Palladium(II)-catalyzed direct ortho arylation of 4-methyl-N-phenylpyridin- 2-amines via C-H activation/C-C coupling and synthetic applications

Article abstract of DOI:10.1021/om401195w

The direct ortho arylation of 4-methyl-N-phenylpyridin-2-amines via palladium(II)-catalyzed C-H activation is described. Treatment of 4-methyl-N-phenylpyridin-2-amine with potassium aryltrifluoroborate using 10 mol % of palladium(II) acetate as the catalyst, 2 equiv of copper(II) acetate as the oxidant, and 1 equiv of p-benzoquinone in tert-butyl alcohol gave ortho-arylated products in modest to excellent yields. This reaction shows good functional group compatibility. A series of ¹H NMR titration experiments and controlled experiments elucidating the reaction mechanism were carried out. The key intermediate, 4-methyl-N-phenylpyridin-2-amine palladacycle, was isolated and characterized by X-ray crystallography. The advanced transformations of ortho-phenylated 4-methyl-N-phenylpyridin-2-amine to N-(4-methylpyridin-2-yl)-9H-carbazole, biphenyl-2-amine, and 3-methyl-6-phenylpyrido[1,2-a]benzimidazole were successfully demonstrated as potential synthetic applications.

Full text of DOI:10.1021/om401195w

Article
pubs.acs.org/Organometallics
Palladium(II)-Catalyzed Direct Ortho Arylation of
4‑Methyl‑N‑phenylpyridin-2-amines via C−H Activation/C−C
Coupling and Synthetic Applications
Jean-Ho Chu,*,† Hao-Ping Huang,† Wen-Ting Hsu,† Shih-Tien Chen,† and Ming-Jung Wu*,†,‡
†Department of Chemistry, National Sun Yat-sen University, Kaohsiung, Taiwan 804
‡Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, Taiwan 807
S
* Supporting Information
ABSTRACT: The direct ortho arylation of 4-methyl-N-
phenylpyridin-2-amines via palladium(II)-catalyzed C−H
activation is described. Treatment of 4-methyl-N-phenyl-
pyridin-2-amine with potassium aryltrifluoroborate using 10
mol % of palladium(II) acetate as the catalyst, 2 equiv of
copper(II) acetate as the oxidant, and 1 equiv of p-
benzoquinone in tert-butyl alcohol gave ortho-arylated products
in modest to excellent yields. This reaction shows good
1
functional group compatibility. A series of H NMR titration
experiments and controlled experiments elucidating the
reaction mechanism were carried out. The key intermediate,
4-methyl-N-phenylpyridin-2-amine palladacycle, was isolated
and characterized by X-ray crystallography. The advanced
transformations of ortho-phenylated 4-methyl-N-phenylpyri-
din-2-amine to N-(4-methylpyridin-2-yl)-9H-carbazole, biphenyl-2-amine, and 3-methyl-6-phenylpyrido[1,2-a]benzimidazole
were successfully demonstrated as potential synthetic applications.
moiety.3b,8e,f In 2011, we applied the directing group
(pyridinyl) methodology on N-phenylpyridin-2-amines via
C−H activation to generate a variety of 9-(pyridin-2-yl)-9H-
carbazoles. In those reactions, we also found the ortho-
monoarylated N-phenylpyridin-2-amines as minor products.3b
INTRODUCTION
■
The utility of transition metals to catalyze direct C−H
activation and functionalization has received great attention
and has been increasingly explored in the past decade.1 It has
been widely recognized as an efficient strategy, both in
synthetic steps and atom-economy aspects, for the construction
of various organic molecules. To date, many practical syntheses
based on the idea have been reported.2,3 Especially in the case
of biaryl, it is an important scaffold found in natural products,4
pharmaceuticals,5 and optoelectronic materials.6 Therefore, the
development of simpler and more efficient protocols regarding
the synthesis of biaryl is still highly desirable. Transition-metal-
catalyzed C−H activation and subsequent C−C coupling has
been recognized as a powerful method to synthesize various
biaryls, and the regioselectivity (e.g., ortho C−H arylation) can
be efficiently controlled by the directing group.
Meanwhile, Schnuch and co-workers reported the direct ortho
̈
arylation of N-phenylpyridin-2-amines using similar palladium-
(II)-catalyzed C−H activation with arylboronic acids in 2012.8f
In their work, a large amount of boronic acid (3 equiv) and a
longer reaction time (24 h) are required.
To further improve these synthetic conditions3b,8f and most
importantly to understand the electronic factors on the
directing group governing the direct ortho arylation of N-
phenylpyridin-2-amines via C−H activation, we carried out
multiple experiments by the variation of electron-donating/-
withdrawing substituents on the directing group. Furthermore,
in order to illustrate the synthetic applications, transformations
of ortho-phenylated 4-methyl-N-phenylpyridin-2-amine to N-
(4-methylpyridin-2-yl)-9H-carbazole, biphenyl-2-amine, and 3-
methyl-6-phenylpyrido[1,2-a]benzimi-dazole were demonstra-
ted.
In 2006, Yu and co-workers successfully demonstrated a
pioneering work on the direct ortho alkylation of 2-oxazolines
and 2-aryl(and/or alkyl)pyridines by the employment of the
directing group to assist the transition-metal-catalyzed C−H
activation and C−C coupling.7 To date, they have already
developed numerous efficient synthetic methods to obtain
versatile organic molecules on the basis of this synthetic
strategy. However, the direct arylation of secondary N-
arylamines via C−H activation has still rarely been studied in
the literature,3b,8 especially at the ortho position of the aniline
Received: December 10, 2013
Published: February 21, 2014
© 2014 American Chemical Society
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amine (3‴a) were isolated during these processes. After
finalizing the optimized reaction conditions, we subsequently
carried out the catalytic reaction of 1 with 2a to study the
reactivity changes influenced by the substituent electronic effect
on the directing group (pyridinyl). These results are
summarized in Table 2.
RESULTS AND DISCUSSION
■
Screening of Oxidants and Solvents for the Direct
Ortho Arylation of N-Phenylpyridin-2-amine and Re-
activity Investigation of the Substituent Electronic
Effect on the Directing Group. We commenced our studies
with the direct ortho coupling of N-phenylpyridin-2-amine (1a)
and potassium phenyltrifluoroborate (2a) to afford N-([1,1′-
biphenyl]-2-yl)pyridin-2-amine (3a) in the presence of
palladium(II) acetate. Various oxidants and solvents were
screened, as shown in Table 1, for this reaction that was carried
Table 2. Reactivity Investigation of the Substituent
Electronic Effect on the Directing Group (Pyridinyl) of 1
Table 1. Screening of Oxidants and Solvents for the Direct
Ortho Phenylation of 1a
a
b
entry
substrate (R)
product ratio (3:3′:3″:3‴)
total yield (%)
c
1
H (1a)
89:0:11:0
35:65:0:0
40:60:0:0
75:0:25:0
100:0:0:0
100:0:0:0
95:0:5:0
69 (57)
2
3-OMe (1b)
3-Me (1c)
3-NO2 (1d)
4-OMe (1e)
4-Me (1f)
85
80
3
product ratio
total yield
a
b
4
55
entry
oxidant
none
solvent
(3a:3′a:3″a:3‴a)
(%)
c
5
90 (82)
87 (80)
47 (37)
85 (80)
75 (70)
0
1
tert-butyl alcohol
100:0:0:0
15 (10)
6
2
Cu(OAc)2 tert-butyl alcohol
Cu(OTf)2 tert-butyl alcohol
89:0:11:0
69 (57)
7
4-NO2 (1g)
5-OMe (1h)
5-Me (1i)
3
0
8
100:0:0:0
100:0:0:0
4
AgNO3
AgOAc
Ag2CO3
Ag2O
tert-butyl alcohol
tert-butyl alcohol
tert-butyl alcohol
tert-butyl alcohol
tert-butyl alcohol
tert-butyl alcohol
92:0:8:0
94:0:6:0
100:0:0:0
59:0:0:41
100:0:0:0
100:0:0:0
27:0:23:50
100:0:0:0
60:0:40:0
89:0:11:0
55:0:45:0
70:0:30:0
100:0:0:0
100:0:0:0
70 (65)
68 (60)
50
9
5
10
11
12
13
5-NO2 (1j)
6-OMe (1k)
6-Me (1l)
6
100:0:0:0
20:0:0:80
20
7
13
11
25
8
K2S2O8
oxone11
53
6-NO2 (1m)
0
9
52
a
The product ratio 3:3′:3″:3‴ was determined by GC-MS for three
10
11
12
13
14
15
16
17
Cu(OAc)2 DMF
56
runs, where 3′ = diphenylated products, 3″ =N-(pyridin-2-yl)-9H-
carbazoles, and 3‴ = N,N-diphenylpyridin-2-amines.
Cu(OAc)2 acetonitrile
Cu(OAc)2 THF
46
31
Cu(OAc)2 1,2-dichloroethane
Cu(OAc)2 1,4-dioxane
Cu(OAc)2 dichloromethane
Cu(OAc)2 benzene
31
30
21
15
Cu(OAc)2 toluene
8
a
The product ratio 3a:3′a:3″a:3‴a was determined by GC-MS for
three runs, where 3′a = diphenylated N-phenylpyridin-2-amine, 3″a =
N-(pyridin-2-yl)-9H-carbazole, and 3‴a = N,N-diphenylpyridin-2-
amine.
b
The total yield was obtained as an average by GC-MS for three runs
c
(using n-octadecane as the internal standard). Values in parentheses
are isolated yields.
In the case of 1a (R  H) bearing a neutral substituent, only
a 69% total yield of products 3a and 3″a was given, and the
product ratio was determined by GC-MS to be 89:11 (entry 1,
Table 2). When an electron-donating or -withdrawing group
such as OMe, Me, or NO2 was tagged on each position (3, 4, 5,
and 6) of the pyridinyl group, a dramatic change in the
reactivity was observed (vide infra). In the cases of 1b−d (R =
3-OMe, 3-Me, 3-NO2, entries 2−4, Table 2), a mixture of 3b,c
(monophenylated products) and 3′b,c (diphenylated products)
was generated in the following product ratios: 3b:3′b = 35:65
(85% total yield) and 3c:3′c = 40:60 (80% total yield), whereas
3d and 3″d (product ratio 75:25) were isolated in 55% total
yield. Furthermore, the cases of 1e−g (R = 4-OMe, 4-Me, 3-
NO2, entries 5−7, Table 2) showed that single products 3e,f
were generated in 90% and 87% yields, respectively, and only a
47% product yield of 3g and 3″g was obtained in the product
ratio 95:5. Single products 3h,i were isolated in 85% and 75%
b
The total yield was obtained as an average by GC-MS for three runs
c
(using n-octadecane as the internal standard). Values in parentheses
are isolated yields.
out at 80−90 °C for 4 h in the presence of p-benzoquinone
(BQ).3,9 Copper(II) acetate, silver(I) nitrate, and silver(I)
acetate were found to be comparable oxidants, and tert-butyl
alcohol was the best solvent for the reaction (see Table 1).
Copper(II) acetate was eventually chosen as the best oxidant
because of its lower cost and good starting substrate
compatibility.10 Trace amounts of the side products N-
(pyridin-2-yl)-9H-carbazole (3″a) and N,N-diphenylpyridin-2-
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Table 3. Direct Ortho Arylation of 1f with 2
a
b
The product yield was obtained as an average by GC-MS for three runs (using n-octadecane as the internal standard). Values in parentheses are
c
isolated yields. The product yield after the comma was obtained by using AgNO3 as the oxidant.
yields, respectively, in the cases of 1h,i (R = 5-OMe, 5-Me,
entries 8 and 9, Table 2), but none of the anticipated product 3j
was observed with only the recovery of the starting substrate in
the case of 1j (R = 5-NO2, entry 10, Table 2). Finally, 1k−m
(R = 6-OMe, 6-Me, 6-NO2, entries 11−13, Table 2) showed
poor results in which only a 20% yield of single product 3k was
obtained and a mixture of 3l and 3‴l (product ratio 20:80) was
generated in 25% total yield. None of the desired product 3m
was obtained, and we only recovered the starting substrate 1m.
On the basis of these experimental results in Table 2, the
electron-donating substituent (e.g., OMe or Me) on the
pyridinyl group can obviously increase the reactivity while the
electron-withdrawing substituent (e.g., NO2) decreases it. This
implies the electron-donating effect on the directing group
might promote the binding affinity of the pyridinyl nitrogen
with the palladium(II) ion and raise the probability of ortho
C−H activation, and that eventually causes the efficient
conversion of 1 to 3. In the study, substitution at the 3-
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Table 4. Direct Ortho Phenylation of 5 with 2a
a
b
The product yield was obtained as an average by GC-MS for three runs (using n-octadecane as the internal standard). The product ratio was
c
determined by GC-MS for three runs. Values in parentheses are isolated yields.
position of the pyridinyl group (i.e., 3-OMe, 3-Me, and 3-NO2)
shows product yields similar to that with the 4-position;
however, the product selectivity is not good while the
diphenylated product (3′b and 3′c) was formed as a major
product with a minor monophenylated product (3b and 3c).
Regarding the diphenylation in these two cases, it might be due
to the steric repulsion between the 3-MeO (or 3-Me) group
and another ortho C−H bond12 and eventually facilitates the
second ortho C−H activation and phenylation. Additionally,
MeO- and Me-substitution at the 5-position led to relatively
lower product yields in comparison to that at the 4-position and
this result might indicate that the electron-donating influence of
MeO (or Me) substituted at the 5-position is slightly poorer
than that at the 4-position in terms of the electron density of
the pyridinyl nitrogen. For the formation of carbazole 3″d in
the reaction of 1d with 2a, it might result from the better
binding affinity of the amine nitrogen with the palladium(II)
ion,13 which then facilitates the second C−H activation and C−
N formation of 3d. Finally, the MeO and/or Me substituent
next to the nitrogen of pyridine (i.e., 6-position) is believed to
offer steric hindrance and prohibit the binding of the pyridinyl
nitrogen with the palladium(II) ion that results in the poor
reactivity. Moreover, the electron-withdrawing effect of the 6-
NO2 substituent is still believed to play as a key factor for the
reactivity in addition to the steric hindrance. In the reaction of
1l with 2a, N,N-diphenylpyridin-2-amine 3‴l was generated as
a predominant product that might be due to the C−N coupling
of the amine group and borane reagent mediated or catalyzed
by copper catalysts.14
Catalytic Reaction of 1f with 2. On the basis of the
investigation of substituent electronic effects on the directing
group, we chose 4-methyl-N-phenylpyridin-2-amine (1f) as the
modeling substrate for the direct arylation.15 With the
optimized conditions in hand, we subsequently carried out
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Figure 1. 1H NMR titration experiments of (a) 1f and (b) 3f with tert-butyl alcohol and of (c) 1f and (d) 3f with 1,4-dioxane in d-chloroform. The
concentrations of 1f and 3f are 2.2 × 10−2 and 1.5 × 10−2 M, respectively, and the amounts of tert-butyl alcohol or 1,4-dioxane are 0, 0.5, 1, 1.5, 2, 4,
6, 8, and 10 equiv (from bottom to top), respectively. Chloroform (CHCl3) was employed as the internal standard.
the palladium(II)-catalyzed direct ortho arylation of 1f with 2.
These experimental results are summarized in Table 3.
According to these experimental results, the expected products
3f and 4 were successfully synthesized in modest to excellent
yields (37−91%). In these reactions, no obvious substituent
electronic effect for the coupling partner 2 was observed and it
gave anticipated products in similar yields for most cases.
Concurrently, the reaction showed good functional group
compatibility. Among this, we found that only a 37% yield of 4e
with the concomitant product 4‴e (9% yield) was obtained in
the case of 2e (entry 5, Table 3). Furthermore, a 56% yield of
4f and a 19% yield of 4‴f were isolated from the reaction of 1f
with 2f (entry 6, Table 3), and 4g was obtained in modest yield
(59%, entry 7, Table 3) under the optimized reaction
conditions. Herein, the generation of 4‴e and 4‴f should be
also due to copper(II) ion mediated or catalyzed intermolecular
C−N coupling of the amine and borane reagents.14b
Interestingly, the yields of 4e−g can be improved to 65%,
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Table 5. Intramolecular C−N Cyclization of 3f via C−H Activation
a
b
entry
oxidant
solvent
temp (°C)
time (h)
product (3″f:8)
yield (%)
1
2
3
4
5
6
7
8
AgOAc
1,4-dioxane
130−140
130−140
130−140
130−140
80−90
80−90
80−90
80−90
2
24
100:0
100:0
100:0
44:56
100:0
100:0
100:0
20:80
>99
>99
AgOAc
tert-butyl alcohol
1,4-dioxane
Cu(OAc)2
Cu(OAc)2
AgOAc
24
>99
tert-butyl alcohol
1,4-dioxane
24
71
2 (24)
24
15 (>99)
21
AgOAc
tert-butyl alcohol
1,4-dioxane
Cu(OAc)2
Cu(OAc)2
24
50
tert-butyl alcohol
24
14
a
b
The product ratio was determined by GC-MS for three runs. The product yield was obtained as an average by GC-MS for three runs (using n-
octadecane as the internal standard).
91%, and 85%, respectively, by using AgNO3 instead of
Cu(OAc)2 (entries 5−7, Table 3).
titration experiments of 1f and 3f with tert-butyl alcohol and
1,4-dioxane, respectively, as shown in Figure 1. According to
the experimental analysis, we found that the amine proton of 1f
was gradually shifted downfield in the presence of an increasing
amount of tert-butyl alcohol (6.58 to 6.70 ppm) and 1,4-
dioxane (6.58 to 6.72 ppm), as shown in Figure 1a,c, but no
obvious changes for chemical shifts of 3f was observed when
either tert-butyl alcohol or 1,4-dioxane was added, as shown in
Next substrate 5, the modified derivative of 1f, was subjected
to direct ortho phenylation. These experimental results are
summarized in Table 4. The expected product 6 was obtained
in modest to excellent yields (60−97%) by the reaction of 5
with 2a, and none of the anticipated product 6i was detected or
isolated in the reaction of 5i with 2a (entry 9, Table 4). A
minor product, N-(4-methylpyridin-2-yl)-3-nitro-9H-carbazole
(6″d), was isolated in the reaction of 5d with 2a, and the
product ratio of 6d and 6″d was determined to be 72:28 (entry
4, Table 4). A possible reason for the formation of 6″d is that
the nitro group of 6d deactivates its aryl ring, and this promotes
the palladium(II)-catalyzed intramolecular C−N coupling of
the amine and another phenyl ring to generate carbazole 6″d.
Moreover, a mixture of 6h and 6′h (90% total yield) was
isolated in the reaction of 5h with 2a, and the product ratio of
6h and 6′h was 80:20 (entry 8, Table 4). Regarding the
formation of diphenylated product 6′h, the para methyl group
of 5h might properly activate its aryl ring, and this resulted in
the occurrence of double C−H activation and diphenylation.
However, we did not detect or isolate the diphenylated product
6′g from the reaction of 5g (R = p-MeO) with 2a (entry 7,
Table 4).
1
Figure 1b,d. On the basis of H NMR titration studies, both
tert-butyl alcohol and 1,4-dioxane are suggested to have a
potential influence on the solution state of 1f. Although no
1
obvious chemical shift changes are observed in the H NMR
titration of 3f, the possibility of steric hindrance for 1,4-dioxane
and hydrogen bonding for tert-butyl alcohol in the solution
state of 3f are not completely excluded.
In addition to 1H NMR titration, we also carried out studies
of the influence of oxidants, solvents, and reaction temperatures
on the palladium(II)-catalyzed C−H activation and intra-
molecular C−N formation of 3f. These experimental results
were summarized in Table 5. In this study, AgOAc and 1,4-
dioxane again act as an excellent oxidant and solvent,
respectively, for the transformation of 3f to carbazole 3″f.
However, the use of Cu(OAc)2 and tert-butyl alcohol will
disfavor the reaction, while an additional compound, pyrido-
[1,2-a]benzimidazole 8, was generated (see Table 5). The
product ratio of 3″f and 8 was determined to be 44:55 (130−
140 °C) and 20:80 (80−90 °C), respectively (entries 4 and 8,
Table 5).16b,c Moreover, a higher reaction temperature (130−
140 °C) was found to be critical for the conversion of 3f to 3″f,
in which the consumption of 3f can be completed within 2 h by
using the reagent system of AgOAc and 1,4-dioxane (entry 1,
Table 5). Finally, a longer reaction time (24 h) was required
when the reaction temperature was reduced to 80−90 °C
(entry 5, Table 5). On the basis of these controlled
experiments, we suggested that the good affinity of the
copper(II) oxidant and amine nitrogen16a might prevent the
coordination of the palladium(II) ion with the amine nitrogen,
eventually leading to the failure of the palladium(II)-catalyzed
second C−H activation and C−N coupling of 3f, especially in
tert-butyl alcohol.
1H NMR Titration Experiments of 1f and 3f and
Controlled Experiments for the Transformation of 3f to
3″f. In our previous work,3b N-(pyridin-2-yl)-9H-carbazole
(3″a) was easily generated as a major product by the reaction of
1a with 2a, where AgOAc and 1,4-dioxane were used as the
oxidant and solvent, respectively. However, some carbazole 3″a
(14% yield) was detected when the solvent (1,4-dioxane) was
changed to tert-butyl alcohol, whereas monophenylated product
3a (85% yield) remained as the predominant product. Similar
results were also observed in the reaction of 1f with 2a,
especially in the use of Cu(OAc)2 and tert-butyl alcohol, which
gave the single product 3f in 87% yield. Therefore, we are
interested in finding out why the reagent system of AgOAc and
1,4-dioxane favors production of a carbazole via a tandem C−H
activation process, while Cu(OAc)2 with tert-butyl alcohol
preferentially leads to monoarylated products in this study. We
1
first carried out these studies of solvent effects by H NMR
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Preparation of 4-Methyl-N-phenylpyridin-2-amine
Palladacycle. In order to isolate the key intermediate for
the catalytic reaction,17 we independently synthesized pallada-
cycle I by the reaction of 1f with a stoichiometric amount of
Pd(OAc)2 (the synthetic procedure is referenced from ref 3b)
and the solid-state structure of I was secured by X-ray
crystallography, which showed a head-to-tail U-shaped overall
structure (Figure 2).18 The coordinated orientation of I is
found to be opposite to that of the N-phenylpyridin-2-amine
palladacycle (a head-to-head U-shaped structure).3b
imidazo-[1,2-a]pyridine (8)19c in 70−99% yields, respectively
(Scheme 1). Interestingly, the acetoxylated product 9 was
isolated and the product ratio of 8 and 9 was determined to be
77:23 by GC-MS using PhI(OAc)2 as the reaction reagent at
ambient temperature.
In contrast with the case of PhI(OAc)2, only compound 8
was isolated in 75% yield by the use of PhI(OTFA)2 (even
when the reaction temperature was raised to 60 °C).
CONCLUSION
■
We have successfully developed a simple, practical, and efficient
protocol for the synthesis of ortho-monoarylated 4-methyl-N-
phenylpyridin-2-amines catalyzed by palladium(II) acetate via
C−H activation. The substituent electronic effect on the
directing group has been systematically investigated, and we
found that the high reactivity is correlated to the electron-
donating effect. The palladium(II)-catalyzed intramolecular C−
N cyclization of ortho-monophenylated 4-methyl-N-phenyl-
pyridin-2-amine via C−H activation to construct the carbazole
skeleton has been investigated, and a possible explanation is
presented. The key intermediate palladacycle has been isolated
and characterized by X-ray crystallography. The synthetic
application to approach the N-(4-methylpyridin-2-yl)-9H-
carbazole, biphenyl-2-amine, and 3-methyl-6-phenylpyrido-
[1,2-a]benzimidazole from ortho-monoarylated 4-methyl-N-
phenylpyridin-2-amine is demonstrated. Finally, we believe that
the developed methodology can be provided as a useful
synthetic tool in the fields of pharmaceuticals and optoelec-
tronic materials.
Figure 2. ORTEP drawing of 4-methyl-N-phenylpyridin-2-amine
palladacycle (I).18 Ellipsoids are shown at the 40% probability level.
Selected bond lengths (Å): Pd1−Pd2 = 2.905(1); Pd1−N1 =
1.998(7); Pd1−C16 = 1.962(9); Pd1−O1 = 2.059(6); Pd1−O4 =
2.156(6); Pd2−N3 = 2.006(7); Pd2−C28 = 1.967(9); Pd2−O2 =
2.176(6); Pd2−O3 = 2.082(6). All hydrogen atoms are omitted for
clarity.
EXPERIMENTAL SECTION
■
General. Solvents and reagents were purchased from commercial
suppliers and used without purification. 1H NMR spectra were
measured on 300 and 500 MHz NMR spectrometers. Natural-
abundance 13C NMR spectra were measured by using 300 and 500
MHz NMR spectrometers operating at 75 and 125 MHz, respectively.
Chemical shifts are given in parts per million (ppm) and coupling
constants J in hertz (Hz) for both nuclei, with the solvent (usually
Synthetic Applications. To demonstrate the potential of
ortho-arylated 4-methyl-N-phenylpyridin-2-amines in synthetic
applications, compound 3f was selected as an example. The
treatment of 3f with a series of reaction conditions can easily
give N-(4-methylmethylpyridin-2-yl)-9H-carbazole (3″f),19a
biphenyl-2-amine (7),19b and 3-methyl-6-phenylbenzo[4,5]-
1
CDCl3) peak as an internal standard. The reference peak for H is δ
7.26 of chloroform, and for 13C it is the central peak at δ 77.0. Low-
and high-resolution mass spectrometry was obtained by the following
Scheme 1. Synthetic Applications of 3f
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ionization method and mass analyzer type: EI-magnetic sector.
Melting points were measured by using open capillary tubes and
uncorrected.
(60/1 to 10/1) as the eluent to give a series of compounds 3. All
product yields were determined by GC-MS using n-octadecane as the
internal standard and shown as follows: 3a, 61% (62 mg, 0.25 mmol);
3″a, 8% (9.7 mg, 0.030 mmol); 3b, 30% (33 mg, 0.12 mmol), 3′b, 55%
(78 mg, 0.22 mmol); 3c, 32% (34 mg, 0.13 mmol), 3′c, 48% (64 mg,
0.19 mmol); 3d, 41% (48 mg, 0.17 mmol); 3″d, 14% (17 mg, 0.060
mmol); 3e, 90% (99.5 mg, 0.360 mmol), 3f, 87% (91 mg, 0.35 mmol);
3g, 45% (52 mg, 0.18 mmol); 3″g, 2% (2.6 mg, 0.010 mmol); 3h, 85%
(94 mg, 0.34 mmol), 3i, 75% (78 mg, 0.30 mmol), 3j, 0% (0 mg, 0
mmol); 3k, 20% (22 mg, 0.080 mmol), 3l, 5% (5.2 mg, 0.020 mmol);
3‴l, 20% (21 mg, 0.080 mmol); 3m, 0% (0 mg, 0 mmol).
General Procedure for the Synthesis of Starting Substrates
1 and 5.20
General Procedure for the Synthesis of Compounds 4 and 6
by Direct Ortho Arylation of 1f and 5 with 2. The synthetic
procedure for 4 and 6 is the same as that for 3. (a) Reaction conditions
for the synthesis of 4 are shown as follows: 4-methyl-N-phenylpyridin-
2-amines 1f (74 mg, 0.40 mmol), potassium aryltrifluoroborates 2 (2b,
24 mg, 0.12 mmol; 2c, 26 mg, 0.12 mmol; 2d, 32 mg, 0.12 mmol; 2e,
37 mg, 0.12 mmol; 2f, 28 mg, 0.12 mmol; 2g, 25 mg, 0.12 mmol; 2h,
26 mg, 0.12 mmol; 2i, 26 mg, 0.12 mmol; 2j, 29 mg, 0.12 mmol; 2k,
24 mg, 0.12 mmol), 10 mol % Pd(OAc)2 (9 mg, 0.04 mmol),
Cu(OAc)2 (145 mg, 0.800 mmol), BQ (43 mg, 0.40 mmol). All
product yields were determined by GC-MS using n-octadecane as the
internal standard and are shown as follows: 4b, 83% (92 mg, 0.33
mmol); 4c, 85% (100 mg, 0.34 mmol); 4d, 81% (110 mg, 0.32 mmol);
4e, 37% (58 mg, 0.15 mmol); 4‴e, 9% (15 mg, 0.040 mmol); 4f, 56%
(67 mg, 0.22 mmol); 4‴f, 19% (24 mg, 0.080 mmol); 4g, 59% (69 mg,
0.24 mmol); 4h, 43% (49 mg, 0.17 mmol); 4i, 85% (20.0 mg, 0.069
mmol); 4j, 76% (95 mg, 0.30 mmol), 4k, 79% (88 mg, 0.32 mmol).
(b) Reaction conditions for the synthesis of 6 are shown as follows: 5a,
81 mg, 0.40 mmol; 5b, 88 mg, 0.40 mmol; 5c, 105 mg, 0.40 mmol; 5d,
92 mg, 0.40 mmol; 5e, 86 mg, 0.40 mmol; 5f, 86 mg, 0.40 mmol; 5g,
86 mg, 0.40 mmol; 5h, 79 mg, 0.40 mmol; 5i, 94 mg, 0.40 mmol;
potassium phenyltrifluoroborate (2a), 110 mg, 0.60 mmol. All product
yields were determined by GC-MS using n-octadecane as the internal
standard and shown as follows: 6a, 73% (81 mg, 0.29 mmol); 6b, 88%
(103 mg, 0.35 mmol); 6c, 77% (105 mg, 0.310 mmol); 6d: ,47% (58
mg, 0.19 mmol); 6″d, 18% (21 mg, 0.070 mmol); 6e, 61% (70 mg,
0.24 mmol); 6f, 65% (76 mg, 0.26 mmol); 6g, 97% (113 mg, 0.39
mmol); 6h, 72% (80 mg, 0.29 mmol); 6′h, 18% (25 mg, 0.070 mmol);
6i, 0% (0 mg, 0 mmol).
Synthesis of Palladacycle I. To a well-stirred solution of 1f (100
mg, 0.54 mmol) was added a stoichiometric amount of palladium(II)
acetate (120 mg, 0.54 mmol) in dichloromethane (20 mL), and the
mixture was then heated to 60−70 °C for 2 h. After the mixture was
cooled to room temperature, the precipitate was collected and the
filtrate was treated with a pad of Celite. The precipitate was dissolved
in dichloromethane again and combined with the previous filtrate. The
organic layer was dried over MgSO4, filtered, and evaporated under
vacuum. The residue was purified by silica gel chromatography using
n-hexane/ethyl acetate (5/1 to 100% ethyl acetate) as the eluent to
give palladacycle I (169 mg, 0.240 mmol) in 90% isolated yield.
Synthesis of Compound 3″f. The synthetic procedure of 3″f
followed the literature report,3b and 99% yield (20 mg, 0.076 mmol)
was obtained. Reagent conditions are as follows: 3f (20 mg, 0.08
mmol), Pd(OAc)2 (2 mg, 0.008 mmol), AgOAc (39 mg, 0.23 mmol),
1,4-dioxane (4 mL), water (5 mL), ethyl acetate (5 mL × 2), eluent
(n-hexane/ethyl acetate 40/1).
A well-stirred solution of 2-bromopyridines 10 (1 equiv) and anilines
11 (1.2 equiv) in toluene (10 mL) was followed by the addition of
potassium tert-butoxide (1.4 equiv). Subsequently, to the solution were
added tris(dibenzylideneacetone)dipalladium(0) (Pd2(dba)3) (0.02
equiv) and bis(2-diphenylphosphinophenyl)ether (DPEphos) (0.04
equiv) under nitrogen gas, and the mixture was heated to 100 °C for
10−12 h. After it was cooled to room temperature, the solution was
washed with water (20 mL) and extracted with ethyl acetate (15 mL ×
3). The organic layers were combined, dried over MgSO4, filtered, and
evaporated under vacuum. The residue was purified by silica gel
chromatography using n-hexane/ethyl acetate (40/1 to 20/1) as the
eluent to give a series of compounds 1 and 5. The amounts used of 10
and 11 are shown as follows. (a) For 10: 10a (R1 = H), 474 mg, 3.00
mmol for 1a; 10b (R1 = 3-OMe), 564 mg, 3.00 mmol for 1b; 10c (R1
= 3-Me), 516 mg, 3.00 mmol for 1c; 10d (R1 = 3-NO2), 609 mg, 3.00
mmol for 1d; 10e (R1 = 4-OMe), 564 mg, 3.00 mmol for 1e; 10f (R1 =
4-Me), 516 mg, 3.00 mmol for 1f; 10g (R1 = 4-NO2), 609 mg, 3.00
mmol for 1g; 10h (R1 = 5-OMe), 564 mg, 3.00 mmol for 1h; 10i (R1
= 5-Me), 516 mg, 3.00 mmol for 1i; 10j (R1 = 5-NO2), 609 mg, 3.00
mmol for 1j; 10k (R1 = 6-OMe), 564 mg, 3.00 mmol for 1k; 10l (R1 =
6-Me), 516 mg, 3.00 mmol for 1l; 10m (R1 = 6-NO2), 609 mg, 3.00
mmol for 1m. (b) For 11: 11a (R2 = H), 335 mg, 3.60 mmol for 1a−
m; 11b (R2 = p-F), 400 mg, 3.6 mmol for 5a; 11c (R2 = p-Cl), 459 mg,
3.60 mmol for 5b; 11d (R2 = p-Br), 619 mg, 3.60 mmol for 5c; 11e
(R2 = p-NO2), 497 mg, 3.60 mmol for 5d; 11f (R2 = o-OMe), 443 mg,
3.60 mmol for 5e; 11g (R2 = m-OMe), 443 mg, 3.60 mmol for 5f; 11h
(R2 = p-OMe), 443 mg, 3.60 mmol for 5g; 11i (R2 = p-Me), 385 mg,
3.60 mmol for 5h; 11j (−C6H4-R2 = 1-naphthyl), 515 mg, 3.60 mmol
for 5i.
All isolated product yields are shown as follows: 1a, 75% (383 mg,
2.25 mmol); 1b, 89% (534 mg, 2.67 mmol); 1c, 80% (442 mg, 2.40
mmol); 1d, 55% (355 mg, 1.65 mmol); 1e, 84% (504 mg, 2.52 mmol);
1f, 90% (497 mg, 2.70 mmol); 1g, 49% (316 mg, 1.47 mmol); 1h, 84%
(504 mg, 2.52 mmol), 1i, 91% (503 mg, 2.73 mmol); 1j, 51% (329 mg,
1.53 mmol); 1k, 89% (534 mg, 2.67 mmol); 1l, 79% (437 mg, 2.37
mmol); 1m, 52% (335 mg, 1.56 mmol); 5a, 81% (491 mg, 2.43
mmol), 5b, 77% (505 mg, 2.31 mmol); 5c, 78% (615 mg, 2.34 mmol);
5d, 42% (288 mg, 1.26 mmol); 5e, 83% (533 mg, 2.49 mmol), 5f, 80%
(514 mg, 2.40 mmol); 5g, 88% (565 mg, 2.64 mmol); 5h, 92% (547
mg, 2.76 mmol); 5i, 68% (478 mg, 2.04 mmol).
General Procedure for the Synthesis of Compound 3
(Reactivity Investigation on the Directing Group). A well-stirred
solution of N-phenylpyridin-2-amines 1 (1a, 68 mg, 0.40 mmol; 1b, 80
mg, 0.4 mmol; 1c, 74 mg, 0.40 mmol; 1d, 86 mg, 0.40 mmol; 1e, 80
mg, 0.40 mmol; 1f, 74 mg, 0.40 mmol; 1g, 86 mg, 0.40 mmol; 1h, 80
mg, 0.40 mmol; 1i, 74 mg, 0.40 mmol; 1j, 86 mg, 0.40 mmol; 1k, 80
mg, 0.40 mmol; 1l, 74 mg, 0.40 mmol; 1m, 86 mg, 0.40 mmol) with
potassium phenyltrifluoroborate (2a; 10 mg, 0.60 mmol), 10 mol %
Pd(OAc)2 (9 mg, 0.04 mmol), Cu(OAc)2 (145 mg, 0.800 mmol), and
BQ (43 mg, 0.40 mmol) in tert-butyl alcohol (7 mL) was heated to
80−90 °C and stirred at this temperature for 4 h. After it was cooled to
room temperature, the solution was filtered through a pad of Celite
and washed with water (15 mL). The solution was then extracted with
ethyl acetate (10 mL × 2). Finally, the organic layers were combined,
dried over MgSO4, filtered, and evaporated under vacuum. The residue
was purified by silica gel chromatography using n-hexane/ethyl acetate
Synthesis of Compound 7. A well-stirred solution of 3f (30 mg,
0.1 mmol) and methyl trifluoromethanesulfonate (MeOTf) (28 mg,
0.17 mmol) in dichloromethane (4 mL) was heated to 80 °C for 6 h.
After it was cooled to room temperature, the solution was evaporated
under vacuum. The residue was then dissolved in a small amount of
methanol (1 mL), followed by the addition of the mixed solution
hydrazine/acetic acid (2.5 mL/0.7 mL). The solution was heated to
130 °C and stirred for 24 h. After it was cooled to room temperature,
the solution was added to water (10 mL) and extracted with
dichloromethane (5 mL × 2). The organic layers were combined,
dried over MgSO4, filtered, and evaporated under vacuum. The residue
was purified by silica gel chromatography using n-hexane/ethyl acetate
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(40/1) as the eluent to give 7 (14 mg, 0.081 mmol) in 70% isolated
yield.
CDCl3) δ 7.02 (bs, 1 H), 7.19 (dd, J = 7.5, 7.5 Hz, 1 H), 7.35−7.43
(m, 5 H), 7.49 (d, J = 1.0 Hz, 1 H), 8.41 (d, J = 5.5 Hz, 1 H); 13C
NMR (125 MHz, CDCl3) δ 100.6 (CH), 107.0 (CH), 121.6 (CH ×
2), 124.7 (CH), 129.7 (CH × 2), 138.7 (Cq), 150.8 (CH), 155.6
(Cq), 158.0 (Cq); MS (EI, m/z) 215 (M+, 87), 214 (M+ − 1, 100),
168 (51); HRMS (EI-magnetic sector) calcd for C11H9N3O2 215.0695,
found 215.0692.
Synthesis of Compounds 8 and 9. A well-stirred solution of 3f
(20 mg, 0.08 mmol) and PhI(OAc)2 (38 mg, 0.12 mmol) or
PhI(OTFA)2 (50 mg, 0.1 mmol) in dichloromethane (4 mL) was kept
at room temperature or 60 °C for 2 h. After that, the solution was
washed with water (10 mL) and the organic layer was dried over
MgSO4, filtered, and evaporated under vacuum. The residue was
purified by silica gel chromatography using n-hexane/ethyl acetate (5/
1 to 1/2) as the eluent to give 8 (15 mg, 0.056 mmol) and 9 (5.3 mg,
0.017 mmol) in 95% total yield for the case of PhI(OAc)2, whereas 8
(15 mg, 0.058 mmol) was obtained in 75% yield for the case of
PhI(OTFA)2.
5-Methoxy-N-phenylpyridin-2-amine (1h): pale yellow viscous
1
liquid; Rf = 0.50 (n-hexane/ethyl acetate 3/1); H NMR (500 MHz,
CDCl3) δ 3.82 (s, 3 H), 6.47 (bs, 1 H), 6.89 (d, J = 9.0 Hz, 1 H), 6.99
(d, J = 7.5, 7.5 Hz, 1 H), 7.16 (dd, J = 9.0, 2.5 Hz, 1 H), 7.25−7.32 (m,
4 H), 7.92 (d, J = 3.0 Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ 56.2
(CH3), 109.7 (CH), 118.9 (CH × 2), 121.9 (CH), 125.1 (CH), 129.3
(CH × 2), 133.6 (CH), 141.4 (Cq), 150.1 (Cq × 2); MS (EI, m/z)
200 (M+, 97), 199 (M+ − 1, 100), 88 (27), 70 (42), 61 (71); HRMS
(EI-magnetic sector) calcd for C12H12N2O 200.0950, found 200.0949.
5-Methyl-N-phenylpyridin-2-amine (1i): colorless solid; mp 101−
102 °C; Rf = 0.60 (n-hexane/ethyl acetate 3/1); 1H NMR (500 MHz,
CDCl3) δ 2.23 (s, 3 H), 6.48 (bs, 1 H), 6.84 (d, J = 9.0 Hz, 1 H), 7.01
(dddd, J = 8.5, 8.5, 1.5, 1.5 Hz, 1 H), 7.27−7.34 (m, 5 H), 8.04 (bs, 1
H); 13C NMR (125 MHz, CDCl3) δ 17.5 (CH3), 108.2 (CH), 119.6
(CH × 2), 122.3 (CH), 124.2 (Cq), 129.3 (CH × 2), 138.6 (CH),
140.9 (Cq), 148.0 (CH), 153.8 (Cq); MS (EI, m/z) 184 (M+, 45), 183
(M+ − 1, 100); HRMS (EI-magnetic sector) calcd for C12H12N2
184.1000, found 184.1001.
Characterization Data of Compounds 1 and 3−9. N-
Phenylpyridin-2-amine (1a): white solid; mp 105−106 °C; Rf =
1
0.45 (n-hexane/ethyl acetate 5/1); H NMR (500 MHz, CDCl3) δ
6.71 (bs, 1 H), 6.74 (dd, J = 7.0, 5.0 Hz, 1 H), 6.88 (d, J = 8.5 Hz, 1
H), 7.05−7.08 (m, 1 H), 7.32−7.36 (m, 4 H), 7.51 (ddd, J = 7.5, 7.5,
2.0 Hz, 1 H), 8.19 (d, J = 5.0 Hz, 1 H); 13C NMR (125 MHz, CDCl3)
δ 108.4 (CH), 115.0 (CH), 120.5 (CH × 2), 123.0 (CH), 129.3 (CH
× 2), 138.0 (CH), 140.2 (Cq), 147.8 (CH), 155.8 (Cq); MS (EI, m/
z) 170 (M+, 26), 169 (M+ − 1, 100).
3-Methoxy-N-phenylpyridin-2-amine (1b): pale yellow viscous
1
liquid; Rf = 0.50 (n-hexane/ethyl acetate 5/1); H NMR (500 MHz,
CDCl3) δ 3.90 (s, 3 H), 6.69 (dd, J = 8.0, 5.0 Hz, 1 H), 6.95−6.99 (m,
2 H), 7.04 (bs,1 H), 7.32 (dd, J = 7.0, 7.0 Hz, 2 H), 7.70 (d, J = 8.5 Hz,
2 H), 7.83 (dd, J = 5.0, 1.5 Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ
55.4 (CH3), 113.9 (CH), 114.6 (CH), 118.8 (CH × 2), 121.5 (CH),
128.9 (CH × 2), 138.2 (CH), 140.5 (Cq), 142.3 (Cq), 146.5 (Cq);
MS (EI, m/z) 200 (M+, 100), 199 (M+ − 1, 100); HRMS (EI-
magnetic sector) calcd for C12H12N2O 200.0950, found 200.0953.
3-Methyl-N-phenylpyridin-2-amine (1c): colorless solid; mp 115−
116 °C; Rf = 0.50 (n-hexane/ethyl acetate 5/1); 1H NMR (500 MHz,
CDCl3) δ 2.24 (s, 3 H), 6.13 (bs, 1 H), 6.71 (dd, J = 7.5, 5.0 Hz, 1 H),
7.00 (dd, J = 7.5, 7.5 Hz, 1 H), 7.32 (dd, J = 8.5, 8.5 Hz, 2 H), 7.36
(dd, J = 7.5, 1.0 Hz, 1 H), 7.55 (d, J = 8.5 Hz, 2 H), 8.11 (d, J = 4.5
Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ 17.4 (CH3), 115.3 (CH),
118.0 (Cq), 119.5 (CH × 2), 121.9 (CH), 128.9 (CH × 2), 137.9
(CH), 140.8 (Cq), 145.4 (CH), 153.9 (Cq); MS (EI, m/z) 184 (M+,
54), 183 (M+ − 1, 100); HRMS (EI-magnetic sector) calcd for
C12H12N2 184.1000, found 184.0997.
5-Nitro-N-phenylpyridin-2-amine (1j): yellow solid; mp 120−121
1
°C; Rf = 0.50 (n-hexane/ethyl acetate 3/1); H NMR (500 MHz,
CDCl3) δ 6.79 (d, J = 9.0 Hz, 1 H), 7.24 (dd, J = 7.5, 7.5 Hz, 1 H),
7.37−7.45 (m, 5 H), 8.25 (dd, J = 9.5, 3.0 Hz, 1 H), 9.09 (d, J = 3.0
Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ 106.3 (CH), 122.6 (CH ×
2), 125.7 (CH), 129.7 (CH × 2), 133.4 (CH), 137.1 (Cq), 137.9
(Cq), 146.7 (CH), 159.6 (Cq); MS (EI, m/z) 215 (M+, 85), 214 (M+
− 1, 100), 168 (44); HRMS (EI-magnetic sector) calcd for
C11H9N3O2 215.0695, found 215.0696.
6-Methoxy-N-phenylpyridin-2-amine (1k): pale yellow viscous
1
liquid; Rf = 0.60 (n-hexane/ethyl acetate 5/1); H NMR (500 MHz,
CDCl3) δ 3.91 (s, 3 H), 6.20 (d, J = 8.0 Hz, 1 H), 6.38 (bs, 1 H), 6.39
(d, J = 8.0 Hz, 1 H), 7.02 (dd, J = 7.5 Hz, 1 H), 7.30−7.33 (m, 2 H),
7.36−7.42 (m, 3 H); 13C NMR (125 MHz, CDCl3) δ 53.4 (CH3),
99.7 (CH), 100.1 (CH), 119.8 (CH × 2), 122.3 (CH), 129.1 (CH ×
2), 140.1 (CH), 140.6 (Cq), 154.3 (Cq), 163.6 (Cq); MS (EI, m/z)
200 (M+, 100), 199 (M+ − 1, 100), 184 (34); HRMS (EI-magnetic
sector) calcd for C12H12N2O 200.0950, found 200.0949.
3-Nitro-N-phenylpyridin-2-amine (1d): orange-red solid; mp 60−
1
61 °C; Rf = 0.60 (n-hexane/ethyl acetate 5/1); H NMR (500 MHz,
CDCl3) δ 6.83 (dd, J = 8.0, 4.5 Hz, 1 H), 7.19 (dd, J = 7.5, 7.5 Hz, 1
H), 7.40 (dd, J = 8.0, 8.0 Hz, 2 H), 7.65 (d, J = 8.0 Hz, 2 H), 8.49 (dd,
J = 4.5, 1.5 Hz, 1 H), 8.53 (dd, J = 8.0, 1.5 Hz, 1 H); 13C NMR (125
MHz, CDCl3) δ 113.9 (CH), 122.6 (CH × 2), 124.9 (CH), 129.0
(CH × 2), 135.5 (CH), 137.8 (Cq), 150.3 (Cq), 155.3 (Cq); MS (EI,
m/z) 215 (M+, 91), 214 (M+ − 1, 100), 168 (86); HRMS (EI-
magnetic sector) calcd for C11H9N3O2 215.0695, found 215.0695.
4-Methoxy-N-phenylpyridin-2-amine (1e): colorless solid; mp 83−
6-Methyl-N-phenylpyridin-2-amine (1l): pale yellow viscous liquid;
Rf = 0.53 (n-hexane/ethyl acetate 5/1); 1H NMR (500 MHz, CDCl3)
δ 2.45 (s, 3 H), 6.61 (d, J = 7.5 Hz, 1 H), 6.65 (bs, 1 H), 6.73 (d, J =
8.0 Hz, 1 H), 7.04 (dddd, J = 7.5, 7.5, 1.5, 1.5 Hz, 1 H), 7.28−7.34 (m,
4 H), 7.40 (dd, J = 8.0, 8.0 Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ
24.1 (CH3), 104.8 (CH), 114.4 (CH), 120.3 (CH × 2), 122.8 (CH),
129.3 (CH × 2), 138.2 (CH), 140.5 (Cq), 155.3 (Cq), 157.1 (Cq);
MS (EI, m/z) 184 (M+, 100), 183 (M+ − 1, 100); HRMS (EI-
magnetic sector) calcd for C12H12N2 184.1000, found 184.1002
6-Nitro-N-phenylpyridin-2-amine (1m): orange solid; mp 83−84
1
84 °C; Rf = 0.49 (n-hexane/ethyl acetate 5/1); H NMR (500 MHz,
CDCl3) δ 3.79 (s, 3 H), 6.35 (dd, J = 6.0, 2.0 Hz, 1 H), 6.39 (d, J = 2.0
Hz, 1 H), 6.62 (bs, 1 H), 7.06 (dd, J = 7.5, 7.5 Hz, 1 H), 7.29−7.35
(m, 4 H), 8.03 (d, J = 6.0 Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ
55.0 (CH3), 92.4 (CH), 103.0 (CH), 120.7 (CH × 2), 123.0 (CH),
129.3 (CH × 2), 140.4 (Cq), 149.5 (CH), 157.7 (Cq), 167.3 (Cq);
MS (EI, m/z) 200 (M+, 58), 199 (M+ − 1, 100); HRMS (EI-magnetic
sector) calcd for C12H12N2O 200.0950, found 200.0953.
4-Methyl-N-phenylpyridin-2-amine (1f): colorless solid; mp 113−
114 °C; Rf = 0.55 (n-hexane/ethyl acetate 3/1); 1H NMR (500 MHz,
CDCl3) δ 2.26 (s, 3 H), 6.58 (d, J = 5.0 Hz, 1 H), 6.61 (bs, 1 H), 6.70
(s, 1 H), 7.04−7.07 (m, 1 H), 7.30−7.35 (m, 4 H), 8.05 (d, J = 5.0 Hz,
1 H); 13C NMR (125 MHz, CDCl3) δ 21.3 (CH3), 108.5 (CH), 116.6
(CH), 120.5 (CH × 2), 122.8 (CH), 129.3 (CH × 2), 140.4 (Cq),
147.7 (CH), 149.1 (Cq), 156.0 (Cq); MS (EI, m/z) 184 (M+, 34), 183
(M+ − 1, 100), 88 (27), 70 (40), 61 (64); HRMS (EI-magnetic
sector) calcd for C12H12N2 184.1000, found 184.1002.
1
°C; Rf = 0.45 (n-hexane/ethyl acetate 2/1); H NMR (500 MHz,
CDCl3) δ 6.93 (bs, 1 H), 7.13 (d, J = 8.0 Hz, 1 H), 7.15−7.19 (m, 1
H), 7.38−7.42 (m, 4 H), 7.62 (d, J = 8.0 Hz, 1 H), 7.36 (d, J = 8.0, 8.0
Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ 107.9 (CH), 113.3 (CH),
121.4 (CH × 2), 124.6 (CH), 129.6 (CH × 2), 138.7 (Cq), 140.5
(CH), 155.5 (Cq), 155.9 (Cq); MS (ESI+, m/z) 215 (M+, 100), 169
(92), 77 (32); HRMS (EI-magnetic sector) calcd for C11H9N3O2
215.0695, found 215.0696.
N-([1,1′-Biphenyl]-2-yl)pyridin-2-amine (3a): See ref 3b.
9-(Pyridin-2-yl)-9H-carbazole (3″a): See ref 3b.
N,N-Diphenylpyridin-2-amine (3‴a): white solid; mp 89−90 °C; Rf
1
= 0.54 (n-hexane/ethyl acetate 5/1); H NMR (300 MHz, CDCl3) δ
6.73−6.79 (m, 2 H), 7.10−7.19 (m, 6 H), 7.29−7.34 (m, 4 H), 7.44
(dd, J = 7.7, 7.7 Hz, 1 H), 8.23 (d, J = 7.2 Hz, 1 H); 13C NMR (125
MHz, CDCl3) δ 113.8 (CH), 116.1 (CH), 124.5 (CH × 2), 126.3
(CH × 4), 129.3 (CH × 4), 137.3 (CH), 146.1 (Cq), 148.3 (CH),
4-Nitro-N-phenylpyridin-2-amine (1g): orange solid; mp 105−106
1
°C; Rf = 0.43 (n-hexane/ethyl acetate 5/1); H NMR (500 MHz,
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159.0 (Cq); MS (EI, m/z) 246 (M+, 16), 245 (M+ − 1, 100); HRMS
(EI-magnetic sector) calcd for C17H14N2 246.1157, found 246.1158.
N-([1,1′-Biphenyl]-2-yl)-3-methoxypyridin-2-amine (3b): colorless
solid; mp 59−60 °C; Rf = 0.60 (n-hexane/ethyl acetate 4/1); 1H NMR
(500 MHz, CDCl3) δ 3.68 (s, 3 H), 6.67 (dd, J = 7.5, 5.0 Hz, 1 H),
6.88 (dd, J = 8.0, 0.8 Hz, 1 H), 7.04 (ddd, J = 7.5, 7.5, 0.5 Hz, 1 H),
7.24 (dd, J = 8.3, 1.5 Hz, 1 H), 7.36−7.40 (m, 2 H), 7.45−7.46 (m, 4
H), 7.83 (dd, J = 5.0, 1.0 Hz, 1 H), 8.64 (d, J = 8.5 Hz, 1 H); 13C
NMR (125 MHz, CDCl3) δ 55.4 (CH3), 113.9 (CH), 114.7 (CH),
119.2 (CH), 121.4 (CH), 127.4 (CH), 128.3 (CH), 128.7 (CH × 2),
129.5 (CH × 2), 130.0 (CH), 131.3 (Cq), 137.6 (Cq), 138.3 (CH),
139.1 (Cq), 142.7 (Cq), 146.7 (Cq); MS (EI, m/z) 276 (M+, 100),
275 (M+ − 1, 57), 199 (30); HRMS (EI-magnetic sector) calcd for
C18H16N2O 276.1263, found 276.1260.
N-([1,1′:3′,1″-Terphenyl]-2′-yl)-3-methoxypyridin-2-amine (3′b):
colorless solid; mp 87−88 °C; Rf = 0.53 (n-hexane/ethyl acetate 4/
1); 1H NMR (500 MHz, CDCl3) δ 3.62 (s, 3 H), 6.21 (bs, 1 H), 6.35
(dd, J = 7.8, 5.5 Hz, 1 H), 6.64 (dd, J = 7.5, 1.0 Hz, 1 H), 7.16−7.25
(m, 6 H), 7.33−7.43 (m, 8 H); 13C NMR (125 MHz, CDCl3) δ 55.2
(CH3), 113.0 (CH), 114.4 (CH), 125.9 (CH), 126.6 (CH × 2), 127.7
(CH × 4), 128.8 (CH × 4), 130.1 (CH × 2), 134.4 (Cq), 138.6 (CH),
139.6 (Cq × 2), 140.5 (Cq × 2), 142.4 (Cq), 148.0 (Cq); MS (EI, m/
z) 352 (M+, 49), 275 (100); HRMS (EI-magnetic sector) calcd for
C24H20N2O 352.1576, found 352.1573.
N-([1,1′-Biphenyl]-2-yl)-3-methylpyridin-2-amine (3c): pale yellow
viscous liquid; Rf = 0.60 (n-hexane/ethyl acetate 12/1); 1H NMR (500
MHz, CDCl3) δ 1.85 (s, 3 H), 6.31 (bs, 1 H), 6.67 (dd, J = 7.0, 5.0 Hz,
1 H), 7.05 (dd, J = 7.5, 7.5 Hz, 1 H), 7.24−7.27 (m, 2 H), 7.36−7.40
(m, 2 H), 7.44−7.48 (m, 4 H), 8.11 (d, J = 5.0 Hz, 1 H), 8.42 (d, J =
8.5 Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ 16.9 (CH3), 115.1
(CH), 118.4 (Cq), 119.6 (CH), 121.6 (CH), 127.6 (CH), 128.3
(CH), 128.9 (CH × 2), 129.4 (CH × 2), 129.9 (CH), 131.5 (Cq),
137.6 (CH), 137.9 (Cq), 139.0 (Cq), 145.3 (CH), 153.9 (Cq); MS
(EI, m/z) 260 (M+, 31), 259 (M+ − 1, 47), 85 (90), 71 (100), 57 (95);
HRMS (EI-magnetic sector) calcd for C18H16N2 260.1313, found
260.1312.
N-([1,1′-Biphenyl]-2-yl)-3-methylpyridin-2-amine (3′c): white
solid; mp 71−72 °C; Rf = 0.55 (n-hexane/ethyl acetate 5/1); 1H
NMR (500 MHz, CDCl3) δ 1.82 (s, 3 H), 5.52 (bs, 1 H), 6.39 (dd, J =
7.0, 5.0 Hz, 1 H), 7.02 (d, J = 7.0 Hz, 1 H), 7.17−7.26 (m, 6 H), 7.32−
7.41 (m, 7 H), 7.73 (d, J = 4.5 Hz, 1 H); 13C NMR (125 MHz,
CDCl3) δ 17.0 (CH3), 114.3 (CH), 117.8 (Cq), 125.5 (CH), 126.7
(CH × 2), 127.9 (CH × 4), 128.8 (CH × 4), 130.1 (CH × 2), 135.2
(Cq), 136.8 (CH), 138.5 (Cq × 2), 140.5 (Cq × 2), 145.4 (CH),
154.8 (Cq); MS (EI, m/z) 336 (M+, 17), 259 (100); HRMS (EI-
magnetic sector) calcd for C24H20N2 336.1626, found 336.1629.
N-([1,1′-Biphenyl]-2-yl)-3-nitropyridin-2-amine (3d): orange-red
solid; mp 61−62 °C; Rf = 0.58 (n-hexane/ethyl acetate 4/1); 1H
NMR (500 MHz, CDCl3) δ 6.77 (dd, J = 8.0, 4.5 Hz, 1 H), 7.26 (ddd,
J = 7.5, 7.5, 1.0 Hz, 1 H), 7.36−7.45 (m, 7 H), 8.16 (d, J = 8.0 Hz, 1
H), 8.42−8.44 (m, 2 H), 9.96 (bs, 1 H); 13C NMR (125 MHz,
CDCl3) δ 113.7 (CH), 123.8 (CH), 125.0 (CH), 127.9 (CH), 128.0
(CH), 128.8 (CH × 2), 129.1 (CH × 2), 130.5 (CH), 135.3 (Cq),
135.4 (CH), 135.5 (Cq), 138.5 (CH), 150.3 (Cq), 155.1 (CH); MS
(EI, m/z) 291 (M+, 100), 290 (M+ − 1, 56), 244 (44), 214 (38);
HRMS (EI-magnetic sector) calcd for C17H13N3O2 291.1008, found
291.1006.
7.36 (m, 3 H), 7.39−7.43 (m, 4 H), 7.71 (d, J = 8.0 Hz, 1 H), 7.97 (d,
J = 5.5 Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ 55.1 (CH3), 92.7
(CH), 103.1 (CH), 121.5 (CH), 123.4 (CH), 127.6 (CH), 128.3
(CH), 128.8 (CH × 2), 129.2 (CH × 2), 130.9 (CH), 133.9 (Cq),
137.3 (Cq), 138.8 (Cq), 149.1 (Cq), 157.7 (Cq), 167.3 (Cq); MS (EI,
m/z) 276 (M+, 92), 275 (M+ − 1, 100), 260 (25), 199 (50); HRMS
(EI-magnetic sector) calcd for C18H16N2O 276.1263, found 276.1261.
N-([1,1′-Biphenyl]-2-yl)-4-methylpyridin-2-amine (3f): pale yellow
viscous liquid; Rf = 0.44 (n-hexane/ethyl acetate 4/1); 1H NMR (300
MHz, CDCl3) δ 2.24 (s, 3 H), 6.34 (bs, 1 H), 6.56 (d, J = 5.1 Hz, 1
H), 6.32 (s, 1 H), 7.11 (ddd, J = 7.2, 7.2, 1.2 Hz, 1 H), 7.28−7.42 (m,
7 H), 7.80 (d, J = 8.4 Hz, 1 H), 8.03 (d, J = 5.1 Hz, 1 H); 13C NMR
(75 MHz, CDCl3) δ 21.2 (CH3), 109.0 (CH), 116.6 (CH), 120.8
(CH), 122.8 (CH), 127.5 (CH), 128.2 (CH), 128.8 (CH × 2), 129.3
(CH × 2), 130.8 (CH), 133.4 (Cq), 137.6 (Cq), 138.9 (Cq), 147.9
(CH), 148.8 (Cq), 156.1 (Cq); MS (EI, m/z) 260 (M+, 100), 259 (M+
− 1, 100), 244 (72), 183 (96); HRMS (EI-magnetic sector) calcd for
C18H16N2, 260.1313 found 260.1315.
9-(4-Methylpyridin-2-yl)-9H-carbazole (3″f): pale yellow viscous
1
liquid; Rf = 0.60 (n-hexane/ethyl acetate 7/1); H NMR (500 MHz,
CDCl3) δ 2.48 (s, 3 H), 7.13 (d, J = 5.0 Hz, 1 H), 7.31 (ddd, J = 7.5,
7.5, 1.0 Hz, 2 H), 7.42−7.45 (m, 3 H), 7.81 (d, J = 8.0 Hz, 2 H), 8.11
(d, J = 8.0 Hz, 2 H), 8.58 (d, J = 5.0 Hz, 1 H); 13C NMR (125 MHz,
CDCl3) δ 21.2 (CH3), 111.1 (CH × 2), 119.7 (CH), 120.2 (CH × 2),
120.7 (CH × 2), 122.5 (CH), 124.2 (Cq × 2), 126.1 (CH × 2), 139.6
(Cq × 2), 149.2 (CH), 150.0 (Cq), 151.8 (Cq); MS (EI, m/z) 258
(M+, 100), 257 (M+ − 1, 57); HRMS (EI-magnetic sector) calcd for
C18H14N2 258.1157, found 258.1154.
N-([1,1′-Biphenyl]-2-yl)-4-nitropyridin-2-amine (3g): orange solid;
mp 81−82 °C; Rf = 0.50 (n-hexane/ethyl acetate 4/1); 1H NMR (500
MHz, CDCl3) δ 6.78 (bs, 1 H), 7.26 (ddd, J = 7.5, 7.5, 1.0 Hz, 1 H),
7.33−7.44 (m, 9 H), 7.74 (d, J = 8.0 Hz, 1 H), 8.34 (d, J = 5.5 Hz, 1
H); 13C NMR (125 MHz, CDCl3) δ 100.8 (CH), 106.9 (CH), 122.3
(CH), 125.0 (CH), 127.8 (CH), 128.6 (CH), 128.9 (CH × 2), 129.1
(CH × 2), 131.1 (CH), 134.8 (Cq), 135.8 (Cq), 138.3 (Cq), 150.7
(CH), 155.4 (Cq), 157.9 (Cq); MS (EI, m/z) 291 (M+, 100), 290 (M+
− 1, 42), 244 (33); HRMS (EI-magnetic sector) calcd for C17H13N3O2
291.1008, found 291.1010.
9-(4-Nitropyridin-2-yl)-9H-carbazole (3″g): yellow solid; mp 175−
176 °C; Rf = 0.50 (n-hexane/ethyl acetate 6/1); 1H NMR (500 MHz,
CDCl3) δ 7.26 (dd, J = 7.5, 7.5 Hz, 2 H), 7.49 (ddd, J = 8.0, 8.0, 1.0
Hz, 2 H), 7.94−7.97 (m, 3 H), 8.13 (d, J = 8.0 Hz, 2 H), 8.42 (d, J =
1.5 Hz, 1 H), 8.98 (d, J = 5.5 Hz, 1 H); 13C NMR (125 MHz, CDCl3)
δ 110.9 (CH), 111.3 (CH × 2), 112.8 (CH), 120.4 (CH × 2), 122.2
(CH × 2), 125.0 (Cq × 2), 126.7 (CH × 2), 138.9 (Cq × 2), 151.6
(CH), 154.1 (Cq), 155.6 (Cq); MS (EI, m/z) 289 (M+, 29), 177
(100), 161 (69); HRMS (EI-magnetic sector) calcd for C17H11N3O2
289.0851, found 289.0852.
N-([1,1′-Biphenyl]-2-yl)-5-methoxypyridin-2-amine (3h): pale yel-
1
low viscous liquid; Rf = 0.43 (n-hexane/ethyl acetate 4/1); H NMR
(500 MHz, CDCl3) δ 3.80 (s, 3 H), 6.38 (bs, 1 H), 6.81 (d, J = 9.0 Hz,
1 H), 7.06 (ddd, J = 7.5, 7.5, 1.0 Hz, 1 H), 7.13 (dd, J = 9.0, 3.0 Hz, 1
H), 7.26−7.36 (m, 3 H), 7.40−7.44 (m, 4 H), 7.72 (d, J = 8.0 Hz, 1
H), 7.87 (d, J = 3.0 Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ 56.2
(CH3), 110.2 (CH), 119.1 (CH), 122.1 (CH), 125.3 (CH), 127.5
(CH), 128.2 (CH), 128.8 (CH × 2), 129.3 (CH × 2), 130.7 (CH),
132.4 (Cq), 133.2 (Cq), 138.3 (CH), 138.9 (Cq), 150.0 (Cq), 150.1
(Cq); MS (EI, m/z) 276 (M+, 100), 275 (M+ − 1, 59), 199 (30);
HRMS (EI-magnetic sector) calcd for C18H16N2O 276.1263, found
276.1265.
N-([1,1′-Biphenyl]-2-yl)-5-methylpyridin-2-amine (3i): pale yellow
viscous liquid; Rf = 0.53 (n-hexane/ethyl acetate 4/1); 1H NMR (500
MHz, CDCl3) δ 2.22 (s, 3 H), 6.31 (bs, 1 H), 6.78 (d, J = 8.0 Hz, 1H),
7.08 (dd, J = 7.5, 7.5 Hz, 1 H), 7.27−7.36 (m, 4 H), 7.39−7.43 (m, 4
H), 7.76 (d, J = 8.0 Hz, 1 H), 8.00 (s, 1 H); 13C NMR (125 MHz,
CDCl3) δ 17.5 (CH3), 108.5 (CH), 119.8 (CH), 122.4 (CH), 124.2
(Cq), 127.5 (CH), 128.2 (CH), 128.8 (CH × 2), 129.3 (CH × 2),
130.7 (CH), 132.8 (Cq), 137.9 (Cq), 138.5 (CH), 138.9 (Cq), 148.1
(CH), 153.8 (Cq); MS (EI, m/z) 260 (M+, 85), 259 (M+ − 1, 100),
9-(3-Nitropyridin-2-yl)-9H-carbazole (3″d): yellow solid; mp 95−
1
96 °C; Rf = 0.60 (n-hexane/ethyl acetate 3/1); H NMR (500 MHz,
CDCl3) δ 7.33−7.43 (m, 6 H), 7.58 (dd, J = 8.0, 4.5 Hz, 1 H), 8.11 (d,
J = 7.5 Hz, 2 H), 8.54 (dd, J = 8.0, 1.5 Hz, 1 H), 8.94 (dd, J = 4.5, 1.5
Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ 109.9 (CH × 2), 120.6
(CH × 2), 121.8 (CH × 2), 122.4 (CH), 124.8 (Cq × 2), 126.5 (CH
× 2), 135.1 (CH), 139.2 (Cq × 2), 144.2 (Cq), 153.2 (CH); MS (EI,
m/z) 289 (M+, 100), 258 (35), 242 (66); HRMS (EI-magnetic sector)
calcd for C17H11N3O2 289.0851, found 289.0851.
N-([1,1′-Biphenyl]-2-yl)-4-methoxypyridin-2-amine (3e): pale yel-
1
low viscous liquid; Rf = 0.53 (n-hexane/ethyl acetate 2/1); H NMR
(500 MHz, CDCl3) δ 3.77 (s, 3 H), 6.30 (s, 1 H), 6.32 (dd, J = 6.0, 2.0
Hz, 1 H), 6.55 (bs, 1 H), 7.14 (ddd, J = 8.0, 8.0, 1.0 Hz, 1 H), 7.31−
1199
dx.doi.org/10.1021/om401195w | Organometallics 2014, 33, 1190−1204

Organometallics
Article
244 (28), 183 (66); HRMS (EI-magnetic sector) calcd for C18H16N2
260.1313, found 260.1313.
N-(4′-Iodo-[1,1′-biphenyl]-2-yl)-4-methylpyridin-2-amine (4e):
pale yellow viscous liquid; Rf = 0.48 (n-hexane/ethyl acetate 4/1);
1H NMR (500 MHz, CDCl3) δ 2.24 (s, 3 H), 6.23 (bs, 1 H), 6.57 (d, J
= 5.0 Hz, 1 H), 6.61 (s, 1 H), 7.11−7.15 (m, 3 H), 7.25−7.27 (m, 1
H), 7.36 (ddd, J = 7.6, 7.6, 1.5 Hz, 1 H), 7.73−7.77 (m, 3 H), 8.03 (d,
J = 5.0 Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ 21.2 (CH3), 93.3
(Cq), 108.8 (CH), 116.8 (CH), 121.3 (CH), 123.2 (CH), 128.6
(CH), 130.5 (CH), 131.2 (CH × 2), 132.4 (Cq), 137.4 (Cq), 137.9
(CH × 2), 138.4 (Cq), 148.0 (CH), 148.9 (Cq), 155.9 (Cq); MS (EI,
m/z) 386 (M+, 88), 385 (M+ − 1, 74), 370 (29), 258 (33), 183 (100);
HRMS (EI-magnetic sector) calcd for C18H15IN2 386.0280, found
386.0277.
N-(4-Iodophenyl)-4-methyl-N-phenylpyridin-2-amine (4‴e): pale
yellow viscous liquid; Rf = 0.40 (n-hexane/ethyl acetate 6/1); 1H
NMR (500 MHz, CDCl3) δ 2.21 (s, 3 H), 6.58 (s, 1 H), 6.67 (d, J =
5.0 Hz, 1 H), 6.90 (d, J = 9.0 Hz, 2 H), 7.14−7.18 (m, 3 H), 7.32−
7.35 (m, 2 H), 7.58 (d, J = 9.0 Hz, 2 H), 8.11 (d, J = 5.0 Hz, 1 H); 13C
NMR (125 MHz, CDCl3) δ 21.1 (CH3), 87.6 (Cq), 114.8 (CH),
118.3 (CH), 125.0 (CH), 126.5 (CH × 2), 127.5 (CH × 2), 129.6
(CH × 2), 138.2 (CH × 2), 145.6 (Cq), 146.0 (Cq), 147.7 (CH),
149.0 (Cq), 158.6 (Cq); MS (EI, m/z) 386 (M+, 56), 385 (M+ −1,
100); HRMS (EI-magnetic sector) calcd for C18H15N2I 386.0280,
found 386.0277.
N-([1,1′-Biphenyl]-2-yl)-6-methoxypyridin-2-amine (3k): pale yel-
low viscous liquid; Rf = 0.53 (n-hexane/ethyl acetate 20/1); 1H NMR
(500 MHz, CDCl3) δ 3.86 (s, 3 H), 6.18 (d, J = 8.0 Hz, 1 H), 6.27 (bs,
1 H), 6.30 (d, J = 8.0 Hz, 1 H), 7.09 (dd, J = 7.5, 7.5 Hz, 1 H), 7.27−
7.46 (m, 8 H), 7.96 (d, J = 8.5 Hz, 1 H); 13C NMR (125 MHz,
CDCl3) δ 53.4 (CH3), 100.0 (CH), 100.1 (CH), 120.8 (CH), 122.5
(CH), 127.6 (CH), 128.1 (CH), 128.9 (CH × 2), 129.4 (CH × 2),
130.6 (CH), 132.7 (Cq), 137.6 (Cq), 138.8 (Cq), 140.0 (CH), 154.5
(Cq), 163.5 (Cq); MS (EI, m/z) 276 (M+, 100), 217 (38); HRMS
(EI-magnetic sector) calcd for C18H16N2O 276.1263, found 276.1261.
N-([1,1′-Biphenyl]-2-yl)-6-methylpyridin-2-amine (3l): pale yellow
1
viscous liquid; Rf = 0.55 (n-hexane/ethyl acetate 4/1); H NMR (500
MHz, CDCl3) δ 2.21 (s, 3 H), 6.37 (bs, 1 H), 6.77 (d, J = 8.5 Hz, 1
H), 7.08 (ddd, J = 7.5, 7.5, 1.0 Hz, 1 H), 7.27−7.36 (m, 4 H), 7.39−
7.43 (m, 4 H), 7.75 (d, J = 8.0 Hz, 1 H), 7.99 (s, 1 H); 13C NMR (125
MHz, CDCl3) δ 17.5 (CH3), 108.5 (CH), 119.9 (CH), 122.4 (CH),
124.1 (Cq), 127.5 (CH), 128.2 (CH), 128.8 (CH × 2), 129.3 (CH ×
2), 130.7 (CH), 132.9 (Cq), 137.9 (Cq), 138.5 (CH), 138.8 (Cq),
147.9 (CH), 153.8 (Cq); MS (EI, m/z) 260 (M+, 100), 259 (M+ − 1,
100), 244 (43), 183 (89); HRMS (EI-magnetic sector) calcd for
C18H16N2 260.1313, found 260.1316.
6-Methyl-N,N-diphenylpyridin-2-amine (3‴l): pale yellow viscous
4-Methyl-N-(3′-nitro-[1,1′-biphenyl]-2-yl)pyridin-2-amine (4f):
yellow viscous liquid; Rf = 0.46 (n-hexane/ethyl acetate 2/1); 1H
NMR (500 MHz, CDCl3) δ 2.23 (s, 3 H), 6.35 (bs, 1 H), 6.57 (s, 2
H), 7.22 (ddd, J = 7.5, 7.5, 1.0 Hz, 1 H), 7.34 (dd, J = 7.5, 1.5 Hz, 1
H), 7.41 (ddd, J = 8.5, 8.5, 1.5 Hz, 1 H), 7.56 (dd, J = 8.0, 8.0 Hz, 1
H), 7.69 (d, J = 8.5 Hz, 1 H), 7.76 (d, J = 7.5 Hz, 1 H), 7.98 (d, J = 5.0
Hz, 1 H), 8.18 (d, J = 8.5 Hz, 1 H), 8.28 (dd, J = 3.5, 3.5 Hz, 1 H); 13C
NMR (125 MHz, CDCl3) δ 21.2 (CH3), 108.8 (CH), 116.9 (CH),
122.4 (CH), 122.6 (CH), 124.1 (CH), 124.2 (CH), 129.5 (CH),
129.6 (CH), 130.8 (CH), 132.1 (Cq), 135.4 (CH), 137.4 (Cq), 140.8
(Cq), 147.5 (CH), 148.6 (Cq), 149.3 (Cq), 155.7 (Cq); MS (EI, m/z)
305 (M+, 93), 304 (M+ − 1, 84), 257 (53), 183 (100); HRMS (EI-
magnetic sector) calcd for C18H15N3O2 305.1164, found 305.1167.
4-Methyl-N-(3-nitrophenyl)-N-phenylpyridin-2-amine (4‴f): yel-
1
liquid; Rf = 0.60 (n-hexane/ethyl acetate 6/1); H NMR (500 MHz,
CDCl3) δ 2.40 (s, 3 H), 6.52 (d, J = 8.0 Hz, 1 H), 6.68 (d, J = 7.5 Hz,
1 H), 7.10 (dd, J = 7.0, 7.0 Hz, 2 H), 7.17−7.19 (m, 4 H), 7.28−7.31
(m, 4 H), 7.35 (dd, J = 8.0, 8.0 Hz, 1 H); 13C NMR (125 MHz,
CDCl3) δ 24.4 (CH3), 111.4 (CH), 115.9 (CH), 123.9 (CH × 2),
125.9 (CH × 4), 129.1 (CH × 4), 137.5 (CH), 146.3 (Cq × 2), 157.2
(Cq), 158.5 (Cq); MS (EI, m/z) 260 (M+, 45), 259 (M+ − 1, 100);
HRMS (EI-magnetic sector) calcd for C18H16N2 260.1313, found
260.1312.
N-(4′-Fluoro-[1,1′-biphenyl]-2-yl)-4-methylpyridin-2-amine (4b):
pale yellow viscous liquid; Rf = 0.40 (n-hexane/ethyl acetate 4/1);
1H NMR (500 MHz, CDCl3) δ 2.23 (s, 3 H), 6.30 (bs, 1 H), 6.57−
6.62 (m, 2 H), 7.08−7.14 (m, 3 H), 7.27 (dd, J = 7.5, 1.5 Hz, 1 H),
7.34−7.38 (m, 3 H), 7.75 (d, J = 8.0 Hz, 1 H), 8.02 (bs, 1 H); 13C
1
low viscous liquid; Rf = 0.43 (n-hexane/ethyl acetate 4/1); H NMR
NMR (125 MHz, CDCl3) δ 21.2 (CH3), 108.8 (CH), 115.8 (d, JC−F
=
(500 MHz, CDCl3) δ 2.23 (s, 3 H), 6.58 (s, 1 H), 6.75 (d, J = 5.0 Hz,
1 H), 7.18−7.26 (m, 3 H), 7.37−7.42 (m, 4 H), 7.86 (ddd, J = 7.5, 2.0,
2.0 Hz, 1 H), 7.97 (dd, J = 2.0, 2.0 Hz, 1 H), 8.13 (d, J = 5.0 Hz, 1 H);
13C NMR (125 MHz, CDCl3) δ 21.1 (CH3), 115.5 (CH), 117.8
21.0 Hz, CH × 2), 116.7 (CH), 121.2 (CH), 123.1 (CH), 128.4
(CH), 130.8 (CH), 131.0 (d, JC−F = 8.3 Hz, CH × 2), 132.6 (Cq),
134.8 (d, JC−F = 3.3 Hz, Cq), 137.5 (Cq), 147.8 (CH), 148.9 (Cq),
155.9 (Cq), 162.3 (d, JC−F = 245.6 Hz, Cq); MS (EI, m/z) 278 (M+,
71), 277 (M+ − 1, 100), 262 (18), 183 (44); HRMS (EI-magnetic
sector) calcd for C18H15FN2 278.1219, found 278.1222.
N-(4′-Chloro-[1,1′-biphenyl]-2-yl)-4-methylpyridin-2-amine (4c):
pale yellow viscous liquid; Rf = 0.45 (n-hexane/ethyl acetate 4/1);
1H NMR (500 MHz, CDCl3) δ 2.23 (s, 3 H), 6.31 (bs, 1 H), 6.57 (d, J
= 5.0 Hz, 1 H), 6.60 (s, 1 H), 7.13 (ddd, J = 7.5, 7.5, 1.0 Hz, 1 H), 7.27
(dd, J = 9.0, 1.0 Hz, 1 H), 7.31−7.39 (m, 5 H), 7.75 (d, J = 8.0 Hz, 1
H), 8.02 (bs, 1 H); 13C NMR (125 MHz, CDCl3) δ 21.2 (CH3), 108.8
(CH), 116.7 (CH), 121.4 (CH), 123.2 (CH), 128.6 (CH), 129.0 (CH
× 2), 130.6 (CH × 2), 132.4 (Cq), 133.6 (Cq), 137.3 (Cq), 137.5
(Cq), 147.8 (CH), 149.0 (Cq), 155.9 (Cq); MS (EI, m/z) 296 (M+ +
2, 34), 294 (M+, 100), 293 (M+ − 1, 100), 278 (39), 183 (100);
HRMS (EI-magnetic sector) calcd for C18H1535ClN2 294.0924, found
294.0921.
(CH), 119.1 (CH), 119.2 (CH), 125.9 (CH), 127.1 (CH), 129.5
(CH), 130.1 (CH × 2), 130.2 (CH), 145.1 (Cq), 147.4 (Cq), 148.0
(CH), 148.9 (Cq), 149.2 (Cq), 158.4 (Cq); MS (EI, m/z) 305 (M+,
51), 304 (M+ − 1, 100), 258 (42), 88 (65), 70 (91), 61 (100); HRMS
(EI-magnetic sector) calcd for C18H15N3O2 305.1164, found 305.1167.
2′-((4-Methylpyridin-2-yl)amino)-[1,1′-biphenyl]-4-carbaldehyde
(4g): pale yellow viscous liquid; Rf = 0.45 (n-hexane/ethyl acetate 3/
2); 1H NMR (500 MHz, CDCl3) δ 2.24 (s, 3 H), 6.31 (bs, 1 H), 6.57
(d, J = 5.0 Hz, 1 H), 6.60 (s, 1 H), 7.18 (ddd, J = 7.5, 7.5, 1.0 Hz, 1 H),
7.33 (dd, J = 8.0, 1.5 Hz, 1 H), 7.40 (ddd, J = 8.3, 8.3, 1.5 Hz, 1 H),
7.59 (d, J = 8.5 Hz, 2 H), 7.75 (d, J = 8.0 Hz, 1 H), 7.92 (d, J = 8.5 Hz,
2 H), 8.01 (d, J = 5.0 Hz, 1 H), 10.03 (s, 1 H); 13C NMR (125 MHz,
CDCl3) δ 21.2 (CH3), 108.8 (CH), 116.8 (CH), 121.9 (CH), 123.5
(CH), 129.2 (CH), 129.9 (CH × 2), 130.2 (CH × 2), 130.6 (CH),
132.6 (Cq), 135.3 (Cq), 137.4 (Cq), 145.4 (Cq), 147.9 (CH), 149.0
(Cq), 155.9 (Cq), 191.8 (CH); MS (EI, m/z) 288 (M+, 29), 287 (M+
− 1, 30), 88 (45), 70 (66), 61 (100); HRMS (EI-magnetic sector)
calcd for C19H16N2O 288.1263, found 288.1260.
N-(4′-Bromo-[1,1′-biphenyl]-2-yl)-4-methylpyridin-2-amine (4d):
1
pale yellow viscous liquid; Rf = 0.45 (n-hexane/ethyl acetate 4/1); H
NMR (500 MHz, CDCl3) δ 2.24 (s, 3 H), 6.24 (bs, 1 H), 6.57 (d, J =
5.0 Hz, 1 H), 6.61 (s, 1 H), 7.12 (ddd, J = 7.5, 7.5, 1.0 Hz, 1 H), 7.26−
7.28 (m, 3 H), 7.36 (ddd, J = 8.5, 8.5, 1.5 Hz, 1 H), 7.54 (d, J = 8.5 Hz,
2 H), 7.76 (d, J = 8.0 Hz, 1 H), 8.02 (d, J = 5.0 Hz, 1 H); 13C NMR
(125 MHz, CDCl3) δ 21.2 (CH3), 108.8 (CH), 116.7 (CH), 121.3
(CH), 121.8 (Cq), 123.2 (CH), 128.6 (CH), 130.6 (CH), 131.0 (CH
× 2), 132.0 (CH × 2), 132.3 (Cq), 137.5 (Cq), 137.8 (Cq), 148.0
(CH), 148.9 (Cq), 155.9 (Cq); MS (EI, m/z) 340 (M+ + 2, 75), 338
(M+, 76), 324 (28), 257 (29), 183 (96); HRMS (EI-magnetic sector)
calcd for C18H1579BrN2 338.0419, found 338.0422.
N-(4′-Methoxy-[1,1′-biphenyl]-2-yl)-4-methylpyridin-2-amine
(4h): pale yellow viscous liquid; Rf = 0.45 (n-hexane/ethyl acetate 3/
1
1); H NMR (500 MHz, CDCl3) δ 2.21 (s, 3 H), 3.83 (s, 3 H), 6.57
(bs, 1 H), 6.14−6.71 (m, 2 H), 6.94 (d, J = 8.5 Hz, 2 H), 7.11 (d, J =
7.5, 7.5 Hz, 1 H), 7.28−7.33 (m, 4 H), 7.74 (d, J = 8.0 Hz, 1 H), 8.01
(bs, 1 H); 13C NMR (125 MHz, CDCl3) δ 21.2 (CH3), 55.3 (CH3),
108.9 (CH), 114.2 (CH × 2), 116.5 (CH), 121.2 (CH), 123.1 (CH),
127.9 (CH), 130.4 (CH × 2), 130.8 (CH), 131.1 (Cq), 133.4 (Cq),
137.5 (Cq), 149.0 (Cq), 156.0 (Cq), 159.0 (Cq); MS (EI, m/z) 290
1200
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(M+, 41), 289 (M+ − 1, 39), 183 (100); HRMS (EI-magnetic sector)
calcd for C19H18N2O 290.1419, found 290.1419.
6.90 (bs, 1 H), 7.56 (d, J = 9.5 Hz, 2 H), 8.18−8.20 (m, 3 H); 13C
NMR (125 MHz, CDCl3) δ 21.2 (CH3), 111.7 (CH), 116.6 (CH ×
2), 118.8 (CH), 125.6 (CH × 2), 141.0 (Cq), 147.1 (Cq), 147.9
(CH), 149.4 (Cq), 153.8 (Cq); MS (EI, m/z) 229 (M+, 64), 228 (M+
− 1, 100), 182 (49); HRMS (EI-magnetic sector) calcd for
C12H11N3O2 229.0851, found 229.0850.
N-(3′-Methoxy-[1,1′-biphenyl]-2-yl)-4-methylpyridin-2-amine
(4i): colorless solid; mp 57−58 °C; Rf = 0.44 (n-hexane/ethyl acetate
3/1); 1H NMR (500 MHz, CDCl3) δ 2.24 (s, 3 H), 3.78 (s, 3 H), 6.41
(bs, 1 H), 6.56 (d, J = 5.0 Hz, 1 H), 6.62 (s, 1 H), 6.88−6.92 (m, 2 H),
6.98 (d, J = 7.5 Hz, 1 H), 7.11 (ddd, J = 7.5, 7.5, 1.0 Hz, 1 H), 7.29−
7.37 (m, 3 H), 7.81 (d, J = 8.5 Hz, 1 H), 8.03 (d, J = 5.0 Hz, 1 H); 13C
NMR (125 MHz, CDCl3) δ 21.2 (CH3), 55.2 (CH3), 109.0 (CH),
113.3 (CH), 114.7 (CH), 116.6 (CH), 120.7 (CH), 121.6 (CH),
122.7 (CH), 128.3 (CH), 129.8 (CH), 130.6 (CH), 133.1 (Cq), 137.6
(Cq), 140.2 (Cq), 147.9 (CH), 148.8 (Cq), 156.0 (Cq), 159.9 (Cq);
MS (EI, m/z) 290 (M+, 64), 289 (M+ − 1, 66), 183 (100); HRMS
(EI-magnetic sector) calcd for C19H18N2O 290.1419, found 290.1422.
N-(4′-(tert-Butyl)-[1,1′-biphenyl]-2-yl)-4-methylpyridin-2-amine
(4j): pale yellow viscous liquid; Rf = 0.54 (n-hexane/ethyl acetate 4/1);
1H NMR (500 MHz, CDCl3) δ 1.35 (s, 9 H), 2.24 (s, 3 H), 6.48 (bs, 1
H), 6.56 (d, J = 5.0 Hz, 1 H), 6.68 (s, 1 H), 7.10 (ddd, J = 7.5, 7.5, 1.0
Hz, 1 H), 7.29−7.34 (m, 4 H), 7.43 (d, J = 8.5 Hz, 2 H), 7.76 (d, J =
8.0 Hz, 1 H), 8.02 (d, J = 3.0 Hz, 1 H); 13C NMR (125 MHz, CDCl3)
δ 21.2 (CH3), 31.3 (CH3), 34.6 (Cq), 109.0 (CH), 116.5 (CH), 120.5
(CH), 122.8 (CH), 125.8 (CH × 2), 128.0 (CH), 128.9 (CH × 2),
130.8 (CH), 133.2 (Cq), 135.7 (Cq), 137.6 (Cq), 147.8 (CH), 148.9
(Cq), 150.4 (Cq), 156.0 (Cq); MS (EI, m/z) 316 (M+, 74), 315 (M+
− 1, 65), 300 (43), 183 (100); HRMS (EI-magnetic sector) calcd for
C22H24N2 316.1939, found 316.1942.
N-(2-Methoxyphenyl)-4-methylpyridin-2-amine (5e): pale yellow
viscous liquid; Rf = 0.40 (n-hexane/ethyl acetate 4/1); 1H NMR (500
MHz, CDCl3) δ 2.67 (s, 3 H), 389 (s, 3 H), 6.58 (d, J = 5.0 Hz, 1 H),
6.69 (s, 1 H), 6.89−6.99 (m, 4 H), 8.02 (dd, J = 7.0, 2.5 Hz, 1 H), 8.10
(d, J = 5.0 Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ 21.1 (CH3), 55.6
(CH3), 109.7 (CH), 110.3 (CH), 116.5 (CH), 118.2 (CH), 120.8
(CH), 121.3 (CH), 130.4 (Cq), 147.7 (CH), 148.5 (Cq), 148.6 (Cq),
155.8 (Cq); MS (EI, m/z) 214 (M+, 24), 183 (100); HRMS (EI-
magnetic sector) calcd for C13H14N2O 214.1106, found 214.1107.
N-(3-Methoxyphenyl)-4-methylpyridin-2-amine (5f): pale yellow
viscous liquid; Rf = 0.40 (n-hexane/ethyl acetate 3/1); 1H NMR (500
MHz, CDCl3) δ 2.25 (s, 3 H), 3.80 (s, 3 H), 6.57−6.60 (m, 2 H), 6.74
(s, 1 H), 6.83 (bs, 1 H), 6.87 (dd, J = 3.0, 1.0 Hz, 1 H), 6.94 (s, 1 H),
7.22 (dd, J = 8.0, 8.0 Hz, 1 H), 8.07 (d, J = 4.0 Hz, 1 H); 13C NMR
(125 MHz, CDCl3) δ 21.2 (CH3), 55.2 (CH3), 106.1 (CH), 107.8
(CH), 108.8 (CH), 112.6 (CH), 116.6 (CH), 129.9 (CH), 141.9
(Cq), 147.9 (CH), 148.8 (Cq), 156.0 (Cq), 160.5 (Cq); MS (EI, m/z)
214 (M+, 56), 213 (M+ − 1, 100), 184 (88), 183 (54); HRMS (EI-
magnetic sector) calcd for C13H14N2O 214.1106, found 214.1103.
N-(4-Methoxyphenyl)-4-methylpyridin-2-amine (5g): colorless
solid; mp 69−70 °C; Rf = 0.51 (n-hexane/ethyl acetate 3/2); 1H
NMR (500 MHz, CDCl3) δ 2.21 (s, 3 H), 3.81 (s, 3 H), 6.47 (bs, 1
H), 6.49 (s, 1 H), 6.51 (d, J = 5.0 Hz, 1 H), 6.90 (d, J = 7.5 Hz, 2 H),
7.22 (d, J = 7.5 Hz, 2 H), 8.01 (d, J = 5.0 Hz, 1 H); 13C NMR (125
MHz, CDCl3) δ 21.2 (CH3), 55.5 (CH3), 107.4 (CH), 114.6 (CH ×
2), 115.8 (CH), 124.3 (CH × 2), 133.3 (Cq), 147.9 (CH), 148.8
(Cq), 156.2 (CH), 157.4 (Cq); MS (EI, m/z) 214 (M+, 100), 199
(89), 184 (81), 88 (33), 70 (51), 61 (76); HRMS (EI-magnetic
sector) calcd for C13H14N2O 214.1106, found 214.1107.
4-Methyl-N-(4′-methyl-[1,1′-biphenyl]-2-yl)pyridin-2-amine (4k):
1
pale yellow viscous liquid; Rf = 0.49 (n-hexane/ethyl acetate 4/1); H
NMR (500 MHz, CDCl3) δ 2.24 (s, 3 H), 2.38 (s, 3 H), 6.44 (bs, 1
H), 6.55 (d, J = 5.0 Hz, 1 H), 6.64 (s, 1 H), 7.10 (ddd, J = 7.5, 7.5, 1.0
Hz, 1 H), 7.22 (d, J = 8.0 Hz, 2 H), 7.28−7.29 (m, 3 H), 7.33 (ddd, J =
8.3, 8.3, 1.5 Hz, 1 H), 7.78 (d, J = 8.0 Hz, 1 H), 8.02 (d, J = 5.0 Hz, 1
H); 13C NMR (125 MHz, CDCl3) δ 21.2 (CH3 × 2), 108.9 (CH),
116.5 (CH), 120.7 (CH), 122.8 (CH), 128.0 (CH), 129.1 (CH × 2),
129.5 (CH × 2), 130.7 (CH), 133.3 (CH), 135.8 (Cq), 137.3 (Cq),
137.5 (Cq), 147.7 (Cq), 148.9 (Cq), 156.0 (Cq); MS (EI, m/z) 274
(M+, 76), 273 (M+ − 1, 100), 258 (29), 183 (40); HRMS (EI-
magnetic sector) calcd for C19H18N2 274.1470, found 274.1467.
N-(4-Fluorophenyl)-4-methylpyridin-2-amine (5a): colorless solid;
mp 93−94 °C; Rf = 0.45 (n-hexane/ethyl acetate 3/1); 1H NMR (500
MHz, CDCl3) δ 2.25 (s, 3 H), 6.44 (bs, 1 H), 6.55 (s, 1 H), 6.57 (d, J
= 5.0 Hz, 1 H), 7.03 (dd, J = 8.5, 8.5 Hz, 2 H), 7.28 (dd, J = 9.0, 4.5
Hz, 2 H), 8.04 (d, J = 5.0 Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ
21.2 (CH3), 108.1 (CH), 115.9 (d, JC−F = 22.4 Hz, CH), 116.5 (CH),
122.9 (d, JC−F = 8.3 Hz, CH), 136.5 (d, JC−F = 2.8 Hz, Cq), 147.9
(CH), 148.9 (Cq), 156.5 (Cq), 158.9 (d, JC−F = 240.5 Hz, Cq); MS
(EI, m/z) 202 (M+, 46), 201 (M+ − 1, 100); HRMS (EI-magnetic
sector) calcd for C12H11FN2 202.0906, found 202.0909.
4-Methyl-N-(p-tolyl)pyridin-2-amine (5h): colorless solid; mp
113−114 °C; Rf = 0.51 (n-hexane/ethyl acetate 3/1); 1H NMR
(500 MHz, CDCl3) δ 2.23 (s, 3 H), 2.33 (s, 3 H), 6.49 (bs, 1 H), 6.54
(d, J = 5.0 Hz, 1 H), 6.34 (s, 1 H), 7.14 (d, J = 8.5 Hz, 2 H), 7.19 (d, J
= 8.5 Hz, 2 H), 8.04 (bs, 1 H); 13C NMR (125 MHz, CDCl3) δ 20.8
(CH3), 21.2 (CH3), 107.9 (CH), 116.2 (CH), 121.3 (CH × 2), 129.8
(CH × 2), 132.7 (Cq), 137.8 (Cq), 148.0 (CH), 148.8 (Cq), 156.7
(Cq); MS (EI, m/z) 198 (M+, 100), 197 (M+ − 1, 100), 182 (53), 98
(56), 91 (37), 80 (38), 65 (52); HRMS (EI-magnetic sector) calcd for
C13H14N2 198.1157, found 198.1158.
4-Methyl-N-(naphthalen-1-yl)pyridin-2-amine (5i): pale yellow
1
solid; mp 109−110 °C; Rf = 0.44 (n-hexane/ethyl acetate 3/1); H
NMR (500 MHz, CDCl3) δ 2.18 (s, 3 H), 6.46 (s, 1 H), 6.57 (d, J =
5.5 Hz, 1 H), 7.06 (bs, 1 H), 7.47−7.57 (m, 4 H), 7.72 (d, J = 8.0 Hz,
1 H), 7.89 (d, J = 8.5 Hz, 1 H), 8.05−8.07 (m, 2 H); 13C NMR (125
MHz, CDCl3) δ 21.3 (CH3), 108.2 (CH), 116.2 (CH), 120.7 (CH),
122.3 (CH), 125.4 (CH), 125.8 (CH), 126.3 (CH × 2), 128.5 (CH),
129.3 (Cq), 134.7 (Cq), 135.7 (Cq), 147.1 (CH), 149.6 (Cq), 157.5
(Cq); MS (EI, m/z) 234 (M+, 100), 233 (M+ − 1, 100); HRMS (EI-
magnetic sector) calcd for C16H14N2 234.1157, found 234.1158.
N-(5-Fluoro-[1,1′-biphenyl]-2-yl)-4-methylpyridin-2-amine (6a):
pale yellow viscous liquid; Rf = 0.50 (n-hexane/ethyl acetate 3/1);
1H NMR (500 MHz, CDCl3) δ 2.22 (s, 3 H), 6.31 (bs, 1 H), 6.46 (s, 1
H), 6.54 (d, J = 5.0 Hz, 1 H), 7.03 (m, 2 H), 7.34−7.43 (m, 5 H), 7.72
(dd, J = 8.5, 5.0 Hz, 1 H), 7.99 (d, J = 5.0 Hz, 1 H); 13C NMR (125
MHz, CDCl3) δ 21.2 (CH3), 108.6 (CH), 114.8 (d, JC−F = 21.9 Hz,
CH), 116.4 (CH), 117.1 (d, JC−F = 22.4 Hz, CH), 123.9 (d, JC−F = 8.3
Hz, CH), 128.0 (CH), 128.9 (CH), 129.0 (CH), 133.3 (d, JC−F = 2.8
Hz, Cq), 135.9 (d, JC−F = 7.8 Hz, Cq), 137.8 (Cq), 147.4 (CH), 149.1
(Cq), 156.3 (Cq), 158.8 (d, JC−F = 241.5 Hz, Cq); MS (EI, m/z) 278
(M+, 100), 277 (M+ − 1, 100), 262 (47), 201 (72); HRMS (EI-
magnetic sector) calcd for C18H15FN2 278.1219, found 278.1221.
N-(5-Chloro-[1,1′-biphenyl]-2-yl)-4-methylpyridin-2-amine (6b):
pale yellow viscous liquid; Rf = 0.49 (n-hexane/ethyl acetate 4/1);
1H NMR (500 MHz, CDCl3) δ 2.24 (s, 3 H), 6.32 (bs, 1 H), 6.52 (s, 1
N-(4-Chlorophenyl)-4-methylpyridin-2-amine (5b): colorless
solid; mp 97−98 °C; Rf = 0.56 (n-hexane/ethyl acetate 3/1); 1H
NMR (500 MHz, CDCl3) δ 2.26 (s, 3 H), 6.56 (bs, 1 H), 6.60 (d, J =
5.0 Hz, 1 H), 6.62 (s, 1 H), 7.26−7.31 (m, 4 H), 8.07 (d, J = 5.0 Hz, 1
H); 13C NMR (125 MHz, CDCl3) δ 21.2 (CH3), 108.9 (CH), 116.9
(CH), 121.3 (CH), 127.2 (Cq), 129.2 (CH), 139.3 (Cq), 148.0 (CH),
149.0 (Cq), 155.7 (Cq); MS (EI, m/z) 220 (M+ + 2, 34), 218 (M+,
100), 217 (M+ − 1, 100), 182 (41), 91 (45), 80 (53), 65 (39); HRMS
(EI-magnetic sector) calcd for C12H1135ClN2 218.0611, found
218.0608.
N-(4-Bromophenyl)-4-methylpyridin-2-amine (5c): white solid;
1
mp 103−104 °C; Rf = 0.50 (n-hexane/ethyl acetate 3/1); H NMR
(500 MHz, CDCl3) δ 2.27 (s, 3 H), 6.50 (bs, 1 H), 6.61 (d, J = 5.0 Hz,
1 H), 6.63 (s, 1 H), 7.25 (d, J = 9.0 Hz, 2 H), 7.41 (d, J = 9.0 Hz, 2 H),
8.07 (d, J = 5.0 Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ 21.2 (CH3),
109.1 (CH), 114.6 (Cq), 117.0 (CH), 121.5 (CH × 2), 132.1 (CH ×
2), 139.8 (Cq), 148.0 (CH), 149.0 (Cq), 155.6 (Cq); MS (EI, m/z)
264 (M+ + 2, 53), 262 (M+, 54), 183 (78); HRMS (EI-magnetic
sector) calcd for C12H1179BrN2 262.0106, found 262.0106.
4-Methyl-N-(4-nitrophenyl)pyridin-2-amine (5d): yellow solid; mp
1
133−134 °C; Rf = 0.40 (n-hexane/ethyl acetate 3/1); H NMR (500
MHz, CDCl3) δ 2.34 (s, 3 H), 6.73 (s, 1 H), 6.77 (d, J = 4.5 Hz, 1 H),
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H), 6.58 (d, J = 5.0 Hz, 1 H), 7.26 (d, J = 4.0 Hz, 1 H), 7.30 (dd, J =
8.5, 6.0 Hz, 1 H), 7.36−7.38 (m, 3 H), 7.42−7.45 (m, 2 H), 7.84 (d, J
= 8.5 Hz, 1 H), 8.03 (d, J = 5.0 Hz, 1 H); 13C NMR (125 MHz,
CDCl3) δ 21.2 (CH3), 109.4 (CH), 116.9 (CH), 121.8 (CH), 127.4
(Cq), 128.1 (CH × 2), 129.0 (CH × 2), 129.1 (CH × 2), 130.3 (CH),
134.4 (Cq), 136.3 (Cq), 137.6 (Cq), 147.7 (CH), 149.0 (Cq), 155.6
(Cq); MS (EI, m/z) 296 (M+ + 2, 36), 294 (M+, 100), 293 (M+ − 1,
100), 278 (47), 217 (75); HRMS (EI-magnetic sector) calcd for
C18H1535ClN2 294.0924, found 294.0923.
N-(5-Bromo-[1,1′-biphenyl]-2-yl)-4-methylpyridin-2-amine (6c):
pale yellow viscous liquid; Rf = 0.50 (n-hexane/ethyl acetate 4/1);
1H NMR (500 MHz, CDCl3) δ 2.24 (s, 3 H), 6.30 (bs, 1 H), 6.53 (s, 1
H), 6.58 (d, J = 5.0 Hz, 1 H), 7.34−7.45 (m, 7 H), 7.82 (d, J = 9.0 Hz,
1 H), 8.03 (d, J = 5.0 Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ 21.1
(CH3), 109.5 (CH), 114.7 (Cq), 117.0 (CH), 121.8 (CH), 128.1
(CH), 129.0 (CH × 2), 129.1 (CH × 2), 131.0 (CH), 133.1 (CH),
134.5 (Cq), 136.8 (Cq), 137.5 (Cq), 147.9 (CH), 148.9 (Cq), 155.5
(Cq); MS (EI, m/z) 340 (M+ + 2, 99), 338 (M+, 100), 324 (33), 322
(33), 263 (52), 261 (54), 71 (62), 57 (71); HRMS (EI-magnetic
sector) calcd for C18H1579BrN2 338.0419, found 338.0416.
4-Methyl-N-(5-nitro-[1,1′-biphenyl]-2-yl)pyridin-2-amine (6d):
yellow solid; mp 79−80 °C; Rf = 0.50 (n-hexane/ethyl acetate 3/1);
1H NMR (500 MHz, CDCl3) δ 2.29 (s, 3 H), 6.57 (s, 1 H), 6.75 (d, J
= 5.0 Hz, 1 H), 6.80 (bs, 1 H), 7.44−7.55 (m, 5 H), 8.13 (d, J = 3.0
Hz, 1 H), 8.17 (d, J = 5.0 Hz, 1 H), 8.22 (dd, J = 9.0, 3.0 Hz, 1 H),
8.43 (d, J = 9.0 Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ 21.1 (CH3),
112.3 (CH), 116.3 (CH), 118.9 (CH), 124.6 (CH), 126.2 (CH),
128.8 (CH), 129.3 (CH × 2), 129.6 (CH × 2), 130.2 (Cq), 136.5
(Cq), 140.8 (Cq), 144.3 (Cq), 147.9 (CH), 149.3 (Cq), 153.7 (Cq);
MS (EI, m/z) 305 (M+, 39), 304 (M+ − 1, 34), 85 (69), 71 (91), 57
(100); HRMS (EI-magnetic sector) calcd for C18H15N3O2 305.1164,
found 305.1168.
N-(5-Methoxy-[1,1′-biphenyl]-2-yl)-4-methylpyridin-2-amine
(6g): pale yellow viscous liquid; Rf = 0.48 (n-hexane/ethyl acetate 2/
1); H NMR (500 MHz, CDCl3) δ 2.19 (s, 3 H), 3.84 (s, 3 H), 6.42
1
(s, 1 H), 6.47 (d, J = 5.0 Hz, 1 H), 6.50 (bs, 1 H), 6.90 (d, J = 3.0 Hz,
1 H), 6.93 (dd, J = 8.5, 3.0 Hz, 1 H), 7.29−7.39 (m, 5 H), 7.52 (d, J =
8.5 Hz, 1 H), 7.92 (d, J = 5.0 Hz, 1 H); 13C NMR (125 MHz, CDCl3)
δ 21.2 (CH3), 55.6 (CH3), 107.8 (CH), 113.9 (CH), 115.6 (CH),
115.8 (CH), 125.5 (CH), 127.5 (CH), 128.6 (CH × 2), 129.0 (CH ×
2), 130.1 (Cq), 137.0 (Cq), 138.9 (Cq), 147.0 (CH), 149.1 (Cq),
156.4 (Cq), 157.1 (Cq); MS (EI, m/z) 290 (M+, 100), 275 (49);
HRMS (EI-magnetic sector) calcd for C19H18N2O 290.1419, found
290.1420.
4-Methyl-N-(5-methyl-[1,1′-biphenyl]-2-yl)pyridin-2-amine (6h):
pale yellow viscous liquid; Rf = 0.40 (n-hexane/ethyl acetate 4/1);
1H NMR (500 MHz, CDCl3) δ 2.22 (s, 3 H), 2.37 (s, 3 H), 6.28 (bs, 1
H), 6.52 (d, J = 5.0 Hz, 1 H), 6.58 (s, 1 H), 7.14 (s, 1 H), 7.16 (dd, J =
8.0, 1.5 Hz, 1 H), 7.32−7.41 (m, 5 H), 7.60 (d, J = 8.0 Hz, 1 H), 7.99
(d, J = 5.0 Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ 20.8 (CH3), 21.2
(CH3), 108.4 (CH), 116.2 (CH), 122.0 (CH), 127.4 (CH), 128.7
(CH × 2), 128.8 (CH), 129.2 (CH × 2), 131.4 (CH), 132.7 (Cq),
134.1 (Cq), 134.8 (Cq), 139.0 (Cq), 147.8 (Cq), 148.8 (CH), 156.5
(Cq); MS (EI, m/z) 274 (M+, 100), 273 (M+ − 1, 99), 258 (32), 197
(57); HRMS (EI-magnetic sector) calcd for C19H18N2 274.1470,
found 274.1468.
4-Methyl-N-(5′-methyl-[1,1′:3′,1″-terphenyl]-2′-yl)pyridin-2-
amine (6′h): white solid; mp 115−116 °C; Rf = 0.40 (n-hexane/ethyl
acetate 3/1); 1H NMR (500 MHz, CDCl3) δ 1.98 (s, 3 H), 2.44 (s, 3
H), 5.93 (s, 1 H), 6.12 (bs, 1 H), 6.24 (d, J = 5.3 Hz, 1 H), 7.19−7.22
(m, 4 H), 7.26−7.29 (m, 4 H), 7.38−7.40 (m, 4 H), 7.72 (d, J = 5.5
Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ 20.9 (CH3), 21.0 (CH3),
107.9 (CH), 115.1 (CH), 127.1 (CH × 2), 128.2 (CH × 4), 128.8
(CH × 4), 131.1 (CH × 2), 131.5 (Cq), 135.4 (Cq), 138.6 (Cq × 2),
139.8 (Cq × 2), 146.9 (CH), 147.9 (Cq), 156.2 (Cq); MS (EI, m/z)
350 (M+, 6), 273 (13), 183 (100); HRMS (EI-magnetic sector) calcd
for C25H22N2 350.1783, found 350.1784.
9-(4-Methylpyridin-2-yl)-3-nitro-9H-carbazole (6″d): yellow solid;
1
mp 139−140 °C; Rf = 0.42 (n-hexane/ethyl acetate 4/1); H NMR
(500 MHz, CDCl3) δ 2.54 (s, 3 H), 7.25 (d, J = 5.0 Hz, 1 H), 7.42
(ddd, J = 7.5, 7.5, 1.0 Hz, 1 H), 7.46 (s, 1 H), 7.54 (ddd, J = 8.0, 8.0,
1.0 Hz, 1 H), 7.75 (d, J = 8.5 Hz, 1 H), 7.82 (d, J = 9.0 Hz, 1 H), 8.19
(d, J = 8.0 Hz, 1 H), 8.34 (d, J = 9.5, 2.5 Hz, 1 H), 8.62 (d, J = 5.0 Hz,
1 H), 9.03 (d, J = 2.0 Hz, 1 H); 13C NMR (125 MHz, CDCl3) δ 21.3
(CH3), 111.1 (CH), 111.6 (CH), 116.9 (CH), 120.2 (CH), 120.9
(CH), 121.9 (CH), 122.1 (CH), 123.6 (Cq), 123.7 (CH), 124.0 (Cq),
127.7 (CH), 140.9 (Cq), 141.9 (Cq), 142.9 (Cq), 149.6 (CH), 150.6
(Cq), 150.7 (Cq); MS (EI, m/z) 303 (M+, 81), 257 (45), 85 (61), 71
(91), 57 (100); HRMS (EI-magnetic sector) calcd for C18H13N3O2
303.1008, found 303.1005.
[1,1′-Biphenyl]-2-amine (7): brown viscous liquid; Rf = 0.60 (n-
hexane/ethyl acetate 7/1); 1H NMR (500 MHz, CDCl3) δ 3.77 (bs, 2
H), 6.77 (d, J = 8.0 Hz, 1 H), 6.82 (ddd, J = 7.5, 7.5, 1.0 Hz, 1 H),
7.12−7.17 (m, 2H), 7.33−7.36 (m, 1 H), 7.42−7.46 (m, 4 H); 13C
NMR (125 MHz, CDCl3) δ 115.6 (CH), 118.6 (CH), 127.1 (CH),
127.6 (Cq), 128.5 (CH), 128.8 (CH × 2), 129.1 (CH × 2), 130.4
(CH), 139.5 (Cq), 143.5 (Cq); MS (EI, m/z) 169 (M+, 19), 111 (32),
97 (46), 85 (53), 71 (75), 57 (100); HRMS (EI-magnetic sector)
calcd for C12H11N 169.0891, found 169.0891.
3-Methyl-6-phenylbenzo[4,5]imidazo[1,2-a]pyridine (8): pale yel-
1
low solid; mp 97−98 °C; Rf = 0.43 (n-hexane/ethyl acetate 1/2); H
N-(3-Methoxy-[1,1′-biphenyl]-2-yl)-4-methylpyridin-2-amine
NMR (500 MHz, CDCl3) δ 2.46 (s, 3 H), 6.70 (d, J = 7.0 Hz, 1 H),
7.37−7.42 (m, 2 H), 7.51−7.54 (m, 3 H), 7.64 (d, J = 7.5 Hz, 1 H),
7.82 (d, J = 8.0 Hz, 1 H), 8.06 (d, J = 7.5 Hz, 2 H), 8.35 (d, J = 7.0 Hz,
1 H); 13C NMR (125 MHz, CDCl3) δ 21.9 (CH3), 109.1 (CH), 113.3
(CH), 116.4 (CH), 120.7 (CH), 124.2 (CH + Cq), 124.7 (CH), 127.3
(CH), 128.5 (CH × 2), 129.3 (CH × 2), 132.4 (Cq), 138.6 (Cq),
140.6 (Cq), 142.6 (Cq), 149.0 (Cq); MS (EI, m/z) 258 (M+, 24), 71
(54), 57 (100); HRMS (EI-magnetic sector) calcd for C18H14N2
258.1157, found 258.1157.
(6e): pale yellow viscous liquid; Rf = 0.46 (n-hexane/ethyl acetate 1/
1
1); H NMR (500 MHz, CDCl3) δ 2.07 (s, 3 H), 3.85 (s, 3 H), 6.01
(s, 1 H), 6.36 (bs, 1 H), 6.40 (d, J = 5.5 Hz, 1 H), 6.97 (dd, J = 8.0, 1.0
Hz, 1 H), 7.02 (dd, J = 8.0, 1.0 Hz, 1 H), 7.20 (dd, J = 7.5, 7.5 Hz, 1
H), 7.24−7.28 (m, 3 H), 7.40 (d, J = 8.9 Hz, 2 H), 7.88 (d, J = 5.5 Hz,
1 H); 13C NMR (125 MHz, CDCl3) δ 21.3 (CH3), 55.8 (CH3), 108.2
(CH), 110.5 (CH), 115.7 (CH), 122.9 (CH), 125.7 (CH), 126.2
(Cq), 127.1 (CH), 128.3 (CH × 2), 128.6 (CH × 2), 138.3 (Cq),
139.5 (Cq), 147.0 (CH), 148.1 (Cq), 154.3 (Cq), 156.5 (Cq); MS
(EI, m/z) 290 (M+, 2), 258 (100); HRMS (EI-magnetic sector) calcd
for C19H18N2O 290.1419, found 290.1417.
N-(4-Methoxy-[1,1′-biphenyl]-2-yl)-4-methylpyridin-2-amine (6f):
white solid; mp 67−68 °C; Rf = 0.49 (n-hexane/ethyl acetate 3/1); 1H
NMR (500 MHz, CDCl3) δ 2.23 (s, 3 H), 3.85 (s, 3 H), 6.56 (d, J =
4.5 Hz, 1 H), 6.62 (bs + s, 2 H), 6.70 (dd, J = 8.5, 2.5 Hz, 1 H), 7.21
(d, J = 8.5 Hz, 1 H), 7.29−7.33 (m, 1 H), 7.37−7.41 (m, 4 H), 7.46
(d, J = 2.5 Hz, 1 H), 8.02 (d, J = 4.5 Hz, 1 H); 13C NMR (125 MHz,
CDCl3) δ 21.2 (CH3), 55.4 (CH3), 106.3 (CH), 108.2 (CH), 109.5
(CH), 116.6 (CH), 125.9 (Cq), 127.2 (CH), 128.8 (CH × 2), 129.4
(CH × 2), 131.4 (CH), 138.4 (Cq), 138.6 (Cq), 147.3 (CH), 149.1
(Cq), 155.6 (Cq), 159.6 (Cq); MS (EI, m/z) 290 (M+, 100), 289 (M+
− 1, 87), 274 (47), 213 (67); HRMS (EI-magnetic sector) calcd for
C19H18N2O 290.1419, found 290.1417.
3-Methyl-6-phenylbenzo[4,5]imidazo[1,2-a]pyridin-8-yl acetate
(9): pale yellow solid; mp 79−80 °C; Rf = 0.53 (n-hexane/ethyl
acetate 3/2); 1H NMR (500 MHz, CDCl3) δ 2.39 (s, 3 H), 2.47 (s, 3
H), 6.73 (d, J = 6.5 Hz, 1 H), 7.38 (d, J = 2.0 Hz, 1 H), 7.40 (d, J = 7.0
Hz, 1 H), 7.51−7.54 (m, 2 H), 7.57 (bs, 1 H), 7.64 (d, J = 2.0 Hz, 1
H), 8.04 (d, J = 7.5 Hz, 2 H), 8.26 (d, J = 7.0 Hz, 1 H); 13C NMR
(125 MHz, CDCl3) δ 21.2 (CH3), 22.0 (CH3), 102.4 (CH), 113.8
(CH), 116.4 (CH), 118.9 (CH), 124.1 (CH), 127.8 (CH), 128.7 (CH
× 2), 128.8 (Cq), 129.2 (CH × 2), 130.2 (Cq), 132.9 (Cq), 134.2
(Cq), 137.5 (Cq), 144.9 (Cq), 149.4 (Cq), 170.0 (Cq); MS (EI, m/z)
316 (M+, 21), 274 (100), 85 (58), 71 (80), 57 (93); HRMS (EI-
magnetic sector) calcd for C20H16N2O2 316.1212, found 316.1209.
4-Methyl-N-phenylpyridin-2-amine palladacycle (I): yellow solid;
mp >146 °C dec; 1H NMR (300 MHz, d8-THF) δ 2.23 (s, 6 H), 2.43
(s, 6 H), 6.48−6.59 (m, 6 H), 6.71 (s, 2 H), 6.81−6.86 (m, 2 H), 7.35
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(d, J = 7.8 Hz, 2 H), 8.39 (m, 2 H), 8.77 (s, 2 H); MS (MALDI-TOF,
m/z) 697 (M+). The solubility of the title compound was found to be
very poor in most solvents. We only obtained its 1H NMR spectrum in
d8-THF, while the 13C NMR signals were too poor to be reported.
4065. (d) Chu, J.-H.; Tsai, S.-L.; Wu, M.-J. Synthesis 2009, 3757−3764.
(e) Chu, J.-H.; Chen, C.-C.; Wu, M.-J. Organometallics 2008, 27,
5173−5176.
(4) (a) Furstner, A.; Kennedy, J. W. J. Chem. Eur. J. 2006, 12, 7398−
̈
7410. (b) Kikuchi, H.; Matsuo, Y.; Katou, Y.; Kubohara, Y.; Oshima, Y.
Tetrahedron 2012, 68, 8884−8889. (c) Morales, J. C. C.; Torres, A. G.;
ASSOCIATED CONTENT
■
́
Gonzalez-Zamora, E. Eur. J. Org. Chem. 2011, 3165−3170.
S
* Supporting Information
(5) (a) Bright, T. V.; Dalton, F.; Elder, V. L.; Murphy, C. D.;
O’Connor, N. K.; Sandford, G. Org. Biomol. Chem. 2013, 11, 1135−
1142. (b) Da, Y.-J.; Yuan, W.-D.; Xin, T.; Nie, Y.-Y.; Ye, Y.; Yan, Y.-J.;
Liang, L.-S.; Chen, Z.-L. Bioorg. Med. Chem. 2012, 20, 7101−7111.
(c) Takeuchi, T.; Oishi, S.; Watanabe, T.; Ohno, H.; Sawada, J.;
Matsuno, K.; Asai, A.; Asada, A.; Kitaura, K.; Fujii, N. J. Med. Chem.
2011, 54, 4839−4846.
(6) (a) Manickam, M.; Iqbal, P.; Belloni, M.; Kumar, S.; Preece, J. A.
Isr. J. Chem. 2012, 52, 917−934. (b) An, B.-K.; Gihm, S. H.; Chung, J.
W.; Park, J. W.; Park, C. R.; Kwon, S.-K.; Park, S. Y. J. Am. Chem. Soc.
2009, 131, 3950−3957. (c) Wang, Z. M.; Song, X. H.; Gao, Z.; Yu, D.
W.; Zhang, X. J.; Lu, P.; Shen, F. Z.; Ma, Y. G. RSC Adv. 2012, 2,
9635−9642.
Tables, figures, and a CIF file giving X-ray crystallographic data
1
for I and H and 13C NMR spectra of new compounds. This
material is available free of charge via the Internet at http://
pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: j_hchu@yahoo.com.tw (J.-H.C.); mijuwu@faculty.
nsysu.edu.tw (M.-J.W.).
■
Notes
The authors declare no competing financial interest.
(7) (a) Chen, X.; Li, J.-J.; Hao, X.-S.; Goodhue, C. E.; Yu, J.-Q. J. Am.
Chem. Soc. 2006, 128, 78−79. (b) Chen, X.; Goodhue, C. E.; Yu, J.-Q.
J. Am. Chem. Soc. 2006, 128, 12634−12635.
ACKNOWLEDGMENTS
■
We thank the National Science Council of the Republic of
China (NSC 101-2113-M-110-014-MY3 and NSC-100-2113-
M-110-006-MY3) for financial support and Mr. Min-Yuan
Hung for his technical support and services for GC-MS at the
Center for Research Resources and Development of Kaohsiung
Medical University (Taiwan).
(8) (a) Wang, X.; Leow, D.; Yu, J.-Q. J. Am. Chem. Soc. 2011, 133,
13864−13867. (b) Wasa, M.; Worrell, B. T.; Yu, J.-Q. Angew. Chem.,
Int. Ed. 2010, 49, 1275−1277. (c) Wasa, M.; Engle, K. M.; Yu, I.-Q. J.
Am. Chem. Soc. 2009, 131, 9886−9887. (d) Wang, D.-H.; Wasa, M.;
Giri, R.; Yu, J.-Q. J. Am. Chem. Soc. 2008, 130, 7190−7191. (e) Yang,
S.; Li, B.; Wan, X.; Shi, Z. J. Am. Chem. Soc. 2007, 129, 6066−6067.
(f) Koley, M.; Dastbaravardeh, N.; Schnurch, M.; Mihovilovic, M. D.
̈
ChemCatChem. 2012, 4, 1345−1352.
REFERENCES
■
(9) BQ has been demonstrated as an efficient promoter in
palladium(II)-catalyzed C−H activation/C−C coupling. See ref 7
and: Giri, R.; Maugel, N.; Li, J.-J.; Wang, D.-H.; Breazzano, S. P.;
Saunders, L. B.; Yu, J.-Q. J. Am. Chem. Soc. 2007, 129, 3510−3511.
(10) In the following exploration of starting substrates, copper(II)
acetate generally showed results better than those for silver(I) salts.
For example, in the synthesis of 6e−g (entries 5−7, Table 4), modest
to excellent product yields were found, but none of the desired
products were isolated by using silver(I) salts. On the other hand, we
did not observe the formation of any copper complexes when substrate
1a and copper(II) acetate were mixed in tert-butyl alcohol at 80−90
°C.
(1) Selected reviews of transition-metal-catalyzed C−H functional-
ization: (a) Kuhl, N.; Hopkinson, M. N.; Wencel-Delord, J.; Glorius, F.
Angew. Chem., Int. Ed. 2012, 51, 10236−10254. (b) Engle, K. M.; Mei,
T.-S.; Wasa, M.; Yu, J.-Q. Acc. Chem. Res. 2012, 45, 788−802.
(c) Colby, D. A.; Tsai, A. S.; Bergman, R. G.; Ellman, J. A. Acc. Chem.
Res. 2012, 45, 814−825. (d) Hartwig, J. F. Acc. Chem. Res. 2012, 45,
864−873. (e) Neufeldt, S. R.; Sanford, M. S. Acc. Chem. Res. 2012, 45,
936−946. (f) Zhang, C.; Tang, C.; Jiao, N. Chem. Soc. Rev. 2012, 41,
3464−3484. (g) Song, G.; Wang, F.; Li, X. Chem. Soc. Rev. 2012, 41,
3651−3678. (h) Yeung, C. S.; Dong, V. M. Chem. Rev. 2011, 111,
1215−1292. (i) Sun, C.-L.; Li, B.-J.; Shi, Z.-J. Chem. Rev. 2011, 111,
1293−1314. (j) Ackerman, L. Chem. Rev. 2011, 111, 1315−1345.
(k) Chen, X.; Engle, K. M.; Wang, D.-H.; Yu, J.-Q. Angew. Chem., Int.
Ed. 2009, 48, 5094−5115.
(11) K2S2O8 and oxone were demonstrated as good terminal oxidants
in palladium-catalyzed C−H functionalization; see: (a) Desai, L. V.;
Malik, H. A.; Sanford, M. S. Org. Lett. 2006, 8, 1141−1144. (b) Gary,
J. B.; Cook, A. K.; Sanford, M. S. ACS Catal. 2013, 3, 700−703.
Unfortunately, only moderate yields (53% for K2S2O8 and 52% for
oxone) of the single product 3a were obtained by using these
peroxide-based oxidants in the reaction.
(12) Two conformers of 3b and 3c are shown as follows. Conformer
A is believed to be more favorable than conformer B from energetic
considerations.
́
(2) (a) Urones, B.; Arrayas, R. G.; Carretero, J. C. Org. Lett. 2013, 15,
1120−1123. (b) Rajeshkumar, V.; Lee, T.-H.; Chuang, S.-C. Org. Lett.
2013, 15, 1468−1471. (c) Leow, D.; Li, G.; Mei, T.-S.; Yu, J.-Q.
Nature 2012, 486, 518−522. (d) Ackermann, L.; Diers, E.; Manvar, A.
Org. Lett. 2012, 14, 1154−1157. (e) Yadav, M. R.; Rit, R. K.; Sahoo, A.
K. Chem. Eur. J. 2012, 18, 5541−5545. (f) Li, B.-J.; Wang, H.-Y.; Zhu,
Q.-L.; Shi, Z.-J. Angew. Chem., Int. Ed. 2012, 51, 3948−3952.
(g) Wencel-Delord, J.; Nimphius, C.; Patureau, F. W.; Glorius, F.
Angew. Chem., Int. Ed. 2012, 51, 2247−2251. (h) Iglesias, A.; Alvarez,
R.; de Lera, A. R.; Muniz, K. Angew. Chem., Int. Ed. 2012, 51, 2225−
̃
2228. (i) Karthikeyan, J.; Cheng, C.-H. Angew. Chem., Int. Ed. 2012,
51, 12343−12347. (j) Jayakumar, J.; Parthasarathy, K.; Cheng, C.-H.
Angew. Chem., Int. Ed. 2012, 51, 197−200. (k) Ye, M.; Edmunds, A. J.
F.; Morris, J.; Sale, D.; Zhang, Y.; Yu, J.-Q. Chem. Soc. 2013, 4, 2374−
2379. (l) Li, G.; Leow, D.; Wan, L.; Yu, J.-Q. Angew. Chem., Int. Ed.
2013, 52, 1245−1247. (m) Pan, F.; Lei, Z.-Q.; Wang, H.; Li, H.; Sun,
J.; Shi, Z.-J. Angew. Chem., Int. Ed. 2013, 52, 2063−2067. (n) Zhang,
L.-S.; Chen, K.; Chen, G.-H.; Li, B.-L.; Luo, S.; Guo, Q.-Y.; Wei, J.-B.;
Shi, Z.-J. Org. Lett. 2013, 15, 10−13.
1
(13) According to the H NMR spectroscopic analysis of 1d, the
(3) Our work in palladium(II)-catalyzed C−H functionalization:
(a) Chu, J.-H.; Wu, C.-C.; Chang, D.-H.; Lee, Y.-M.; Wu, M.-J.
Organometallics 2013, 32, 272−282. (b) Chu, J.-H.; Lin, P.-S.; Lee, Y.-
M.; Shen, W.-T.; Wu, M.-J. Chem. Eur. J. 2011, 17, 13613−13620.
(c) Chu, J.-H.; Lin, P.-S.; Wu, M.-J. Organometallics 2010, 29, 4058−
chemical shift of the amine proton is shifted down to 10.11 ppm which
indicates a strong intramolecular hydrogen bond formed between the
nitro and amine groups, shown as follows. A similar result is also
observed for 3d, for which the chemical shift of the amine proton
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appears at 9.96 ppm. This phenomenon suggests that a more negative
charge on the amine nitrogen is formed.
(14) (a) A possible model of 1l interacting with the palladium(II)
and copper(II) ions is illustrated as follows. (b) For a related paper on
copper(II)-mediated or -catalyzed C−N coupling, see: Wang, X.; Jang,
H.-Y. Bull. Korean Chem. Soc. 2012, 33, 1785−1787 and references
cited therein.
(15) Although substrate 1e (R = 4-OMe) showed a product yield
higher than that of 1f (R = 4-Me), but more synthetic steps for the
preparation of 1e were required, we thus chose 1f as the model
substrate.
(16) (a) Das, S.; Banerjee, P.; Peng, S.-M.; Lee, G.-H.; Kim, J.;
Goswami, S. Inorg. Chem. 2006, 45, 562−570. The formation of
pyrido[1,2-a]benzimidazole 8 might be due to the copper-catalyzed
direct intramolecular C−N coupling of 3f; see the related report:
(b) Wang, H.; Wang, Y.; Peng, C.; Zhang, J.; Zhu, Q. J. Am. Chem. Soc.
2010, 132, 13217−13219. (c) Masters, K.-S.; Rauws, T. R. M.; Yadav,
A. K.; Herrebout, W. A.; Van der Veken, B.; Maes, B. U. W. Chem. Eur.
J. 2011, 17, 6315−6320.
(17) A similar catalytic mechanism was already presented in our
previous paper; please refer to ref 3a.
(18) A copy of the deposited crystallographic data CCDC-955701
(I) can be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
(19) All reaction conditions were referred to the following. (a)
Reference 3b.. References 3a, 8f, and: (b) Pan, S.; Endo, K.; Shibata,
T. Org. Lett. 2011, 13, 4692−4695. (c) Pastine, S. J.; Gribkov, D. V.;
Same, D. J. Am. Chem. Soc. 2006, 128, 14220−14221. (d) Kutsumura,
N.; Kunimatsu, S.; Kagawa, K.; Otani, T.; Saito, T. Synthesis 2011,
3235−3240.
(20) The synthetic procedure followed that given in ref 3b and:
Sadighi, J. P.; Harris, M. C.; Buckwald, S. L. Tetrahedron Lett. 1998, 39,
5327−5330.
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