperature for 1
h. Then the reaction was worked up with 2ml of 1N solution of HCl and
left stirring for 1 hour. The reaction mixture was extracted three times
with ethyl acetate (10ml). The organic layers were combined and dried
with magnesium sulphate and filtered. The crude was adsorbed in silica
gel, and purified by flash chromatography (SiO2, hexane/ethyl acetate),
yielding the corresponding (hetero)biaryl.
1
4-(furan-2-yl)benzonitrile (2e). H NMR (600 MHz, CDCl3, 298 K): δ ppm
7.73 (d, J = 8.3 Hz, 2H), 7.64 (d, J = 8.3 Hz, 2H), 7.53 (d, J = 1.0 Hz, 1H),
6.81 (d, J = 3.5 Hz, 1H), 6.52 (dd, J = 1.6, 3.3 Hz, 1H); 13C NMR (150
MHz, CDCl3, 298 K): δ ppm 151.9, 143.7, 134.6, 132.5, 123.9, 118.9,
112.2, 110.2, 108.1; HRMS (EI): m/z: calc for C11H7NO [M+]: 169.0528,
found: 169.0520; Column Chromatography: 95:5 (Hex-AcOEt).
1
Methyl 4-(furan-2-yl)benzoate (2f). H NMR (600 MHz, CDCl3, 298 K): δ
ppm 8.05 (d, J = 8.5 Hz, 2H), 7.72 (d, J = 8.5 Hz, 2H), 7.52 (br, 1H), 6.79
(d, J = 3.4 Hz, 1H), 6.51 (dd, J = 1.8, 3.4 Hz, 1H), 3.92 (s, 3H); 13C NMR
(150 MHz, CDCl3, 298 K): δ ppm 166.8, 152.9, 143.1, 134.7, 130.1,
General procedure for the one-pot coupling from the aniline
(Method B).
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128.5, 123.4, 112.0, 107.2, 52.1; HRMS (EI): m/z: calc for C12H10O3 [M+]:
202.0630; found: 202.0627; Column Chromatography: 95:5 (Hex-AcOEt).
2-(4-chlorophenyl)thiophene (2o). 1H NMR (600 MHz, CDCl3, 298 K): δ
ppm 7.54 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.4 Hz, 2H), 7,30-7.28 (m, 2H),
7.08 (dd, J = 3.9, 4.7 Hz, 1H); 13C NMR (150 MHz, CDCl3, 298 K): δ ppm
143.1, 133.2, 132.9, 129.0, 128.1, 127.1, 125.2, 123.4; HRMS (EI): m/z:
calc for C10H7S35Cl [M+]: 193.9957, found: 193.9956 / calc for C10H7S37Cl
[M+]: 195.9927, found: 195.9925; Column Chromatography: 95:5 (Hex-
AcOEt).
2-(4-methoxyphenyl)furan (2g). 1H NMR (600 MHz, CDCl3, 298 K): δ
ppm 7.61 (d, J = 8.7 Hz, 2H), 7.43 (d, J = 1.0 Hz, 1H), 6.92 (d, J = 8.7 Hz,
2H), 6.51 (d, J = 3.4 Hz, 1H), 6.45 (dd, J = 1.7, 3.1 Hz, 1H), 384 (s, 3H);
13C NMR (150 MHz, CDCl3, 298 K): δ ppm 159.0, 154.0, 141.4, 125.2,
124.1, 114.1, 111.5, 103.4, 55.3; HRMS (EI): m/z: calcd for C11H10O2
[M+]: 174.0681, found: 174.0683; Column Chromatography: 95:5 (Hex-
AcOEt).
4-(thiophen-2-yl)benzonitrile (2p). 1H NMR (600 MHz, CDCl3, 298 K): δ
ppm 7.69 (d, J = 8.7 Hz, 2H), 7.64 (d, J = 8.7 Hz, 2H), 7.42 (d, J = 3.6 Hz,
1H), 7.40 (d, J = 5.0 Hz, 1H), 7.13 (dd, J = 3.9, 4.9 Hz, 1H); 13C NMR
(150 MHz, CDCl3, 298 K): δ ppm 142.0, 138.6, 132.7, 128.5, 127.0,
126.0, 125.0, 118.8, 110.5; HRMS (EI): m/z: calc for C11H7NS [M+]:
185.0299, found: 185.0302; Column Chromatography: 95:5 (Hex-AcOEt).
2-(3-nitrophenyl)furan (2h). 1H NMR (600 MHz, CDCl3, 298 K): δ ppm
8.49 (s, 1H), 8.08 (dt, J = 8.0, 1.0 Hz, 1H), 7.95 (d, J = 7.8 Hz, 1H), 7.55
(d, J = 8.0 Hz, 1H), 7.53 (d, J = 0.6 Hz, 1H), 6.81 (d, J = 3.6 Hz, 1H), 6.53
(m, 1H); 13C NMR (180 MHz, CDCl3, 298 K): δ ppm 151.4, 148.5, 143.2,
132.2, 129.7, 129.2, 121.6, 118.4, 112.1, 107.2; HRMS (EI): m/z: calcd
for C10H7NO3 [M+]: 189.0426, found: 189.0428; Column Chromatography:
95:5 (Hex-AcOEt)
Methyl 4-(thiophen-2-yl)benzoate (2q). 1H NMR (600 MHz, CDCl3, 298
K): δ ppm 8.04 (d, J = 7.8 Hz, 2H), 7.67 (d, J = 7.8 Hz, 2H), 7.41 (d, J =
3.5 Hz, 1H), 7.36 (d, J = 5.1 Hz, 1H), 7.11 (dd, J = 3.7, 4.9 Hz, 1H); 13C
NMR (150 MHz, CDCl3, 298 K): δ ppm 166.7, 143.1, 138.6, 130.2, 128.3,
126.2, 125.5, 124.5, 52.1; HRMS (EI): m/z: calc for C12H10O2S[M+]:
218.0402, found: 218.0399; Column Chromatography: 95:5 (Hex-AcOEt).
2-(2-nitrophenyl)furan (2i). 1H NMR (600 MHz, CDCl3, 298 K): δ ppm
7.71 (d, J = 7.8 Hz, 1H), 7.68 (d, J = 8.1 Hz, 1H), 7.58 (t, J = 7.7 Hz, 1H),
7.51 (d, J = 1.0 Hz, 1H), 7.41 (t, J = 7.7 Hz, 1H), 6.67 (d, J = 3.4 Hz, 1H),
6.50 (dd, J = 3.2, 1.8 Hz); 13C NMR (180 MHz, CDCl3, 298 K): δ ppm
148.4, 147.4, 143.9, 132.0, 128.9, 128.3, 124.1, 123.9, 111.9, 109.7;
HRMS (EI): m/z: calcd for C10H7NO3 [M+]: 189.0426, found: 189.0427;
Column Chromatography: 95:5 (Hex-AcOEt).
tert-butyl 2-(4-cyanophenyl)-1H-pyrrole-1-carboxylate (2r). 1H NMR (600
MHz, CDCl3, 298 K): δ ppm 7.62 (d, J = 8.3, 2H), 7.45 (d, J = 8.2, 2H),
7.38 (dd, J = 1.8, 3.2, 1H), 6.27 (dd, J = 1.8, 3.3, 1H), 6.25 (dd, J = 3.3,
1H), 1.41 (s, 9H); 13C NMR (150 MHz, CDCl3, 298 K): δ ppm 148.8,
138.7, 133.0, 131.2, 129.4, 123.8, 118.8, 116.0, 110.9, 110.4, 84.2, 27.6;
HRMS (ESI): m/z: calcd for C16H16N2O2Na [M+]: 291.1109, found:
291.1104; Column Chromatography: 95:5 (Hex-AcOEt).
2-(4-(trifluoromethyl)phenyl)furan (2j). 1H NMR (600 MHz, CDCl3, 298 K):
δ ppm 7.76 (d, J = 8.3 Hz, 2H), 7.63 (d, J = 8.3 Hz, 2H), 7.52 (s, 1H),
6.77 (d, J = 3.3 Hz, 1H), 6.52 (m, 1H); 13C NMR (180 MHz, CDCl3, 298
K): δ ppm 152.4, 143.0, 133.9, 125.7, 125.6, 123.7, 111.9, 106.9; HRMS
(EI): m/z: calcd for C11H7OF3 [M+]: 212.0449, found: 212.0455; Column
Chromatography: Hexane.
tert-butyl 2-(4-(methoxycarbonyl)phenyl)-1H-pyrrole-1-carboxylate (2s).
1H NMR (600 MHz, CDCl3, 298 K): δ ppm 8.02 (d, J = 8.3, 2H), 7.42 (d, J
= 8.3, 2H), 7.38 (dd, J = 1.8, 3.1, 1H), 6.26 (dd, J = 1.8, 3.2, 1H), 6.24 (dd,
J = 3.3, 1H), 3.92 (s, 3H), 1.37 (s, 9H); 13C NMR (150 MHz, CDCl3, 298
K): δ ppm 166.9, 149.1, 138.9, 133.9, 128.9, 128.5, 123.4, 115.4, 110.8,
84.0, 52.0, 27.6; HRMS (EI): m/z: calcd for C17H19O4NNa [M+]: 324.1212,
found: 324.1205; Column Chromatography: 95:5 (Hex-AcOEt).
2-(3,5-di-tert-butylphenyl)furan (2k). 1H NMR (600 MHz, CDCl3, 298 K): δ
ppm 7.52 (d, J = 1.53 Hz, 2H), 7.46 (s, 1H), 7.34 (s, 1H), 6.64 (d, J =
3.10 Hz, 1H), 6.47 (dd, J = 3.19, 1.72, 1H), 1.35 (s, 18H); 13C NMR (180
MHz, CDCl3, 298 K): δ ppm 154.9, 151.1, 141.7, 130.1, 121.7, 118.3,
111.6, 105.5, 34.9, 31.4; HRMS (ESI): m/z: calc for C18H24ONa [M+Na+]:
279.1725; found: 279.1720; Column Chromatography: Hexane.
4-chloro-1,1'-biphenyl (2t). 1H NMR (600 MHz, CDCl3, 298 K): δ ppm
7.57-7.52 (m, 4H), 7.46-7.37 (m, 5H); 13C NMR (150 MHz, CDCl3, 298
K): δ ppm 140.0, 139.6, 133.3, 128.9, 128.9, 128.4, 127.6, 127.0; HRMS
(EI): m/z: calc for C12H9OCl [M+]: 188.0393, found: 188.0388; Column
Chromatography: 90:10 (Hex-AcOEt).
2-(4-azidophenyl)furan (2l).1H NMR (600 MHz, CDCl3, 298 K): δ ppm
7.65 (d, J = 8.5 Hz, 2H), 7.47 (d, J = 0.7 Hz, 1H), 7.04 (d, J = 8.5 Hz, 2H),
6.62 (d, J = 3.3 Hz, 1H), 6.48 (dd, J = 1.7, 3.1 Hz, 1H); 13C NMR (150
MHz, CDCl3, 298 K): δ ppm 153.1, 142.0, 138.6, 127.7, 125.1, 119.2,
111.7, 104.8; HRMS (EI): m/z: calc for C10H7N3O [M+]: 185.0589; found:
185.0593; Column Chromatography: 98:2 (Hex-AcOEt)
[1,1'-biphenyl]-4-carbonitrile (2u). 1H NMR (600 MHz, CDCl3, 298 K): δ
ppm 7.73 (d, J = 8.0 Hz, 2H), 7.69 (d, J = 8.0 Hz, 2H), 7.59 (d, J = 7.2 Hz,
2H), 7.49 (t, J = 7.4 Hz, 2H), 7.43 (t, J = 7.4 Hz, 1H); 13C NMR (150 MHz,
CDCl3, 298 K): δ ppm 145.6, 139.1, 132.6, 129.1, 128.6, 127.7, 127.1,
118.9, 110.9; HRMS (EI): m/z: calc for C13H9N [M+]: 179.0735, found:
179.0729; Column Chromatography: 90:10 (Hex-AcOEt).
((4-(furan-2-yl)phenyl)ethynyl)trimethylsilane (2m). 1H NMR (600 MHz,
CDCl3, 298 K): δ ppm 7.61 (d, J = 8.2 Hz, 2H), 7.48 (m, 3H), 6.69 (d, J =
3.3 Hz, 1H), 6.48 (dd, J = 1.6, 2.9 Hz, 1H), 0.27 (s, 9H); 13C NMR (150
MHz, CDCl3, 298 K): δ ppm 153.2, 142.5, 132.3, 130.6, 123.3, 121.6,
111.8, 106.0, 105.0, 94.6; HRMS (EI): m/z: calc for C15H16OSi [M+]:
240.0970; found: 240.0978; Column Chromatography: Hexane.
Methyl [1,1'-biphenyl]-4-carboxylate (2v). 1H NMR (600 MHz, CDCl3, 298
K): δ ppm 8.11 (d, J = 8.4 Hz, 2H), 7.67 (d, J = 8.4 Hz, 2H), 7.63 (d, J =
7.3 Hz, 2H), 7.47 (t, J = 7.6 Hz, 2H), 7.40 (t, J = 7.6 Hz, 1H), 3.95 (s, 3H);
13C NMR (150 MHz, CDCl3, 298 K): δ ppm 167.0, 145.6, 140.0, 130.1,
128.9, 128.1, 127.2, 127.0, 52.1; HRMS (EI): m/z: calc for C14H12O2 [M+]:
212.0837, found: 212.0834; Column Chromatography: 90:10 (Hex-
AcOEt).
1
1-(3-(furan-2-yl)phenyl)ethan-1-one (2n). H NMR (600 MHz, CDCl3, 298
K): δ ppm 8.24 (s, 1H), 7.85 (d, J = 7.7 Hz, 1H), 7.83 (d, J = 7.7 Hz, 1H),
7,50 (m, 1H), 7.47 (t, J = 7.7 Hz, 1H), 6.74 (d, J = 3.2 Hz, 1H), 6.50 (dd, J
= 1.6, 3.2 Hz, 1H), 2.64 (s, 3H); 13C NMR (150 MHz, CDCl3, 298 K): δ
ppm 198.1, 152.8, 142.5, 137.3, 131.2, 128.9, 128.0, 127.0, 123.4, 111.8,
105.9, 26.8; HRMS (ESI): m/z: calc for C12H10O2Na [M+Na+]: 209.0578,
found: 209.0572; Column Chromatography: 90:10 (Hex-AcOEt).
4-nitro-1,1'-biphenyl (2w). 1H NMR (500 MHz, CDCl3, 298 K): δ ppm 8.30
(d, J = 8.7, 2H), 7.74 (d, J = 8.7, 2H), 7.74 (dd, J = 1.4, 7.3, 2H), 7.50 (dd,
J = 7.1, 7.5, 2H), 7.45 (dd, J = 7.3, 7.3, 1H); 13C NMR (150 MHz, CDCl3,
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298 K): δ ppm 147.7, 147.1, 138.8, 129.3, 129.0, 127.9, 127.5, 124.2;
Column Chromatography: 90:10 (hexane:EtOAc)
137.5, 132.8, 132.2, 128.4, 127.1, 126.6, 126.4, 125.8, 124.6, 123.9,
118.6, 116.0, 111.0, 14.5, 14.3; HRMS (EI): m/z: calc for C22H13NS2F6Na
[M+Na+]: 492.0291; found: 492.0294; Column Chromatography: 95:5
(Hex-AcOEt)
4-bromo-1,1'-biphenyl (2x). 1H NMR (500 MHz, CDCl3, 298 K): δ ppm
7.58-7.54 (m, 4H), 7.48-7.42 (m, 4H), 7.39-7.35 (m, 1H); 13C NMR (150
MHz, CDCl3, 298 K): δ ppm 140.2, 140.1, 132.0, 129.0, 128.9, 127.8,
127.1, 121.6; Column Chromatography: n-hexane.
Acknowledgements
2-nitro-1,1'-biphenyl (2aa). 1H NMR (600 MHz, CDCl3, 298 K): δ ppm
7.86 (d, J = 8.1, 1H), 7.63 (dd, J = 7.5, 7.5, 1H), 7.49 (dd, J = 7.7, 7.7,
1H), 7.47-7.39 (m, 4H), 7.33 (d, J = 7.1, 1H); 13C NMR (150 MHz, CDCl3,
298 K): δ ppm 137.4, 136.4, 132.4, 132.0, 128.8, 128.3, 128.2, 127.9,
124.2; Column Chromatography: 95:5 (hexane:EtOAc)
Authors thank Julio Rodríguez-López for his technical support
with the NMR. This work has been funded by Ministerio de
Economía y Competitividad-MINECO (CTQ2015-73234-JIN and
CTQ2014-56362-C2-1-P), co-financed by the European
Regional Development Fund (ERDF). D. M. M. thanks MINECO
for a FPI fellowship.
4'-chloro-2,5-dimethyl-1,1'-biphenyl (2ab). 1H NMR (500 MHz, CDCl3,
298 K): δ ppm 7.37 (d, J = 8.5, 2H), 7.24 (d, J = 8.5, 2H), 7.15 (d, J = 7.8,
1H), 7.08 (dd, J = 1.3, 7.7, 1H), 7.01 (d, J = 1.3, 1H), 2.34 (s, 3H), 2.21 (s,
3H); 13C NMR (150 MHz, CDCl3, 298 K): δ ppm 140.6, 135.5, 132.9,
132.2, 130.6, 130.5, 128.4, 128.3, 21.0, 20.0; Column Chromatography:
hexane.
Keywords: Radical reactions • C-C coupling • Heterocycles •
Diazo compounds • Dyes/pigments
[1]
a) J. Hassan, M. Sevignon, C. Gozzi, E. Schulz, M. Lemaire, Chem.
Rev., 2002, 102, 1359-1470, and references therein; b) J.-P. Corbet, G.
Mignani, Chem. Rev. 2006, 106, 2651-2710.
4'-chloro-2,4,6-trimethyl-1,1'-biphenyl (2ac). 1H NMR (500 MHz, CDCl3,
298 K): δ ppm 7.40 (d, J = 8.5, 2H), 7.09 (d, J = 8.5, 2H), 7.01 (s, 2H),
2.34 (s, 3H), 2.00 (s, 6H); 13C NMR (150 MHz, CDCl3, 298 K): δ ppm
139.6, 137.8, 137.1, 136.0, 132.5, 130.8, 128.8, 128.3, 21.2, 20.9;
Column Chromatography: hexane.
[2]
[3]
P. Anastas, N. Eghbali, Chem. Soc. Rev. 2010, 39, 301-312.
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4-(3-methyl-1,4-dioxo-1,4-dihydronaphthalen-2-yl)benzonitrile (3). 1H
NMR (600 MHz, CDCl3, 298 K): δ ppm 8.16-8,13 (m, 1H), 8.11-8.08 (m,
1H), 7.76 (m, 4H), 7.36 (d, J = 8.1 Hz, 2H), 2.06 (s, 3H); 13C NMR (150
MHz, CDCl3, 298 K): δ ppm 185.0, 183.4, 144.8, 144.4, 138.4, 133.9,
133.9, 131.9, 131.7, 130.3, 126.6, 126.4, 118.4, 112.5, 14.6; HRMS (EI):
m/z: calc for C18H11NO2 [M+]: 273.0790, found: 273.0789; Column
Chromatography: 90:10 (Hex-AcOEt)
[4]
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a) A. J. Eberhart, H. Shrives, Y. Zhang, A. Carrër, A. V. S.Parry, D. J.
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2-butyl-6-(furan-2-yl)-1H-benzo[de]isoquinoline-1,3(2H)-dione (4) (Very
sensitive). 1H NMR (500 MHz, CDCl3, 298 K): δ ppm 8.87 (dd, J = 0.9,
8.4 Hz, 1H), 8.86 (dd, J = 0.9, 7.2 Hz, 1H), 8.60 (d, J = 7.7 Hz, 1H), 7.98
(d, J = 7.7 Hz, 1H), 7.78 (dd, J = 7.4, 8.6 Hz, 1H), 7.72 (d, J = 1.1 Hz, 1H),
6.95 (d, J = 3.4 Hz, 1H), 6.66 (dd, J = 1.8, 3.4 Hz, 1H), 4.19 (t, J = 7.5 Hz,
2H), 1.76-1.70 (m, 2H), 1.50-1.42 (m, 2H), 0.98 (t, J = 7.3, 3H); 13C NMR
(100 MHz, CDCl3, 298 K): δ ppm 164.3, 163.9, 152.0, 144.2 134.1,
133.8, 132.2, 131.2, 130.8, 128.2, 127.2, 125.9, 123.1, 121.8, 112.2,
112.1, 40.3, 30.2, 20.4, 13.8; HRMS (ESI): m/z: calc for C20H17NO3Na
[M+Na+]: 342.1106; found: 342.1107; Column Chromatography: 95:5
(Hex-AcOEt)
[6]
For some examples of mild, transition metal-free generation of aryl
radicals, see: a) D. Hari, P. Schroll, B. König, J. Am. Chem. Soc. 2012,
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9039; e) T. Amaya, D. Hata, T. Moriuchi, T. Hirao, Chem. Eur. J. 2015,
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Commun. 2015, 51, 3121-3123; g) M.-J. Bu, G.-P. Lua, C. Cai, Org.
Chem. Front., 2016, 3, 630-634.
2-(5-(2-butyl-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-6-
yl)thiophen-2-yl)acetonitrile (5). 1H NMR (500 MHz, CDCl3, 298 K): δ ppm
8.66 (dd, J = 1.0, 7.2 Hz, 1H), 8.86 (d, J = 7.6 Hz, 1H), 8.57 (d, J = 0.9,
8.5 Hz, 1H), 7.80-7.77 (m, 2H), 7.23-7.21 (m, 2H), 4.22-4.19 (m, 2H),
4.03 (s, 2H), 1.76-1.70 (m, 2H), 1.50-1.42 (m, 2H), 0.99 (t, J = 7.4, 3H);
13C NMR (125 MHz, CDCl3, 298 K): δ ppm 164.1, 163.8, 140.5, 138.0,
133.2, 131.8, 131.5, 130.5, 129.9, 128.9, 128.8, 128.7, 128.0, 127.4,
123.1, 122.5, 40.3, 30.2, 20.4, 18.9, 13.8; HRMS (ESI): m/z: calc for
C22H18N2O2SNa [M+Na+]: 397.0987; found: 397.0980; Column
Chromatography: 90:10 (Hex-AcOEt)
[7]
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E. Bamberger, Ber. Dtsch. Chem. Ges. 1896, 29, 446-473.
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[10] Augood and Williams described the Gomberg-Bachmann reaction
almost as useless in their review on homolytic aromatic arylations: “The
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low, ca. 10-20 per cent of the amine, with the formation of large
quantities of intractable tar.” See page 129 in D. R. Augood, G. H.
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4-(4-(3,3,4,4,5,5-hexafluoro-2-(2-methylthiophen-3-yl)cyclopent-1-en-1-
yl)-5-methylthiophen-2-yl)benzonitrile (6). 1H NMR (600 MHz, CDCl3, 298
K): δ ppm 7.66 (d, J = 8.6 Hz, 2H), 7.61 (d, J = 7.9 Hz, 2H), 7.36 (s, 1H),
7.19 (d, J = 5.7 Hz, 1H), 7.06 (d, J = 5.0 Hz, 1H), 1.97 (s, 3H), 1.93 (s,
3H); 13C NMR (150 MHz, CDCl3, 298 K): δ ppm 143.4, 141.8, 139.8,
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[21] Park and coworkers have synthesized almost the same compound but
with
a different alkyl chain on the imide. They started from the
expensive 2-(5-bromothiophen-2-yl)acetonitrile, which is transformed
into the stannate in 47% yield, and then coupled with the 4-bromo-N-(2-
ethylhexyl)-1,8-naphthalimide by palladium catalysis in 57% yield. The
global yield is 25%. See reference 21.
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[16] Oxidation of the lactol
1
to the corresponding lactone was
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Y. Xu, Chem. Commun. 2014, 50, 1485-1487.
unsuccessfully attempted by several methods. See the Supporting
Information.
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[17] For further information on the control experiments, see the Supporting
Information.
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Diego M. Monzón, Tanausú Santos, F.
Pinacho-Crisóstomo, Víctor S. Martín,
Romen Carrillo*
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Mild-Base-Promoted Arylation of
(Hetero)Arenes with Anilines
Basic Instinct: Mild-base-promoted arylation has been optimized, and applied to
the synthesis of molecular cores for material sciences and organic electronics.
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