Efficient palladium-catalyzed amination of aryl chlorides using di(dicyclohexylamino)phenylphosphine as a PN2 ligand

Article abstract of DOI:10.1016/j.tet.2011.10.059

The palladium-catalyzed amination of a variety of aryl chlorides has been accomplished by using di(dicyclohexylamino)phenylphosphine (1) as a bulky electron-rich monoaryl phosphine ligand. The optimized condition for the palladium-catalyzed amination of aryl chloride is the followings: aniline (3.0 mmol, 1.0 equiv), chlorobenzene (3.15 mmol, 1.05 equiv), ligand 1 (1 mol %, 0.03 mmol), KO^tBu (4.5 mmol, 1.5 equiv), Pd₂(dba)₃ (1 mol %, 0.03 mmol), and toluene as solvent at reflux temperature. We report on couplings of various amines or chloroamines with chlorobenzenes and heteroaryl chloride.

Full text of DOI:10.1016/j.tet.2011.10.059

Tetrahedron 68 (2012) 287e293
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Efficient palladium-catalyzed amination of aryl chlorides using
di(dicyclohexylamino)phenylphosphine as a PN2 ligand
,
a
a
a
b
Bo Ram Kim a, Su-Dong Cho a , Eun Jung Kim , In-Hye Lee , Gi Hyeon Sung , Jeum-Jong Kim ,
*
Sang-Gyeong Lee a, Yong-Jin Yoon a
,b,
*
a Department of Chemistry, Research Institute of Natural Science, Graduate School for Materials and Nanochemistry, Gyeongsang National University, Jinju 660-701, Republic of Korea
b Advanced Solar Technology Research Department, ETRI, Daejeon 305-700, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 1 April 2011
Received in revised form 12 October 2011
Accepted 14 October 2011
Available online 21 October 2011
The palladium-catalyzed amination of a variety of aryl chlorides has been accomplished by using di(-
dicyclohexylamino)phenylphosphine (1) as a bulky electron-rich monoaryl phosphine ligand. The opti-
mized condition for the palladium-catalyzed amination of aryl chloride is the followings: aniline
(3.0 mmol, 1.0 equiv), chlorobenzene (3.15 mmol, 1.05 equiv), ligand 1 (1 mol %, 0.03 mmol), KOtBu
(4.5 mmol, 1.5 equiv), Pd2(dba)3 (1 mol %, 0.03 mmol), and toluene as solvent at reflux temperature. We
report on couplings of various amines or chloroamines with chlorobenzenes and heteroaryl chloride.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Palladium-catalyzed amination of aryl
chlorides
PN2 ligand
CeN coupling reaction
Palladium-catalyst
Di(dicyclohexylamino)phenylphosphine
1. Introduction
these reactions. While several ligands exhibiting improved abilities
in assisting the palladium-catalyzed aryl aminations are now
Over the past decade, one of the foremost accomplishment in
the field of catalysis has been the discovery of the palladium-
catalyzed carbonenitrogen bond forming process commonly
known as the BuchwaldeHartwig amination reaction.1 The
palladium-catalyzed formation of CeN bonds is also a rapidly
expanding area of research.1a,2 Since the first general procedures
were discovered,3 efforts have been made toward increasing the
substrate scope and efficiency. Although the use of alternative ba-
ses or solvents can be beneficial, electronic, and steric tuning of the
supporting ligand has the most impact on increasing efficacy and
reactivity in these processes.1c,2 A major impetuses to this field was
provided by the ability to activate the notoriously unreactive but
relatively cheap aryl chlorides. Not surprisingly, a plethora of pal-
ladium-catalyst systems featuring a palladium-bound ligand is now
accessible for achieving the aforementioned transformation in-
volving aryl chlorides. Typically, the electronically rich sterically
hindered ligands belonging to the trialkylphosphine,4e6 ferroce-
nyldialkylphosphine,7 aryldialkylphosphine,8e10 phosphinous
acid,11 palladacycle,12,13 heterocyclic carbene14e16 or tri-
aminophosphine (PN3)1d,17e20 classes have been investigated for
available, a general solution has not yet been completely found for
the metal-catalyzed aryl aminations of all substrates.
Thus, as part of our ongoing efforts to develop efficient methods
for the amination of aryl chloride, we investigated the synthesis
and coupling reaction of novel air stable phenyl backbone-derived
PN2 ligands that are easily prepared. The reaction setup is experi-
mentally simple and does not require the use of a glove box for
these reactions. In previous paper,21 amination of aryl chlorides
using
dicyclohexylamino[(2,6-dimethyl)morphorino]phenyl-
phosphine as a PN2 ligand has been reported (Scheme 1).
Scheme 1. Bulky electron-rich ligands used in the amination of aryl chlorides.
We designed ligand 1e4 as novel phenyl backbone-derived PN2
ligands. Ligand 4 is commercially available, and ligand 3 was
* Corresponding authors. Tel. þ82 055 772 1481; fax: þ82 055 772 1489; e-mail
address: yjyoon@gnu.ac.kr (Y.-J. Yoon).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.10.059

288
B.R. Kim et al. / Tetrahedron 68 (2012) 287e293
prepared by the literature method.22 Ligands 1 and 2 were syn-
thesized from dichlorophenylphosphine (5) according to reported
method.21 Here, we report the results for amination of aryl chloride
with amines by using compound 1 as a novel PN2 ligand.
in Table 2). However, reaction using Pd(PPh3)4 or Pd/C failed to pro-
vide complete conversion even after 24 h (entry 4 and 6 in Table 2).
Table 2
Screening of Pd-catalystsa
2. Results and discussion
Reaction of dichlorophenylphosphine (5) with dicyclohexyl-
amine (6) or 2,6-dimethylmorphorine (7) in the presence of trie-
thylamine in refluxing dichloromethane or toluene gave the
corresponding ligands 1 (78%) or 2 (85%). Ligands 1e3 in coupling
reaction was used without further purification. The structures of
ligands 1 and 2 were established by IR, NMR, and elemental anal-
ysis (Scheme 2).
Entry
Palladium-catalyst
Time (h)
10ab (%)
1
2
3
4
5
6
Pd2(dba)3
PdCl2
Pd(OAc)2
Pd(PPh3)4
PdCl2(PPh3)2
Pd/C
4
5
5
24
8
24
93
91
90
5c
85
4c
a
Reaction conditions: aniline (9a, 3.0 mmol, 1.0 equiv), chlorobenzene (8a,
3.15 mmol, 1.05 equiv), ligand 1 (1 mol %, 0.03 mmol), KOtBu (1.5 equiv), Pd-catalyst
(1 mol %, 0.03 mmol), toluene (20 mL) at reflux temperature.
b
Isolated yield after silica gel chromatography.
The starting materials were recovered.
c
Scheme 2. Synthesis of ligands 1, 2, and 3.
We next optimized the coupling of chlorobenzene (8a) with
aniline (9a) by the Pd2(dba)3/1/KOtBu in toluene. The Pd2(dba)3
(2 mol%)/1 (1 mol %)/KOtBu (1.5 equiv)systemin toluene showedthe
best result (entry 6 in Table 3). On the other hand, the yields are low
at below the reflux temperature. Applying the Pd2(dba)3 (1 mol %)/1
(1 mol %)/KOtBu (1.5 equiv)/toluene system (entry 2 in Table 3),
however, we evaluated the scope of the coupling of aryl chlorides
with various aminesbecause it requiresthe small amountof catalyst.
To test the feasibility of the ideas described above, we initially
conducted a reaction of chlorobenzene (8a) with aniline (9a) in
refluxing toluene. We used 1 mol % of Pd2(dba)3 in combination
with 1 mol % of ligand 1, and this reaction proceeded successfully to
afford the desired product 10a in a 93% isolated yield after 4 h. This
result was encouraging, and we evaluated the efficiency of the
three ligands 2e4 in the same screening. This reaction did not occur
when ligands 2e4 were used.
Next, we investigated a variety of solvents and bases for the
aforementioned coupling reaction catalyzed by the Pd2(dba)3/li-
gand 1 system. Toluene was found to be the most efficacious sol-
vent among six solvents, such as toluene, acetonitrile, ethanol, 1,4-
dioxane, THF, and water. This reaction, however, in other solvents
did not occur. Among the bases explored, potassium tert-butoxide
gave the best result (entry 1 in Table 1). However, reaction involving
Cs2CO3, K3PO4, K2CO3, and Rb2CO3 as a base failed to provide
complete conversion even after 49e60 h (entry 2e5 in Table 1).
Table 3
Optimization for the coupling of chlorobenzene (8a) with aniline (9a) using 1a
Entry
1 (mol %)
Pd2(dba)3 (mol %)
Time (h)
10ab (%)
1
2
3
4
5
6
1
1
2
5
10
1
0.5
1
1
1
1
17
4
4
4
4
84
93
89
90
90
91
Table 1
Screening of basesa
2
2
a
Reaction conditions: aniline (9a, 3.0 mmol, 1.0 equiv), chlorobenzene (8a,
3.15 mmol, 1.05 equiv), ligand 1(1 mol %, 0.03 mmol), KOtBu (1.5 equiv), Pd2(dba)3,
toluene (20 mL) at reflux temperature.
b
Isolated yield after silica gel chromatography.
It is clear from Table 4 that chlorobenzenes containing electron-
withdrawing groups, such as cyano and benzenesulfonyl groups are
coupled fast with aniline (9a) (entries 8 and 9 in Table 4), whereas
chlorobenzene containing electron-donating groups, such as
methyl and methoxy groups are coupled slowly with aniline (9a)
(entries 2 and 5 in Table 4). The position effect of the substituents
for MeO and CN in benzene was evaluated. The para substituted-
chlorobenzene 8e (p-OMe) and 8h (p-CN) showed the best results
(entries 5 and 8 in Table 4), but the ortho or the meta substituted
derivatives gave the products in the low yield (entries 3 and 6 in
Table 4) or unknown products (entries 4 and 7 in Table 4). On the
other hand, the coupling 4-nitrochlorobenzene (8j) with aniline
under our system gave 2-chlorophenazine as the main product
instead of the corresponding coupling product (entry 10 in Table 4).
This is similar to Pachter’s result.24 The coupling of chlorobenzene
(8a) with various amines using our optimized system gave the
Entry
Base
Time (h)
10ab (%)
1
2
3
4
5
KOtBu
Cs2CO3
K3PO4
K2CO3
Rb2CO3
4
49
56
60
60
93
56c
55c
5c
3c
a
Reaction conditions: aniline (9a, 3.0 mmol, 1.0 equiv), chlorobenzene (8a,
3.15 mmol, 1.05 equiv), ligand 1 (1mol%, 0.03 mmol), base (1.5 equiv), Pd2(dba)3
(1 mol %, 0.03 mmol), toluene (20 mL) at reflux temperature.
b
Isolated yield after silica gel chromatography.
The starting materials were recovered.
c
Also, we investigated the effect of a variety of palladium com-
pounds for this reaction. Among the palladium compounds explored,
Pd2(dba)3 gave the fastest reaction rates and the excellent yields al-
thoughPdCl2 andPd(OAc)2 werealsoasuitablereagent(entry2and3

B.R. Kim et al. / Tetrahedron 68 (2012) 287e293
289
Table 4
Palladium-catalyzed amination of aryl chloridesa
Entry
1
AreCl 8
Amine 9
Time (h)
Product 10b (%)
10a(93)
4
8a
9a
2
3
34
32
10b (25)c
8b
8c
9a
9a
10c (10)c
__d
4
32
9a
8d
8e
8f
5
6
32
5
9a
9a
10d (32)c
10e(48)c
__d
7
3
9a
8g
8
2
4
9a
9a
8h
8i
10f (82)
9
10g (89)
__e
10
11
8j
9a
9b
5
3
8a
8a
10h (89)
12
9c
(continued on next page)

Table 4 (continued )
Entry
AreCl 8
Amine 9
Time (h)
Product 10b (%)
13
14
15
16
4
8a
9d
10j (84)
0.5
8a
9e
10k (93)
10
8a
10l (67)f
9f
11
8a
10m (53)f
9g
17
16
8a
9h
10b (93)
10d (75)
10n (90)
10o(71)
10p (56)
18
19
20
21
22
15
3
8a
9i
9j
8a
8e
8e
5
9j
6
9h
16
9a
8k
8l
10q (52)
23
5
9a
10r (59)
Reaction condition: amine (9, 3.0 mmol, 1.0 equiv), aryl chloride (8, 3.15 mmol, 1.05 equiv), ligand 1 (1 mol %, 0.03 mol), KOtBu (4.5 mmol, 1.5 equiv), Pd2(dba)3 (1 mol %,
a
0.03 mmol), toluene (20 mL) at reflux temperature.
b
Isolated yield after silica gel chromatography.
The unreacted starting materials were recovered.
c
d
Some unknown products were detected.
e
The main product is 2-chlorophenazine.24
f
Double-coupling product was also detected on TLC.

B.R. Kim et al. / Tetrahedron 68 (2012) 287e293
291
corresponding mono-coupling products involving the double-
coupling products as the traces in moderate to excellent yields
(entries 11e19 in Table 4). Although chlorobenzene (8a) of coupling
with various amines do not show a general tendency that depended
on the kind of amines, the reaction of amines containing chlorine
gave the corresponding double-coupling products by the coupling
of the first product with starting chloramines or chlorobenzene
(entries 12, 15, and 16 in Table 4).
Calcd for C30H49N2P: C, 76.88; H, 10.54; N, 5.98. Found: C, 76.93;
10.61; N, 6.01.
4.2.2. 4,40-(Phenylphosphinediyl)bis(2,6-dimethylmorpholine)
(2). Yield: 85%. Colorless oil. IR (KBr) 3012, 2904, 1436, 1366, 1120,
1048 cmꢁ1
.
1H NMR (300 MHz, CDCl3)
d
1.8 (s, 6H), 1.10 (s, 6H),
2.40e2.44 (m, 2H), 2.99 (d, 4H, J¼12.16 Hz), 3.44e3.51 (m, 2H),
3.78e3.87(m, 4H), 7.30e7.81 (m, 5H). 13CNMR(75MHz,CDCl3)
11.69,
d
The coupling of chloroheterocycles, such as 2-chloroquinoline
(8k) and 2-chloropyrazine (8l) with aniline (9a) using our system
also gave the corresponding CeN coupling products 10q and 10r
(entries 22 and 23 in Table 4). The structures of all products were
established by IR, NMR, HMRS, and elemental analysis. The struc-
tures of the known compounds also were confirmed by comparing
the literature data.
47.92, 68.71, 128.15, 128.32, 129.60, 129.40. Anal. Calcd for
C18H29N2O2P: C, 64.26; H, 8.69;N, 8.33. Found:C, 64.30; H, 8.60; N, 8.37.
4.3. Typical CeN coupling of amines and aryl chlorides
A dried resealable Schlenk tube was charged with Pd2(dba)3
(0.03 mmol, 1 mol % of Pd), amine (3.0 mmol), ligand 1 (1 mol %)
and KOtBu (4.5 mmol) in dried toluene (20 mL). The Schlenk tube
was capped with a rubber septum, evacuated, and backfilled with
nitrogen. This evacuation/backfill sequence was repeated two or
three additional times. Aryl chloride (3.15 mmol) and toluene
(2 mLꢀ2) were added through the septum. After the septum was
replaced with a Teflon screwcap, the mixture was refluxed until the
starting amine had been completely consumed as judged by GC or
TLC. The reaction mixture was then cooled to room temperature,
diluted with dichloromethane (10 mLꢀ2), filtered, and concen-
trated in vacuo. The crude material was purified by flash chroma-
tography on silica gel using n-hexane/dichloromethane (1/1, v/v) to
afford CeN coupled product.
3. Conclusion
In conclusion, we developed ligand 1 as a new PN2 ligand for Pd-
catalyzed amination of aryl chloride. This ligand 1 also has some
advantages: as an efficient ligand for Pd-catalyzed amination of aryl
chlorides, it is stable in air at high temperature, and easily prepared
from cheap and commercially available dichlorophenylphosphine.
4. Experimental
4.1. General
4.3.1. Diphenylamine (10a). Mp 53e54 ꢂC (lit.21 mp 53e54 ꢂC). IR
(KBr) 3392, 3318, 1602, 1486, 1324, 740 cmꢁ1. 1H NMR (300 MHz,
Melting points were determined with a capillary apparatus and
uncorrected. 1H and 13C NMR spectra were recorded on a 300 MHz
CDCl3)
d 5.60 (br s, NH, D2O exchangeable), 6.87e6.93 (m, 2H),
7.01e7.04 (m, 4H), 7.19e7.26 (m, 4H). 13C NMR (75 MHz, CDCl3)
spectrometer with chemical shift values reported in
d units (ppm)
d
117.96, 121.10, 129.43, 143.27. Anal. Calcd for C12H11N: C, 85.17; H,
relative to an internal standard (TMS). IR spectra were obtained on
a Mattson Genesis Series FT-IR spectrophotometer. Elemental
analyses were performed with a PerkineElmer 240C. Mass spectra
were obtained on a JMS-700, JEOL. The open-bed chromatography
was carried out on silica gel (70e230 mesh, Merck) using gravity
flow. The column was packed with slurries made from the elution
solvent.
6.55; N, 8.28. Found: C, 85.14; H, 6.54; N, 8.27. HRMS (m/z): [M]þ
calcd for C12H11N 169.0891. Found: 169.0891.
4.3.2. Phenyl-p-tolylamine (10b). Mp 87e88 ꢂC (lit.21 mp
87e88 ꢂC). IR (KBr) 3400, 3010, 2912,1596,1508,1304, 744 cmꢁ1. 1H
NMR (300 MHz, CDCl3)
changeable), 6.84e6.89 (m, 1H), 6.97e7.00 (m, 4H), 7.06e7.08 (m,
2H), 7.19e7.25 (m, 2H). 13C NMR (75 MHz, CDCl3)
20.69, 116.95,
d 2.29 (s, 3H), 5.55 (br s, NH, D2O ex-
d
4.2. Typical preparation of PN2 ligands
118.99, 120.35, 129.33, 129.88, 130.97, 140.39, 144.04. Anal. Calcd for
C13H13N: C, 85.21; H, 7.15; N, 7.64. Found: C, 85.20; H, 7.13; N, 7.65.
HRMS (m/z): [M]þ calcd for C13H13N 183.1048. Found: 183.1048.
A mixture of amine (2 equiv), triethylamine (2.2 equiv), and
dichloromethane (50 mL) was stirred for 10 min at room temper-
ature. A dichloromethane solution of dichlorophenylphosphine 5
(20 mmol of 5 in 200 mL dichloromethane) was slowly dropped to
the above amine solution, and the mixture was refluxed for 24 h
until phosphine 5 disappeared. After evaporating the solvent under
reduced pressure, the resulting residue was triturated in n-hexane,
filtered, and washed with n-hexane. The filtrates-containing the
product were combined and evaporated under reduced pressure.
The resulting residue was applied to the top of an open-bed silica
gel column (3.0ꢀ7 cm). The column was eluted with dichloro-
methane/diethyl ether (10/1, v/v). Fractions containing the product
were combined and evaporated under reduced pressure to give
di(dicyclohexylamino)phenyl phosphine (1), 4,40-(phenylhosphi-
nediyl)bis(2,6-dimethylmorpholine) (2) or di(diisopropylamino)-
phenylphosphine (3) as a PN2 ligand. Ligand in coupling reaction
was used without further purification.
4.3.3. (2-Methoxyphenyl)phenylamine (10c). Yellow oil. IR (KBr)
3414, 2923, 2850, 1637, 1594, 1518, 1495, 1462, 1420, 1296, 1235,
1176, 1115, 1026 cmꢁ1. 1H NMR (300 MHz, CDCl3)
d 3.88 (s, 3H), 6.14
(br s, NH, D2O exchangeable), 6.83e6.95 (m, 4H), 7.14 (d, 2H,
J¼7.51 Hz), 7.23e7.32 (m, 3H). 13C NMR (75 MHz, CDCl3)
d 55.57,
110.51, 114.67, 118.59, 119.88, 120.82, 121.15, 129.27, 133.00, 142.73,
148.27. Anal. Calcd for C13H13NO: C, 78.36; H, 6.58; N, 7.03. Found:
C, 78.37; H, 6.60; N, 7.02. HRMS (m/z): [M]þ calcd for C13H13NO
199.0997. Found: 199.1008.
4.3.4. (4-Methoxyphenyl)phenylamine (10d). Mp 98e99 ꢂC (lit.21
mp 99e100 ꢂC). IR (KBr) 3428, 3056, 2992, 2950, 1600, 1502, 1300,
1242, 1038, 744 cmꢁ1. 1H NMR (300 MHz, CDCl3)
d
3.79 (s, 3H), 5.46
(br s, NH, D2O exchangeable), 6.80e6.91 (m, 5H), 7.05e7.08 (m, 2H),
7.18e7.23 (m, 2H). 13C NMR (75 MHz, CDCl3)
55.61, 114.74, 115.73,
d
119.61, 122.24, 129.32, 135.84, 145.24, 155.36. Anal. Calcd for
C13H13NO: C, 78.36; H, 6.58; N, 7.03. Found: C, 78.35; H, 6.60; N, 7.01.
HRMS (m/z): [M]þ calcd for C13H13NO 199.0997. Found: 199.1008.
4.2.1. Di(dicyclohexylamino)phenylphosphine (1). Yield: 78%. Col-
orless oil. IR (KBr) 2926, 2846, 2776, 2740, 1460,1378, 1042 cmꢁ1. 1H
NMR (300 MHz, CDCl3)
7.34e7.43 (m, 3H), 7.69e7.74 (m, 2H). 13C NMR (75 MHz, CDCl3)
14.07, 22.63, 25.48, 31.57, 128.10, 129.15, 130.54, 130.82. Anal.
d 0.83e2.02 (m, 40H), 2.93e2.98 (m, 4H),
4.3.5. 2-(Phenylamino)benzonitrile (10e). Mp 48e49 ꢂC (lit.23mp
50e51 ꢂC). IR (KBr) 3343, 3048, 2926, 2216, 1625, 1593, 1573, 1515,
d

292
B.R. Kim et al. / Tetrahedron 68 (2012) 287e293
1497, 1472, 1456, 1318, 1292, 1163 cmꢁ1. 1H NMR (300 MHz, CDCl3)
6.98e7.02 (m, 2H), 7.13 (d, 2H, J¼7.65 Hz), 7.24e7.33 (m, 3H),
7.48e7.54 (m, 1H), 7.65e7.68 (m, 1H), 8.46 (br s, NH, D2O ex-
changeable). 13C NMR (75 MHz, CDCl3)
101.17, 117.87, 118.26,
119.56, 120.98, 122.33, 129.71, 134.39, 134.65, 142.36, 147.36. Anal.
Calcd for C13H10N2: C, 80.39; H, 5.19; N, 14.42. Found: C, 80.40; H,
5.21; N, 14.40. HRMS (m/z): [M]þ calcd for C13H10N2 194.0844.
Found: 194.0842.
d
3.32 (s, 8H), 6.81e6.98 (m, 6H), 7.15e7.20 (t, J¼8.07 Hz, 1H),
d
7.25e7.31 (m, 2H). 13C NMR (75 MHz, CDCl3)
d
48.92, 49.29, 114.13,
116.04, 116.41, 119.62, 120.22, 129.62, 130.10, 135.06, 151.13, 152.30.
Anal. Calcd for C16H17ClN2: C, 70.45; H, 6.28; N, 10.27. Found: C,
70.44; H, 6.25; N, 10.25. HRMS (m/z): [M]þ calcd for C16H17ClN2
272.1080. Found: 272.1080.
d
4.3.13. 1-((4-Chlorophenyl)(phenyl)methyl)-4-phenylpiperazine
(10m). Thin yellow liquid. IR (KBr) 3044, 1578, 1422 cmꢁ1. 1H NMR
4.3.6. 4-(Phenylamino)benzonitrile (10f). Mp 134e135 ꢂC (lit.21 mp
134e135 ꢂC). IR (KBr) 3246, 2248, 1634, 1600, 1390, 1098 cmꢁ1. 1H
(300 MHz, CDCl3)
1H), 6.79e6.89 (m, 3H), 7.16e7.30 (m, 7H), 7.35e7.41 (m, 4H). 13C
NMR (75 MHz, CDCl3) 49.25, 51.94, 75.52, 115.88, 119.61, 127.31,
127.92, 128.72, 128.79, 129.14, 129.27, 132.73, 141.35, 142.15, 151.33.
Anal. Calcd for C23H23ClN2: C, 76.12; H, 6.39; N, 7.72. Found: C,
76.10; H, 6.38; N, 7.70. HRMS (m/z): [M]þ calcd for for C23H23ClN2
362.1550. Found: 362.1550.
d 2.51e2.54 (m, 4H), 3.15e3.19 (m, 4H), 4.24 (s,
NMR (300 MHz, CDCl3)
6.95e6.99 (m, 2H), 7.04e7.10 (m, 1H), 7.36e7.43 (m, 4H), 7.81e7.84
(m, 2H). 13C NMR (75 MHz, CDCl3)
121.53, 123.22, 128.24, 128.72,
d
4.81 (br s, NH, D2O exchangeable),
d
d
129.58, 130.50, 134.23, 136.64, 149.32. Anal. Calcd for C13H10N2: C,
80.39; H, 5.19; N, 14.42. Found: C, 80.38; H, 5.19; N, 14.39. HRMS (m/
z): [M]þ calcd for C13H10N2 194.0844. Found: 194.0837.
4.3.14. (4-Phenoxyphenyl)phenylamine (10n). Mp 95e98 ꢂC. IR (KBr)
4.3.7. N-Phenyl-4-(phenylsulfonyl)benzenamine
206e207 ꢂC. IR (KBr) 3369, 3022, 1581, 1520, 1490, 1340, 1290, 1146,
1100 cmꢁ1 1H NMR (300 MHz, CDCl3)
6.17 (s, NH, D2O ex-
(10g). Mp
3374, 3048, 3020, 1594, 1492, 1200, 740 cmꢁ1 1H NMR (300 MHz,
.
CDCl3)
NMR (CDCl3) d
d
5.78 (br s, NH, D2O exchangeable), 6.86e7.59 (m, 14H). 13
117.25, 118.31, 120.65, 120.82, 122.99, 129.41, 129.70,
C
.
d
changeable), 6.95e6.99 (m, 2H), 7.06e7.15 (m, 3H), 7.30e7.35 (m,
130.03, 144.26, 144.26, 151.46, 158.56. Anal. Calcd for C18H15NO: C,
82.73; H, 5.79; N, 5.36. Found: C, 82.72; H, 5.77; N, 5.35. HRMS (m/
z): [M]þ calcd for C18H15NO 261.1154. Found: 261.1155.
2H), 7.44e7.55 (m, 3H), 7.73e7.76 (m, 2H), 7.89e7.92 (m, 2H). 13C
NMR (75 MHz, CDCl3)
d 114.72, 121.25, 123.93, 127.14, 129.60,
129.75, 130.65, 132.62, 140.08, 142.79, 148.69. Anal. Calcd for
C18H15NO2S: C, 69.88; H, 4.89; N, 4.53. Found: C, 69.86; H, 4.84; N,
4.50. HRMS (m/z): [M]þ calcd for C18H15NO2S 309.0823. Found:
309.0825.
4.3.15. (4-Methoxyphenyl)(4-phenoxyphenyl)amine
81e82 ꢂC. IR (KBr) 3422, 3047, 2952, 1594, 1508, 1490, 1240, 1130,
820 cmꢁ1.1H NMR (300 MHz, CDCl3)
3.77 (s, 3H), 5.39 (br s, NH, D2O
exchangeable), 6.81e7.05 (m, 11H), 7.25e7.32 (m, 2H). 13C NMR
(75 MHz, CDCl3) 55.63, 114.81, 117.64, 117.79, 120.81, 121.29, 122.37,
129.59, 136.60, 141.19, 149.91, 155.07, 158.58. Anal. Calcd for
C19H17NO2: C, 78.33; H, 5.88; N, 4.81. Found: C, 78.30; H, 5.89; N, 4.80.
HRMS (m/z): [M]þ calcd for C19H17NO2 291.1259. Found: 291.1259.
(10o). Mp
d
4.3.8. Phenyl-((S)-1-phenylethyl)amine (10h). Coloress oil. IR (KBr)
d
3426, 3056, 3044, 2996, 1606, 1504, 1320, 750, 698 cmꢁ1. 1H NMR
(300 MHz, CDCl3)
d
1.69 (d, 3H, J¼6.72 Hz), 4.21 (br s, NH, D2O
exchangeable), 4.69 (q, 1H, J¼6.72 Hz), 6.72e6.76 (m, 2H),
6.89e6.92 (m, 1H), 7.30e7.60 (m, 7H). 13C NMR (75 MHz, CDCl3)
d
25.15, 53.65, 113.60, 117.49, 126.09, 127.09, 128.71, 128.86, 145.49,
4.3.16. 4-Methoxy-N-p-tolylbenzenamine (10p). Mp 81e83 ꢂC (lit.21
147.56. Anal. Calcd for C14H15N: C, 85.24; H, 7.66; N, 7.10. Found: C,
mp 81e83). IR (KBr) 3396, 3028, 1588, 1500 cmꢁ1 1H NMR
.
85.21; H, 7.64; N, 7.09. HRMS (m/z): [M]þ calcd for C14H15
N
(300 MHz, CDCl3)
exchangeable), 6.81e6.85 (m, 4H), 6.98e7.04 (m, 4H). 13C NMR
(75 MHz, CDCl3) 20.53, 55.62, 114.72, 116.63, 121.14, 129.35,
d 2.27 (s, 3H), 3.78 (s, OCH3), 5.36 (br s, NH, D2O
197.1204. Found: 197.1203.
d
4.3.9. N-(4-Chlorophenyl)-N-methylbenzenamine(10i). Colorless oil. IR
129.80, 136.71, 142.45, 154.86. Anal. Calcd for C14H15NO: C, 78.84; H,
7.09; N, 6.57. Found: C, 78.80; H, 7.10; N, 6.56. HRMS (m/z): [M]þ
calcd for C14H15NO 213.1154. Found: 213.1155.
(KBr) 3050, 2900, 1592, 1498, 1342, 1260, 1136, 820, 750, 700 cmꢁ1. 1H
NMR (300 MHz, CDCl3)
(m, 3H), 7.12e7.17 (m, 2H), 7.20e7.27 (m, 2H). 13C NMR (75 MHz,
CDCl3) 40.40, 120.59, 120.72, 121.64, 122.40, 125.70, 129.19, 129.32,
d 3.22 (s, 3H), 6.83e6.87 (m, 2H), 6.94e7.01
d
4.3.17. N-Phenylquinolin-2-amine (10q). Mp 162e163 ꢂC. IR (KBr)
129.51. Anal. Calcd for C13H12ClN: C, 71.72; H, 5.56; N, 6.43. Found: C,
71.71; H, 5.53; N, 6.43. HRMS (m/z): [M]þ calcd for C C13H12ClN
217.0658. Found: 217.0659.
3305, 3057, 3045,1593,1504,1423, 1344,1328, 1294, 823, 698 cmꢁ1
.
1H NMR (300 MHz, CDCl3)
7.23e7.98 (m, 11H). 13C NMR (75 MHz, CDCl3)
d
6.36 (br s, NH, D2O exchangeable),
117.81, 124.80,
d
125.68, 125.89, 127.21, 127.90, 128.16, 129.38, 129.50, 136.99, 144.54,
147.39, 156.61. Anal. Calcd for C15H12N2: C, 81.79; H, 5.49; N, 12.72.
Found: C, 81.78; H, 5.47; N, 12.71. HRMS (m/z): [M]þ calcd for
C15H12N2 220.1000. Found: 220.1000.
4.3.10. N-Benzyl-N-methylphenylamine (10j). Colorless oil. IR (KBr)
3026, 1902, 1600, 1502, 1450, 1346, 748, 722, 690 cmꢁ1 1H NMR
.
(300 MHz, CDCl3)
d
2.95 (s, 3H), 4.48 (s, 2H), 6.66e6.74 (m, 3H),
38.60, 56.80, 112.60,
7.16e7.30 (m, 7H). 13C NMR (75 MHz, CDCl3)
d
116.77, 126.93, 127.02, 128.71, 129.34, 139.20, 149.96. Anal. Calcd for
C14H15N: C, 85.24; H, 7.66; N, 7.10. Found: C, 85.21; H, 7.65; N, 7.07.
HRMS (m/z): [M]þ calcd for C14H15N 197.1204. Found: 197.1213.
4.3.18. N-Phenylpyrazin-2-amine (10r). Mp 133e135 ꢂC. IR (KBr)
3302, 3072, 3122, 3026, 2950, 1636, 1592, 1530, 1454, 1360, 1144,
1014, 760 cmꢁ1. 1H NMR (300 MHz, CDCl3)
d 7.04e7.09 (m, 1H), 7.37
(br s, NH, D2O exchangeable), 7.30e7.46 (m, 4H), 7.94 (d, 1H,
4.3.11. 4-Phenylmorpholine (10k). Mp 51e53 ꢂC (lit.21 mp 51e53 ꢂC).
J¼2.67 Hz), 8.08 (d, 1H, J¼1.22 Hz), 8.23 (s, 1H). 13C NMR (75 MHz,
IR (KBr) 3062, 2970, 2865, 2826, 1600, 1494, 1444, 1222, 1110, 920,
CDCl3) d 120.22,123.41,129.32,133.21,134.57,139.44,141.87,152.52.
864 cmꢁ1. 1H NMR (300 MHz, CDCl3)
d
3.12e3.16 (m, 4H), 3.83e3.86
(m, 4H), 6.85e6.92 (m, 3H), 7.23e7.30 (m, 2H). 13C NMR (75 MHz,
CDCl3) 49.41, 66.96, 115.74, 120.05, 129.19, 151.34. Anal. Calcd for
Anal. Calcd for C10H9N3: C, 70.16; H, 5.30; N, 24.54. Found: C, 70.15;
H, 5.30; N, 24.51. HRMS (m/z): [M]þ calcd for C10H9N3 171.0796.
Found: 171.0795.
d
C10H13NO: C, 73.59; H, 8.03; N, 8.58. Found: C, 73.60; H, 8.01; N, 8.55.
HRMS (m/z): [M]þ calcd for C10H13NO 163.0997. Found: 163.0997.
Acknowledgements
4.3.12. 1-(3-Chlorophenyl)-4-phenylpiperazine (10l). Thin yellow
This study was financially supported by GNU Chemistry Re-
search Fund 2011.
liquid. IR (KBr) 3028, 1592, 1484 cmꢁ1. 1H NMR (300 MHz, CDCl3)

B.R. Kim et al. / Tetrahedron 68 (2012) 287e293
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