Cooperatively assisted N-arylation using organic ionic base-Br?nsted acid combination under controlled microwave heating

Article abstract of DOI:10.1016/j.tet.2012.11.078

A new synthetic strategy is developed for the construction of C-N bond through the assistance of Br?nsted acid/[DBU][HOAc] without adding any metal catalyst. This is the first efficient S_NAr methodology utilizing fluoro, chloro, bromo, and iodoarenes as coupling partners, which offers excellent yield up to 94% within a very short time.

Full text of DOI:10.1016/j.tet.2012.11.078

Tetrahedron 69 (2013) 1038e1042
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Cooperatively assisted N-arylation using organic ionic
baseeBrønsted acid combination under controlled microwave
heating
*
Rahul Singh, Bharat Kumar Allam, Dushyant Singh Raghuvanshi, Krishna Nand Singh
Department of Chemistry, Centre of Advanced Study, Faculty of Science, Banaras Hindu University, Varanasi 221005, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 10 October 2012
Received in revised form 23 November 2012
Accepted 25 November 2012
Available online 29 November 2012
A new synthetic strategy is developed for the construction of CeN bond through the assistance of
Brønsted acid/[DBU][HOAc] without adding any metal catalyst. This is the first efficient SNAr method-
ology utilizing fluoro, chloro, bromo, and iodoarenes as coupling partners, which offers excellent yield up
to 94% within a very short time.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Microwave methodology
CeN cross coupling
Catalyst free
Organic ionic base
Brønsted acid
1. Introduction
In CeN bond forming reactions, inorganic bases are usually
employed to facilitate the deprotonation/coordination of the nu-
The CeN bond formation is an important key reaction having
wide applications in the synthesis of organic functional molecules.1
Usually, CeN bonds are constructed by copper and palladium-
catalyzed amination of aryl halides as well as aryl boronic acids.2
During the recent past, significant advances have been made in
the area of amination reactions, which include the development of
novel transition metal catalysts and design of new ligands.3
Although these reaction protocols are endowed with extensive
applications, they have limitations, such as usage of toxic transition
metals, use of costly ligands, and the successive contamination of
the product by these catalysts. Subsequently, there stands enough
scope for further exploration and improvement toward amination
reactions. In this perspective, transition-metal-free protocol
cleophile. However, they suffer from demerits, such as low solu-
bility, high melting points, and sensitivity toward moisture, thereby
compelling the use of more polar solvents and inert atmosphere. To
overcome these drawbacks, organic ionic bases have been
introduced as new and promising promoters for coupling re-
actions.9 DBU is widely used as an organic base,10aec and DBU based
ionic liquids, such as [DBU][HOAc] are particularly useful as a non-
nucleophilic task specific organic ionic base (Fig. 1).10d
The construction of CeN bond can be achieved through SNAr
type substitution pattern. However, the existing reports are appli-
cable to highly activated fluorobenzenes and relatively low yields
are observed with unactivated fluorobenzenes.11 Very recently, the
research group of Fairlie has described a catalyst free N-arylation
strategy with unactivated fluorobenzenes using an excess of K3PO4
(5 equiv) at 150e190 ꢀC to achieve the desired transformation.12
An up to date literature survey reveals that there is no SNAr
substitution protocol, which is applicable to chloro, bromo, and
iodoarenes. With an objective to explore an SNAr type N-arylation
appears particularly attractive.4 Very recently, the research groups
5a
of Laszlo Kurti, James P. Morken,5b and Jianbo Wang5c have
revealed some interesting metal-free amination protocols.
Ionic liquids (ILs) have emerged as novel catalysts and reaction
media, because of their attractive applications and properties.6
Microwave Assisted Organic Synthesis (MAOS) has attained the
status of a new discipline in organic synthesis.7 According to the
current synthetic requirements, relevance of microwave (MW)
methodology using ionic liquids is particularly welcome.8
ꢀ
ꢀ
€
* Corresponding author. Tel.: þ91 0542 2575196; fax: þ91 0542 2368127; e-mail
addresses: knsingh@bhu.ac.in, knsinghbhu@yahoo.co.in (K.N. Singh).
Fig. 1. Structure of the DBU[HOAc].
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.11.078

R. Singh et al. / Tetrahedron 69 (2013) 1038e1042
1039
against the well established metal-catalyzed cross coupling pro-
tocols, we formulated our strategy to exploit the synthetic potential
of various basic ionic liquids for N-arylation of N-nucleophiles. In
light of the above and as a part of our ongoing research to design
new protocols,13 we describe herein our results on CeN bond for-
mation using a new combination of an organic ionic base with an
organic acid under controlled MW (Scheme 1). To the best of our
knowledge this is an efficient and conceptually new methodology
applied first time for SNAr type reactions.
may be attributed to the fact that [DBU][HOAc] increases the nu-
cleophilicity of the amines and acts as a benign medium to drive
the process. Brønsted acids as additives played crucial role as is
evident from entries 8e12 (Table 1). The effect of different MW
power, temperature and time was then studied in detail resulting
in an optimum condition of 100 W, 165 ꢀC and 50 min (Table 1,
entry 15). Aniline (2.0 equiv) and p-TSA/TFA (1.0 equiv) were
established as sufficient to obtain the maximum yield. Some other
additives were also screened but none of them could match the
efficacy of p-TSA or TFA (Table 1, entries 5e8). Further, we refrained
from the use of TFA as an additive because of its high toxicity, low
boiling point, and problems of functional group tolerance, and
therefore resorted on the use of cheaper and safe p-TSA. To confirm
the cooperative role of [DBU][HOAc]-[p-TSA], the reaction was
conducted in the sole presence of p-TSA (entry 1) or [DBU][HOAc]
(entry 4), which was either futile or ended with poor result. These
consequences clearly showcase the fundamental cooperative
function of [DBU][HOAc]-[p-TSA] at play. As there are recent re-
ports regarding the role of metal contaminants in metal free cross
coupling reactions,14 it was thought worthwhile to investigate and
exclude the effect of different metal salts on the present in-
vestigation. As an effect, addition of 3 mol % of CuI or Pd(OAc)2 or
Ni(OAc)2 to either [DBU][HOAc] or p-TSA alone did not bring about
any noticeable change (entries 25e28), thus not counting the
mediation of metal contaminants. The observation (24% yield)
using [DBU][HOAc] without an additive under the optimized
conditions (entry 31) further approved the role of p-TSA as
a unique and important additive in this process. A control exper-
iment in the sole presence of DBU[p-TSA] was conducted with no
observable product (entry 32).
Scheme 1. Comparative illustration of previous and present work.
2. Results and discussion
In order to optimize the reaction conditions, a model re-
action between bromobenzene and aniline was initially carried
out by varying different parameters and the outcome is given in
Table 1.
In general, the presence of electron withdrawing groups on aryl
halides and electron donating groups on N-nucleophiles enhanced
A number of basic ionic liquids with diverse counter ions
were screened and [DBU][HOAc] was found to be the best. This
Table 2
Table 1
Coupling of AreX with a range of N-nucleophilesa
MW-assisted optimization of the reaction conditions
Entry
1.
N-Nucleophile
t (min)
Product
Yield (%)b
Entry PheNH2 Organic ionic base/ Additive (equiv) T (ꢀC) t min Yield
(equiv)
metal salt (equiv)
(%)a
50
75(X¼I)
80(X¼Br)
23(X¼Cl)
84(X¼F)
1.
2.
3.
4.
5.
6.
7.
8.
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.3
1.5
2.0
2.3
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
d
p-TSA (0.5)
p-TSA (0.5)
p-TSA (0.5)
d
140
140
140
140
140
140
140
140
140
140
140
140
140
140
140
140
150
160
165
170
165
165
165
165
165
50
50
50
30
30
30
30
45
45
45
45
45
45
45
45
45
45
45
45
45
45
45
45
45
50
50
50
50
50
50
50
50
00
Trace
Trace
15
20
22
20
52
41
61
43
64
65
70
73
73
76
79
81
79
81
70
45
39
22
20
22
00
00
00
24
00
Bmim[PF6]
Bmim[OH]
[DBU][HOAc]
[DBU][HOAc]
[DBU][HOAc]
[DBU][HOAc]
[DBU][HOAc]
[DBU][HOAc]
[DBU][HOAc]
[DBU][HOAc]
[DBU][HOAc]
[DBU][HOAc]
[DBU][HOAc]
[DBU][HOAc]
[DBU][HOAc]
[DBU][HOAc]
[DBU][HOAc]
[DBU][HOAc]
[DBU][HOAc]
[DBU][HOAc]
[DBU][Lac]
[DBU][n-Pr]
[DBU][n-Bu]
[DBU][HOAc]
[DBU][HOAc]
[DBU][HOAc]
CuI (0.03)
Pd(OAc)2 (0.03)
Ni(OAc)2 (0.03)
[DBU][HOAc]
[DBU][p-TSA]
DABCO (1.0)
L-proline (1.0)
2.
3.
4.
35
50
35
85(X¼I)
BF3$Et2O (1.0)
AcOH (1.0)
p-TSA (0.5)
p-TSA (1.0)
TFA (0.5)
89(X¼Br)
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
TFA (1.0)
77(X¼I)
p-TSA (1.0)
p-TSA (1.0)
p-TSA (1.0)
p-TSA (1.0)
p-TSA (1.0)
p-TSA (1.0)
p-TSA (1.0)
p-TSA (1.0)
TFA (1.0)
p-TSA (1.0)
p-TSA (1.0)
p-TSA (1.0)
CuI (0.03)
Pd(OAc)2 (0.03) 165
Ni(OAc)2 (0.03) 165
p-TSA (1.0)
p-TSA (1.0)
p-TSA (1.0)
d
81(X¼Br)
79(X¼I)
82(X¼Br)
5.
6.
60
55
60(X¼I)
64(X¼Br)
165
165
165
165
165
69(X¼I)
74(X¼Br)
d
a
Isolated product yield based on bromobenzene (1 equiv) at 100 W.
(continued on next page)

1040
R. Singh et al. / Tetrahedron 69 (2013) 1038e1042
Table 2 (continued )
Table 3
Coupling of a range of aryl halides with anilinea
Entry
N-Nucleophile
t (min)
Product
Yield (%)b
Entry
1.
AreX
t (min)
Product
Yield (%)b
75
7.
55
64(X¼I)
68(X¼Br)
50
8.
9.
45
55
66(X¼I)
70(X¼Br)
85(X¼F)
2.
50
79
82(X¼I)
91(X¼Br)
92(X¼F)
3.
4.
50
50
83
85
10.
11.
50
55
71(X¼I)
75(X¼Br)
88(X¼F)
86(X¼I)
83(X¼Br)
94(X¼F)
5.
6.
50
64
12.
13.
14.
50
50
50
54(X¼I)
57(X¼Br)
40
45
87
82
60(X¼I)
67(X¼Br)
7.
58(X¼I)
63(X¼Br)
70(X¼F)
a
Conditions: aryl halide (1 mmol), aniline (2 mmol), p-TSA (1.0 mmol), [DBU]
[HOAc] (1.5 mL) at 100 W, 165 ꢀC.
b
Isolated yield based on aryl halide.
79(X¼I)
15.
55
45
81(X¼Br)
remove water at 60 ꢀC under vacuum and then washed with
diethyl ether. The recovered ionic liquid was reused for five times
without significant loss of the activity. Results were represented in
Fig. 2.
16.
63(X¼I)
69(X¼Br)
a
Using Aryl halide (1 mmol), N-nucleophile (2 mmol), p-TSA (1.0 mmol), [DBU]
[HOAc] (1.5 mL) at 100 W, 165 ꢀC.
b
Isolated yield based on aryl halide.
the product yield considerably (Table 3, entries 2e6; Table 2, en-
tries 2e4). Further, ortho-substituted amines/aryl halides showed
lower yields in contrast to meta/para-substituted analogues,
probably due to steric factors (Table 2, entries 3 and 5; Table 3,
entry 2). Chlorobenzene, when used as a coupling partner, affor-
ded low yield, although 2,4-dinitrochlorobenzene provided good
yield (Table 3, entry 5). Heterocyclic amines, such as indole, pyr-
role, imidazole, and pyrazole underwent fast coupling to provide
good to excellent yields (Table 2, entries 8e11). Substrates like
morpholine, piperidine, cyclohexylamine, and hexylamine affor-
ded reasonably good yields (Table 2, entries 12, 13, 14, and 16),
whereas benzylamine performed excellent (Table 2, entry 15).
Functional groups appended to aryl halides as well as to
N-nucleophiles were well tolerated in this coupling process. No
biaryls were formed out of the homo-coupling of aryl halides
during the investigations.
Fig. 2. Reusability of the ionic liquid.
3. Conclusion
In conclusion, we have demonstrated an efficient Brønsted
acid accelerated CeN cross coupling reaction in an organic
ionic base under controlled MW without the aid of any metal
catalyst. Further applications of this approach are underway
in our laboratory in order to develop a better understanding of
The recyclability of the ionic liquid was investigated with the
same reaction as a model reaction. Upon completion of the re-
action, the product was isolated via standard work up procedure,
while the aqueous layer containing [DBU][AcOH] was dried to

R. Singh et al. / Tetrahedron 69 (2013) 1038e1042
1041
the overall reaction as well as to make this transformation
4.4. Physical and spectral data of products
more useful and practical.
4.4.1. Diphenylamine (3a).17 Colorless solid; mp 52e54 ꢀC. 1H NMR
(300 MHz, CDCl3, 25 ꢀC, TMS):
¼7.27 (t, J¼6.9 Hz, 4H, ArH), 7.07 (d,
J¼6.9 Hz, 4H, ArH), 6.94 (t, J¼6.6 Hz, 2H, ArH), 5.67 ppm (br s,1H, NH).
13CNMR(75MHz, CDCl3, 25ꢀC,TMS):
¼143.0,129.2,120.9,117.7 ppm.
d
4. Experimental section
4.1. General remarks
d
4.4.2. 4-Methoxy-N-phenylaniline (3b).17 Colorless solid; mp
106e107 ꢀC. 1H NMR (300 MHz, CDCl3, 25 ꢀC, TMS):
Microwave reactions were performed in a CEM Discover
benchMate single-mode microwave reactor with a new sealed
pressure regulation 10-mL pressurized vial with ‘snap-on’ cap and
Teflon-coated magnetic stir bar. The standard temperature control
system for the Discover System consists of a non-contact cali-
brated infrared sensor, which monitors and controls the temper-
ature conditions of the reaction vessel located in the instrument
cavity. The glassware used in the experiments was carefully
cleaned with aqua regia before use. Column chromatography was
performed using Merck silica gel (100e200 mesh). Thin layer
chromatography (TLC) was performed using silica gel 60/Kiesel-
guhr F254 precoated on Aluminum sheets (thickness 0.2 mm),
commercially available from Merck. Visualization of spots on TLC
plate was accomplished with UV light and by staining in I2
chamber.
d¼7.24e7.17 (m,
2H, ArH), 7.08 (d, J¼8.7 Hz, 2H, ArH), 6.91e6.79 (m, 5H, ArH), 5.48 (br
s, 1H, NH), 3.79 ppm (s, 3H, OCH3). 13C NMR (75 MHz, CDCl3, 25 ꢀC,
TMS):
d¼155.3,145.1,135.7,129.3,122.2,119.5,115.6,114.6, 55.6 ppm.
4.4.3. 2-Methoxy-N-phenylaniline (3c).17 Yellow oil. 1H NMR
(300 MHz, CDCl3, 25 ꢀC, TMS):
¼7.29e7.25 (m, 3H, ArH), 7.15e7.12
(m, 2H, ArH), 6.95e6.85 (m, 4H, ArH), 6.14 (br s, 1H, NH), 3.88 ppm
(s, 3H, OCH3).13C NMR (75 MHz, CDCl3, 25 ꢀC, TMS):
d
d
¼148.2,142.7,
133.0, 129.2, 121.6, 121.1, 120.8, 118.6, 114.6, 110.5, 55.6 ppm.
4.4.4. 4-Methyl-N-phenylaniline (3d).17 Colorless solid; mp
86e87 ꢀC. 1H NMR (300 MHz, CDCl3, 25 ꢀC, TMS):
d
¼7.25e7.21 (m,
3H, ArH), 7.10e7.01 (m, 5H, ArH), 6.87 (br s,1H, ArH), 5.61 (br s,1H,
NH), 2.30 ppm (s, 3H, CH3). 13C NMR (75 MHz, CDCl3, 25 ꢀC, TMS):
All the melting points were determined in open capillary tubes
and are uncorrected. 1H and 13C NMR spectra were recorded on
300 MHz and 75 MHz JEOL AL300 FTNMR spectrometer, re-
spectively, at a temperature of 300 K. NMR chemical shifts are
d
¼143.9, 140.2, 130.9, 129.8, 129.3, 120.2, 118.9, 116.8, 20.7 ppm.
4.4.5. 2-Nitro-N-phenylaniline powder; mp
(3e).18 Yellow
73e75 ꢀC. 1H NMR (300 MHz, CDCl3, 25 ꢀC, TMS):
¼9.49 (br s, 1H,
d
expressed in
d values with reference to tetramethylsilane (TMS) as
NH), 8.20 (d, J¼8.4 Hz, 1H, ArH), 7.43e7.33 (m, 3H, ArH), 7.28e7.20
internal standard. Product yields refer to isolated yields after col-
umn chromatography.
(m, 4H, ArH), 6.78 ppm (t, J¼7.2 Hz, 1H, ArH). 13C NMR (75 MHz,
CDCl3, 25 ꢀC, TMS):
124.4, 117.5, 116.0 ppm.
d
¼143.1, 138.7, 135.7, 133.1, 129.7, 126.6, 125.6,
4.2. Reagents
4.4.6. 3-Nitro-N-phenylaniline (3f).18 Red solid; mp 85e87 ꢀC. 1H
All the chemicals (including aryl halides and amines) were
purchased from SigmaeAldrich, USA and E. Merck, Germany. New
reagent bottles (Aldrich) of BF3$OEt2 [ꢁ46.5% BF3 basis], 1,8-dia-
NMR (300 MHz, CDCl3, 25 ꢀC, TMS):
d
¼7.84 (s, 1H, ArH), 7.70 (d,
J¼7.8 Hz, 1H, ArH), 7.36e7.25 (m, 4H, ArH), 7.15e7.05 (m, 3H, ArH),
5.94 ppm (br s, 1H, NH). 13C NMR (75 MHz, CDCl3, 25 ꢀC, TMS):
zabicyclo[5.4.0]undec-7-ene (DBU) [ꢁ99.0%], -proline [ꢁ98.0%],
L
d¼149.3,145.1,140.9,130.0,129.7,123.2,121.8,119.9,114.7,110.2 ppm.
1,4-diazabicyclo[2.2.2]octane (DABCO) [ꢁ99.0%], 1-butyl-3-
methylimidazolium hexafluorophosphate (bmIm[PF6]) [ꢁ98.5%],
1-butyl-3-methylimidazolium bromide (bmIm[Br]) [ꢁ97.0%], acetic
acid (ꢁ99.99%, based on metal analysis), trifluoroacetic acid [ꢁ99%]
and p-toluenesulfonic acid monohydrate [ꢁ98.5%] were used. 1-
Butyl-3-methylimidazolium hydroxide (bmIm[OH]), [DBU][HOAc],
DBU[n-propionic acid], DBU[lactic acid], DBU[n-butyric acid], and
DBU[p-TSA] were prepared according to the reported literature
procedures.15,16
4.4.7. 4-Nitro-N-phenylaniline (3g).17 Yellow solid; mp 132e133 ꢀC.
1H NMR (300 MHz, CDCl3, 25 ꢀC, TMS):
d
¼8.13 (d, J¼9.0 Hz, 2H, ArH),
7.41 (t, J¼7.8 Hz, 2H, ArH), 7.25e7.14 (m, 3H, ArH), 6.93 (d, J¼9.3 Hz,
2H, ArH), 6.25 ppm (br s, 1H, NH). 13C NMR (75 MHz, CDCl3, 25 ꢀC,
TMS):
d¼153.4, 145.6, 140.1, 129.9, 126.5, 125.7, 125.4, 118.1 ppm.
4.4.8. N-Phenyl-imidazole (3h).17 Light yellow oil. 1H NMR
(300 MHz, CDCl3, 25 ꢀC, TMS):
¼7.85 (s, 1H, ArH), 7.49e7.44 (m,
d
2H, ArH), 7.39e7.36 (m, 3H, ArH), 7.28 (s, 1H, ArH), 7.20 ppm (s, 1H,
4.3. General procedure for the MW-assisted CeN cross
coupling
ArH). 13C NMR (75 MHz, CDCl3, 25 ꢀC, TMS):
129.8, 127.4, 121.4, 118.2 ppm.
d¼137.3, 135.6, 130.4,
In a new sealed pressure regulation 10-mL pressurized vial
were placed aryl halide (1 mmol), p-toluenesulfonic acid (1 mmol,
0.172 g), [DBU][HOAc] (1.5 mL), N-nucleophile (2 mmol), and
a Teflon-coated magnetic stir bar. The vessel was closed with
a snap-on cap, stirred at room temperature for 5 min and then
placed into the MW cavity. Microwave irradiation of 100 W at
a set temperature of 165 ꢀC was used and the reaction mixture
was held under these conditions for the specified time. After
completion of the reaction (monitored through TLC), the mixture
was cooled to room temperature and was poured to a vessel
containing distilled water. This was extracted with ethyl acetate
(3ꢂ10 mL) and the combined organic phase was washed
with brine (2ꢂ10 mL), dried over Na2SO4, and was concentrated
under rotary vacuum evaporator. The crude product was
purified by column chromatography using a mixture of ethyl
acetate/n-hexane as eluent.
4.4.9. N-Phenyl-indole (3i).17 Colorless oil. 1H NMR (300 MHz,
CDCl3, 25 ꢀC, TMS):
d
¼7.68 (d, J¼7.2 Hz, 1H, ArH), 7.56 (d, J¼8.1 Hz,
1H, ArH), 7.50e7.45 (m, 4H, ArH), 7.32e7.29 (m, 2H, ArH), 7.20e7.15
(m, 2H, ArH), 6.69 ppm (d, J¼8.4 Hz, 1H, ArH). 13C NMR (75 MHz,
CDCl3, 25 ꢀC, TMS):
122.3, 121.1, 120.3, 110.5, 103.5 ppm.
d
¼139.8, 135.8, 129.6, 129.3, 127.9, 126.4, 124.3,
4.4.10. N-Phenyl pyrazole (3j).19 Light yellow oil. 1H NMR
(300 MHz, CDCl3, 25 ꢀC, TMS):
d
¼7.87 (d, J¼2.1 Hz, 1H, ArH),
7.70e7.65 (m, 3H, ArH), 7.42 (t, J¼7.5 Hz, 2H, ArH), 7.26 (t, J¼7.5 Hz,
1H, ArH), 6.41 ppm (s, 1H, ArH). 13C NMR (75 MHz, CDCl3, 25 ꢀC,
TMS):
d¼140.9, 140.0, 129.2, 126.6, 126.2, 119.0, 107.4 ppm.
4.4.11. N-Phenyl pyrrole (3k).17 Clear crystalline solid; mp
58e60 ꢀC. 1H NMR (300 MHz, CDCl3, 25 ꢀC, TMS):
¼7.44e7.39 (m,
4H, ArH), 7.29e7.21 (m, 1H, ArH), 7.10 (t, J¼5.1 Hz, 2H, ArH),
d

1042
R. Singh et al. / Tetrahedron 69 (2013) 1038e1042
6.36 ppm (t, J¼1.8 Hz, 2H, ArH). 13C NMR (75 MHz, CDCl3, 25 ꢀC,
Biomol. Chem. 2011, 9, 3154e3157; (c) Fischer, C.; Koenig, B. Beilstein J. Org.
Chem. 2011, 7, 59e74; (d) Ueda, S.; Su, M.; Buchwald, S. L. J. Am. Chem. Soc.
2012, 134, 700e706; (e) Hili, R.; Yudin, A. K. Nat. Chem. Biol. 2006, 2,
284e287.
2. (a) Ley, S. V.; Thomas, A. W. Angew. Chem., Int. Ed. 2003, 42, 5400e5449; (b)
Beletskaya, I. P.; Cheprakov, A. V. Coord. Chem. Rev. 2004, 248, 2337e2364; (c)
Ma, D.; Cai, Q. Acc. Chem. Res. 2008, 41, 1450e1460; (d) Monnier, F.; Taillefer, M.
Angew. Chem., Int. Ed. 2009, 48, 6954e6971; (e) Bellina, F.; Rossi, R. Adv. Synth.
Catal. 2010, 352, 1223e1276; (f) Kantam, M. L.; Venkanna, G. T.; Sridhar, C.;
Sreedhar, B.; Choudary, B. M. J. Org. Chem. 2006, 71, 9522e9544; (g) Lam, P. Y.
S.; Clark, C. G.; Saubern, S.; Adams, J.; Winters, M. P.; Chan, M. T.; Combs, A.
Tetrahedron Lett. 1998, 39, 2941e2944; (h) Quach, T. D.; Batey, R. A. Org. Lett.
2003, 5, 4397e4400.
3. (a) Wang, D.; Zhang, F.; Kuang, D.; Yu, J.; Li, J. Green Chem. 2012, 14, 1268e1271;
(b) Jiao, J.; Zhang, X.-R.; Chang, N.-H.; Wang, J.; Wei, J.-F.; Shi, X.-Y.; Chen, Z.-G.
J. Org. Chem. 2011, 76, 1180e1183; (c) Yang, H.; Xi, C.; Miao, Z.; Chen, R. Eur. J.
Org. Chem. 2011, 3353e3360; (d) Surry, D. S.; Buchwald, S. L. Angew. Chem., Int.
Ed. 2008, 47, 6338e6361; (e) Toma, G.; Fujita, K.-i; Yamaguchi, R. Eur. J. Org.
Chem. 2009, 4586e4588; (f) Teo, Y.-C.; Chua, G.-L. Chem.dEur. J. 2009, 15,
3072e3075; (g) Guo, D.; Huang, H.; Xu, J.; Jiang, H.; Liu, H. Org. Lett. 2008, 10,
4513e4516; (h) Maligres, P. E.; Krska, S. W.; Dormer, P. G. J. Org. Chem. 2012, 77,
7646e7651.
TMS):
d
¼140.7, 129.5, 125.6, 120.5, 119.3, 110.4 ppm.
4.4.12. N-Phenyl-morpholine (3l).17 Pale crystalline solid; mp
51e53 ꢀC. 1H NMR (300 MHz, CDCl3, 25 ꢀC, TMS):
d
¼7.30 (t,
J¼7.5 Hz, 2H, ArH), 6.92e6.87 (m, 3H, ArH), 3.87e3.84 (m, 4H, CH2),
3.16e3.13 ppm (m, 4H, CH2). 13C NMR (75 MHz, CDCl3, 25 ꢀC, TMS):
d¼151.3, 129.1, 120.0, 115.7, 66.9, 49.3 ppm.
4.4.13. N-Phenyl-piperidine (3m).17 Colorless liquid. 1H NMR
(300 MHz, CDCl3, 25 ꢀC, TMS):
d
¼7.26 (t, J¼7.5 Hz, 2H, ArH), 6.95 (d,
J¼8.1 Hz, 2H, ArH), 6.83 (t, J¼7.2 Hz, 1H, ArH), 3.16 (t, J¼5.7 Hz, 4H,
CH2), 1.74e1.69 (m, 4H, CH2), 1.60e1.57 ppm (m, 2H, CH2). 13C NMR
(75 MHz, CDCl3, 25 ꢀC, TMS):
24.3 ppm.
d
¼152.2, 129.0, 119.1, 116.5, 50.7, 25.9,
4.4.14. N-Cyclohexylaniline (3n).17 Colorless oil. 1H NMR (300 MHz,
CDCl3, 25 ꢀC, TMS):
4. Significant transition-metal free amination reactions: (a) Shi, L.; Wang, M.; Fan,
d
¼7.16 (t, J¼7.2 Hz, 2H, ArH), 6.66 (t, J¼6.6 Hz,
ꢀ
C.-A.; Zhang, F.-M.; Tu, Y.-Q. Org. Lett. 2003, 5, 3515e3517; (b) Cano, R.; Ramon,
1H, ArH), 6.58 (d, J¼7.5 Hz, 2H, ArH), 3.48 (br s, 1H, NH), 3.28e3.19
(m, 1H), 2.06e2.02 (m, 2H), 1.77e1.72 (m, 2H), 1.66e1.62 (m, 1H),
1.38e1.07 ppm (m, 5H). 13C NMR (75 MHz, CDCl3, 25 ꢀC, TMS):
D. J.; Yus, M. J. Org. Chem. 2011, 76, 654e660.
€
5. (a) Zhu, C.; Li, G.; Ess, D. H.; Falck, J. R.; Kurti, L. J. Am. Chem. Soc. 2012, 134,
18352e18356; (b) Mlynarski, S. N.; Karns, A. S.; Morken, J. P. J. Am. Chem. Soc.
2012, 134, 16449e16451; (c) Xiao, Q.; Tian, L.; Tan, R.; Xia, Y.; Qiu, D.; Zhang, Y.;
Wang, J. Org. Lett. 2012, 14, 4230e4233.
6. (a) Torimoto, T.; Tsuda, T.; Okazaki, K.-i.; Kuwabata, S. Adv. Mater. 2010, 22,
1196e1221; (b) Lee, J. W.; Shin, J. Y.; Chun, Y. S.; Jang, H. B.; Song, C. E.; Lee, S. eg
Acc. Chem. Res. 2010, 43, 985e994; (c) Hallett, J. P.; Welton, T. Chem. Rev.
2011, 111, 3508e3576; (d) Dong, K.; Zhang, S. Chem.dEur. J. 2012, 18,
2748e2761.
d¼147.3, 129.2, 116.7, 113.1, 51.6, 33.4, 25.9, 25.0 ppm.
4.4.15. N-Benzylaniline (3o).20 Colorless oil. 1H NMR (300 MHz,
CDCl3, 25 ꢀC, TMS):
¼7.35e7.13 (m, 7H, ArH), 6.73e6.61 (m, 3H,
d
ArH), 4.31 (s, 2H, PhCH2), 4.01 ppm (br s,1H, NH). 13C NMR (75 MHz,
CDCl3, 25 ꢀC, TMS):
112.9, 48.3 ppm.
d
¼148.2, 139.5, 129.3, 128.7, 127.5, 127.3, 117.6,
7. (a) Gutmann, B.; Schwan, A. M.; Reichart, B.; Gspan, C.; Hofer, F.; Kappe, C. O.
Angew. Chem., Int. Ed. 2011, 50, 7636e7640; (b) Moseley, J. D.; Kappe, C. O. Green
Chem. 2011, 13, 794e806.
8. Polshettiwar, V.; Varma, R. S. Acc. Chem. Res. 2008, 41, 629e639.
9. Yang, C.-T.; Fu, Y.; Huang, Y.-B.; Yi, J.; Guo, Q.-X.; Liu, L. Angew. Chem., Int. Ed.
2009, 48, 7398e7401.
4.4.16. N-Hexylaniline (3p).22 Colorless liquid. 1H NMR (300 MHz,
CDCl3, 25 ꢀC, TMS):
d
¼7.24e7.13 (m, 2H, ArH), 6.98e6.89 (m, 1H,
ꢀ
10. (a) Larrivee Aboussafy, C.; Jones, B. P.; Price, K. E.; Hardink, M. A.; McLaughlin,
ArH), 6.69e6.57 (m, 2H, ArH), 3.57 (br s, 1H, NH), 3.11 (t, J¼6.9 Hz,
R. W.; Lillie, B. M.; Hawkins, J. M.; Vaidyanathan, R. Org. Lett. 2010, 12, 324e327;
(b) Peterson, S. L.; Stucka, S. M.; Dinsmore, C. J. Org. Lett. 2010, 12, 1340e1343;
(c) De Rycke, N.; Couty, F.; David, O. R. P. Chem.dEur. J. 2011, 17, 12852e12871;
(d) Ying, A.-G.; Liu, L.; Wu, G.-F.; Chen, G.; Chen, X.-Z.; Ye, W.-D. Tetrahedron
Lett. 2009, 1653e1657.
2H, CH2), 1.65e153 (m, 2H, CH2), 1.32e1.31 (m, 6H, CH2), 0.89 ppm
(br s, 3H, CH3). 13C NMR (75 MHz, CDCl3, 25 ꢀC, TMS):
129.2, 121.0, 120.9, 117.0, 112.7, 44.0, 31.6, 29.5, 26.8, 22.6, 14.0 ppm.
d
¼148.5,
11. (a) Amii, H.; Uneyama, K. Chem. Rev. 2009, 109, 2119e2183; (b) Otsuka, M.;
Endo, K.; Shibata, T. Chem. Commun. 2010, 336e338; (c) Dehe, D.; Munstein, I.;
Reis, A.; Thiel, W. R. J. Org. Chem. 2011, 76, 1151e1154; (d) Clot, E.; Eisenstein, O.;
Jasim, N.; Macgregor, S. A.; Mcgrady, J. E.; Perutz, R. N. Acc. Chem. Res. 2011, 44,
333e348.
12. Diness, F.; Fairlie, D. P. Angew. Chem., Int. Ed. 2012, 51, 8012e8016.
13. (a) Guntreddi, T.; Allam, B. K.; Singh, K. N. Synlett 2012, 2635e2638; (b) Allam,
B. K.; Singh, K. N. Tetrahedron Lett. 2011, 52, 5851e5854; (c) Allam, B. K.; Singh,
K. N. Synthesis 2011, 1125e1131; (d) Raghuvanshi, D. S.; Singh, K. N. Synlett 2011,
373e377; (e) Gupta, A. K.; Rao, G. T.; Singh, K. N. Tetrahedron Lett. 2012, 53,
2218e2221; (f) Kumari, K.; Raghuvanshi, D. S.; Jouikov, V.; Singh, K. N. Tetra-
hedron Lett. 2012, 53, 1130e1133; (g) Raghuvanshi, D. S.; Singh, K. N. Tetrahe-
dron Lett. 2011, 52, 5702e5705; (h) Raghuvanshi, D. S.; Gupta, A. K.; Singh, K. N.
Org. Lett. 2012, 14, 4326e4329.
14. (a) Leadbeater, N. E. Nat. Chem. 2010, 2,1007e1009; (b) Thome, I.; Nijs, A.; Bolm, C.
Chem. Soc. Rev. 2012, 41, 979e987; (c) Crabtree, R. H. Chem. Rev. 2012, 112,
1536e1554.
15. Ranu, B. C.; Banerjee, S. Org. Lett. 2005, 7, 3049e3052.
16. (a) Ying, A.-G.; Wang, L.-M.; Deng, H.-X.; Chen, J.-H.; Chen, X.-Z.; Ye, W.-D.
ARKIVOC 2009, 288e298; (b) Coady, D. J.; Fukushima, K.; Horn, H. W.; Rice, J. E.;
Hedrick, J. L. Chem. Commun. 2011, 3105e3107.
4.4.17. 2,4-Dinitro-N-phenylaniline (3q).21 Orange-red solid; mp
156e157 ꢀC. 1H NMR (300 MHz, CDCl3, 25 ꢀC, TMS):
d¼9.97 (br s,
1H, NH), 9.18 (s, 1H, ArH), 8.18 (d, J¼9.3 Hz, 1H, ArH), 7.50 (d,
J¼7.2 Hz, 1H, ArH), 7.40e7.14 ppm (m, 5H, ArH). 13C NMR (75 MHz,
CDCl3, 25 ꢀC, TMS):
125.5, 124.0, 116.0 ppm.
d
¼147.0, 137.4, 136.7, 131.1, 130.2, 129.9, 127.7,
Acknowledgements
We are thankful to the Council of Scientific and Industrial Re-
search (CSIR), New Delhi for financial assistance. We are grateful to
Dr. Y. Sriramulu, Former Associate Professor, Berhampur University,
Odisha for his valuable suggestions.
Supplementary data
17. Rout, L.; Saha, P.; Jammi, S.; Punniyamurthy, T. Adv. Synth. Catal. 2008, 350,
395e398.
Copies of 1H and 13C NMR spectra for all the products are pro-
vided in Supplementary Data. Supplementary data related to this
article can be found at http://dx.doi.org/10.1016/j.tet.2012.11.078.
18. Chen, S.; Huang, H.; Liu, X.; Shen, J.; Jiang, H.; Liu, H. J. Comb. Chem. 2008, 10,
358e360.
19. Taillefer, M.; Xia, N.; Ouali, A. Angew. Chem. 2007, 119, 952e954 Angew. Chem.,
Int. Ed. 2007, 46, 934e936.
20. Kwong, F. Y.; Klapars, A.; Buchwald, S. L. Org. Lett. 2002, 4, 581e584.
21. Gulevskaya, A. V.; Tyaglivaya, I. N.; Verbeeck, S.; Maes, B. U. W.; Tkachuk, A. V.
ARKIVOC 2011, 238e251.
References and notes
22. Sahli, Z.; Sundararaju, B.; Achard, M.; Bruneau, C. Org. Lett. 2011, 13,
3964e3967.
1. (a) Hartwig, J. F. Nature 2008, 455, 314e322; (b) Lee, H.-Y.; Chang, J.-Y.; Chang,
L.-Y.; Lai, W.-Y.; Lai, M.-J.; Shih, K.-H.; Kuo, C.-C.; Chang, C.-Y.; Liou, J.-P. Org.