Transition-Metal-Free, Potassium tert -Butoxide/Dimethyl Sulfoxide Mediated Amination between Tertiary Amines and Aryl Halides

Article abstract of DOI:10.1055/s-0034-1379367

A transition-metal-free, C-N bond-formation reaction between tertiary amines and aryl halides is reported. Under the optimal conditions, various aromatic and aliphatic tertiary amines react with aryl halides, including iodides, bromides, and chlorides, to give mono-aminated products, N,N-dialkylanilines and N-alkyl-N-arylanilines, in good to high yields. Based on the experimental results, the reaction is believed to occur via an aryne intermediate derived from the aryl halide.

Full text of DOI:10.1055/s-0034-1379367

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
© Georg Thieme Verlag Stuttgart · New York
2015, 47, 221–227
paper
221
P. Huang et al.
Paper
Synthesis
Transition-Metal-Free, Potassium tert-Butoxide/Dimethyl Sulfoxide
Mediated Amination between Tertiary Amines and Aryl Halides
N-Alkyl-N-arylanilines
Pei Huang
X
R1
R2
Bang-Yue He
Hui-Min Wang
Jian-Mei Lu*
R1
N
N
KOt-Bu
+
R2
R2
DMSO, dioxane
80–120 °C, 12 h
R3
College of Chemistry and Materials Engineering, Wenzhou Uni-
versity, Chashan University Town, Wenzhou 325035, Zhejiang
Province, P. R. of China
ljm@wzu.edu.cn
R3
64–99%
+
8
6
5
(
7
7
8
)
6
6
8
9
3
0
0
R1 = Me, Et, Bu Ph, 4-Tol, 3-Tol, 4-MeOC6H4, 2-MeOC6H4, 4-FC6H4
R2 = Me, Et, Bu
R
3 = H, 4-Me, 3-Me, 2-Me, 4-F
X = I, Br, Cl
Received: 08.08.2014
Accepted after revision: 30.09.2014
Published online: 06.11.2014
cost. However, to the best of our knowledge, only primary
and secondary amines have been used as the nucleophile in
the transition-metal-free amination of aryl halides, and
there has been no report of the application of aromatic ter-
tiary amines as nucleophiles to date.8,9 In our continuing
program to develop new methodologies for the formation
of C–N bonds,10 we found that both aromatic and aliphatic
tertiary amines and aryl halides can be coupled mediated
by potassium tert-butoxide and dimethyl sulfoxide in the
absence of a transition metal. Herein, we report these re-
sults in detail.
DOI: 10.1055/s-0034-1379367; Art ID: ss-2014-h0503-op
Abstract A transition-metal-free, C–N bond-formation reaction be-
tween tertiary amines and aryl halides is reported. Under the optimal
conditions, various aromatic and aliphatic tertiary amines react with
aryl halides, including iodides, bromides, and chlorides, to give mono-
aminated products, N,N-dialkylanilines and N-alkyl-N-arylanilines, in
good to high yields. Based on the experimental results, the reaction is
believed to occur via an aryne intermediate derived from the aryl halide.
Key words transition-metal-free, tertiary amines, aryl halides, amina-
At the outset of our investigation, a mixture of N,N-di-
methylaniline (1a, 0. 55 mmol), iodobenzene (2a, 3.0
equiv), and dimethyl sulfoxide (3.0 equiv) in dioxane (0.9
mL) was stirred at 80 °C for 12 hours to evaluate the effects
of various bases. Representative results are shown in Table
1. To our delight, using potassium tert-butoxide (4.0 equiv)
as the base gave the desired C–N coupling product 3a in 89%
yield (entry 1).11 However, other bases, such as lithium tert-
butoxide, sodium tert-butoxide, sodium hydroxide, potassi-
um hydroxide, potassium carbonate, cesium carbonate, po-
tassium hydrogen carbonate, and tripotassium phosphate
trihydrate, gave either very low yields of 3a or no reaction
was observed (entries 2–9). Subsequently, the conditions
were further tuned using potassium tert-butoxide as the
base. For example, decreasing the amount of potassium
tert-butoxide from four to three equivalents gave a slight
decrease in the yield of 3a to 82% (entry 10). In addition,
three equivalents of dimethyl sulfoxide were also found to
be essential for this reaction. For instance, decreasing the
amount of dimethyl sulfoxide from three to two equivalents
or in the absence of dimethyl sulfoxide gave 3a in only 73
and 23% yields, respectively (entries 11 and 12).12 Further-
more, to achieve a satisfactory result, three equivalents of
iodobenzene (2a) were also necessary. For example, using
two equivalents of 2a resulted in a drastically reduced yield
of 3a of 68% (entry 13). Furthermore, the use of a variety of
tion reaction, synthetic method
Arylamines, which can be frequently found in natural
products as compounds with biological and pharmaceutical
activity, are very interesting molecules in organic synthe-
sis.1 Recent syntheses of such compounds are the palladi-
um-catalyzed Buchwald–Hartwig2 and copper-catalyzed
Ullmann couplings between primary or secondary amines
and aryl halides.3 However, the Buchwald–Hartwig cou-
pling requires the use of expensive palladium complexes
and the Ullmann couplings usually require excess of the
copper salts and higher temperatures. In addition, transi-
tion-metal contaminants are commonly unavoidable,
which is unacceptable, especially in pharmaceutical fine
chemicals. These shortcomings have prompted the pursuit
of transition-metal-free methods for the synthesis of aryl-
amines. However, compared to numerous reports on transi-
tion-metal-catalyzed amination reactions, there are only a
few reports of transition-metal-free couplings between pri-
mary or secondary amines and aryl halides.4 In addition,
transformations involving other electrophiles such as aryl-
boronic acids and their derivatives,5 o-silylaryl triflates,6
and diaryliodonium salts7 rather than aryl halides have also
been developed. Among these electrophiles, aryl halides are
the most desirable due to their easy availability and lower
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222
P. Huang et al.
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Synthesis
solvents was examined, and it was found that 1,2-dimeth-
oxyethane, tetrahydrofuran, and toluene gave lower yields
compared to dioxane (entries 1 and 14–16); dimethyl sulf-
oxide was also a suitable solvent giving 3a in good yield
(entry 17). However, further studies showed that dimethyl
sulfoxide was unsuitable for other substrates tested. Thus,
the optimized reaction conditions are those shown in Table
1, entry 1.13
1a and electron-poor groups, such as 4-F 1e, are all tolerat-
ed to give products 3a–e in good to high yields (entries 1–4,
6–10, and 12–14). Moderate yields can still be achieved
when substrate 1f bearing a sterically hindered 2-methoxy
group was used as the substrate (entries 5 and 11). In addi-
tion, it seems that higher yields can be obtained if anilines
bearing electron-rich substituents were used as the sub-
strates. For instance, highest yields were observed when 4-
methoxy-N,N-dimethylaniline (1d) was used (entries 3, 9,
and 14). Halobenzenes also had some effect on the reac-
tions. For example, for reactions involving bromobenzene
(2b) and chlorobenzene (2c), higher temperatures (100 and
120 °C) are necessary to achieve satisfactory results (entries
6–14). It was worthy of noting here that with the increase
of the electronegative of the halogen atoms, the reaction
conditions became harsher. For example, the reactions in-
volving iodides can be performed at 80 °C, while those of
bromides and chlorides should be carried out at 100 and
120 °C, respectively. Based on these results, the conclusion
may be drawn that aryl fluorides will not be good sub-
strates in such transformations as harsher conditions, such
as higher temperature or stronger base, will be necessary.
Table 1 Optimization for the Reaction of N,N-Dimethylaniline (1a)
with Iodobenzene (2a)
Me
Me
I
N
Me
N
base, DMSO
+
solvent, 80 °C, 12 h
1a
2a
3a
Entrya
Base
Solvent
Yieldb (%)
1
KOt-Bu
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
DME
89
<5
<5
<5
<5
2
LiOt-Bu
NaOt-Bu
NaOH
3
4
Table 2 Reactions of N,N-Dimethylanilines 1 with Halobenzenes 2
5
KOH
c
Me
Me
6
K2CO3
–
Me
N
N
X
c
7
Cs2CO3
KHCO3
K3PO4·3H2O
KOt-Bu
KOt-Bu
KOt-Bu
KOt-Bu
KOt-Bu
KOt-Bu
KOt-Bu
KOt-Bu
–
KOt-Bu (4.0 equiv)
c
8
–
+
DMSO (3.0 equiv)
dioxane, 12 h
c
9
–
R
R
1
2
3
10d
11e
12f
13g
14
15
16
17
82
73
23
68
78
75
63
82
Entrya
1
R
Halide
X
Temp (°C) Prod- Yieldb
uct (%)
1
1b
4-Me
3-Me
4-OMe
4-F
2a
2a
2a
2a
2a
2b
2b
2b
2b
2b
2b
2c
2c
2c
I
80
3b
91
2
1c
1d
1e
1f
I
80
3c
3d
3e
3f
91
99
83
67
96
94
90
99
84
70
83
72
93
THF
3
I
80
toluene
DMSO
4
I
80
5
2-OMe
H
I
80
a Reaction conditions: 1a (0.55 mmol), 2a (3.0 equiv), base (4.0 equiv),
DMSO (3.0 equiv), solvent (0.9 mL), 80 °C, 12 h.
b Isolated yields.
6
1a
1b
1c
1d
1e
1f
Br
Br
Br
Br
Br
Br
Cl
Cl
Cl
100
100
100
100
100
100
120
120
120
3a
3b
3c
3d
3e
3f
7
4-Me
3-Me
4-OMe
4-F
c Not reported.
8
d KOt-Bu (3.0 equiv) was used.
e DMSO (2.0 equiv) was used.
f No DMSO was added.
9
g 2a (2.0 equiv) was used.
10
11
12
13
14
2-OMe
4-Me
3-Me
4-OMe
Under the optimal conditions, the reaction was first in-
vestigated using a variety of N,N-dimethylanilines 1 and
halobenzenes 2, such as iodobenzene (2a), bromobenzene
(2b), and chlorobenzene (2c) as the substrate. As can be
seen from Table 2, all reactions proceeded smoothly to give
the desired aminated products 3a–f in moderate to high
yields. Substituents on the anilines did not affect the reac-
tions significantly. For example, electron-rich substituents,
such as 4-Me 1b, 3-Me 1c, and 4-OMe 1d, electron-neutral
1b
1c
1d
3b
3c
3d
a Reaction conditions: 1 (0.55 mmol), 2 (3.0 equiv), KOt-Bu (4.0 equiv),
DMSO (3.0 equiv), dioxane (0.9 mL), 12 h.
b Isolated yields.
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Synthesis
Encouraged by these results, the reactions of N,N-di-
methylaniline (1a) with various aryl halides 2 bearing elec-
Table 3 Reactions of N,N-Dimethylaniline (1a) with Aryl Halides 2
Me
Me
Me
N
tron-poor,
electron-rich,
and
sterically
hindered
X
N
substituents were also examined under the optimal condi-
tions. It seems that the structure of the aryl halide 2 also
has some effect on these reactions. For instance, the desired
C–N coupling products can be obtained in moderate to high
yields for all the reactions investigated (Table 3). However,
the steric and electronic effects of the substituents on the
aryl halides will result in different regioselective aminated
products 3.14 Based on the results shown in Table 3, the
conclusion can be drawn that the direct C–N coupling be-
tween aromatic tertiary amines and aryl halides takes place
via aryne intermediates.15 Based on this assumption, the
steric and electronic effect of the substituents on the aryl
halides can thus be explained. For example, the reactions of
N,N-dimethylaniline (1a) with 4-iodotoluene (2d) and 3-io-
dotoluene (2e) give a mixture of para- and meta-aminated
products 3b and 3c in both cases (entries 1 and 2), implying
that the same aryne intermediate was formed. For the reac-
tion of sterically hindered 2-bromotoluene (2g), only the
meta-aminated product 3c is isolated in 64% yield (entry 4),
probably due to the steric effect of the methyl group on the
aryne intermediate formed, which thus resulted in solely in
meta-amination.
Furthermore, the reactions of 4-methoxy-N,N-dimeth-
ylaniline (1d) with 4-, 3-, or 2-chlorotoluenes 2m–o were
also investigated under the optimal conditions. As can be
seen from Table 4, all reactions took place to give the de-
sired aminated products in good to almost quantitative
yields. For the reactions involving 4-chlorotoluene (2m)
and 3-chlorotoluene (2n), the para- and meta-aminated
products 3j and 3k were both obtained in very high yields,
respectively, perhaps due to the same aryne intermediate
being formed in both cases (Table 4, entries 1 and 2). For
the reaction involving 2-chlorotoluene (2o), only the meta-
aminated product 3k was obtained in 80% yield (entry 3),
similarly due to the steric hindrance of the aryne interme-
diate formed.
KOt-Bu (4.0 equiv)
+
DMSO (3.0 equiv)
dioxane, 12 h
R
R
1a
2
3
Entrya
2
R
X
Temp
(°C)
Yieldb (%)
1c
2c
2d 4-Me
I
I
80
3b, 36
3b, 27
3c, 38
3c, 43
2e
3-Me
4-F
100
Me
N
3
2f
I
120
3e, 82
F
3g, 17
4
2g 2-Me
2h 4-Me
Br
Br
Br
100
100
100
3c, 64
3b, 48
3b, 31
5c
6c
3c, 45
3c, 53
2i
3-Me
Br
Me
N
7
8
100
100
2j
3h, 77
3e, 82
2k
4-F
Br
Br
3g, 12
Me
N
9
2l
3,4-Me2
100
3i, 65
a Reaction conditions: 1a (0.55 mmol), 2 (3.0 equiv), KOt-Bu (4.0 equiv),
DMSO (3.0 equiv), dioxane (0.9 mL), 12 h.
b Isolated yields.
c Mixture of 3b and 3c was obtained after flash column chromatography
(see Supporting Information for details).
Br
R
The transition-metal-free amination of aliphatic tertia-
ry amines such as triethylamine (1g) and tributylamine
(1h) with bromobenzene (2b) was also examined. As can be
seen from Scheme 1, both reactions proceeded well under
the optimal conditions to give the desired aminated prod-
ucts 3l and 3m, respectively, in good yields. Therefore, com-
pared to the previously reported methods, which were
limited to the reactions of aromatic or aliphatic tertiary
amines, respectively,8,9 both aromatic and aliphatic tertiary
amines can be tolerated in this method, implying its broad-
er substrate compatibility.
KOt-Bu (4.0 equiv)
R
R
N
+
N
R
R
DMSO (3.0 equiv)
dioxane, 100 °C, 12 h
3
2b
1g R = Et
1h R = n-Bu
3l R = Et, 84%
3m R = n-Bu, 77%
Scheme 1 Reactions of aliphatic tertiary amines with bromobenzene.
Reagents and conditions: 1 (0.55 mmol), 2b (3.0 equiv), KOt-Bu (4.0
equiv), DMSO (3.0 equiv), dioxane (0.9 mL), 100 °C, 12 h.
It should be noted that in these reactions no diarylated
amines were isolated by column chromatography. In addi-
tion, it was indeed found that the above products 3l and 3m
were not suitable substrates in the reaction with bromo-
benzene under the optimal conditions and predominantly
the unreacted starting materials were recovered (Scheme
2).
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Synthesis
Table 4 Reactions of 4-Methoxy-N,N-dimethylaniline (1d) with Chlo-
rotoluenes 2m–o
Me
Br
N
N
KOt-Bu (4.0 equiv)
+
Me
Me
Me
N
DMSO (3.0 equiv)
dioxane, 100 °C, 12 h
Cl
Me
N
1i
2b
KOt-Bu (4.0 equiv)
3o, 30%
+
DMSO (3.0 equiv)
dioxane, 120 °C, 12 h
Scheme 3 Reaction of N-butyl-N-methylaniline with bromobenzene.
Reagents and conditions: 1i (0.55 mmol), 2b (3.0 equiv), KOt-Bu (4.0
equiv), DMSO (3.0 equiv), dioxane (0.9 mL), 100 °C, 12 h.
Me
2
OMe
OMe
1d
3
Entrya
2
Substitu-
tion
Yieldb (%)
on the experiments, the reaction is believed to occur via
aryne intermediates derived from aryl halides. Efforts are
underway to expand this methodology toward other reac-
tions rather than just C–N coupling.
Me
N
1c
2m
4-Me
Me
N
NMR spectra were recorded at 500 (for 1H NMR) and 125 MHz (for 13
C
NMR), respectively. 1H NMR and 13C NMR spectra recorded in CDCl3
solutions were referenced to TMS (δ = 0.00 ppm) and the residual sol-
vent peak (δ = 77.0 ppm), respectively. Organic solvents used were
dried by standard methods. Other commercially obtained reagents
were used without further purification. Flash column chromatogra-
phy was performed on silica gel.
OMe
OMe
3j, 51
3j, 37
3k, 48
3k, 55
2c
3
2n
2o
3-Me
2-Me
3k, 80
a Reactions conditions: 1d (0.55 mmol), 2 (3.0 equiv), KOt-Bu (4.0 equiv),
DMSO (3.0 equiv), dioxane (0.9 mL), 120 °C, 12 h.
b Isolated yields.
Amination between Tertiary Amines and Aryl Halides; General
Procedure
c A mixture of 3j and 3k was obtained after flash column chromatography
(see Supporting Information for details).
Under an atmosphere of N2, KOt-Bu (2.2 mmol), dioxane (0.9 mL),
DMSO (1.65 mmol), tertiary amine 1 (0.55 mmol), and aryl halide 2
(1.65 mmol) were successively added to a Schlenk reaction tube. The
mixture was stirred vigorously at 80–120 °C for 12 h. Then the mix-
ture was diluted with EtOAc, washed with sat. brine, and dried (anhyd
Na2SO4). Then the solvent was removed under reduced pressure and
the residue was purified by flash column chromatography (petroleum
ether and petroleum ether–EtOAc, 100:1 for the methoxy group de-
rived products) to give pure products 3.
R
R
R
N
Br
N
KOt-Bu (4.0 equiv)
+
DMSO (3.0 equiv)
dioxane, 100 °C, 12 h
3n R = Et, 22%
3o R = n-Bu, 6%
2b
3l R = Et
3m R = n-Bu
N-Methyldiphenylamine (3a)10f
Scheme 2 Reactions of N,N-diethylaniline and N,N-dibutylaniline with
bromobenzene. Reagents and conditions: 3l or 3m (0.55 mmol), 2b (3.0
equiv), KOt-Bu (4.0 equiv), DMSO (3.0 equiv), dioxane (0.9 mL), 100 °C,
12 h.
Colorless liquid; yield: 89.6 mg (89%).
1H NMR (500 MHz, CDCl3, TMS): δ = 7.25 (t, J = 8.0 Hz, 4 H), 7.01 (d, J =
8.0 Hz, 4 H), 6.93 (t, J = 8.0 Hz, 2 H), 3.29 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 149.0, 129.1, 121.2, 120.4, 40.2.
Furthermore, the reaction of N-butyl-N-methylaniline
(1l) with bromobenzene (2b) was also carried out under
the optimal conditions. In this case, only the demethylated
product 3o was isolated in 30% yield, and most of the start-
ing aniline was recovered, suggesting that in such transfor-
mations only the CH3–N bond is cleaved (Scheme 3).
In conclusion, we have developed a facile and conve-
nient C–N coupling of aromatic and aliphatic tertiary
amines with aryl halides. It may be worthy of note here that
this is the first example of such a transformation between
aromatic tertiary amines and aryl halides in the absence of
any transition metals. A variety of aromatic and aliphatic
tertiary amines and aryl halides are tolerated to give the de-
sired aminated products in moderate to high yields. Based
N,4-Dimethyl-N-phenylaniline (3b)16
Colorless liquid; yield: 98.6 mg (91%).
1H NMR (500 MHz, CDCl3, TMS): δ = 7.22 (t, J = 7.5 Hz, 2 H), 7.11 (d, J =
8.0 Hz, 2 H), 6.99 (d, J = 8.0 Hz, 2 H), 6.92 (d, J = 7.5 Hz, 2 H), 6.86 (t, J =
7.5 Hz, 1 H), 3.28 (s, 3 H), 2.32 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 149.3, 146.6, 132.0, 129.9, 129.0,
122.5, 119.8, 118.2, 40.3, 20.7.
N,3-Dimethyl-N-phenylaniline (3c)17
Colorless liquid; yield: 98.9 mg (91%).
1H NMR (500 MHz, CDCl3, TMS): δ = 7.24 (t, J = 8.5 Hz, 2 H), 7.14 (t, J =
7.5 Hz, 1 H), 6.98 (d, J = 8.5 Hz, 2 H), 6.91 (t, J = 7.5 Hz, 1 H), 6.84–6.82
(m, 2 H), 6.77 (d, J = 7.5 Hz, 1 H), 3.27 (s, 3 H), 2.28 (s, 3 H).
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P. Huang et al.
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Synthesis
13C NMR (125 MHz, CDCl3): δ = 149.1, 149.0, 138.9, 129.1, 129.0,
122.3, 121.4, 120.9, 120.1, 117.9, 40.2, 21.5.
4-Methoxy-N-methyl-N-(4-tolyl)aniline (3j) and
4-Methoxy-N-methyl-N-(3-tolyl)aniline (3k)
Inseparable mixture; colorless liquid; yield: 123.6 mg (99%).
4-Methoxy-N-methyl-N-phenylaniline (3d)16
IR (neat): 3040, 2994, 2934, 2822, 2802, 2597, 1577, 1507, 1461,
1438, 1334, 1235, 1175, 1126, 1036, 917, 836, 766, 697 cm–1
Colorless liquid; yield: 116.0 mg (99%).
.
1H NMR (500 MHz, CDCl3, TMS): δ = 7.19 (dd, J = 9.0, 7.0 Hz, 2 H), 7.08
(d, J = 9.0 Hz, 2 H), 6.88 (d, J = 8.5 Hz, 2 H), 6.79–6.76 (m, 3 H), 3.80 (s,
3 H), 3.25 (s, 3 H).
1H NMR (500 MHz, CDCl3, TMS): δ (3j) = 7.01 (d, J = 8.0 Hz, 4 H), 6.84
(d, J = 8.0 Hz, 2 H), 6.75 (d, J = 8.0 Hz, 2 H), 3.77 (s, 3 H), 3.21 (s, 3 H),
2.26 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 156.3, 149.8, 142.3, 128.9, 126.1,
13C NMR (125 MHz, CDCl3): δ (3j) = 155.5, 147.5, 142.8, 129.5, 128.5,
118.4, 115.8, 114.8, 55.5, 40.4.
124.5, 117.4, 114.7, 55.4, 40.5, 20.4.
1H NMR (500 MHz, CDCl3, TMS): δ (3k) = 7.09–7.05 (m, 3 H), 6.87 (d,
J = 8.5 Hz, 2 H), 6.61–6.59 (m, 3 H), 3.78 (s, 3 H), 3.22 (s, 3 H), 2.26 (s, 3
4-Fluoro-N-methyl-N-phenylaniline (3e)16
Colorless liquid; yield: 91.7 mg (83%).
H).
1H NMR (500 MHz, CDCl3, TMS): δ = 7.24–7.21 (m, 2 H), 7.04–6.96 (m,
13C NMR (125 MHz, CDCl3): δ (3k) = 156.1, 149.8, 142.3, 138.6, 128.7,
4 H), 6.88–6.85 (m, 3 H), 3.25 (s, 3 H).
126.0, 119.4, 116.6, 114.6, 113.1, 55.4, 40.6, 21.7.
13C NMR (125 MHz, CDCl3): δ = 158.6 (d, JC-F = 240.3 Hz), 149.2, 145.1,
129.1, 124.2 (d, JC-F = 7.9 Hz), 120.0, 117.9, 115.9 (d, JC-F = 22.1 Hz),
40.5.
MS (ESI): m/z = 228 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C15H18NO: 228.1383; found:
228.1379.
2-Methoxy-N-methyl-N-phenylaniline (3f)18
4-Methoxy-N-methyl-N-(2-tolyl)aniline (3k)
Colorless liquid; yield: 78.5 mg (67%).
Colorless liquid; yield: 100.0 mg (80%).
1H NMR (500 MHz, CDCl3, TMS): δ = 7.24–7.14 (m, 4 H), 6.99–6.94 (m,
2 H), 6.71 (t, J = 7.5 Hz, 1 H), 6.65 (dd, J = 9.0, 1.0 Hz, 2 H), 3.76 (s, 3 H),
3.21 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 155.9, 149.3, 136.7, 129.1, 128.7,
126.9, 121.2, 117.1, 113.4, 112.6, 55.6, 39.0.
IR (neat): 3033, 2835, 1603, 1580, 1511, 1487, 1338, 1239, 1179,
1033, 915, 833, 768, 692 cm–1
.
1H NMR (500 MHz, CDCl3, TMS): δ = 7.09–7.06 (m, 3 H), 6.87 (d, J = 9.0
Hz, 2 H), 6.61–6.59 (m, 3 H), 3.78 (s, 3 H), 3.22 (s, 3 H), 2.26 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 156.0, 149.7, 142.2, 138.6, 128.7,
126.0, 119.3, 116.4, 114.6, 113.0, 55.4, 40.5, 21.7.
MS (ESI) : m/z = 228 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C15H18NO: 228.1383; found:
228.1386.
3-Fluoro-N-methyl-N-phenylaniline (3g)
Colorless liquid; yield: 18.8 mg (17%).
IR (neat): 3060, 2875, 2822, 2352, 1613, 1587, 1491, 1348, 1259,
1186, 1152, 1123, 1027, 995, 952, 939, 833, 755, 698 cm–1
.
1H NMR (500 MHz, CDCl3, TMS): δ = 7.35–7.31 (m, 2 H), 7.12–7.07 (m,
4 H), 6.65–6.63 (m, 1 H), 6.59–6.56 (m, 1 H), 6.56–6.51 (m, 1 H), 3.29
(s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 163.7 (d, JC-F = 242.1 Hz), 150.84,
150.76, 148.3, 129.9 (d, JC-F = 9.9 Hz), 129.5, 123.7 (d, JC-F = 5.1 Hz),
112.8, 105.9 (d, JC-F = 21.4 Hz), 104.1 (d, JC-F = 24.9 Hz), 40.2.
N,N-Diethylaniline (3l)19
Yellow liquid; yield: 68.8 mg (84%).
1H NMR (500 MHz, CDCl3, TMS): δ = 7.20 (t, J = 7.5 Hz, 2 H), 6.67 (d, J =
7.5 Hz, 2 H), 6.63 (t, J = 7.5 Hz, 1 H), 3.24 (q, J = 7.0 Hz, 4 H), 1.14 (t, J =
7.0 Hz, 6 H).
13C NMR (125 MHz, CDCl3): δ = 147.7, 129.2, 115.3, 111.8, 44.2, 12.5.
MS (ESI): m/z = 202 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C13H13FN: 202.1027; found:
202.1020.
N,N-Dibutylaniline (3m)20
Yellow liquid; yield: 86.8 mg (77%).
1H NMR (500 MHz, CDCl3, TMS): δ = 7.19 (dd, J = 9.0, 7.5 Hz, 2 H),
6.65–6.60 (m, 3 H), 3.25 (t, J = 7.5 Hz, 4 H), 1.58–1.53 (m, 4 H), 1.38–
1.31 (m, 4 H), 0.95 (t, J = 7.5 Hz, 6 H).
13C NMR (125 MHz, CDCl3): δ = 148.2, 129.1, 115.1, 111.7, 50.7, 29.4,
20.3, 14.0.
N-Methyl-N-phenylnaphthalen-2-amine (3h)9
Colorless liquid; yield: 98.7 mg (77%).
1H NMR (500 MHz, CDCl3, TMS): δ = 7.73–7.65 (m, 3 H), 7.41–7.38 (m,
1 H), 7.34–7.27 (m, 4 H), 7.20 (dd, J = 9.0, 7.5 Hz, 1 H), 7.10 (d, J = 7.5
Hz, 2 H), 7.01 (t, J = 7.5 Hz, 1 H), 3.40 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 148.9, 146.4, 134.6, 129.3, 129.1,
128.6, 127.5, 126.7, 126.2, 123.8, 122.0, 121.7, 121.4, 114.6, 40.7.
N-Ethyldiphenylamine (3n)21
Pale yellow liquid; yield: 23.8 mg (22%).
1H NMR (500 MHz, CDCl3, TMS): δ = 7.27–7.24 (m, 4 H), 7.00–6.98 (m,
4 H), 6.95–6.92 (m, 2 H), 3.77 (q, J = 7.0 Hz, 2 H), 1.22 (t, J = 7.0 Hz, 3
H).
N,3,4-Trimethyl-N-phenylaniline (3i)9
Colorless liquid; yield: 75.5 mg (65%).
1H NMR (500 MHz, CDCl3, TMS): δ = 7.22 (t, J = 8.0 Hz, 2 H), 7.07 (d, J =
8.0 Hz, 1 H), 6.92–6.90 (m, 3 H), 6.86–6.83 (m, 2 H), 3.27 (s, 3 H), 2.23
(s, 3 H), 2.22 (s, 3 H).
13C NMR (125 MHz, CDCl3): δ = 149.3, 146.8, 137.5, 131.0, 130.4,
128.9, 124.1, 120.3, 119.5, 117.8, 40.3, 19.9, 19.1.
13C NMR (125 MHz, CDCl3): δ = 147.7, 129.2, 121.1, 120.9, 46.4, 12.7.
N-Butyldiphenylamine (3o)22
Pale yellow liquid; yield: 37.1 mg (30%).
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1H NMR (500 MHz, CDCl3, TMS): δ = 7.25–7.21 (m, 4 H), 6.98–6.97 (m,
4 H), 6.93–6.90 (m, 2 H), 3.67 (t, J = 7.5 Hz, 2 H), 1.67–1.61 (m, 2 H),
1.39–1.31 (m, 2 H), 0.91 (t, J = 7.5 Hz, 3 H).
13C NMR (125 MHz, CDCl3): δ = 148.1, 129.2, 121.0, 120.9, 52.1, 29.6,
20.3, 13.9.
(6) (a) Liu, Z.-J.; Larock, R. C. Org. Lett. 2003, 5, 4673. (b) Liu, Z.-J.;
Larock, R. C. J. Org. Chem. 2006, 71, 3198.
(7) (a) Carroll, M. A.; Wood, R. A. Tetrahedron 2007, 63, 11349.
(b) Guo, F.-L.; Wang, L.-M.; Wang, P.-Q.; Yu, J.-J.; Han, J.-W. Asian
J. Org. Chem. 2012, 1, 218.
(8) In a preliminary paper, Wang and co-workers reported the tran-
sition-metal-free amination between aliphatic tertiary amines
and aryl halides, see: Fang, Y.; Zheng, Y.-Q.; Wang, Z.-Y. Eur. J.
Org. Chem. 2012, 1495.
Acknowledgment
(9) In a preliminary communication, Biju and co-workers reported
the transition-metal-free amination of aromatic tertiary amines
with o-silylaryl triflates, see: Bhojgude, S. S.; Kaicharla, T.; Biju,
A. T. Org. Lett. 2013, 15, 5452.
Pei Huang thanks Science and Technology Department of Zhejiang
Province (Xinmiao Program) for financial support (No.
2013R424057).
(10) (a) Huang, P.; Wang, Y.-X.; Yu, H.-F.; Lu, J.-M. Organometallics
2014, 33, 1587. (b) Chen, W.-X.; Zhang, C.-Y.; Shao, L.-X.
Tetrahedron 2014, 70, 880. (c) Chen, W.-X.; Zhang, C.-Y.; Lu, J.-M.
J. Chem. Res. 2013, 611. (d) Chen, W.-X.; Shao, L.-X. J. Org. Chem.
2012, 77, 9236. (e) Zhu, L.; Ye, Y.-M.; Shao, L.-X. Tetrahedron
2012, 68, 2414. (f) Zhu, L.; Gao, T.-T.; Shao, L.-X. Tetrahedron
2011, 67, 5150.
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0034-1379367.
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(11) It should be noted here that KOt-Bu should be strictly dry
(anhydrous), i.e. it is a very good powder with no bulky solid. If
it contains some bulky solid, which maybe due to the hydrolysis
of KOt-Bu, lower yield will be obtained. KOt-Bu was purchased
from J&K Scientific Ltd. in 25-g packaging (99% purity). During
our investigations we found that the reproducibility of different
batches of such KOt-Bu was sufficient.
(12) It is well established that the combination of a base and DMSO
acts as a super base. For some selected papers, please see refer-
ences 4f, 4g, and 8, and also: Baars, H.; Beyer, A.; Kohlhepp, S.
V.; Bolm, C. Org. Lett. 2014, 16, 536.
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