Chemoselective reductive amination of carbonyl compounds for the synthesis of tertiary amines using SnCl2·2H2O/PMHS/MeOH

Article abstract of DOI:10.1021/acs.joc.5b00156

Stannous chloride catalyzed chemoselective reductive amination of a variety of carbonyl compounds with aromatic amines has been developed for the synthesis of a diverse range of tertiary amines using inexpensive polymethylhydrosiloxane as reducing agent in methanol. The present method is also applicable for the synthesis of secondary amines including heterocyclic ones.

Full text of DOI:10.1021/acs.joc.5b00156

Note
pubs.acs.org/joc
Chemoselective Reductive Amination of Carbonyl Compounds for
the Synthesis of Tertiary Amines Using SnCl2·2H2O/PMHS/MeOH
Onkar S. Nayal,† Vinod Bhatt,†,‡ Sushila Sharma,†,‡ and Neeraj Kumar*,†,‡
†Natural Product Chemistry and Process Development Division, CSIR-Institute of Himalayan Bioresource Technology, Palampur,
Himachal Pradesh 176 061, India
‡Academy of Scientific and Innovative Research, Anusandhan Bhawan, 2 Rafi Marg, New Delhi 110001, India
S
* Supporting Information
ABSTRACT: Stannous chloride catalyzed chemoselective reduc-
tive amination of a variety of carbonyl compounds with aromatic
amines has been developed for the synthesis of a diverse range of
tertiary amines using inexpensive polymethylhydrosiloxane as
reducing agent in methanol. The present method is also applicable
for the synthesis of secondary amines including heterocyclic ones.
ertiary amines are the most common structural feature of
of phenyl silane15 and Baba et al. also reported Bu2SnClH-
Tnaturally occurring biologically active alkaloids, industrial pyridine-N-oxide as a catalyst with diphenylsilane/phenylsilane
as a reducing agent.16 However, these methods were limited for
the synthesis of secondary amines.
fine chemicals, pharmaceuticals and agrochemicals.1 Direct
reductive amination (DRA) of carbonyl compounds is the most
convenient and preferred procedure for the preparation of
amines. However, while DRA was widely used for the synthesis
of secondary amines in which various types of heterogeneous
and homogeneous catalysts have been reported,2−10 few reports
are available for the synthesis of tertiary amines through
reductive amination. DRA involving aromatic and aliphatic
carbonyl compounds with secondary amines is difficult as the
steric hindrance disfavors the iminium ion/enamine formation
in equilibrium. Also, the in situ transfer hydrogenation of
iminium ion is difficult.
Magid et al. reported sodium triacetoxyborohydride as a
reagent for the reductive amination of carbonyl compounds
with different aliphatic and aromatic primary and sterically
unhindered aliphatic secondary amines; however, the method
was not applicable to secondary aromatic amines.11 Ishii and
co-workers also developed a method for the alkylation of
secondary aliphatic amines with aldehydes.12 Lee et al.
described the reductive amination of aldehydes and aliphatic
ketones with secondary amines using InCl3 as catalyst with
triethylsilane as reducing agent.6 Recently, Moulin et al.
demonstrated substituted cyclopentadienyl−iron complex
catalyzed reductive amination of aliphatic aldehydes with
secondary amines using H2 as hydrogen source.13 Herein, a
protocol has been developed for DRA of carbonyl compounds
with primary and secondary amines using easily available, water
and air endurance, less corrosive stannous chloride as a catalyst
in the presence of polymethylhydrosiloxane (PMHS) and
methanol. PMHS is a cheap, easy to handle, air and moisture
stable, environment friendly reducing agent, and its byproduct,
polysiliconate, is used in silicon industries as an absorbent.14
Very few reports have shown the use of tin based catalyst for
reductive amination. Xiao group demonstrated reductive
amination using catalytic amount of Bu2SnCl2 in the presence
The present protocol is a versatile method tolerating a variety
of carbonyl and amine substrates, including aliphatic and
aromatic ketones as well as aldehydes. In our earlier reports, the
role of Lewis acidic character of CoPc and AlCl3 was revealed in
catalyzing the reductive amination reaction.9,10 Although these
methods were very effective in DRA of carbonyl compounds
with primary and secondary amines, unfortunately DRA of
ketones with secondary amines was not effective. In this
context, we focused on the DRA of carbonyl compounds with
secondary amines and screened various Lewis acidic salts. To
optimize the reaction conditions, the reductive amination of
anisaldehyde with N-methylaniline was investigated with
variation in reaction parameters such as catalyst, reducing
agent, solvent, temperature and time (Table 1). Surprisingly, in
the absence of catalyst, the reaction proceeded to afford the
product in 15% yield (Table 1, entry 1) which was further
lowered in the presence of strong Lewis acids such as AlCl3 and
FeCl3 (Table 1, entries 2−3). While no reaction was observed
with copper, nickel or cobalt based catalysts (Table 1, entries
4−6), zinc chloride showed some activity toward the reaction
(Table 1, entry 7). The best yield of the product was observed
with 20 mol % of SnCl2·2H2O and 2 equiv of PMHS as a
reducing agent at 70 °C for 6 h in methanol (Table 1, entry 8).
Further, a lower catalyst loading led to lower conversion (Table
1, entry 9), whereas no significant change in the yield of the
product was observed with higher catalyst loading (Table 1,
entry 10). The investigation of different reducing agents
revealed PMHS as the most efficient hydrogen source
providing the product in 86% yield (Table 1, entry 8).
Comparable yields were recorded with other silanes such as
Received: February 10, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.5b00156
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The Journal of Organic Chemistry
Note
With the best reaction conditions in hand, the scope and
limitation of SnCl2 catalyzed reductive amination with PMHS
was explored for a variety of carbonyl compounds in
combination with different amines. The reactions condition
was found to be viable to a wide variety of substrate classes
including aromatic and aliphatic aldehydes (Scheme 1).
Table 1. Optimisation of Reaction Conditions for DRA of
Anisaldehyde with N-Methylaniline
a
Halogen substituted aldehydes were well tolerated, and the
corresponding amines were obtained in good to excellent yields
(Scheme 1, 3a−3e). The reductive amination of aldehydes
bearing electron-donating groups with N-methylaniline pro-
ceeded smoothly to afford the desired product in excellent
yields (Scheme 1, 3f−3h). The reaction of polysubstituted
aldehydes with N-methylaniline, a less studied challenging
substrate combination, gave good to excellent yield of the
desired product (Scheme 1, 3i−3l). Sterically hindered
aldehydes provided the desired product in good yield (Scheme
1, 3m−3o). One of the major predicament associated with
reductive amination is intolerance of CC bonds;17 however,
in the present case >99% chemoselectivity was observed with
conjugated as well as isolated CC bonds containing
aldehydes (Scheme 1, 3p−3s). Reductive amination of 2-
furaldehyde, anthraldehyde, and aliphatic aldehyde, i.e., 3-
phenylpropionaldehyde, proceeded smoothly to give 3t, 3u,
and 3v in good (70−87%) yield. The reductive amination of
aldehydes with other secondary amines, N-ethylaniline and N-
benzylanisidine, provided an excellent yield of the product
(Scheme 1, 3w−3x). Unfortunately, no reaction was observed
with aliphatic amines under the present reaction condition
(Table S2 in the Supporting Information).
One of the merits of the present method is the reductive
amination of aromatic and aliphatic ketones with secondary
amines which are otherwise considered difficult substrates for
this reaction resulting in low yields of the product.18 Under the
present reaction conditions, the reductive amination of different
aliphatic and aromatic ketones with secondary amines afforded
the desired products in excellent to moderate yields (Scheme
2). Cyclopentanone and cyclohexanone reacted with N-methyl
aniline to afford 5a and 5b in 83 and 90% yields, respectively.
Substituted cyclohexanone also gave excellent yield of the
desired product (Scheme 2, 5c−5d). Reductive amination of 4-
methylcyclohexanone and cyclopentanone with sterically
hindered diphenylamine provided moderate yield of the desired
product (Scheme 2, 5e−5f). In the case of acetophenones,
while no reaction occurred under the present reaction
conditions, moderate yield of the corresponding products
were observed when the reaction was carried out in toluene
with 3 equiv MeOH at 120 °C (Scheme 2, 5g−5i).
b
entry
catalyst
reducing agent
solvent
yield (%)
1
-
PMHS
PMHS
PMHS
PMHS
PMHS
PMHS
PMHS
PMHS
PMHS
PMHS
Et3SiH
Ph3SiH
TMDS
PhSiH3
PMHS
-
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
H2O
15
2
AlCl3
12
3
FeCl3
9
4
CuCl2·2H2O
NiCl2·6H2O
CoCl2·6H2O
ZnCl2
NR
NR
NR
33
5
6
7
8
SnCl2·2H2O
SnCl2·2H2O
SnCl2·2H2O
SnCl2·2H2O
SnCl2·2H2O
SnCl2·2H2O
SnCl2·2H2O
SnCl2·2H2O
SnCl2·2H2O
SnCl2·2H2O
SnCl2·2H2O
SnCl2·2H2O
SnCl2·2H2O
SnCl2·2H2O
SnCl2·2H2O
SnCl2·2H2O
SnCl2·2H2O
86
c
9
64
d
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
86
57
55
61
68
e
75
f
0
PMHS
PMHS
PMHS
PMHS
PMHS
PMHS
PMHS
PMHS
55
45
27
24
52
31
EtOH
iPrOH
nBuOH
Toluene
THF
g
MeOH
MeOH
35
h
86
a
Reaction conditions: Catalyst (20 mol %), 1 (1.1 mmol), 2 (1
mmol), reducing agent (2 mmol), MeOH (3 mL), 70 °C, 6 h. GC
yield using hexadecane as internal standard. Quantity of catalyst used
was 15 mol %. Quantity of catalyst used was 25 mol %. The reaction
was carried out using 1.5 mmol PMHS. Iminum ion observed. The
reaction was carried out at rt. The reaction was carried out at 120 °C.
b
c
d
e
f
g
h
Et3SiH, Ph3SiH, TMDS and PhSiH3 (Table 1, entries 11−14).
Lowering the quantity of PMHS resulted in the lower yield of
the desired product (Table 1, entry 15). As expected, no
product was formed in the absence of PMHS; however,
iminium ion was observed as major intermediate (Table 1,
entry 16). Further, different solvents were screened to
investigate the influence of solvent on the yield as the
interaction of solvent molecules with Lewis acids drastically
influences catalytic activity and methanol was found to be most
efficient compared to other solvents. Moderate yield of the
product was observed in water and ethanol (Table 1, entries 17
and 18), whereas sterically hindered alcohols such as iPrOH
and nBuOH gave lower yield of the desired product (Table 1,
entries 19−20).
In the case of aprotic solvents such as toluene and THF,
moderate yield of the desired product was observed (Table 1,
entries 21 and 22) which further decreased in dry toluene.
Similarly, in complete anhydrous condition with stannous
chloride in dry methanol, significant lowering in the yield was
observed which indicated the supportive role of water in
catalyzing the reaction (Table S1 in the Supporting
Information). A decrease in the yield of the desired product
was observed at lower temperature, while no change in the
yield was observed at 120 °C (Table 1, entries 23 and 24).
Further, the scope of the method was extended for the
reductive animation of carbonyl compounds with primary
amines which afforded excellent yield of the corresponding
secondary amines with high chemoselectivity (Scheme 3).
Excellent yield was observed with electron deficient N-
heteroaromatic primary amines (Scheme 3, 7a−7b). Bogolub-
sky et al. reported an efficient method for the reductive
amination of heterocyclic amines, but the use of NaBH(OAc)3
as a reducing agent which is not eco-friendly and economically
favorable limits its viability.19 Electron donating substituents
present on amines as well as aldehydes were well tolerated and
gave excellent yields of the desired products (Scheme 3, 7c−
7f). One of the major advantages of the present method is the
reductive amination with primary amines bearing electron
withdrawing substituents such as −COOH, −COCH3, and
−NO2 (Scheme 3, 7g−7i) which were otherwise considered as
B
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Note
a
Scheme 1. Reductive Amination of Aldehydes with Secondary Amines
a
Reaction conditions: SnCl2·2H2O (20 mol %), 1 (1.1 mmol), 2 (1 mmol), PMHS (2 mmol), MeOH (3 mL), 70 °C, 6 h. Isolated yield.
Scheme 2. Reductive Amination of Ketones with Secondary
Amines
Scheme 3. Reductive Amination of Carbonyl Compounds
with Primary Amines
a
a
a
Reaction condition: SnCl2·2H2O (20 mol %), 4 (1.1 mmol), 2 (1
mmol), PMHS (2 mmol),MeOH (3 mL), at 70 °C for 6 h. Isolated
b
yield. Reaction carried out at 120 °C, MeOH (3 mmol) in toluene (3
c
mL). Reaction carried out at 120 °C in toluene (3 mL).
a
difficult substrates.20 Aliphatic as well as aromatic ketones were
transformed to the desired products in excellent yields (Scheme
3, 7j−7m).
Reaction conditions: SnCl2·2H2O (20 mol %), 4 (1 mmol), 6 (1
mmol), PMHS (2 mmol), 3 mL MeOH, 70 °C, 6 h. Isolated yield.
To get insight into the reaction mechanism, different control
experiments were carried out. ESI-MS, UV−vis, and FT-IR
spectra of SnCl2·2H2O/MeOH indicated the initial formation
of tin methanol complex (A). Although exact role of tin catalyst
is not clear, the in situ formation of tin hydride complex has
been assumed. Being highly unstable,21 direct detection of tin
hydride complex (B) was not possible; however, various
indirect evidence in favor of B were collected. Addition of
PMHS to SnCl2·2H2O/MeOH led to the disappearance of
vSi−H (2162 cm−1) band in FT-IR spectrum. 1H NMR of
PMHS/SnCl2·2H2O/MeOH mixture also showed disappear-
ance of δH 4.75 signal of Si-H. Furthermore, the reduction of
imine did not proceed in the presence of PMHS/MeOH
system alone, hence indicating the formation of B via activation
of PMHS by A. The hydride transfer from B to in situ generated
iminium ion resulted in the formation of product. It has been
observed that the role of water as an additive is crucial for the
product formation as complete anhydrous condition led to
C
DOI: 10.1021/acs.joc.5b00156
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Note
7.24−7.27 (m, 3H), 7.62 (d, 1H, J = 7.8 Hz); 13C NMR (CDCl3, 150
MHz) δ 38.8, 57.4, 112.0, 116.6, 122.7, 127.5, 127.9, 128.4, 129.2,
132.8, 137.4, 149.2; HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C14H15BrN 276.0388; found 276.0367.
N-(3-Chlorobenzyl)-N-methylaniline (3b). Pale yellow oil (162 mg,
70% yield), 1H NMR (CDCl3, 600 MHz) δ 3.06 (s, 3H), 4.53 (s, 2H),
6.78−6.81 (m, 3H), 7.16−7.12 (m, 1H), 7.26−7.30 (m, 5H); 13C
NMR (CDCl3, 150 MHz) δ 38.6, 56.4, 112.5, 117.0, 124.9, 126.8,
127.1, 129.3, 129.9, 134.6, 141.5, 149.5; HRMS (ESI-TOF) m/z: [M +
H]+ calcd for C14H15ClN 232.0893; found 232.0875.
significant decrease in product yield (Table S1 in the
Supporting Information).
On the basis of the above experimental results and literature
findings,22 a plausible reaction mechanism is proposed in
Scheme 4. First, SnCl2·2H2O in the presence of MeOH formed
Scheme 4. Plausible Reaction Mechanism
N-(4-Bromo-2-fluorobenzyl)-N-methylaniline (3c). Pale yellow oil
1
(214.6 mg, 73% yield), H NMR (CDCl3, 300 MHz) δ 3.10 (s, 3H),
4.59 (s, 2H), 6.78−6.85 (m, 3H), 7.12 (t, 1H, J = 8.07 Hz), 7.24−7.33
(m, 4H); 13C NMR (CDCl3, 75 MHz) δ 39.1, 50.7 (d, J = 3.6 Hz),
112.8, 117.5, 119.4 (d, J = 24.6 Hz), 121.1 (d, J = 9.3 Hz), 125.4 (d, J
= 14.7 Hz), 127.9 (d, J = 3.3 Hz), 129.7, 130.2 (d, J = 5.2 Hz), 149.6,
161.0 (d, J = 249.9 Hz); HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C14H14BrFN 294.0294; found 294.0289.
N-(4-Bromobenzyl)-N-methylaniline (3d). Colorless oil (229 mg,
83% yield), 1H NMR (CDCl3, 600 MHz) δ 3.04 (s, 3H), 4.51 (s, 2H),
6.78 (overlapped, 3H), 7.15 (d, 2H, J = 7.9 Hz), 7.26−7.29 (m, 2H),
7.47 (dd, 2H, J = 6.8, 1.5 Hz); 13C NMR (CDCl3, 150 MHz) δ 38.6,
56.2, 112.5, 116.9, 120.6, 128.5, 129.3, 131.7, 138.1, 149.5; HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C14H15BrN 276.0388; found
276.0345.
N-(4-Chlorobenzyl)-N-methylaniline (3e). Colorless oil (189.4 mg,
82% yield), 1H NMR (CDCl3, 600 MHz) δ 3.13 (s, 3H), 4.61 (s, 2H),
6.89 (d, 3H, J = 7.5 Hz), 7.31 (t, 2H, J = 7.7 Hz), 7.39−7.42 (m, 4H);
13C NMR (CDCl3, 150 MHz) δ 38.5, 56.2, 112.5, 116.9, 128.1, 128.7,
129.2, 132.5, 137.5, 149.5; HRMS (ESI-TOF) m/z: [M + H]+ calcd
for C14H15ClN 232.0893; found 232.0876.
the complex A which further reacted with PMHS and resulted
in the formation of tin hydride complex B.22b Water promoted
reduction of in situ generated iminium ion (C) in the presence
of B resulted in the formation of product along with tin
hydroxide complex (D). Finally, the complex B was
regenerated in the presence of PMHS for another catalytic
cycle.22c
In conclusion, the present paper discloses SnCl2·2H2O as
highly efficient and versatile catalyst for the synthesis of a series
of tertiary and secondary amines by reductive amination of
aliphatic as well as aromatic carbonyl compounds utilizing
inexpensive, stable and easy to handle PMHS as reducing agent.
The reductive amination of a variety of substrates in high yield
and chemoselectivity with broad functional group tolerance, air
insensitive, and ambient reaction conditions are the remarkable
features of the present protocol.
N-(4-Methoxybenzyl)-N-methylaniline (3f). Yellow oil (183.8 mg,
81% yield), 1H NMR (CDCl3, 600 MHz) δ 3.04 (s, 3H), 3.36 (s, 3H),
4.13 (s, 2H), 6.76 (t, 1H, J = 7.1 Hz), 6.81 (d, 2H, J = 8.1 Hz), 6.90 (d,
2H, J = 8.3 Hz), 7.20 (d, 2H, J = 8.2 Hz), 7.27 (t, 2H, J = 8.1 Hz); 13C
NMR (CDCl3, 150 MHz) δ 38.3, 55.3, 56.1, 112.5, 114.0, 116.5, 128.0,
129.2, 130.9, 149.9, 158.6. HRMS (ESI-TOF) m/z: [M + H]+ calcd
for C15H18NO 228.1388; found 228.1380.
N-(3-Hydroxy-4-methoxybenzyl)-N-methylaniline (3g). Pale yel-
low solid (120 mg, 75% yield), mp. 73−74 °C. 1H NMR (CDCl3, 300
MHz) δ 3.06 (s, 3H), 3.90 (s, 3H), 4.50 (s, 2H), 6.79−6.86 (m, 5H),
6.91 (d, 1H, J = 1.7 Hz), 7.27−7.32 (m, 2H); 13C NMR (CDCl3, 75
MHz) δ 38.8, 56.4, 56.6, 111.2, 112.9, 113.6, 116.9, 118.6, 129.6,
132.7, 146.0, 146.2, 150.2; HRMS (ESI-TOF) m/z: [M + H]+ calcd
for C15H18NO2 244.1338; found 244.1341.
N-(3-Hydroxybenzyl)-N-methylaniline (3h). Greenish oil (187.4
mg, 88% yield), 1H NMR (CDCl3, 600 MHz) δ 3.03 (s, 3H), 4.50 (s,
2H), 6.72 (t, 2H, J = 7.3 Hz), 6.78−6.81 (m, 3H), 6.85 (d, 1H, J = 7.5
Hz), 7.21 (t, 1H, J = 7.7 Hz), 7.26−7.29 (m, 2H); 13C NMR (CDCl3,
150 MHz) δ 38.6, 56.5, 112.6, 113.6, 114.0, 116.8, 119.2, 129.3, 129.9,
141.0, 149.7, 155.9; HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C14H16NO 214.1232; found 214.1242.
EXPERIMENTAL SECTION
■
General. High grade solvents were used for all reactions. Column
chromatography was carried out with 60−120 mesh silica gel and
monitored with TLC on silica gel 60 F254 plates using UV light as
1
visualizing agent. H NMR and 13C NMR experiments were recorded
on 300 and 600 MHz instruments. Chemical shifts are reported in
parts per million (ppm) downfield from an internal standard. Mass
spectra were recorded on electrospray ionization quadrupole time-of-
flight (ESI-QTOF-MS) mass spectrometer. The GC analysis was
carried out on Gas Chromatogram, an AOC-20i autosampler coupled,
and a DB-5MS capillary column (30 m × 0.25 mm i.d., 0.25 μm). The
initial temperature of the column was held at 70 °C for 4 min and was
programmed to 230 °C at 4 °C min−1, then held for 15 min at 230 °C;
the sample injection volume was 1 μL in GC grade dichloromethane.
Nitrogen was used as the carrier gas at a flow rate of 1.1 mL min−1 on
split mode (1:50). UV−vis spectra were recorded on a UV−vis
spectrophotometer.
Typical Procedure for the Reductive Amination. To a stirred
solution of SnCl2·2H2O (0.2 mmol) in MeOH (3 mL) were added
carbonyl compound (1.1 mmol), amine (1.0 mmol) and PMHS (2.0
H equiv) at room temperature, and then the temperature was raised to
70 °C. After 6 h, the reaction mixture was allowed to cool, filtered and
passed through anhydrous sodium sulfate. The crude product was
purified by column chromatography over silica gel (60−120 mesh)
with an appropriate mixture of n-hexane and ethyl acetate.
N-(3-Iodo-4,5-dimethoxybenzyl)-N-methylaniline (3i). Greenish
yellow solid (268 mg, 70% yield), mp 69−70 °C. IR ν (KBr)
̃
(cm−1): 690, 744, 835, 997, 1032, 1120, 1255,1371, 1479, 1508, 2929.
1H NMR (CDCl3, 600 MHz) δ 3.02 (s, 3H), 3.81 (s, 3H), 3.86 (s,
3H), 4.44 (s, 2H), 6.77−6.80 (m, 4H), 7.27 (t, 3H J = 7.2 Hz); 13C
NMR (CDCl3, 150 MHz) δ 38.6, 56.0, 56.3, 60.4, 92.6, 111.3, 112.8,
117.1, 128.4, 129.2, 137.3, 147.8, 149.8, 152.8; HRMS (ESI-TOF) m/
z: [M + H]+ calcd for C16H19INO2 384.0461; found 384.0482.
N-(3,4,5-Trimethoxybenzyl)-N-methylaniline (3j). Brown solid
(272.6 mg, 95% yield), mp 50−51 °C. 1H NMR (CDCl3, 600
MHz) δ 3.04 (s, 3H), 3.83 (s, 6H), 3.90 (s, 3H), 4.49 (s, 2H), 6.53 (s,
2H), 6.76−6.85 (m, 3H), 7.25−7.31 (m, 2H); 13C NMR (CDCl3, 150
MHz) δ 38.8, 56.4, 57.5, 61.2, 103.9, 113.1, 117.3, 129.6, 135.3, 137.2,
150.4, 153.4; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C17H22NO3
288.1600; found 288.1621.
N-(2-Bromobenzyl)-N-methylaniline (3a). Pale yellow oil (124 mg,
83% yield), 1H NMR (CDCl3, 600 MHz) δ 3.13 (s, 3H), 4.59 (s, 2H),
6.71 (d, 2H, J = 8.1 Hz), 6.76 (t, 1H, J = 7.1 Hz), 7.14−7.19 (m, 2H),
N-(2,3,4-Trimethoxybenzyl)-N-methylaniline (3k). Pale yellow oil
(232.5 mg, 81% yield), H NMR (CDCl3, 300 MHz) δ 3.07 (s, 3H),
3.89 (s, 3H), 3.99−4.00 (overlapped, 6H), 4.58 (s, 2H), 6.65 (d, 1H, J
1
D
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Note
= 8.5 Hz), 6.78 (t, 1H, J = 7.1 Hz), 6.85 (d, 2H, J = 8.1 Hz), 6.89 (d,
1H, J = 8.5 Hz), 7.30 (t, 2H, J = 7.5 Hz); 13C NMR (CDCl3, 75 MHz)
δ 38.3, 51.7, 56.0, 60.7, 60.8, 107.2, 112.4, 116.4, 122.2, 124.4, 129.2,
142.4, 149.4, 151.7, 152.9; HRMS (ESI-TOF) m/z: [M + H]+ calcd
for C17H22NO3 288.1600; found 288.1621.
(s, 3H), 4.06 (s, 2H), 6.51 (s, 1H), 6.83−6.91 (m, 3H), 7.28−7.47 (m,
7H); 13C NMR (CDCl3, 75 MHz) δ 16.4, 38.6, 61.4, 112.7, 116.8,
125.3, 126.7, 128.5, 129.4, 129.6, 135.2, 138.3, 150.4; HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C17H20N 238.1596; found 238.1575.
N-2-Furfuryl-N-methylaniline (3t). Pale yellow oil (163 mg, 87%
1
N-(3-Ethoxy-4-hydroxybenzyl)-N-methylaniline (3l). Brown solid
yield), H NMR (CDCl3, 600 MHz) δ 3.06 (s, 3H), 4.53 (s, 2H),
1
(154 mg, 60% yield), mp 50−51 °C. H NMR (CDCl3, 300 MHz), δ
6.21−6.22 (m, 1H), 6.36−6.37 (m, 1H), 6.83 (t, 1H, J = 7.2 Hz), 6.91
(d, 2H, J = 7.9 Hz), 7.33 (dd, 2H, J = 3.2 Hz), 7.42 (s, 1H); 13C NMR
(CDCl3, 150 MHz) δ 38.3, 49.9, 107.3, 110.2, 113.1, 117.2, 129.2,
141.9, 149.4, 152.4; HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C12H14NO 188.1075; found 188.1067.
1.46 (t, 3H, J = 6.9 Hz), 3.30 (s, 3H), 4.06−4.13 (q, 2H, J = 6.9 Hz),
4.50 (s, 2H), 6.78−6.87 (m, 5H), 6.95 (d, 1H, J = 8.5 Hz), 7.30 (t, 2H,
J = 5.3 Hz); 13C NMR (CDCl3, 75 MHz) δ 15.2, 38.6, 57.0, 64.8,
110.7, 113.2, 114.7, 117.2, 120.0, 129.6, 131.1, 145.1, 146.4, 150.4.
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C16H20NO2 258.1494;
found 258.1490.
N-(9-Anthracenylmethyl)-N-methylaniline (3u). Yellow solid (229
mg, 81% yield), mp 145−146 °C. IR ν
̃
(KBr) (cm−1): 688, 731, 746,
885, 1315, 1344, 1371, 1442, 1436, 1597, 2846, 2916. 1H NMR
(CDCl3, 600 MHz) δ 2.58 (s, 3H), 5.23 (s, 2H), 6.96 (t, 1H, J = 7.3
Hz), 7.13 (d, 2H, J = 7.9 Hz), 7.45−7.48 (m, 2H), 7.51−7.54 (s, 4H),
8.06−8.08 (m, 2H), 8.27−8.28 (m, 2H), 8.50 (s, 1H); 13C NMR
(CDCl3, 150 MHz) δ 34.7, 46.9, 113.2, 117.4, 124.4, 125.1, 126.4,
128.0, 128.7, 129.2, 129.4, 131.5, 131.5, 150.7; HRMS (ESI-TOF) m/
z: [M + H]+ calcd for C22H20 N 298.1596; found 298.1585.
N-(2,4-Dimethoxybenzyl)-N-methylaniline (3m). Yellow oil (197.8
mg, 77% yield), IR ν
̃
(KBr) (cm−1): 690, 744, 821, 1033, 1116, 1153,
1207, 1247, 1298, 1379, 1456, 1500, 1585, 1614, 2924. 1H NMR
(CDCl3, 600 MHz) δ 3.08 (s, 3H), 3.83 (s, 3H), 3.88 (s, 3H), 4.52 (s,
2H), 6.45 (d, 1H, J = 3.6 Hz), 6.55 (d, 1H, J = 2.3 Hz), 6.75 (t, 1H, J =
7.2 Hz), 6.79 (d, 2H, J = 8.2 Hz), 7.04 (d, 1H, J = 8.3 Hz), 7.25−7.29
(m, 2H); 13C NMR (CDCl3, 150 MHz) δ 38.4, 51.5, 55.2, 55.3, 98.5,
103.8, 112.2, 116.1, 118.0, 128.0, 129.1, 149.8, 158.2, 159.9; HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C16H20NO2 258.1494; found
258.1478.
N-(3-Phenylpropyl)-N-methylaniline (3v),. Colorless oil (157.5 mg,
1
70% yield), H NMR (CDCl3, 600 MHz) δ 1.90−1.95 (m, 2H), 2.66
(t, 2H, J = 7.6 Hz), 2.93 (s, 3H), 3.35 (t, 2H, J = 7.4 Hz), 6.68 (d, 2H,
J = 8.3 Hz), 7.20−7.23 (m, 5H), 7.26−7.31 (m, 3H); 13C NMR
(CDCl3, 150 MHz) δ 28.1, 33.3, 38.2, 52.2, 112.2, 116.0, 125.8, 128.3,
128.3, 129.1, 141.8, 149.3; HRMS (ESI-TOF) m/z: [M + H]+ calcd
for C16H20N 226.1596; found 226.1578.
N-(2-Hydroxy-4-methoxybenzyl)-N-methylaniline (3n). Yellow oil
1
(206.5 mg, 85% yield), H NMR (CDCl3, 600 MHz) δ 2.83 (s, 3H),
3.77 (s, 3H), 4.34 (s, 2H), 6.67 (brs, 1H), 6.76−6.78 (m, 1H), 6.82 (d,
1H, J = 8.7 Hz), 7.03 (t, 1H, J = 7.3 Hz), 7.14 (d, 2H, J = 8.2 Hz), 7.33
(t, 2H, J = 7.9 Hz); 13C NMR (CDCl3, 150 MHz) δ 40.2, 55.7, 59.0,
113.6, 114.5, 116.8, 118.5, 122.1, 123.0, 129.3, 150.7, 150.7, 153.0;
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C15H18NO2 244.1338;
found 244.1345.
N-(4-Methoxybenzyl)-N-ethylaniline (3w). Pale yellow oil (178.4
1
mg, 83% yield), H NMR (CDCl3, 600 MHz) δ 1.23 (t, 3H, J = 6.9
Hz), 3.49 (q, 2H, J = 6.4 Hz), 3.82 (s, 3H), 4.50 (s, 2H), 6.71 (t, 1H, J
= 6.9 Hz), 6.75 (d, 2H, J = 7.5 Hz), 6.89 (d, 2H, J = 4.1 Hz), 7.20−
7.26 (m, 4H); 13C NMR (CDCl3, 150 MHz) δ 12.1, 44.9, 53.3, 55.3,
112.3, 114.0, 116.0, 127.7, 129.2, 131.1, 148.6, 158.5; HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C16H20NO 242.1545; found 242.1535.
N,N-Dibenzyl-4-methoxyaniline (3x). Brown solid (288 mg, 95%
N-(2-Hydroxy-3-methoxybenzyl)-N-methylaniline (3o). Brown
1
solid (158 mg, 65% yield), mp 56−57 °C. H NMR (CDCl3, 600
MHz) δ 3.05 (s, 3H), 3.93 (s, 3H), 4.58 (s, 2H), 6.79 (d, 1H, J = 6.9
Hz), 6.82−6.88 (m, 3H), 6.94 (d, 2H, J = 8.1 Hz), 7.31 (t, 2H, J = 7.8
Hz); 13C NMR (CDCl3, 150 MHz) δ 39.2, 53.7, 56.0, 109.8, 114.3,
118.2, 119.4, 120.2, 124.0, 129.2, 144.2, 146.9, 150.1; HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C15H18NO2 244.1338; found
244.1327.
1
yield), mp 76−77 °C. H NMR (CDCl3, 600 MHz) δ 3.75 (s, 3H),
4.60 (s, 4H), 6.74 (d, 2H, J = 9.0 Hz), 6.80 (d, 2H J = 9.1 Hz), 7.26−
7.30 (m, 6H), 7.35 (t, 4H, J = 7.5 Hz); 13C NMR (CDCl3, 150 MHz)
δ 55.2, 55.7, 114.6, 114.7, 126.8, 126.9, 128.5, 139.0, 143.8, 151.7.
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C21H22NO 304.1701;
found 304.1691.
N-(2-Hydroxy-3-methoxy-5-prop-2-eneylbenzyl)-N-methylaniline
(3p). Dark brown oil (218 mg, 77% yield), IR ν
̃
(KBr) (cm−1): 1070,
1143, 1188, 1207, 1230, 1255, 1292, 1303, 1342, 1355, 1371, 1435,
N-Cyclopentyl-N-methylaniline (5a). Colorless oil (145 mg, 83%
yield), 1H NMR (CDCl3, 600 MHz) δ 1.62−1.64 (m, 4H), 1.74−1.76
(m, 2H), 1.88−1.92 (m, 2H), 2.82 (s, 3H), 4.16−4.21 (m, 1H), 6.74
(t, 1H, J = 7.2 Hz), 6.87 (d, 2H, J = 8.1 Hz), 7.25−7.27 (m, 2H); 13C
NMR (CDCl3, 150 MHz) δ 24.3, 28.7, 32.6, 60.3, 114.1, 116.8, 129.0,
151.1; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C12H18N
176.1439; found 176.1428.
N-Cyclohexyl-N-methylaniline (5b). Yellow oil (170 mg, 90%
yield), 1H NMR (CDCl3, 600 MHz) δ 1.22−1.29 (m, 2H), 1.45−1.51
(m, 2H), 1.54−1.60 (m, 2H), 1.81 (d, 1H, J = 12.7 Hz), 1.94 (dd, 4H,
J = 12.6, 11.8), 2.89 (s, 3H), 3.69 (t, 1H, J = 11.3 Hz), 6.81 (t, 1H, J =
8.0 Hz), 6.90 (d, 2H, J = 7.9 Hz), 7.35 (t, 2H, J = 7.4 Hz); 13C NMR
(CDCl3, 150 MHz) δ 26.1, 26.4, 30.2, 31.3, 58.3, 113.4, 116.4, 129.0,
150.2; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C13H20N
190.1596; found 190.1589.
1
1492, 1598,2914, 3442. H NMR (CDCl3, 600 MHz) δ 3.01 (s, 3H),
3.34 (d, 2H, J = 6.5 Hz), 3.92 (s, 3H), 4.53 (s, 2H), 5.09−5.13 (m,
2H), 5.96−6.02 (m, 1H), 6.63 (s, 1H), 6.70 (s, 1H), 6.88 (t, 1H, J =
7.2 Hz), 6.97 (d, 2H, J = 8.0 Hz), 7.32 (t, 2H, J = 7.5 Hz); 13C NMR
(CDCl3, 150 MHz) δ 39.2, 40.0, 54.2, 56.0, 110.3, 114.7, 115.5, 118.5,
120.1, 123.6, 129.2, 131.2, 137.9, 142.6, 146.9, 150.3. HRMS (ESI-
TOF) m/z: [M + Na]+ calcd for C18H21NNaO2 306.1470; found
306.1462.
N-(4-Methoxycinnamyl)-N-methylaniline (3q). Yellow solid (185
mg, 73% yield), mp 61−62 °C. IR ν
̃
(KBr) (cm−1): 690, 748, 802, 974,
1035, 1228, 1240, 1346, 1448, 1463, 1502, 1593, 2954. 1H NMR
(CDCl3, 300 MHz) δ 3.02 (s, 3H), 3.38 (s, 3H), 4.51 (s, 2H), 6.14−
6.20 (m, 1H), 6.54 (d, 1H, J = 15.7 Hz), 6.81−6.92 (m, 5H), 7.30−
7.37 (m, 4H); 13C NMR (CDCl3, 75 MHz) δ 38.4, 55.4, 55.7, 113.1,
114.4, 117.0, 123.8, 127.9, 129.6, 130.1, 131.2, 150.0, 159.5; HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C17H20NO 254.1545; found
254.1529.
N-(4-Methylcyclohexyl)-N-methylaniline (5c). Colorless oil (173
1
mg, 85% yield), H NMR (CDCl3, 600 MHz) δ 1.01 (cis, d, 3H, J =
6.4 Hz), 1.10 (trans, d, 3H, J = 7.1 Hz), 1.09−1.17 (m, 2H), 1.43 (s,
1H), 1.58−1.63 (m, 4H), 1.69−1.88 (m, 10H), 2.03 (s, 1H), 2.84 (cis,
s, 3H), 2.88 (trans, s, 3H), 3.60−3.66 (m, 2H), 6.76−6.88 (m, 2H),
6.87 (t, 4H, J = 6.7 Hz), 7.31 (t, 4H, J = 7.3 Hz); 13C NMR (CDCl3,
150 MHz) δ (cis + trans) 17.6, 22.4, 24.1, 26.7, 29.6, 31.3, 31.5, 31.7,
32.5, 34.9, 58.2, 58.5, 113.3, 113.5, 116.3, 116.5, 129.2, 150.3; HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C14H22N 204.1752; found
204.1776.
N-Cinnamyl-N-methylaniline (3r). Colorless oil (167 mg, 75%
1
yield), H NMR (CDCl3, 600 MHz) δ 3.01 (s, 3H), 4.11 (d, 2H, J =
4.9 Hz), 6.27−6.30 (m, 1H), 6.56 (d, 1H, J = 15.8 Hz), 6.76 (t, 1H, J =
6.9 Hz), 6.88 (d, 2H, J = 7.8 Hz), 7.23−7.34 (m, 5H), 7.38 (d, 2H, J =
7.3 Hz); 13C NMR (CDCl3, 150 MHz) δ 38.0, 54.9, 112.7, 116.7,
125.7, 126.3, 127.4, 128.5, 129.2, 131.3, 136.9, 149.6; HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C16H18N 224.1439; found 224.1429.
N-(3-Phenyl-2-methylpropeneyl)-N-methylaniline (3s). Brown
N-(3-Methylcyclohexyl)-N-methylaniline (5d). Yellow oil (178.7
solid (187 mg, 79% yield), mp 45−46 °C. IR ν
̃
(KBr) (cm−1): 686,
740, 933, 1031, 1120, 1192, 1215, 1257, 1363, 1440, 1492, 1504, 1597,
mg, 88% yield), IR ν
̃
(KBr) (cm−1): 688, 744, 1103, 1321, 1454, 1502,
1
1597, 2922. H NMR (CDCl3, 300 MHz) δ 1.01 (cis, d, 3H, J = 6.4
Hz), 1.16 (trans, d, 3H, J = 7.1 Hz), 1.34−1.91 (m, 17H), 2.22−2.26
1
2852, 2914, 3059. H NMR (CDCl3, 300 MHz) δ 2.00 (s, 3H), 3.12
E
DOI: 10.1021/acs.joc.5b00156
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
(m, 1H), 2.83 (cis+trans, s, 6H), 3.64−3.72 (m, 1H), 3.87−3.96 (m,
1H), 6.76 (t, 2H, J = 7.1 Hz), 6.85 (d, 4H, J = 7.9 Hz), 7.29 (t, 4H, J =
7.7 Hz); 13C NMR (CDCl3) 75 MHz) δ (cis+trans) 18.6, 21.2, 23.0,
25.9, 28.7, 29.7, 30.9, 31.6, 31.7, 33.1, 35.1, 35.7, 39.0, 52.8, 58.3,
113.7, 116.7, 129.5, 150.6; HRMS (ESI-TOF) m/z: [M + H]+ calcd
for C14H22N 204.1752; found 204.1732.
(s, 3H), 3.83 (s, 3H), 4.23 (s, 2H), 6.64 (d, 2H, J = 8.8 Hz), 6.81 (d,
2H, J = 8.8 Hz), 6.91 (d, 2H, J = 8.5 Hz), 7.32 (d, 2H, J = 8.1 Hz), 13
C
NMR (CDCl3, 75 MHz) δ 49.1, 55.6, 56.2, 114.4, 114.5, 115.3, 129.2,
142.9, 152.5, 159.2; HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C15H18NO2 244.1338; found 244.1328.
N-(4-Methoxycinnamyl)aniline (7e). White solid (208 mg, 87%
N-Cyclopentyl-N,N-diphenylamine (5e). Colorless oil (154 mg,
1
yield), mp 75−76 °C. H NMR (CDCl3, 300 MHz) δ 3.85 (s, 3H),
65% yield), IR ν
̃
(KBr) (cm−1): 690, 742, 1236, 1283, 1319, 1489,
3.95 (d, 2H, J = 5.8 Hz), 6.16−6.29 (m 1H), 6.57−6.81 (m, 4H), 6.91
(d, 2H, J = 8.6 Hz), 7.25 (t, 2H, J = 7.6 Hz), 7.36 (d, 2H, J = 8.6 Hz);
13C NMR (CDCl3, 75 MHz) δ 46.7, 55.7, 113.4, 114.4, 117.9, 125.1,
127.9, 129.7, 130.1, 131.5, 148.5, 159.6. HRMS (ESI-TOF) m/z: [M +
Na]+ calcd for C16H17NNaO 262.1208; found 262.1225
1587, 2868, 2957. 1H NMR (CDCl3, 600 MHz) δ 1.51−1.56 (m, 2H),
1.63−1.66 (m, 4H), 2.04−2.08 (m, 2H), 4.31−4.37 (m, 1H), 6.96 (d,
4H, J = 7.6 Hz), 7.07 (t, 2H, J = 7.3 Hz), 7.34 (t, 4H, J = 5.2 Hz); 13C
NMR (CDCl3, 150 MHz) δ 23.1, 30.5, 60.0, 121.7, 123.2, 129.1,
147.4; HRMS (ESI-TOF) m/z: [M + H]+ calcd for C17H20N
238.1596; found 238.1591.
N-(3,4,5-Trimethoxybenzyl)-4-bromoaniline (7f). Yellow oil (126
mg, 95% yield), 1H NMR (CDCl3, 300 MHz) δ 3.84 (s, 9H), 4.22 (s,
2H), 6.51 (d, 2H, J = 8.6 Hz), 6.58 (s, 2H), 7.24 (d, 2H, J = 8.5 Hz);
13C NMR (CDCl3, 75 MHz) δ 48.9, 56.5, 61.2, 104.6, 109.5, 114.8,
132.3, 135.1, 137.4, 147.5, 153.8; HRMS (ESI-TOF) m/z: [M + H]+
calcd for C16H19BrNO3 352.0548; found 352.0538.
N-(4-Methylcyclohexyl)-N,N-diphenylamine (5f). Brownish oil
1
(159 mg, 60% yield), H NMR (CDCl3, 300 MHz) δ 0.84 (cis, d,
3H, J = 7.1 Hz), 0.91 (trans, d, 3H, J = 6.4 Hz), 1.13−1.25 (m, 6H),
1.37−1.46 (m, 2H), 1.57 (d, 2H, J = 13.9 Hz), 1.66−1.71 (m, 2H),
1.78 (t, 4H, J = 13.5 Hz), 2.03 (d, 2H, J = 12.0 Hz), 3.82−3.86 (cis
+trans, m, 2H), 6.86 (t, 8H, J = 8.2), 7.00(t, 4H, J = 6.9 Hz), 7.26−
7.30 (m, 8H, J = 7.1 Hz); 13CNMR (CDCl3, 75 MHz) δ 17.6, 22.3,
25.9, 26.7, 31.3, 31.5, 32.2, 34.8, 56.6, 57.1, 121.9, 121.5, 122.8, 122.8,
129.1, 129.2, 146.4, 146.5; HRMS (ESI-TOF) m/z: [M + H]+ calcd
for C19H24N 266.1909; found 266.1901.
1-(4-Benzylaminophenyl)ethanone (7g). Yellow solid (168 mg,
1
75% yield), mp 95−96 °C. H NMR (CDCl3, 300 MHz) δ 2.49 (s,
3H), 4.41 (s, 2H), 6.61 (d, 2H, J = 8.7 Hz), 7.36 (brd s, 5H), 7.83 (d,
2H, J = 8.7 Hz), 13C NMR (CDCl3, 75 MHz) δ 26.4, 47.9, 112.0,
127.2, 127.7, 127.9, 129.2, 131.2, 138.7, 152.5, 196.9; HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C15H16NO 226.1232; found 226.1224.
N-Benzyl-4-carboxyaniline (7h). White solid (136 mg, 60% yield),
mp 163−164 °C. 1H NMR (CD3OD, 600 MHz) δ 4.18 (s, 2H), 6.41
(d, 2H, J = 7.2 Hz), 7.03 (t, 1H, J = 6.4 Hz), 7.11−7.15 (m, 4H), 7.58
(d, 2H, J = 8.7 Hz), 13C NMR (CD3OD, 150 MHz) δ 49.1, 113.8,
119.8, 129.3, 129.5, 130.8, 134.0, 141.9, 155.6, 172.1; HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C14H14NO2 228.1025; found
228.1024.
N-(1-Phenylethyl)-N-methylaniline (5g). Yellow oil (120 mg, 57%
1
yield), H NMR (CDCl3, 600 MHz) δ 1.61 (d, 3H, J = 6.9 Hz), 2.74
(s, 3H), 5.19 (q, 1H, J = 6.8 Hz), 6.79 (t, 1H, J = 7.2 Hz), 6.91 (d, 2H,
J = 8.1 Hz), 7.29−7.33 (m, 3H), 7.38−7.40 (m, 4H) 13CNMR
(CDCl3, 150 MHz) δ 16.3, 31.9, 56.6, 113.1, 116.1, 126.8, 126.9,
128.4, 129.2, 142.8, 150.2; HRMS (ESI-TOF) m/z: [M + H]+ calcd
for C15H18N 212.1439; found 212.1425.
N-(1-Phenylethyl)-N-methyl-4-fluoroaniline (5h). Yellow oil (137
mg, 60% yield), IR ν
̃
(KBr) (cm−1): 698, 783, 812, 1109, 1109, 1226,
1373, 1448, 1506, 2924. 1H NMR (CDCl3, 600 MHz) δ 1.54 (d, 3H, J
= 6.8 Hz), 2.67 (s, 3H), 5.01 (q, 1H, J = 6.6 Hz), 6.80 (q, 2H, J = 4.2
Hz), 6.98 (t, 2H, J = 8.5 Hz), 7.28 (q, 1H, J = 7.4 Hz), 7.33−7.38 (m,
4H); 13C NMR (CDCl3, 150 MHz) δ 16.3, 32.6, 58.1, 115.0 (d, J = 7.0
Hz), 115.5 (d, J = 21.9 Hz), 126.9, 128.4, 142.7, 147.0, 155.6 (d, J =
235.7 Hz); HRMS (ESI-TOF) m/z: [M + H]+ calcd for C15H17NF
230.1345; found 230.1342.
N-Benzyl 4-nitroaniline (7i). Dark yellow solid (141.4 mg, 62%
yield), mp 148−149 °C. 1H NMR (CDCl3, 600 MHz) δ 4.43 (s, 2H),
4.98 (brd s, 1H NH), 6.57 (d, 2H, J = 9.0 Hz), 7.31−7.38 (m, 5H),
8.06 (d, 2H, J = 8.9 Hz),13C NMR (CDCl3, 150 MHz) δ 47.6, 111.3,
126.4, 127.3, 127.8, 128.9, 137.4, 138.3, 153.1; HRMS (ESI-TOF) m/
z: [M + H]+ calcd for C13H13N2O2 229.0977; found 229.0974.
N-(1-Phenylethyl)aniline (7j). Yellow oil (138 mg, 70% yield),
1HNMR (CDCl3, 600 MHz) δ 1.56 (d, 3H, J = 6.7 Hz), 4.53 (q, 1H, J
= 6.7 Hz), 6.56 (d, 2H, J = 7.9 Hz), 6.70 (t, 1H, J = 7.2 Hz), 7.14 (t,
2H, J = 7.8 Hz), 7.28 (t, 2H, J = 7.2 Hz), 7.37 (t, 2H, J = 7.6 Hz), 7.42
(d, 2H, J = 7.3 Hz); 13C NMR (CDCl3, 150 MHz) δ 25.0, 53.3, 113.3,
117.3, 125.9, 126.9, 128.7, 129.1, 145.2, 147.3; HRMS (ESI-TOF) m/
z: [M + H]+ calcd for C14H16N 198.1283; found 198.1279.
N-Isobutylaniline (7k). Colorless oil (138.6 mg, 93% yield), 1H
NMR (CDCl3, 600 MHz) δ 1.06 (t, 3H, J = 7.4 Hz), 1.28 (d, 3H, J =
6.3 Hz), 1.53−1.75 (m, 2H), 3.47−3.53 (m, 1H), 6.67−6.80 (m, 3H),
7.27 (t, 2H, J = 7.7 Hz); 13C NMR (CDCl3, 150 MHz) δ 10.8, 20.7,
30.1, 50.2, 113.6, 117.2, 129.7, 148.2; HRMS (ESI-TOF) m/z: [M +
H]+ calcd for C10H16N 150.1283; found 150.1274.
N-Isobutyl-4-methoxyaniline (7l). Yellow oil (170 mg, 95% yield),
1H NMR (CDCl3, 300 MHz) δ 1.01 (t, 3H, J = 7.4 Hz), 1.21 (d, 3H, J
= 6.3 Hz), 1.43−1.70 (m, 2H), 3.32−3.43 (m, 1H), 3.79 (s, 3H), 6.62
(d, 2H, J = 8.9 Hz), 8.84 (d, 2H, J = 6.7 Hz); 13C NMR (CDCl3, 75
MHz) δ 10.8, 20.6, 30.0, 51.2, 56.1, 115.1, 115.3, 142.4, 152.2; HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C11H18NO 180.1388; found
180.1374.
N-Cyclohexyl aniline (7m). Greenish yellow oil (159.2 mg, 91%
yield), 1H NMR (CDCl3, 300 MHz) δ 1.23−1.62 (m, 6H), 1.79−1.96
(m, 3H), 2.22 (q, 2H, J = 4.2 Hz), 3.36−3.46 (m, 1H), 6.75 (d, 2H, J =
7.7 Hz), 6.84 (t, 1H, J = 7.3 Hz), 7.33 (t, 2H, J = 7.8 Hz); 13C NMR
(CDCl3, 75 MHz) δ 25.6, 26.5, 34.0, 52.2, 113.7, 117.3, 129.8, 147.9;
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C12H18N 176.1439;
found 176.1425.
N-(1-(4-Bromophenyl)ethyl)-N-methylaniline (5i). Yellow oil (142
1
mg, 49% yield), H NMR (CDCl3, 600 MHz) δ 1.56 (d, 3H, J = 6.9
Hz), 2.69 (s, 3H), 5.09 (q, 1H, J = 6.7 Hz), 6.78 (t, 1H, J = 7.0 Hz),
6.86 (d, 2H, J = 8.2 Hz), 7.22 (d, 2H, J = 8.2 Hz), 7.28 (t, 2H, J = 7.4
Hz); 13C NMR (CDCl3, 150 MHz) δ 16.3, 31.9, 56.3, 113.3, 117.1,
120.7, 128.7, 129.3, 131.5, 141.9, 150.0; HRMS (ESI-TOF) m/z: [M +
H]+ calcd for C15H17BrN 290.0544; found 290.0534.
(6-Chloropyridin-3-yl)-N-(4-methoxybenzyl)amine (7a). Yellow
1
solid (240.5 mg, 97% yield), mp 87−88 °C. H NMR (CDCl3, 300
MHz) δ 3.79 (s, 3H), 4.23 (s, 2H), 6.83−6.89 (m, 3H), 7.03−7.06 (d,
1H, J = 8.5 Hz), 7.25 (d, 2H, J = 8.2 Hz), 7.76 (s, 1H); 13C NMR
(CDCl3, 75 MHz) δ 47.7, 55.7, 114.5, 122.6, 124.4, 129.0, 130.4,
134.9, 139.1, 143.6, 159.4. HRMS (ESI-TOF) m/z: [M + H]+ calcd
for C13H14ClN2O 249.0795; found 249.0793.
N-Benzyl-(6-chloropyridin-3-yl)amine (7b). White solid (207 mg,
1
95% yield), mp 95−96 °C. H NMR (CDCl3, 300 MHz) δ 4.32 (s,
2H), 6.84−6.88 (dd, 1H, J = 5.8 Hz), 7.06 (d, 1H, J = 8.5 Hz), 7.27−
7.34 (m, 5H), 7.79 (s, 1H); 13C NMR (CDCl3, 75 MHz) δ 48.3,
122.6, 124.4, 127.7, 128.0, 129.2, 135.0, 138.4, 139.3, 143.6; HRMS
(ESI-TOF) m/z: [M + Na]+ calcd for C12H11ClN2Na 241.0508; found
241.0503.
N-Benzyl-4-methoxyaniline (7c). Yellow solid (178 mg, 83% yield),
1
mp 50−51 °C. H NMR (CDCl3, 600 MHz) δ 3.53 (s, 3H), 4.06 (s,
2H), 6.40 (d, 2H, J = 8.8 Hz), 6.61 (d, 2H, J = 8.8 Hz), 7.09 (t, 1H, J =
7.0 Hz), 7.15−7.19 (m, 4H); 13C NMR (CDCl3, 150 MHz) δ 49.3,
55.8, 114.2, 115.0, 127.3, 127.7, 128.7, 139.9, 142.6, 152.3; HRMS
(ESI-TOF) m/z: [M + H]+ calcd for C14H16NO 214.1232; found
214.1224.
N-(4-Methoxybenzyl)-4-methoxyaniline (7d). White solid (228
1
mg, 94% yield), mp 95−96 °C. H NMR (CDCl3, 300 MHz) δ 3.77
F
DOI: 10.1021/acs.joc.5b00156
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
(c) Bellegarde, B.; Pereyre, M.; Valade, J. Bull. Soc. Chim. Fr. 1967,
3082.
ASSOCIATED CONTENT
■
S
* Supporting Information
Copies of 1H, 13C NMR, ESI-MS, IR and UV−vis spectra. The
Supporting Information is available free of charge on the ACS
Publications website at DOI: 10.1021/acs.joc.5b00156.
AUTHOR INFORMATION
Corresponding Author
*E-mail: neerajnpp@rediffmail.com, neeraj@ihbt.res.in.
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors are grateful to Director of the Institute, CSIR-
IHBT, for encouragement and support. V.B. and S.S. also thank
UGC for granting research fellowship. Financial support from
CSIR (ORIGIN, CSC-0108) is also acknowledged.
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DOI: 10.1021/acs.joc.5b00156
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