An efficient palladium-catalysed amination of aryl chlorides in presence of 1,3-bis-(2,6-diisopropylphenyl)imidazolinium chloride

Article abstract of DOI:10.3184/030823410X12680525004303

1,3-bis-(2,6-diisopropylphenyl)imidazolinium chloride (SIPr·HCl), a precursor for an N-heterocyclic carbene, was examined as a pro-ligand in C-N coupling reactions. Thus SIPr·HCl associated with a palladium catalyst was found to be efficient for the amination of aryl chlorides under mild conditions.

Full text of DOI:10.3184/030823410X12680525004303

JOURNAL OF CHEMICAL RESEARCH 2010
RESEARCH PAPER 163
MARCH, 163–166
An efficient palladium-catalysed amination of aryl chlorides in presence
of 1,3-bis-(2,6-diisopropylphenyl)imidazolinium chloride
Huafeng Shen, Zhong-Ping Zhang and Jing-Hua Li*
College of Pharmaceutical Sciences, Zhejiang University ofTechnology, 310032, P. R. China
1,3-bis-(2,6-diisopropylphenyl)imidazolinium chloride (SIPr·HCl), a precursor for an N-heterocyclic carbene, was
examined as a pro-ligand in C–N coupling reactions. Thus SIPr·HCl associated with a palladium catalyst was found
to be efficient for the amination of aryl chlorides under mild conditions.
Keywords: imidazolinium chloride, N-heterocyclic carbene, palladium, amination, aryl chlorides
As well known, aromatic amine moieties are important
building blocks for organic compounds involved in natural
products, pharmaceuticals, agrochemicals, dyes and poly-
mers.1–8 Therefore, the development of efficient methods to
synthesise these compounds attracts much attention from
organic chemists.
Desmarets et al. reported that SIPr·HCl performed highly
effectively in the Ni(acac) –NaH system.45,46 However, in our
investigation only a 40% 2yield occurred with NaH replaced
by KOtBu (entry 3 in Table 1). The transformation was also
observed when Co(acac) was used in association with
SIPr·HCl. No more conve2rsion was observed with a longer
reaction time (entry 4 in Table 1). Then we turned to another
efficient catalyst palladium.
Methods for synthesis of aromatic amines from aryl halides
have been reported in recent years.9,10 Palladium-catalysed
amination of aryl halides has become one of the most widely
used methods, and is now extensively used in academe and
industry.11–27 Buchwald and Hartwig, as well as other workers,
have developed novel palladium catalyst systems for the cross-
coupling of amines with aryl halides.28 In most cases, aryl
chlorides are cheaper and more widely available than bromides
or iodides, so development of coupling reactions of aryl chlo-
rides as substrates has been the focus of recent research.29,30
However, amination of aryl chlorides is more difficult than that
of bromides or iodides, because of their lower reactivity.
In recent years, more and more ligands have been found
and applied to C–N bond-forming reactions in association
with metal catalysts.8,31–40 Typically, phosphine ligands such as
PtBu3 and PCy were widely applied in the reactions. Recently,
N-heterocyclic3carbenes (NHCs) and their adducts were found
to display good activity in coupling reactions with aryl bro-
mides and aryl chlorides.31,41,42 So further development of
the application of NHCs and their derivatives in C–N bond-
forming reactions is significant for synthetic chemistry. In our
research, an imidazolinium salt, an air-stable and easily pre-
pared43 precursor for an NHC was used in association with
Pd catalysts in the reaction, and this procedure has been found
to be of good activity and efficient in the amination of aryl
chlorides.
Four palladium catalysts, Pd(OAc)2, Pd(acac)2, Pd (dba) .
dba and [Pd(allyl)Cl]2 were used, the latter three of2 whic3h
were easily prepared from PdCl2.47–79 In order to investigate the
activity of the catalysts in the reaction of chlorobenzene and
aniline, comparative experiments were carried out and good
results were obtained in the case of [Pd(allyl)Cl]2 combined
with SIPr·HCl (see entries 8, 10, 11 and 14 in Table 1). When
Pd(OAc) and Pd(acac)2 were applied in the reaction, almost
the same2yields of product were obtained 5 or 10 h later (entries
7 and 8, 9 and 10 in Table 1). The yields were not further
improved on prolonging the reaction time, which shows
that the two catalysts were not suitable for this reaction.
Pd2(dba)3·dba and [Pd(allyl)Cl]2 exhibited good activities in
the reaction, when they were associated with SIPr·HCl, excel-
lent yields of products were obtained with appropriate reaction
times (entries 11 and 14 inTable 1). Compared to Pd2(dba)3·dba,
[Pd(allyl)Cl]2 has more advantages, the reaction time is shorter
and the yield is higher.50 A widely used ligand in the Suzuki
reaction,51 however, PPh3 combined with [Pd(allyl)Cl]2, did
not facilitate the reaction (entry 12 in Table 1). The use of
Cs2CO (entry 13 in Table 1) as the base was entirely ineffec-
tive. It3 might be that this base is too weak to deprotonate
SIPr·HCl to form the corresponding carbene with which
[Pd(allyl)Cl]2 was integrated.
In this investigation on the amination of aryl chlorides, the
coupling of chlorobenzene and aniline was selected as a model
reaction (Scheme 1). Different metal catalysts were chosen,
and the results are summarised in Table 1, from which we
found that the combination of NiCl2, or VO(acac)2 with 1,3-
bis(2,6-diisopropylphenyl)imidazolinium chloride (SIPr·HCl)
gave no reaction (entries 1 and 6 in Table 1). Although copper
catalysts have been used extensively in aryl–aryl bond forming
reactions,44 when CuCl and Cu(acac) accompanied with
SIPr·HCl were employed in the reaction2s, there were none of
the expected products found in the reactions (entries 2 and 5 in
Table 1). It might be that the activities of NiCl2, VO(acac) and
CuCl are too low to activate the Cl-aryl bond. Gradel et al2. and
Table 1 Screening of conditions for C–N coupling with amine
in the presence of SIPr·HCla
Entry Catalyst
(mol %)
Ligand
(mol %)
Base
Time Yield
/h
/%b
1
2
NiCl2 (0.5)
SIPr.HCl (1) KOtBu
SIPr.HCl (1) KOtBu
SIPr.HCl (1) KOtBu
SIPr.HCl (1) KOtBu
SIPr.HCl (1) KOtBu
SIPr.HCl (1) KOtBu
SIPr.HCl (1) KOtBu
SIPr.HCl (1) KOtBu
SIPr.HCl (1) KOtBu
SIPr.HCl (1) KOtBu
10
10
10
10
10
10
5
10
5
10
5
10
NRc
NR
40
CuCl (0.5)
3
Ni(acac)2 (0.5)
Co(acac) (0.5)
Cu(acac)22 (0.5)
VO(acac)2 (0.5)
Pd(OAc) (0.5)
Pd(OAc)22 (0.5)
Pd(acac) (0.5)
Pd(acac)2 (0.5)
4
40
5
NR
NR
48
6
7
8
50
9
55
10
11
12
13
14
55
Pd2(dba)32·dba (0.5) SIPr.HCl (1) KOtBu
97
[Pd(allyl)Cl] (0.5) PPh3 (1)
KOtBu
NR
NR
99
[Pd(allyl)Cl]2 (0.5) SIPr.HCl (1) Cs2CO3 10
[Pd(allyl)Cl]22 (0.5) SIPr.HCl (1) KOtBu
3
a Reaction conditions: chlorobenzene (1.0 equiv), aniline (1.1
equiv), base (1.5 equiv), THF (65 °C).
b Isolated yield.
Scheme 1
* Correspondent. E-mail: lijh@zjut.edu.cn
c NR, no reaction.

164 JOURNAL OF CHEMICAL RESEARCH 2010
Table 3 Coupling of aryl chlorides with amines catalysed by
[Pd(allyl)Cl]2 and SIPr·HCla
Entry
R1
Ar
Product
Yield %b
1
2
H
C6H5
3a
3b
3c
3d
3e
3f
3g
3h
3i
3b
3j
3k
3l
3d
3k
3m
3n
3o
3p
3e
3l
3o
3r
5a
5b
5c
99
97
98
99
99
95
98
98
55
95
90
99
99
99
95
98
99
99
99
55
50
55
Trace
99
99
98
Scheme 2
H
2-CH C H
3-CH3C6H4
4-CH3C66H4
4-CH33OC64H4
2-C2H5C H4
3,5-(CH36)2C6H3
2-Naphthyl
2,6-(iPr)2C6H3
C6H5
3
H
4
H
In our study, we found ethers were suitable solvents for the
reaction (Scheme 2), the three solvents were examined in the
reaction (Table 2). It is observed from Table 2 that the reaction
time was shortened when the temperature reached 100 °C
(refluxing temperature in 1,4-dioxane). So 1,4-dioxane was
chosen as solvent, and amination of aryl chlorides was realized
at 100 °C in 1.5 h to give a good yield.
5
H
6
H
7
H
8
H
9
H
10
11
12
13
14
15
14
17
18
19
20
21
22
23
24c
25c
26c
2-CH
2-CH3
2-CH3
2-CH3
4-CH3
4-CH3
4-CH3
4-CH3
4-CH3
4-CH3
4-CH3O
4-CH3O
4-CH3O
4-CF 3
2-Cl 3
2-Cl
2-Cl
2-CH C H
4-CH3C66H4
4-CH33OC64H4
C6H5
2-CH C H
3-CH3C6H4
4-CH3C66H4
4-CH33OC 4H
3,5-(CH3)62C46H3
C6H5
Under the optimal condition, a range of couplings between
various anilines 2 and aryl chlorides 1 was carried out to give
products 3 (Scheme 3); the results are summarised in Table 3.
From Table 3, it is easily observed that the reactions
were probably sensitive to the electronic effects of aryl
chlorides. Unexpectedly, the reaction was inhibited by both
electron-donating substituents and electron-withdrawing
substituents on the aryl chloride. The coupling of 4-methoxy-
chlorobenzene with amines gave only 50–55% yields (entries
20–22 in Table 3), and, according to TLC, ethoxy- and tert-
butoxychlorobenzenes gave similar results. Coupling 4-
chlorotrifluoromethylbenzene with aniline gave very low yield
(entry 23 in Table 3). However, electron-donating substituents
on the ring of amine did not affect the coupling reaction, the
yield was very high (entries 5, 13 and 18 in Table 3). When
4-nitrobenzenamine coupled with chlorobenzene, there was
no reaction (unlisted in Table 3) observed under the standard
conditions. It was also observed that the yield of coupling
o-toluidine with aryl chlorides was slightly lower than ortho-
unsubstituted anilines (entries 2, 3, 4 and entries 15, 14, 17
in Table 3). This shows that the coupling reaction was
affected by steric hindrance in the aromatic amine, which is
further supported by the fact that the coupling of 2,6-
diisopropylbenzenamine with chlorobenzene only gave 55%
yield (entry 9 in Table 3).
2-CH C H
4-CH33C66H44
C H
C66H55
4-CH3C6H
3,5-(CH3)24C6H3
a Reaction conditions: 1 (1.0 equiv), 2 (1.1 equiv), [Pd(allyl)Cl]2
(0.5 mol%), SIPr·HCl (1 mol%), KOtBu (1.5 equiv), 1,4-dioxane
(100 °C), 1.5 h.
b Isolated yield.
c Reaction conditions: 4 (1.0 equiv), 2 (2.2 equiv), [Pd(allyl)Cl]2
(0.5 mol%), SIPr·HCl (1mol%), KOtBu (3 equiv), 1,4-dioxane
(100 °C), 2 h.
1,2-Dichlorobenzene 4 was coupled with two equivalent
of amines 2 to give its double-substituted derivatives 5 (Scheme
4). Three amines were used for these reactions and the yields
of products were very high (entries 24–26 in Table 3). Unex-
pectedly, however, preliminary studies of 1,4-dichlorobenzene
indicated that it gave a mixture of its corresponding single and
double substituted derivatives with moderate conversion even
with an excess of aniline employed.
Scheme 4
22
Nolan and coworkers
reported that an adduct of
[Pd(allyl)Cl]2, and NHC, prepared in advance, could readily
mediate the arylation of anilines in a nitrogen glove box. Also
other researchers reported that an NHC/Pd adduct had a good
result in the amination of aryl chlorides under similar con-
ditions.52 As a contrast, however, the reaction was examined
under our present conditions (without a glove box) and we
found that almost no product was obtained. It might be due to
NHC or the process of the reaction being sensitive to air and
moisture.
In conclusion, we have developed an efficient palladium-
catalysed amination of aryl chlorides. Coupling of aryl
chlorides with aromatic amines catalysed by [Pd(allyl)Cl]2 in
association with SIPr·HCl, a precursor for NHC, in presence
of KOtBu has been achieved.
Table 2 The solvent influence on amination of
chlorobenzene.
Entry Solventa
Temperature/°C
Time/h
Yield/%b
1
2
3
THF
65
80
100
3
2.5
1.5
99
99
99
DME
1,4-Dioxane
a THF (tetrahydrofuran), DME (1,2-dimethoxyethane).
b Isolated yield.
Experimental
Melting points are uncorrected. 1H NMR and 13C NMR spectra were
determined on a Varian Plus 500 instrument using TMS as an internal
standard and CDCl3 as a solvent. ESI-MS spectra were performed
on an AEI MS-902 apparatus. Elemental analyses were performed on
a Carlo-Erba 1106 analytical instrument.
Scheme 3

JOURNAL OF CHEMICAL RESEARCH 2010 165
General procedure for preparation of 3a–p
δ = 142.1, 141.2, 130.9, 130.5, 129.9, 127.1, 126.8, 121.2, 118.7,
117.4, 20.7, 17.9; m.p. 50–52 °C [lit.58 53 °C].
N-(4-Methoxyphenyl)-2-methylbenzenamine (3l): 1H NMR (500
MHz, CDCl3): δ = 2.25 (s, 3H), 3.80 (s, 3H), 5.25 (s, br, 1H),
6.80–6.87 (m, 3H), 6.99–7.15 (m, 5H). 13C NMR (125 MHz, CDCl3):
δ = 155.1, 143.3, 136.3, 130.8, 126.8, 125.3, 122.1, 120.0, 115.3,
114.7, 55.6, 17.8; m.p. 81–82 °C [lit.59 81.5–82 °C].
CAUTION: 2-Naphthylamine (β-naphthylamine, naphtha-
lene-2-amine) is a known potent carcinogen. A series of
studies of workers with occupational exposure to it has
shown clear evidence of a link between exposure and blad-
der cancer. In the UK, it appears in Schedule 2 of the Control
of Substances Hazardous to Health Regulations (COSSH)
1999 which prohibits its “manufacture and use for all
purposes”.
3-Methyl-N-p-tolylbenzenamine (3m): 1H NMR (500 MHz, CDCl3):
δ = 2.29 (s, 3H), 2.30 (s, 3H), 5.55 (s, br, 1H), 6.69–6.71 (m, 1H),
6.81–6.82 (m, 2H), 6.98–6.99 (m, 2H), 7.07–7.23 (m, 3H). 13C NMR
(125 MHz, CDCl3): δ = 144.0, 140.4, 139.2, 130.8, 129.9, 129.2,
121.2, 119.0, 117.6, 114.0, 21.6, 20.7. oil. 58
To a dried tube was added under nitrogen atmosphere chloroben-
zene (1 mmol), the amine (1.1 mmol) and dry 1,4-dioxane (2 mL).
Then the reaction tube was charged with KOtBu (1.5 mmol, 148 mg),
[Pd(allyl)Cl] (0.5 mol%, 1.8 mg) and SIPr·HCl (1 mol%, based on
aryl chloride2, 4.3 mg) and the reaction mixture was heated at 100 °C
for 1.5 h. The reaction mixture was allowed to cool to room tempera-
ture and was filtered through a pad of silica gel. The silica gel pad was
washed with ethyl acetate (10 mL×3). The combined organic phases
were evaporated under reduced pressure, and the residue was purified
by column chromatography on silica gel with petroleum ether and
ethyl acetate (10:1) eluant to give the diarylamine.
1
Di-p-tolylamine (3n): H NMR (500 MHz, CDCl3): δ = 2.29 (s,
6H), 5.83 (s, br, 1H), 6.95 (d, 8.0 Hz, 2H), 7.06 (d, 8.5 Hz, 2H). 13
C
NMR (125 MHz, CDCl3): δ = 141.1, 130.2, 129.8, 118.0, 20.6; m.p.
58–60 °C [lit.58 60–61 °C].
4-Methoxy-N-p-tolylbenzenamine (3o): 1H NMR (500 MHz,
CDCl3): δ = 2.28 (s, br, 3H) , 3.79 (s, 3H), 5.79 (s, br, 1H), 6.83–6.85
(m, 4H), 7.03–7.04 (m, 4H). 13C NMR (125 MHz, CDCl3): δ = 154.9,
142.4, 136.6, 129.8, 129.4, 121.2, 114.6, 114.7, 55.6, 20.6; m.p.
79–80 °C [lit.60 80–81 °C].
3,5-Dimethyl-N-p-tolylbenzenamine (3p): 1H NMR (500 MHz,
CDCl3): δ = 2.25 (s, 6H), 2.30 (s, 3H), 5.65 (s, br, 1H), 6.54 (s, 1H),
6.65 (s, 2H), 6.98–7.0 (m, 2H), 7.07–7.24 (m, 2H). 13C NMR (125
MHz, CDCl3): δ = 143.9, 140.5, 139.0, 130.8, 129.8, 122.3, 119.1,
114.7, 21.4, 20.7. oil.61
Diphenylamine (3a):1H NMR (500 MHz, CDCl3): δ = 5.70 (s,
br, 1H), 6.91–6.94 (m, 2H), 7.05–7.08 (m, 4H), 7.24–7.28 (m, 4H).
13C NMR (125 MHz, CDCl3): δ = 143.1, 129.3, 121.0, 117.8; m.p.
76–77 °C [lit.53 78–79 °C].
2-Methyl-N-phenylbenzenamine (3b): 1H NMR (500 MHz, CDCl3):
δ = 2.23 (s, 3H), 5.33 (s, br, 1H), 6.86–6.94 (m, 4H), 7.10–7.13
(m, 1H), 7.17–7.21 (m, 1H), 7.22–7.24 (m, 3H). 13C NMR (125 MHz,
CDCl3): δ =144.1, 141.3, 131.0, 129.4, 128.4, 126.8, 122.1, 120.5,
119.0, 117.5, 18.0; m.p. 35–36 °C [lit.54 37 °C].
General procedure for amination of 1,2-dichlorobenzene 5a–c
To a dried tube was added under nitrogen atmosphere 1,2-dichloro-
benzene (1 mmol), amine (2.2 mmol) and dry 1,4-dioxane (2 mL).
Then the reaction tube was charged with KOtBu (3 mmol, 330 mg),
[Pd(allyl)Cl] (0.5 mol%, 1.8 mg) and SIPr·HCl (1 mol%, based on
aryl chloride2, 4.3 mg) and the reaction mixture was heated at 100 °C
for 2 h. The reaction mixture was allowed to cool to room temperature
and filtered through a pad of silica gel. The silica gel pad was washed
with ethyl acetate (10 mL×3). The combined organic phases were
evaporated under reduced pressure, and the residue was purified by
column chromatography on silica gel with petroleum ether and ethyl
acetate (10:1) to give the N,N′-diarylbenzene-1,2-diamine.
3-Methyl-N-phenylbenzenamine (3c): 1H NMR (500 MHz, CDCl3):
δ = 2.30 (s, 3H), 5.66 (s, br, 1H), 6.74–6.76 (m, 1H), 6.87–6.93
(m, 3H), 7.04–7.07 (m, 2H), 7.13–7.14 (m, 1H), 7.23–7.27 (m, 1H).
13C NMR (125 MHz, CDCl3): δ = 143.3, 143.2, 139.3, 129.4, 129.2,
122.0, 120.9, 118.6, 117.9, 115.0, 21.6. oil [lit.55 30–31 °C].
4-methyl-N-phenylbenzenamine (3d): 1H NMR (500 MHz, CDCl3):
δ = 2.30 (s, 3H), 5.89 (s, br, 1H), 6.87–6.90 (m, 1H), 7.00–7.03
(m, 4H), 7.09–7.10 (m, 2H), 7.22–7.26 (m, 2H). 13C NMR (125 MHz,
CDCl3): δ = 143.9, 140.3, 131.0, 129.8, 129.3, 120.3, 118.9, 114.9,
20.7; m.p. 84–85 °C [lit.39 85–86 °C]
N,N′-Diphenylbenzene-1,2-diamine (5a): 1H NMR (500 MHz,
CDCl3): δ = 5.67 (s, br, 2H), 6.88–6.98 (m, 8H), 7.22–7.30 (m, 6H).
13C NMR (125 MHz, CDCl3): δ = 144.0, 135.0, 129.4, 123.1, 120.7,
120.3, 117.3; m.p. 100–101 °C [lit.62109 °C].
4-Methoxy-N-phenylbenzenamine (3e): 1H NMR (500 MHz,
CDCl3): δ = 3.79 (s, 3H), 5.52 (s, br, 1H), 6.81–6.91 (m, 5H), 7.06–
7.08 (m, 2H), 7.19–7.25 (m, 2H). 13C NMR (125 MHz, CDCl3):
δ =155.3, 145.1, 135.7, 129.3, 122.2, 119.5, 115.6, 114.6, 55.5; m.p.
100–101 °C [lit.55 101–103 °C].
N,N′-Di-p-tolylbenzene-1,2-diamine (5b): 1H NMR (500 MHz,
CDCl3): δ = 2.28 (s, 6H), 5.50 (s, br, 2H), 6.83–6.86 (m, 4H), 6.90–
6.92 (m, 2H), 7.04 (d, 8.0 Hz, 4H), 7.19–7.23 (m, 2H). 13C NMR (125
MHz, CDCl3): δ = 144.4, 135.3, 130.2, 129.9, 122.6, 119.6, 117.9,
20.6; m.p. 35–36 °C.63
1
2-Ethyl-N-phenylbenzenamine (3f): H NMR (500 MHz, CDCl3):
N,N′-Di(3,5-dimethylphenyl)benzene-1,2-diamine (5c): 1H NMR
(500 MHz, CDCl3): δ = 2.24 (s, 12H), 5.50 (s, br, 2H), 6.55–6.56 (m,
6H), 6.95–6.97 (m, 2H), 7.25–7.28 (m, 2H). 13C NMR (125 MHz,
CDCl3): δ = 144.0, 139.0, 135.1, 122.8, 122.5, 120.5, 115.0, 21.4.
ESI-MS: 317 (M+H+). Elemental Anal. Calcd C, 83.50; H, 7.64;
N, 8.85. Found: C, 83.40; H, 7.58; N, 8.81%; m.p. 45–47 °C.
δ = 1.31–1.36 (m, 3H), 2.71 (q, 7.0 Hz, 2H), 5.48 (s, br, 1H),
6.96–7.03 (m, 3H), 7.08–7.11 (m, 1H), 7.21–7.28 (m, 1H), 7.33–7.36
(m, 4H). 13C NMR (125 MHz, CDCl3): δ =144.6, 140.6, 134.9, 129.4,
129.0, 126.7, 122.7, 120.3, 120.2, 117.1, 24.4, 14.0. oil.46
3,5-Dimethyl-N-phenylbenzenamine (3g):1H NMR (500 MHz,
CDCl3): δ = 2.26 (m, 6H), 5.58 (s, br, 1H), 6.58 (s, 1H), 6.70 (s, 2H),
6.92 (t, 7.0Hz, 1H), 7.03–7.05 (m, 2H), 7.22–7.26 (m, 2H). 13C NMR
(125 MHz, CDCl3): δ = 143.4, 143.1, 139.1, 129.3, 122.9, 120.8,
117.9,115.7, 21.4; m.p. 52–53 °C [lit.56 52–53 °C].
1
N,N′-Diphenylbenzene-1,4-diamine: H NMR (500 MHz, DMSO-
d6): δ = 7.85 (s, 2H), 7.15–7.19 (m, 4H), 7.03 (s, 4H), 6.96 (d, J = 8Hz,
4H), 6.68–6.72 (m, 2H); m.p. 143–145 °C [lit.64 146–148 °C].
1
N-Phenylnaphthalen-2-amine(3h): H NMR (500 MHz, CDCl3):
Received 14 November 2009; accepted 4 March 2010
Paper 090872 doi: 10.3184/030823410X12680525004303
Published online: 23 March 2010
δ = 5.95 (s, br, 1H), 6.96–6.99 (m, 1H), 7.15–7.17 (m, 2H), 7.20–7.23
(m, 1H), 7.28–7.32 (m, 3H), 7.38–7.43 (m, 2H), 7.64 (d, 8.0 Hz, 1H),
7.74 (d, 8.5 Hz, 2H). 13C NMR (125 MHz, CDCl3): δ = 142.9, 140.9,
134.6, 129.5, 129.2, 129.1, 126.5, 126.4, 123.5, 121.5, 120.1, 118.3,
111.7; m.p. 109–110 °C [lit.55 108–110 °C].
References
1
2,6-Diisopropyl-N-phenylbenzenamine (3i): H NMR (500 MHz,
1
2
3
J. Buckingham, Dictionary of natural products, University Press:
Cambridge, MA, 1994.
M. Negwer, Organic drugs and their synonyms, 7th edn, Akademie Verlag
GmbH, Berlin, Germany, 1994.
J.H. Montgomery, Agrochemicals desk reference: environmental data,
Lewis Publishers, Chelsea, MI, 1993.
CDCl3): δ = 1.14 (d, 7.0Hz,12H), 3.14–3.24 (m, 2H), 5.11 (s, br, 1H),
6.47–6.48 (m, 2H), 6.69–6.72 (m, 1H), 7.12–7.30 (m, 5H). 13C NMR
(125 MHz, CDCl3): δ = 148.3, 147.8, 135.4, 129.4, 127.4, 124.0,
117.9, 113.2, 28.4, 24.1. oil.46
Di-o-tolylamine (3j): 1H NMR (500 MHz, CDCl3): δ = 2.25 (s, 6H),
5.13 (s, br, 1H), 6.88–6.91 (m, 2H), 6.97–6.99 (m, 2H), 7.09–7.12
(m, 2H), 7.18–7.22 (m, 2H). 13C NMR (125 MHz, CDCl3): δ =
142.1, 130.9, 127.6, 126.9, 121.5, 118.4, 17.9; m.p. 46–48 °C [lit.57
47–49 °C].
4
5
B. Schlummer and U. Scholz, Adv. Synth. Catal., 2004, 346, 1599.
R.O. Loufy, C.K. Hsiao and P.M. Kazmaier, Photogr. Sci. Eng., 1983, 27,
5.
6
7
P.A. Lewis, ed., Pigment handbook, John Wiley, New York, 1988.
G.D. Aprano, M. Leclerc, G. Zotti and G. Schiavon, Chem.Mater., 1995, 7,
33
2-Methyl-N-p-tolylbenzenamine (3k): 1H NMR (500 MHz, CDCl3):
δ = 2.23 (s, 3H), 2.29 (s, 3H), 5.26 (s, br, 1H), 6.86–6.90 (m, 3H),
7.05–7.09 (m, 3H), 7.14–7.14 (m, 2H). 13C NMR (125 MHz, CDCl3):
8
G. Manolikakes, A. Gavryushin and P. Knochel, J. Org. Chem., 2008, 73,
1429.

166 JOURNAL OF CHEMICAL RESEARCH 2010
9
I. Sapountzis and P. Knochel, Angew.Chem., Int. Ed., 2004, 43, 897.
38 L.E. Hagopiana, A.N. Campbell, J.A. Golen, A.L. Rheingold and C.
Nataro, J. Organomet Chem., 2006, 691, 4890.
39 C. Chen and L.M. Yang, J. Org. Chem., 2007, 72, 6324.
40 H.H. Rao, Y. Jin, H. Fu, Y.Y. Jiang and Y.F. Zhao, Chem. Eur. J., 2006, 12,
3636.
10 V. del Amo, S.R. Dubbaka, A. Krasovskiy and P. Knochel, Angew.Chem.,
Int. Ed., 2006, 45, 7838.
11 J.F. Hartwig, Angew. Chem., Int. Ed., 1998, 37, 2046.
12 J.F. Hartwig, Acc. Chem. Res., 1998, 31, 852.
13 J.P. Wolfe, S. Wagaw, J.F. Marcaoux and S.L. Buchwald, Acc. Chem. Res.,
1998, 31, 805
14 B.H. Yang and S.L. Buchwald, J. Organomet. Chem., 1999, 576, 125.
15 A.R. Muci and S.L. Buchwald, Top. Curr. Chem., 2002, 219, 131.
16 H.U. Blaser, A. Indolese, F. Naud, U. Nettekoven and A. Schnyder, Adv.
Synth. Catal., 2004, 346, 1583.
41 N. Marion, O. Navarro, J.G. Mei, E.D. Stevens, N.M. Scott and S.P. Nolan,
J. Am. Chem. Soc., 2006, 128, 4101.
42 M.S. Viciu, R.F. Germaneau, O.N. Fernandez, E.D. Stevens and S.P. Nolan,
Organomet., 2002, 21, 5470.
43 A.J. Arduengo III, R. Krafczyk and R. Schmutzler, Tetrahedron, 1999, 55,
14523.
17 S. Harkal, F. Rataboul, A. Zapf, C. Fuhrmann, T. Riermeier, A. Monsees
and M. Beller, Adv. Synth. Catal., 2004, 346, 1742.
18 A.S. Gajare, K. Toyota, M. Yoshifuji and F. Ozawa, J. Org. Chem., 2004,
69, 6504.
44 J. Hassan, M. Sévignon, C. GoNi, E. Schulz and M. Lemaire, Chem. Rev.,
2002, 102, 1359.
45 B. Gradel, E. Brenner, R. Schneider and Y. Fort, Tetrahedron Lett., 2001,
42, 5689.
19 L. Ackermann and R. Born, Angew. Chem., Int. Ed., 2005, 44, 2444.
20 L.J. Goossen, J. Paetzold, O. Briel, A. Rivas-Nass, R. Karch and B. Kayser,
Synlett., 2005, 2, 275.
21 S. Shekhar, P. Ryberg and J.F. Hartwig, J. Am. Chem. Soc., 2006, 128,
3584.
46 C. Desmarets, R. Schneider and Y. Fort, J. Org. Chem., 2002, 67, 3029.
47 V.S. Kach, D.S. Suslov, M. Gomboogiin, G.V. Ratovskii and F.K. Shmidt,
Russ. J. Appl. Chem., 2006, 79, 85.
48 L. Djakovitch, M. Wagner, C.G. Hartung, M. Beller and K.J. Koehler,
Mol. Catal. A: Chem., 2004, 219, 121.
22 N. Marion, O. Navarro, J. Mei, E.D. Stevens, N.M. Scott and S.P. Nolan,
J. Am. Chem. Soc., 2006, 128, 4101.
23 N. Marion, E.C. Escarnot, O. Navarro, D. Amoroso, A. Bell and S.P. Nolan,
J. Org. Chem., 2006, 71, 3814.
49 P.R. Auburn, P.B. Mackenzie and B. Bosnich, J. Am. Chem. Soc., 1985,
107, 2033.
50 S.R. Stauffer, S. Lee, J.P. Stambuli, S.I. Hauck and J. F. Hartwig, Org. Lett.,
2000, 2, 1423.
24 R.E. Tundel, K.W. Anderson and S.L. Buchwald, J. Org. Chem., 2006, 71,
430.
25 K.W. Anderson, R.E. Tundel, T. Ikawa, R.A. Altman and S.L. Buchwald,
Angew. Chem., Int. Ed., 2006, 45, 6523.
26 E.R. Strieter and S.L. Buchwald, Angew. Chem., Int. Ed., 2006, 45, 925.
27 D.S. Surry and S.L. Buchwald, J. Am. Chem. Soc., 2007, 129, 10354.
28 A. De Meijere and F. Diederich, Metal-catalysed cross-coupling ceactions,
2nd edn. Wiley-VCH: Weinheim, Germany, 2004.
29 A.F. Littke and G.C. Fu, Angew. Chem., Int. Ed., 2002, 41, 4176.
30 R.B. Bedford, C.S.J. Cazin and D. Holder, Coord. Chem. Rev., 2004, 248,
2283.
51 C. Chen and L.M. Yang, Tetrahedron Lett., 2007, 48, 2427.
52 L.R. Titcomb, S. Caddick, F.G.N. Cloke, D.J. Wilson and D. McKerrecher,
Chem. Commun., 2001, 1388.
53 M.H. Ali and S.L. Buchwald, J. Org. Chem., 2001, 66, 2560.
54 K.W. Anderson, M. Mendez-Perez, J. Priego and S.L. Buchwald, J. Org.
Chem., 2003, 68, 9563.
55 C.Y. Gao and L.M. Yang, J. Org. Chem., 2008, 73, 1424.
56 S. Doherty, J.G. Knight, C.H. Smyth, R.W. Harrington, and W. Clegg,
Organometallics, 2008, 27, 1479.
57 H.S. Freeman, J.R. Butle and L.D. Freedman, J. Org. Chem., 1978, 43,
4975.
31 R.B. Bedford, M. Betham, M.E. Blake, R.M. Frost, P.N. Horton and M.B.
Hursthouse, Dalton Trans., 2005, 2774.
32 X. Chen, J.F. Gong and Y.J. Wu, Tetrahedron Lett., 2007, 48, 1419.
33 K. Ishibashi, H. Tsue, S. Tokita, K. Matsui, H. Takahashi and R. Tamura,
Org. Lett., 2006, 26, 5991.
34 M. Guino and K.K.M. Hii, Tetrahedron Lett., 2005, 46, 7363.
35 M. Guino and K.K.M. Hii, Tetrahedron Lett., 2005, 46, 6911.
36 L. Rout , S. Jammi and T. Punniyamurthy, Org. Lett., 2007, 17, 3397.
37 J.Y. Li, M.J. Cui, A.J. Yu and Y.J. Wu, J. Organomet. Chem., 2007, 692,
3732.
58 H.D. Law, Proc. Chem. Soc., 1912, 27, 310.
59 Y. Yu, J. Srogl and L.S. Liebeskind, Org. Lett., 2004, 6, 2631.
60 S.L. Buchwald, WO 2004052939, 2004.
61 C.A. Fleckenstein and H. Plenio, Organometallics, 2007, 26, 2758.
62 G.R. Clemo, W.H. Perkin and R. Robinson, J. Chem. Soc., Trans., 1924,
125, 1751.
63 N. Palibroda, C. Cristea, L.A. Silberg and L. Chirtoc, Rapid Commun.
Mass Spectrom., 1999, 13, 2227.
64 L.T. Highma, K. Konno, J.L. Scott, C.R. Strauss and T. Yamaguchi, Green
Chem., 2007, 9, 80.