Alkylation of Aromatic Amines with Trialkyl Amines Catalyzed by a Defined Iridium Complex with a 2-Hydroxypyridylmethylene Fragment

Article abstract of DOI:10.1021/acs.organomet.9b00172

Six Cp?Ir complexes containing NN-bitentate chelate ligands [Cp?IrCl(C₅H₄CH₂C₅H₃OH)][Cl] (1), [Cp?IrCl(C₅H₄CH₂C₅H₃O)] (2), [Cp?IrCl(C₅H₄C₅H₃OH)] [Cl] (3), [Cp?IrCl(C₅H₄CH₂C₅H₄)][Cl] (4), [Cp?IrCl(CH₃OC₅H₃CH₂C₅H₃OCH₃)][Cl] (5), and [Cp?IrCl(CH₃OC₅H₃CH₂C₅H₃OH)][Cl] (6) were synthesized and characterized. Complex 1 could be transformed to 2 when reacted with NaO^tBu or NEt₃ via -OH deprotonation. These six complexes were tested as catalysts for mono-N-alkylation of amines with trialkyl amines, and complex 1 exhibited highest activity. The coupling reactions proceed under air condition, with 1 mol % catalyst loading without extra base in methanol at 120 °C and can be further accelerated by adding NR₃·HCl.

Full text of DOI:10.1021/acs.organomet.9b00172

Article
pubs.acs.org/Organometallics
Cite This: Organometallics XXXX, XXX, XXX−XXX
Alkylation of Aromatic Amines with Trialkyl Amines Catalyzed by a
Defined Iridium Complex with a 2‑Hydroxypyridylmethylene
Fragment
Danfeng Deng, Bowen Hu, Ziyu Zhang, Shengkai Mo, Min Yang, and Dafa Chen*
MIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, School of Chemical Engineering &
Technology, Harbin Institute of Technology, Harbin 150001, PR China
S
* Supporting Information
ABSTRACT: Six Cp*Ir complexes containing NN-bitentate
chelate ligands [Cp*IrCl(C5H4CH2C5H3OH)][Cl] (1), [Cp*IrCl-
(C5H4CH2C5H3O)] (2), [Cp*IrCl(C5H4C5H3OH)] [Cl] (3),
[ C p * I r C l ( C 5 H 4 C H 2 C 5 H 4 ) ] [ C l ] ( 4 ) , [ C p * I r C l -
(CH3OC5H3CH2C5H3OCH3)][Cl] (5), and [Cp*IrCl-
(CH3OC5H3CH2C5H3OH)][Cl] (6) were synthesized and char-
acterized. Complex 1 could be transformed to 2 when reacted with
NaOtBu or NEt3 via −OH deprotonation. These six complexes
were tested as catalysts for mono-N-alkylation of amines with
trialkyl amines, and complex 1 exhibited highest activity. The
coupling reactions proceed under air condition, with 1 mol % catalyst loading without extra base in methanol at 120 °C and can
be further accelerated by adding NR3·HCl.
quinazolinones,7c and quinolines,7d via borrowing hydrogen
INTRODUCTION
■
strategies (Figure 1, left). On the basis of their works, our
group designed a similar iridium complex [Cp*IrCl-
(HOC5H3CH2C5H3OH)][Cl] with two 2-hydroxypyridyl
moieties for methylation of amines and ketones with methanol
(Figure 1, middle).8 In these catalytic cycles, the ligands are
converted to bipyridonate forms through a metal−ligand
cooperative process. Transition metal complexes bearing mono
2-hydroxypyridyl moiety can also undergo a similar metal−
ligand cooperation.9 Thus, we were curious about the catalytic
activity of NN-Cp*Ir complexes containing one 2-hydroxypyr-
idyl fragment. As an update of our continuous interest in
borrowing hydrogen reactions,9g−i herein we report the
synthesis and reactivity of a new Cp*Ir complex [Cp*IrCl-
(C5H4CH2C5H3OH)][Cl] (1) bearing a 2-hydroxy-6-(2-
pridinylmethyl)pyridine ligand (C5H4CH2C5H3OH, L1) (Fig-
ure 1, right). Although the catalytic activity for methylation of
amines and ketones with methanol was not discovered,
complex 1 shows high catalytic efficiency and selectivity for
the mono-N-alkylation of aromatic amines with trialkyl amines
without extra base. It is worth mentioning that the reaction was
carried out under relatively mild conditions (120 °C) in
methanol which is regarded as an abundant atom-economical
and environmentally friendly solvent.
Amines have drawn considerable attention, as their motifs are
applied in pharmaceuticals, dyes, polymer materials, and
agrochemicals.1 Nevertheless, traditional approaches to amines
still suffer from many deficiencies. For instance, the best-
known ones for the synthesis of secondary amines are the N-
alkylation of primary amines utilizing alkyl halides as the
alkylating agents, which are mostly toxic and may suffer from
overalkylation.2 Therefore, it is significative to explore more
fresh syntheses to afford secondary amines.
The borrowing hydrogen reaction, which is also known as
hydrogen autotransfer, has become an efficient protocol to
synthesize secondary amines.3 One of the strategies is to use
alcohols,4 and the other is to use amines,5,6 as alkylating
reagents to react with primary amines. The latter method is
less well studied, and only a few examples have been reported
in the literature in which homogeneous catalysts were utilized
for the reactions of primary amines with trialkyl amines. As
shown in Scheme 1, Beller et al. reported an effective transfer
process for the reaction of aniline with trialkyl amines by the
Shvo catalyst in 24 h in 2008.6b In 2009, Williams and co-
workers explored an iridium catalyst to achieve the coupling of
primary amines with (iPr)2NH in high yield and excellent
selectivity at high temperature, and NEt3 was also applicable.6f
Ding and Wang’ groups also independently reported the
alkylation of aromatic amines with triethylamine in moderate
yields in the presence of AgNTf2 or base additive.6i−k
In recent years, the Li’s group employed a NN-Cp*Ir
complex bearing a functional 6,6′-dihydroxy-2,2′-bipyridine
(HOC5H3C5H3OH) ligand for the synthesis of different kinds
of organic compounds, such as α-alkylated ketones,7a,b
Received: March 14, 2019
© XXXX American Chemical Society
A
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DMSO-d6 shows one singlet for the −OH group at 13.03 ppm,
seven signals between 8.71 and 7.02 ppm for its aromatic
protons, two doublets at 4.68 and 3.70 ppm for the methylene
protons, and one singlet for Cp* at 1.56 ppm.
Scheme 1. State-of-the-Art N-Alkylation of Aniline with
Triethylamine
The molecular structure of 1 (Figure 2) was further
confirmed by X-ray crystallography. In the solid state, it is a
Figure 2. Molecular structure of complex 1. Hydrogen atoms (except
H1), solvent and Cl− anion have been omitted for clarity. Selected
bond distances (Å) and angle (deg): Ir(1)−N(1), 2.113(3); Ir(1)−
N(1A), 2.113(3); Ir(1)−Cl(1), 2.4101(15); C(1)−O(1), 1.428(7);
C(1)−N(1), 1.354(6); N(1)−C(5), 1.363(5); C(4)−C(5),
1.369(6); C(3)−C(4), 1.385(7); C(2)−C(3), 1.372(7); C(1)−
C(2), 1.382(7); N(1)−Ir(1)−N(1A), 85.6(2); N(1)−Ir(1)−Cl(1),
84.44(10); C(5)−C(6)−C(5A), 111.1(5).
cationic complex with the central Ir atom coordinating with
two pyridyl, one Cl atom and one Cp* group. The two
pyridine rings of the dipyridyl ligands are not coplanar, and the
C(5)−C(6)−C(5A) angle is 111.1(5)°. The C−C bonds in
the hydroxypyridyl ring are in the range of 1.385(7)−1.369(6)
Å, and the C(1)−O(1) distance (1.428(7) Å) is consistent
with a C−O single bond.10 The distances of Ir(1)−N(1), and
Ir(1)−Cl(1) are 2.113(3) and 2.4101(15)Å, respectively.
Complex 1 was further treated with 1.2 equiv of NaOtBu in
water at room temperature and [Cp*IrCl(C5H4CH21C5H3O)]
(2) was produced in 79% yield (Scheme 3). The H NMR
Figure 1. Li’s iridium complex a (left), our previous iridium complex
b (middle), and complex 1 in this work (right).
RESULTS AND DISCUSSION
■
Scheme 3. Synthesis of 2
Synthesis and Characterization of the Ligand
Precursor and Ir Complexes. As shown in Scheme 2, L1
was synthesized by the reaction of HBr with 2-methoxy-6-(2-
pyridinylmethyl)pyridine at reflux for 3 h in 90% yield. When
L1 was treated with [Cp*IrCl2]2 in refluxing CH3OH for 24 h,
complex [Cp*IrCl(C5H4CH2C5H3OH)][Cl] (1) was isolated
1
as a yellow solid in 82% yield. The H NMR spectrum of 1 in
Scheme 2. Synthesis of L1 and 1
spectrum of 2 in DMSO-d6 shows seven signals between 8.72
and 6.48 ppm for its aromatic protons, two doublets for the
methylene group at 4.41 and 3.60 ppm, and one singlet at 1.55
ppm for Cp*. 2 could also be generated by treating 1 with 2
equiv of triethylamine in 76% yield. X-ray diffraction analysis
shows the iridium center is coordinated with two pyridyl, one
Cl atom and one Cp* group (Figure 3), which is similar to 1.
The N(1)−Ir(1)−N(2), N(1)−Ir(1)−Cl(1) and N(2)−
Ir(1)−Cl(1) angles are 86.8, 88.1, and 83.6°, respectively.
The distances of Ir(1)−N(1), Ir(1)−N(2) and Ir(1)−Cl(1)
are 2.125(11), 2.108(13) and 2.421(3) Å, respectively. The
B
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different from complex b shown in Figure 1,8 no activity was
discovered, suggesting the bipyridonate structure is important
for methanol dehydrogenation. Fortunately, these complexes
can catalyze the alkylation of aromatic amines with trialkyl
amines. To find the optimal conditions, the reaction of aniline
with NEt3 was selected as the model reaction (Table 1). At
Table 1. Optimization of Reaction Conditions for the
a
Alkylation of Aniline
Figure 3. Molecular structure of complex 2. Hydrogen atoms and
solvent have been omitted for clarity. Selected bond distances (Å) and
angle (deg): Ir(1)−N(1), 2.125(11); Ir(1)−N(2), 2.108(13); Ir(1)−
Cl(1), 2.421(3); C(1)−O(1), 1.25(3); C(1)−N(1), 1.41(3); N(1)−
C(5), 1.34(3); C(4)−C(5), 1.39(3); C(3)−C(4), 1.38(3); C(2)−
C(3), 1.37(3); C(1)−C(2), 1.40(3); N(1)−Ir(1)−N(2), 86.8(7);
N(1)−Ir(1)−Cl(1), 88.1(3); N(2)−Ir(1)−Cl(1), 83.6(4); C(5)−
C(6)−C(7), 114.8(16).
NEt3·HCl
conversion
yield
c
b
entry cat. NEt3 (mmol)
(%)
(%)
(%)
1
2
3
4
5
6
7
8
1
2
3
4
5
6
1
2
1
2
1
2
1
1
1
2
2
2
2
2
2
1
1
2
2
2
2
0
0
0
0
0
0
0
0
10
10
20
20
0
0
20
20
74
65
65
17
20
49
55
30
92
93
100
100
0
70
58
62
11
16
41
50
24
87
90
94
96
0
C(1)−N(1) bond is 1.41(3) Å, and the C(1)−C(2) distance is
1.40(3) Å, obviously longer than the other bonds in the same
ring, suggesting they are more similar to single bonds. The
O(1)−C(1) distance (1.25(3) Å) is comparable to those of a
pyridonate ruthenium complex supported by deprotonated
6,6′-dihydroxyterpyridine developed by Szymczak’s group,
suggesting a CO bond.10
9
10
11
12
13
14
15
16
d
e
f
ethylamine
diethylamine
2
2
Complexes [Cp*IrCl(C5H4C5H3OH)][Cl] (3), [Cp*IrCl-
( C 5 H 4 C H 2 C 5 H 4 ) ] [ C l ] ( 4 ) , [ C p * I r C l -
(CH3OC5H3CH2C5H3OCH3)][Cl] (5), and [Cp*IrCl-
(CH3OC5H3CH2C5H3OH)][Cl] (6) were synthesized follow-
ing a similar procedure as described for 1 (Scheme 4). When
0
100
0
0
93
0
g
a
Aniline (1.0 mmol), methanol (2 mL), air, catalyst (1 mol %), 120
°C, 12 h. Determined by GC analysis on the basis of aniline. Yields
determined by GC analysis by using p-xylene as the internal standard.
Reaction was carried out with 2 mmol ethylamine. Reaction was
carried out with 2 mmol diethylamine. Reaction was carried out
under N2. Reaction was carried out without catalyst.
b
c
d
e
Scheme 4. Synthesis of 3−6
f
g
120 °C, in the presence of 1 mol % complexes 1−6 and 2 mL
of CH3OH, the reactions proceeded in a 25 mL Schlenk tube
under air condition. When 2 equiv of NEt3 were added, the
product N-ethylbenzenamine was afforded in 70% yield when
1 was used as catalyst (Table 1, entry 1). Complexes 2−6 were
not as active as 1 under the same condition, giving yields of 58,
62, 11, 16, and 41%, respectively (Table 1, entries 2−6). If the
amount of NEt3 was decreased to 1 equiv, the yields were
lowered, but 1 was still more active than 2 (Table 1, entries 7
and 8). The results were surprising, because as described
above, complex 1 can react with NEt3 to produce complex 2,
so 2 should be the intermediate of 1. We speculated that the
other product of 1 with NEt3, NEt3·HCl, might act as a
facilitator for this reaction. In order to testify our inference, 10
and 20% NEt3·HCl were added, respectively, and the yields
were increased obviously, no matter if 1 or 2 as the catalyst
(Table 1, entries 9−12). The other product, NHEt2, was also
detected in around 64% yield by GC analysis under the
reaction conditions of entry 11 in Table 1. The results further
proved that 2 is the intermediate of 1 and suggest NEt3·HCl
might act as the acceptor of the generated NHEt2. Another two
aliphatic amines, ethylamine and diethylamine, were tested,
and no conversion was found (Table 1, entries 13 and 14).
The N2 atmosphere had almost no influence on the reaction
(Table 1, entry 15). When the reaction was carried out without
6-hydroxy-2,2′-bipyridine,11 2-(2-pyridylmethyl)pyridine,12 2-
methoxy-6-((6-methoxypyridin-2-yl)methyl)pyridine,8 and 2-
hydroxy-6-((6-methoxypyridin-2-yl)methyl)pyridine were trea-
ted with [Cp*IrCl2]2 in refluxing CH3OH for 24 h, complexes
3−6 were isolated as yellow solids in 90, 84, 89, and 91%
yields, respectively. The 1H NMR spectrum of 3 exhibits seven
signals between 8.93 and 7.31 ppm for its aromatic protons.
For complex 4, besides the aromatic protons, two doublets at
4.90 and 3.78 ppm for its −CH2− group appear. While for
1
complexes 5 and 6, the H NMR spectra show uncoupled
methylene signals at 4.05 and 3.86 ppm, respectively, similar to
the complex [Cp*IrCl(HOC5H3CH2C5H3OH)][Cl] reported
in another work.8
Catalysis. Initially, complexes 1−6 were tried as catalysts
for methylation of amines and ketones with methanol, while
C
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catalyst, no product was detected (Table 1, entry 16). In
addition, different solvents had been screened and the results
showed that CH3OH is most suitable for this reaction (Table
2).
Table 3. Ir-Catalyzed Selective Mono-Alkylation of
Anilines
a
a
Table 2. Solvent Screening
b
c
entry
solvent
conversion (%)
yield (%)
1
2
3
4
5
CH3OH
CH3CH2OH
H2O
toluene
THF
100
89
27
5
94
85
20
2
16
12
a
Aniline (1.0 mmol), methanol (2 mL), NEt3 (2.0 mmol), NEt3·HCl
(20%, 0.2 mmol), catalyst 1 (1 mol %), 120 °C, 12 h, air.
b
c
Determined by GC analysis on the basis of aniline. Yields
determined by GC analysis by using p-xylene as the internal standard.
With the optimized reaction conditions, various aromatic
amines were tested for the alkylation reaction and these results
are listed in Table 3. In general, the reaction is applicable to
most aromatic amines. Reactions of ortho-, meta-, and para-
brominated anilines gave the corresponding products in 83−
95% yields (Table 3, entries 2−4). Other para-substituted
anilines, such as 4-chloroaniline, 4-(1H-pyrrol-1-yl)aniline, p-
toluidine, and 4-methoxyaniline, also reacted with NEt3 to
afford mono-N-alkylated aniline derivatives in high yields (83−
94%) (Table 3, entries 4−8). A strong electron-withdrawing
group in the para position (4-nitroaniline) decreased the
isolated yield to 69% (Table 3, entry 9). The ortho-methyl and
-methoxy substituted anilines gave relatively lower yields,
probably due to steric hindrance effect (Table 3, entries 10 and
11). 2-Naphthylamine was also tested, and the corresponding
product was isolated in moderate yield (Table 3, entries 12).
When two amino groups were present, both could be
monoalkylated (Table 3, entry 13). For the substrates
containing a coordination group, such as 2-aminopyridine, 4-
cyanoaniline, and benzooxazol-2-ylamine, the yields were
much lower (30−55%) (Table 3, entries 14−16). In addition,
when the reaction was carried out with 2 mmol of N,N-
dipropyl-1-propanamine, it afforded the product N-propylani-
line in 83% yield. Similarly, if 20% HCl was added, the reaction
was accelerated (Table 3, entry 17). When the alkylating
reagent was replaced by an unsymmetrical trialkylamine, N-
butyldimethylamine, the ratio of N-methylbenzenamine and N-
butylbenzenamine was about 5:95 according to GC analysis,
and the isolated yield of N-butylbenzenamine was about 85%
(Table 3, entry 18).
The reaction mechanism of our work may proceed through a
borrowing hydrogen mechanism (Scheme 5).5,6 In the
presence of NEt3, complex 1 is first transformed to 2. The
Cl atom then leaves as an anion, and intermediate A with an
open site forms. After the coordination with NEt3, β-hydride
elimination occurs, with the conversion of B to C,
accompanied by the formation of iminium ion D. It is possible
that one of the pyridyl rings dissociates from the Ir center
during this step, because β-hydride elimination needs an open
site. Aromatic amine then attacks the iminium ion, followed by
the release of NHEt2. At last, the hydride connecting with Ir
transfers to newly formed iminium ion F, and the final
a
Aniline (1.0 mmol), methanol (2 mL), NEt3 (2.0 mmol), NEt3·HCl
b
(20%, 0.2 mmol), catalyst 1 (1 mol %), 120 °C, 12 h, air. Yields of
isolated product. Reaction was carried out with 2 mmol N,N-
dipropyl-1-propanamine, without NEt3·HCl. Reaction was carried
out with 2 mmol N,N-dipropyl-1-propanamine and 20% HCl, without
NEt3·HCl. Reaction was carried out with 2 mmol N-butyldimethyl-
amine without NEt3·HCl.
c
d
e
secondary amine is formed, with the regeneration of A. As
described in Table 1, NHEt2 and NH2Et are not suitable for
this methodology, probably due to iminium ion D being less
D
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Scheme 5. Proposed Mechanism of Alkylation with Iridium Catalyst
million (ppm) relative to the carbon resonance of CDCl3 (77.0 ppm)
or DMSO-d6 (39.5 ppm). Elemental analyses were performed on a
PerkinElmer 240C analyzer. The high-resolution mass spectrum (HR-
MS) was recorded on a Varian 7.0 T FTICR-MS by the ESI
technique. Single-crystal X-ray diffraction was carried out as follows:
Suitable crystals were placed in a cooled N2 stream at 173(2) K on a
Bruker D8 Quest X-ray diffractometer. Data collections were
performed using four-circle kappa diffractometers equipped with
CCD detectors. Data were reduced and then corrected for
absorption.13 Solution, refinement, and geometrical calculations for
all crystal structures were performed by SHELXTL.14 All the GC
measurements were performed on Agilent GC7890A equipment using
Agilent 19091B-102 (25 m, 220 μm) column.
stable, which also explains the selectivity when N-butyldime-
thylamine was selected as the alkylating reagent (Table 3, entry
18).
CONCLUSIONS
■
In summary, six well-defined Cp*Ir complexes (1−6)
containing NN-bitentate chelate ligands were synthesized
and characterized. Complex 1 contains a 2-hydroxypyridyl
fragment, which was translated into pyridonate complex 2 in
the presence of a base. Complex 1 is an efficient catalyst for
monoalkylation of amines with trialkyl amines, and 2 is its
intermediate. The catalytic reaction proceeds under relatively
mild conditions (120 °C) in methanol under air. No extra base
is needed, and the reaction can be promoted by NR3·HCl.
Furthermore, it is highly selective, and no imine derivatives and
disubstituted aniline were detected. Our current work provides
an alternative method for the monoalkylation of primary
amines, and other experimental studies are ongoing to explore
more active transition-metal catalysts.
Synthesis of 2-Methoxy-6-((pyridinyl)methyl)pyridine. A
solution of n-BuLi (16.7 mL, 2.4 M, 40.0 mmol) was added to 2-
methoxy-6-methylpyridine (4.9 g, 40.0 mmol) in 50 mL of THF at
−78 °C. When temperature naturally warmed to −20 °C, 2-
fluoropyridine (1.9 g, 20.0 mmol) was added. The reaction mixture
was stirred at −20 °C for 3 h and refluxed overnight. After addition of
25 mL of water, the water phase was extracted with CH2Cl2. The
crude product was purified by column chromatography on silica gel
(petroleum ether/ethyl acetate, v/v = 10:1) to give 2-methoxy-6-
((pyridinyl)methyl)pyridine (3.5 g, 87%) as a yellow liquid. HR-MS
EXPERIMENTAL SECTION
■
1
(ESI) Calcd for C12H12N2O + H: 201.1028. Found: 201.1025. H
All the manipulations were carried out under an atmosphere of dry
nitrogen using vacuum-line and oven-dried standard Schlenk
techniques if not otherwise mentioned. All solvents were distilled
from appropriate drying agents under N2 before use. All reagents were
obtained from commercial suppliers and used without further
purification. The 1H and 13C NMR spectra were recorded on a
NMR (400 MHz, CDCl3, ppm): 8.56 (d, J = 4.8 Hz, 1H), 7.63 (t, J =
8.0 Hz, 1H), 7.50 (d, J = 8.4 Hz, 1H), 7.33 (t, J = 5.2 Hz, 1H), 7.17−
1.14 (m, 1H), 6.81 (d, J = 7.2 Hz, 1H), 6.59 (d, J = 8.0 Hz, 1H), 4.26
(s, 2H), 3.91 (s, 3H). 13C NMR (100 Hz, CDCl3, ppm): 163.7, 159.7,
157.0, 149.2, 138.9, 123.7, 121.3, 115.9, 108.1, 53.2, 46.9.
Synthesis of L1. A solution of 2-methoxy-6-((pyridinyl)methyl)-
pyridine (2.65 g, 13.3 mmol) in 10 mL of HBr (40% in water) was
heated at reflux for 3 h. After cooling to room temperature, the yellow
1
Bruker Avance 400 spectrometer. The H NMR chemical shifts were
referenced to the residual solvent as determined relative to Me4Si (δ =
0 ppm). The 13C{1H} chemical shifts were reported in parts per
E
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solution was neutralized by slow addition of a saturated aqueous
solution of NaOH. The water phase was extracted with CH2Cl2. The
combined organic extracts were dried over Na2SO4, filtered, and
concentrated to afford L1 as a white solid (2.30 g, 93%). Mp: 155−
159 °C. HR-MS (ESI) Calcd for C11H10N2O + H: 187.0871. Found:
Method B. NEt3 (0.017 g, 0.16 mmol) was added into a solution of
1 (0.05 g, 0.08 mmol) in CH3OH (5 mL) under stirring for 1 h.
Then, the precipitate was filtered off and the filtrate was concentrated.
The crude product was washed with ether to give 2 as a yellow
powder (0.036 g, 76%).
Synthesis of 3. A solution of 6-hydroxy-2,2′-bipyridine (0.1 g,
0.58 mmol) and [Cp*IrCl2]2 (0.24 g, 0.29 mmol) was refluxed in
dried CH3OH (15 mL) with stirring for 24 h. The mixture was
allowed to cool to room temperature, and the yellow precipitate was
collected, washed with acetone, and dried under vacuum to provide 3
as a yellow powder (0.15 g, 90%). Mp: 178 °C (dec.). Anal. Calcd for
C20H23Cl2IrN21O: C, 42.10; H, 4.06; N, 4.91. Found: C, 42.26; H,
4.07; N, 4.88. H NMR (400 MHz, DMSO-d6, ppm): 13.78 (s, 1H),
8.93 (d, J = 4.8 Hz, 1H), 8.64 (d, J = 8.4 Hz, 1H), 8.26 (t, J = 8.0 Hz,
1H), 8.14 (d, J = 7.6 Hz, 1H), 8.05 (t, J = 8.0 Hz, 1H), 7.80 (t, J = 6.4
Hz, 1H), 7.31 (d, J = 7.6 Hz, 1H), 1.60 (s, 15H). No satisfactory 13C
NMR data could be obtained due to low solubility.
Synthesis of 4. A solution of 2-(2-pyridylmethyl)pyridine (0.25 g,
1.47 mmol) and [Cp*IrCl2]2 (0.6 g, 0.74 mmol) was refluxed in dried
CH3OH (20 mL) with stirring for 24 h. The mixture was allowed to
cool to room temperature, and the yellow precipitate was collected,
washed with acetone, and dried under vacuum to provide 4 as a
yellow powder (0.23 g, 84%). Mp: 175−177 °C (dec.). Anal. Calcd
for C21H25Cl2IrN2: C, 44.36; H, 4.43; N, 4.93. Found: C, 44.23; H,
4.47; N, 4.84. 1H NMR (400 MHz, DMSO-d6, ppm): 8.76 (d, J = 5.8
Hz, 2H), 8.09 (t, J = 7.6 Hz, 2H), 7.91 (d, J = 7.6 Hz, 2H), 7.57 (t, J =
5.8 Hz, 2H), 4.90 (d, J = 15.6 Hz, 1H), 3.78 (d, J = 15.6 Hz, 1H),
1.55 (s, 15H). 13C NMR (100 Hz, DMSO-d6, ppm): 156.3, 155.6,
141.3, 126.3, 126.1, 88.6, 46.0, 8.8.
1
187.0872. H NMR (400 MHz, CDCl3, ppm): 8.62 (d, J = 4.0 Hz,
1H), 7.70 (t, J = 8.0 Hz, 1H), 7.38−7.34 (m, 2H), 7.27−7.24 (m,
1H), 6.45 (d, J = 8.8 Hz, 1H), 6.14 (d, J = 6.8 Hz, 1H), 4.04 (s, 2H)
(the −OH proton did not appear). 13C NMR (100 Hz, CDCl3, ppm):
165.3, 156.6, 149.5, 146.6, 141.7, 137.1, 123.7, 122.2, 117.7, 106.0,
41.2.
Synthesis of 2-(tert-Butoxy)-6-((6-methoxypyridin-2-yl)-
methyl)pyridine. A solution of n-BuLi (11.7 mL, 2.4 M, 28.1
mmol) was added to 2-methoxy-6-methylpyridine (3.6 g, 28.1 mmol)
in 50 mL of THF at −78 °C. When temperature naturally warmed to
−20 °C, 2-bromo-6-tert-butoxypyridine (3.2 g, 13.9 mmol) was
added. The reaction mixture was stirred at −20 °C for 3 h and
refluxed overnight. After addition of 25 mL of water, the water phase
was extracted with CH2Cl2. The crude product was purified by
column chromatography on silica gel (petroleum ether/ethyl acetate,
v/v = 5:1) to give 2-(tert-butoxy)-6-((6-methoxypyridin-2-yl)methyl)-
pyridine (3.0 g, 80%) as a yellow liquid. HR-MS (ESI) Calcd for
1
C16H20N2O2 + H: 273.1603. Found: 273.1601. H NMR (400 MHz,
CDCl3, ppm): 7.48−7.40 (M, 2H), 6,78−6.76 (M, 2H), 6.55 (d, J =
8.4 Hz, 1H), 6.47 (d, J = 8.4 Hz, 1H), 4.08 (s, 2H), 3.90 (s, 3H), 1.51
(s, 9H). 13C NMR (100 Hz, CDCl3, ppm): 163.6, 163.3, 157.7, 156.8,
138.7, 116.1, 115.4, 110.4, 107.7, 79.3, 53.2, 46.6, 28.6.
Synthesis of 2-Hydroxy-6-((6-methoxypyridin-2-yl)methyl)-
pyridine. A solution of 2-(tert-butoxy)-6-((6-methoxypyridin-2-
yl)methyl)pyridine (0.6 g, 2.2 mmol) in 5 mL of CH2Cl2 and 8 mL
of CF3COOH was stirred for 30 min at room temperature. The
solution was neutralized by slow addition of a saturated aqueous
solution of NaOH. The water phase was extracted with CH2Cl2. The
combined organic extracts were dried over Na2SO4, filtered, and
concentrated to afford 2-hydroxy-6-((6-methoxypyridin-2-yl)methyl)-
pyridine as a yellow solid (0.44 g, 91%). Mp: 146 °C. HR-MS (ESI)
Synthesis of 5. A solution of 2-methoxy-6-((6-methoxypyridin-2-
yl)methyl)pyridine (0.10 g, 0.43 mmol) and [Cp*IrCl2]2 (0.18 g, 0.22
mmol) was refluxed in dried CH3OH (15 mL) with stirring for 24 h.
The mixture was allowed to cool to room temperature, and the
precipitate was collected, washed with acetone, and dried under
vacuum to provide 5 as a yellow powder (0.12 g, 89%). Mp: 171 °C
(dec.). Anal. Calcd for C23H29Cl2IrN2O2: C, 43.95; H, 4.65; N, 4.46.
1
Calcd for C12H12N2O2 + H: 217.0977. Found: 217.0979. H NMR
1
Found: C, 43.93; H, 4.65; N, 4.69. H NMR (400 MHz, DMSO-d6,
(400 MHz, CDCl3, ppm): 12.43 (s, 1H), 7.50 (t, J = 8.0 Hz, 1H),
7.36−7.32 (m, 1H), 6.87 (d, J = 7.2 Hz, 1H), 6.63 (d, J = 8.0 Hz,
1H), 6.43 (d, J = 9.2 Hz, 1H), 6.10 (d, J = 6.8 Hz, 1H), 3.94 (s, 2H),
3.93 (s, 3H). 13C NMR (100 Hz, CDCl3, ppm): 164.9, 163.8, 153.8,
146.5, 141.5, 139.4, 117.7, 115.9, 109.3, 105.6, 53.5, 40.7.
ppm): 7.62 (t, J = 7.6 Hz, 2H), 6.86 (d, J = 7.2 Hz, 2H), 6.64 (d, J =
8.0 Hz, 2H), 4.05 (s, 2H), 3.81 (s, 6H), 1.63 (s, 15H). 13C NMR
(100 Hz, DMSO-d6, ppm): 163.5, 157.4, 139.9, 116.6, 108.4, 92.6,
55.4, 53.3, 8.7.
Synthesis of 6. A solution of 2-hydroxy-6-((6-methoxypyridin-2-
yl)methyl)pyridine (0.10 g, 0.46 mmol) and [Cp*IrCl2]2 (0.19 g, 0.23
mmol) was refluxed in dried CH3OH (15 mL) with stirring for 24 h.
The mixture was allowed to cool to room temperature and the
precipitate was collected, washed with acetone and dried under
vacuum to provide 6 as a yellow powder (0.13 g, 91%). Mp: 170 °C
(dec.). Anal. Calcd for C22H27Cl2IrN2O2: C, 42.99; H, 4.43; N, 4.56.
Synthesis of 1. A solution of L1 (0.09 g, 0.48 mmol) and
[Cp*IrCl2]2 (0.2 g, 0.25 mmol) was refluxed in dried CH3OH (20
mL) with stirring for 24 h. The mixture was allowed to cool to room
temperature and the yellow precipitate was collected, washed with
acetone, and dried under vacuum to provide 1 as a yellow solid (0.23
g, 82%). Single crystals suitable for X-ray crystallographic determi-
nation were grown with CH3OH/ether at 0 °C. Mp: 195 °C (dec.).
Anal. Calcd for C21H25Cl2IrN2O: C, 43.15; H, 4.31; N, 4.79. Found:
1
Found: C, 42.78; H, 4.55; N, 4.55. H NMR (400 MHz, DMSO-d6,
1
ppm): 11.6 (s, 1H), 7.66 (t, J = 7.6 Hz, 1H), 7.34 (t, J = 7.6 Hz, 1H),
6.89 (d, J = 7.2 Hz, 1H), 6.69 (d, J = 8.4 Hz, 1H), 6.17 (d, J = 8.4 Hz,
1H), 5.98 (d, J = 5.6 Hz, 1H), 3.86 (s, 2H), 3.81 (s, 3H), 1.63 (s,
15H). 13C NMR (100 Hz, DMSO-d6, ppm): 163.6, 163.5, 155.4,
147.5, 141.5, 140.3, 117.5, 116.3, 109.0, 105.0, 92.6, 55.4, 53.4, 8.7.
General Procedure for the Alkylation of Anilines. Under air
condition, in a 25 mL Schlenk tube, a mixture of amines (1.0 mmol),
methanol (2 mL), complex 1 (5.8 mg, 1 mol %), trialkyl amines (2.0
mmol), and NEt3·HCl (20%, 0.2 mmol) were stirred at 120 °C for 12
h. Then, it was allowed to cool to room temperature, and 0.1 mL of
the reaction mixture was sampled and immediately diluted with 5 mL
of CH3OH precooled to 0 °C for GC analysis for calculating
conversation and product selectivity of the reaction. After the reaction
was completed, the reaction mixture was condensed under reduced
pressure and subjected to purification by flash silica gel column
chromatography to afford the target product, which was identified by
NMR analyses. All analytical data of the known compounds are
consistent with those reported in the literature.
C, 43.43; H, 4.32; N, 4.81. H NMR (400 MHz, DMSO-d6, ppm):
13.03 (s, 1H), 8.71 (d, J = 5.6 Hz, 1H), 8.04 (t, J = 7.6 Hz, 1H), 7.83
(d, J = 7.6 Hz, 1H), 7.78 (t, J = 8.0 Hz, 1H), 7.52 (t, J = 6.4 Hz, 1H),
7.26 (d, J = 7.2 Hz, 1H), 7.02 (d, J = 8.4 Hz, 1H), 4.68 (d, J = 14.8
Hz, 1H), 3.70 (d, J = 14.8 Hz, 1H), 1.56 (s, 15H). 13C NMR (100
Hz, DMSO-d6, ppm):165.6, 157.4, 155.7, 153.4, 142.6, 141.0, 125.6,
125.3, 116.7, 111.4, 88.1, 49.1, 9.2.
Synthesis of 2. Method A. NaOtBu (0.039 g, 0.41 mmol) was
added into a solution of 1 (0.2 g, 0.34 mmol) in H2O (10 mL) under
stirring for 1 h. Then, the precipitate was filtered off, and the filtrate
was concentrated. The crude product was recrystallized with
CH3OH/ether to give 2 as a yellow powder (0.15 g, 79%). Mp:
180 °C (dec.). Anal. Calcd for C21H24ClIrN2O: C, 46.02; H, 4.41; N,
5.11. Found: C, 46.31; H, 4.54; N, 5.06. 1H NMR (400 MHz,
DMSO-d6, ppm): 8.72 (d, J = 5.6 Hz, 1H), 7.99 (t, J = 7.6 Hz, 1H),
7.76 (d, J = 7.6 Hz, 1H), 7.47 (t, J = 6.8 Hz, 1H), 7.37 (br s, 1H),
6.69 (br s, 1H), 6.48 (br s, 1H), 4.41 (d, J = 14.4 Hz, 1H), 3.60 (d, J =
14.4 Hz, 1H), 1.55 (s, 15H). 13C NMR (100 Hz, DMSO-d6, ppm):
168.4, 159.3, 155.8, 150.7, 140.1, 136.6, 124.7, 124.2, 115.5, 104.1,
86.7, 47.9, 9.4.
N-Ethylaniline.6h 1H NMR (400 MHz, CDCl3, ppm): 7.17 (t, J =
7.2 Hz, 2H), 6.69 (t, J = 7.6 Hz, 1H), 6.61 (d, J = 7.6 Hz, 2H), 3.16
F
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(q, J = 7.2 Hz, 2H), 1.25 (t, J = 7.2 Hz, 3H). 13C NMR (100 Hz,
CDCl3, ppm): 148.5, 129.3, 117.2, 112.8, 38.5, 14.9.
(t, J = 7.2 Hz, 3H). 13C NMR (100 Hz, CDCl3, ppm): 162.2, 148.5,
143.0, 123.9, 120.7, 116.1, 108.7, 38.0, 15.2.
2-Bromo-N-ethylaniline.6i 1H NMR (400 MHz, CDCl3, ppm):
7.40 (d, J = 7.6 Hz, 1H), 7.17 (t, J = 7.2 Hz, 1H), 6.61 (d, J = 8.0 Hz,
1H), 6.55 (t, J = 7.6 Hz, 1H), 3.19 (q, J = 7.2 Hz, 2H), 1.30 (t, J = 7.2
Hz, 3H). 13C NMR (100 Hz, CDCl3, ppm): 145.2, 132.4, 128.5,
117.5, 111.3, 109.6, 38.4, 14.7.
N-Propylaniline.5c 1H NMR (400 MHz, CDCl3, ppm): 7.16 (t, J =
8.8 Hz, 2H), 6.68 (t, J = 7.6 Hz, 1H), 6.60 (d, J = 3.6 Hz, 2H), 3.07
(t, J = 6.8 Hz, 2H), 1.68−1.59 (m, 2H), 0.99 (t, J = 7.2 Hz, 3H). 13C
NMR (100 Hz, CDCl3, ppm): 148.5, 129.2, 117.1, 112.7, 45.8, 22.8,
11.7.
3-Bromo-N-ethylaniline.15 1H NMR (400 MHz, CDCl3, ppm):
7.00 (t, J = 8.0 Hz, 1H), 6.79 (d, J = 7.6 Hz, 1H), 6.72 (t, J = 2.0 Hz,
1H), 6.49 (d, J = 7.6 Hz, 1H), 3.12 (q, J = 6.8 Hz, 2H), 1.24 (t, J = 6.8
Hz, 3H). 13C NMR (100 Hz, CDCl3, ppm): 149.7, 130.5, 123.3,
119.8, 115.1, 111.5, 38.3, 14.7.
N-Butylaniline.5c 1H NMR (400 MHz, CDCl3, ppm): 7.17 (t, J =
8.4 Hz, 2H), 6.69 (t, J = 7.6 Hz, 1H), 6.60 (d, J = 7.6 Hz, 2H), 3.11
(t, J = 6.8 Hz, 2H), 1.64−1.57 (m, 2H), 1.47−1.38 (m, 2H), 0.95 (t, J
= 7.2 Hz, 3H). 13C NMR (100 Hz, CDCl3, ppm): 148.6, 129.2, 117.1,
112.7, 43.7, 31.7, 20.3, 14.0.
4-Bromo-N-methylaniline.16 1H NMR (400 MHz, CDCl3, ppm):
7.23 (d, J = 8.8 Hz, 2H), 6.46 (d, J = 8.8 Hz, 2H), 3.11 (q, J = 6.8 Hz,
2H), 1.23 (t, J = 7.2 Hz, 3H). 13C NMR (100 Hz, CDCl3, ppm):
147.5, 131.9, 114.3, 108.6, 38.5, 14.8.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.9b00172.
■
S
4-Chloro-N-ethylaniline.6i 1H NMR (400 MHz, CDCl3, ppm):
7.10 (d, J = 8.8 Hz, 2H), 6.50 (d, J = 8.8 Hz, 2H), 3.11 (q, J = 7.2 Hz,
2H), 1.23 (t, J = 7.2 Hz, 3H). 13C NMR (100 Hz, CDCl3, ppm):
147.1, 129.0, 121.6, 113.8, 38.6, 14.8.
Crystallographic details for complexes 1 and 2, and
NMR spectra of the new compounds (PDF)
4-(Cyclopenta-2,4-dien-1-yl)-N-ethylaniline. 1H NMR (400 MHz,
CDCl3, ppm): 7.20 (d, J = 8.8 Hz, 2H), 6.96 (t, J = 2.0 Hz, 2H), 6.64
(d, J = 8.8 Hz, 2H), 6.29 (t, J = 2.0 Hz, 2H), 3.18 (q, J = 7.2 Hz, 2H),
1.28 (t, J = 7.2 Hz, 3H). 13C NMR (100 Hz, CDCl3, ppm): 146.7,
131.9, 122.5, 119.8, 113.2, 109.3, 38.8, 14.9. HR-MS (ESI) Calcd for
C12H14N2 + H: 187.1235. Found: 187.1232.
Accession Codes
CCDC 1880041 and 1880042 contain the supplementary
crystallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
N-Ethyl-4-methylaniline.6h 1H NMR (400 MHz, CDCl3, ppm):
6.98 (d, J = 8.0 Hz, 2H), 6.54 (d, J = 8.4 Hz, 2H), 3.13 (q, J = 7.2 Hz,
2H), 2.23 (s, 3H), 1.23 (t, J = 7.2 Hz, 3H). 13C NMR (100 Hz,
CDCl3, ppm): 146.4, 129.8, 126.5, 113.1, 38.9, 20.5, 15.0.
N-Ethyl-4-methoxyaniline.6h 1H NMR (400 MHz, CDCl3, ppm):
6.78 (d, J = 9.2 Hz, 2H), 6.58 (d, J = 8.8 Hz, 2H), 3.74 (s, 3H), 3.11
(q, J = 7.2 Hz, 2H), 1.23 (t, J = 7.2 Hz, 3H). 13C NMR (100 Hz,
CDCl3, ppm): 152.1, 142.9, 114.9, 114.1, 55.8, 39.4, 15.0.
N-Ethyl-2-methylaniline.16 1H NMR (400 MHz, CDCl3, ppm):
7.12 (d, J = 7.6 Hz, 1H), 7.04 (d, J = 7.2 Hz, 1H), 6.67−6.60 (m,
2H), 3.19 (q, J = 7.2 Hz, 2H), 2.13 (s, 3H), 1.30 (t, J = 7.2 Hz, 3H).
13C NMR (100 Hz, CDCl3, ppm): 146.4, 130.0, 127.2, 121.7, 116.8,
109.7, 38.4, 17.5, 15.0.
AUTHOR INFORMATION
Corresponding Author
*E-mail: dafachen@hit.edu.cn.
■
ORCID
Bowen Hu: 0000-0001-9815-8938
Min Yang: 0000-0002-2319-8086
Dafa Chen: 0000-0002-7650-4024
N-Ethyl-2-methoxyaniline.17 1H NMR (400 MHz, CDCl3, ppm):
6.87 (T, J = 7.6 Hz, 1H), 6.76 (d, J = 8.0 Hz, 1H), 6.68−6.60 (m,
2H), 3.84 (s, 3H), 3.17 (q, J = 7.2 Hz, 2H), 1.29 (t, J = 7.2 Hz, 3H).
13C NMR (100 Hz, CDCl3, ppm): 146.8, 138.4, 121.3, 116.3, 109.8,
109.3, 55.4, 38.2, 14.9.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
N-Ethylnaphthalen-2-amine.18 1H NMR (400 MHz, CDCl3,
ppm): 7.66 (d, J = 8.0 Hz, 1H), 7.60 (d, J = 8.8 Hz, 2H), 7.35 (t, J =
7.6 Hz, 1H), 7.18 (t, J = 7.6 Hz, 1H), 6.85 (d, J = 8.8 Hz, 1H), 6.79
(d, J = 2.4 Hz, 1H), 3.24 (q, J = 7.2 Hz, 2H), 1.30 (t, J = 7.2 Hz, 3H).
13C NMR (100 Hz, CDCl3, ppm): 146.3, 129.0, 127.9, 127.7, 126.5,
126.2, 122.1, 118.3, 104.4, 38.6, 14.9.
This work was supported by the National Natural Science
Foundation of China (Nos. 21672045 and 21871068), the
National Science and Technology Pillar Program during the
Twelfth Five-Year Plan Period (2015BAD15B0502), the China
Postdoctoral Science Foundation (2016M591519), the
Heilongjiang Postdoctoral Foundation (LBH-Z16069), and
the National Natural Science Foundation of Heilongjiang
(Nos. B2018005 and LC2018005).
N,N′-Dietheylbenzidine.19 1H NMR (400 MHz, CDCl3, ppm):
7.37 (d, J = 7.6 Hz, 4H), 6.65 (d, J = 8.8 Hz, 4H), 3.18 (q, J = 7.2 Hz,
4H), 1.26 (t, J = 7.2 Hz, 6H). 13C NMR (100 Hz, CDCl3, ppm):
147.0, 130.7, 127.2, 113.2, 38.7, 15.0.
REFERENCES
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6.37 (d, J = 8.4 Hz, 1H), 3.30 (q, J = 7.2 Hz, 2H), 1.26 (t, J = 7.2 Hz,
3H). 13C NMR (100 Hz, CDCl3, ppm): 158.9, 148.1, 137.4, 112.6,
106.4, 36.8, 14.8.
■
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