Cobalt-Rhodium Heterobimetallic Nanoparticle-Catalyzed N-Alkylation of Amines with Alcohols to Secondary and Tertiary Amines

Article abstract of DOI:10.1021/acs.joc.8b01109

Without the requirement for base or other additives, Co₂Rh₂/C can selectively catalyze both mono- and bis-N-alkylation through the coupling of simple alcohols with amines, yielding a range of secondary and tertiary amines in good to excellent isolated yields. The reaction can be applied to benzyl alcohol with optically active 1-phenylethan-1-amines, and secondary amines were isolated in quantitative yields with an excellent enantiomeric excess (ee > 94%). Selectivity is achieved by varying the reaction temperature and amount of catalyst used. This catalytic system has several advantages including eco-friendliness and a simple workup procedure. The catalyst can be successfully recovered and reused ten times without any significant loss of activity.

Full text of DOI:10.1021/acs.joc.8b01109

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Article
Cobalt-Rhodium Heterobimetallic Nanoparticle-Catalyzed N-
Alkylation of Amines with Alcohols to Secondary and Tertiary Amines
Hyunho Chung, and Young Keun Chung
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01109 • Publication Date (Web): 17 Jul 2018
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The Journal of Organic Chemistry
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Cobalt-Rhodium Heterobimetallic Nanoparticle-Catalyzed N-Alkylation
of Amines with Alcohols to Secondary and Tertiary Amines
Hyunho Chung and Young Keun Chung*
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Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul 08826, Korea.
ykchung@snu.ac.kr
ABSTRACT: Without the requirement for base or other additives, Co2Rh2/C can selectively catalyze both mono- and bis-N-
alkylation through the coupling of simple alcohols with amines, yielding a range of secondary and tertiary amines in good to
excellent isolated yields. The reaction can be applied to benzyl alcohol with optically active 1-phenylethan-1-amines and
secondary amines were isolated in quantitative yields with an excellent enantiomeric excess (ee >94%). Selectivity is
achieved by varying the reaction temperature and amount of catalyst used. This catalytic system has several advantages
including eco-friendliness and a simple workup procedure. The catalyst can be successfully recovered and reused ten times
without any significant loss of activity.
Introduction
Several years ago, cobalt-rhodium nanoparticles derived
from Co2Rh2(CO)12 were immobilized on charcoal (herein-
after denoted as Co2Rh2/C).10 It was used as a catalyst in
the Pauson–Khand reaction and carbonylations.11 A recent
study demonstrated the usefulness of Co2Rh2/C in the hy-
drogenation of nitroarenes.12 To determine a new catalytic
system for the alkylation of amines with alcohols, we de-
cided to use Co2Rh2/C as the catalyst without an external
base or additive. The catalytic system was determined to
be effective in neat at the specific reaction temperature
(80–165 °C) depending upon the reaction partners. The
proposed catalytic system does not require the addition of
a base to function effectively, and thus, represents a green-
er catalytic system compared to other reported hydrogen
borrowing catalysts.
Secondary and tertiary alkylated amines play an im-
portant role as building blocks in many organic synthesis
reactions and are important components of agrochemicals,
drug molecules, and functional materials.1 Consequently,
many useful synthetic methods have been established.2
However, they suffer from several drawbacks including
low selectivity and the formation of stoichiometric
amounts of waste.3 Recently, the catalytic N-alkylation of
amines with alcohols has attracted considerable attention
because it provides a green and atom-economic pathway
for the synthesis of substituted amines.4 Since the first re-
port on the catalytic use of a well-defined [RhH(PPh3)4] in
N-alkylations of amines with alcohols in 1981,5 many use-
ful homogeneous catalysts based on ruthenium,6 iron,7 and
other transition metals8 have been developed. However,
the homogeneous systems have the drawbacks of low cata-
lyst reusability and/or the indispensable use of large
amounts of additives or co-catalysts. Heterogeneous tran-
sition metal catalysts9 can overcome some of the draw-
backs of homogeneous catalysts; however, they frequently
suffer from harsh reaction conditions, use of toxic and ex-
pensive ligands, use of large amount of toxic solvents, cata-
lysts having poor recyclability, and excessive amount of
alcohols to obtain satisfactory yields. Therefore, the devel-
opment of more active and selective heterogeneous cata-
lysts for the N-alkylation of amines with alcohols remains a
challenge.
Results and discussion
To examine the catalytic activity of Co2Rh2/C, N-
alkylation of aniline with 4-methylbenzyl alcohol was cho-
sen initially as a model reaction in the presence of 5 mol%
Co2Rh2/C at 90 °C for 24 h (eq 1). After workup, a monoal-
kylation product, N-(4-methylbenzyl)aniline (1a), was
isolated with 83% yield and no imine was detected. The
reactions did not require the addition of molecular sieves
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to scavenge the water. Thus, we selected a neat alcohol as the t-butyl and phenoxy groups. Interestingly, no steric
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the reaction media: the reaction was studied without using
a solvent. To optimize the reaction conditions for the
mono-alkylation of aniline, reaction parameters such as
reaction temperature, reaction time, and the amount of the
catalyst used were screened (Table 1). The optimum reac-
tion conditions were established as follows: 5 mol%
Co2Rh2/C at 100 °C for 24 h for monoalkylation and 10 mol%
Co2Rh2/C at 140 °C for 24 h for dialkylation.13. In a gram
scale synthesis, a stoichiometric amount of alcohol was
enough to carry out the reaction (see Supporting Infor-
mation). However, due to the experimental easiness, we
used an excess of alcohol in small scale experiments. Other
metal nanoparticles such as Co/C and Rh/C, were exam-
effect was observed for 3,5-dimethylaniline (1k, 83%).
Under the reaction conditions for the formation of sec-
amines, the formation of the corresponding tert-amines
was not observed or negligible for all the substrates. Next,
we examined the reactions of different anilines with 4-
methylbenzyl alcohol under optimized reaction conditions
for double N-alkylations (10 mol% Co2Rh2/C at 140 °C for
24 h). Excellent yields (1aa-1ee, 92–99%) were obtained
with all anilines and alcohol reactants used. However,
anilines with 4-chloro or 4-bromo group were not a good
substrate under our reaction conditions (5 mol% Co2Rh2/C
at 100 °C for 24 h). They afforded only ca 10% of their
corresponding products. Our results were surprising com-
pared with those of heterogeneous Pt-Sn/γ-Al2O3 cata-
lyst.14 In the presence of Pt-Sn/γ-Al2O3, arylamines and
heteroarylamines could not be utilized to synthesize ter-
tiary amines, although they could efficiently react with
primary alcohols to afford the corresponding secondary
amine products.
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ined. When Rh/C was used as
a catalyst, N-(4-
methylbenzyl)aniline was isolated with a 71% yield. Con-
versely, a trace amount of the secondary amine was
formed in the presence of Co/C.
Table 2. Reaction of Anilines with Benzyl Alcohols
Table 1. Optimization of the Reaction Conditions
Entry
Time
(h)
Temp
oC
Co2Rh2
(mol%)
Yield(%)a)
(
)
1a
1aa
0
1
2
24
24
18
24
24
24
24
24
24
90
5
5
83
99
74
99
87
54
7
100
100
110
120
120
140
150
100
0
3
5
0
4
5
0
5
5
12
43
92
89
0
6
10
10
10
5
7
8
9b)
10
98
a)All yields are isolated yields. b) 6 mmol of amine, 6.5 mmol of
alcohol, and 5 mol% (540 mg) of Co2Rh2/C.
The substrate scope was next investigated. First, we
tested the reactions of aniline with different benzyl alco-
hols under optimized reaction conditions (5 mol%
Co2Rh2/C at 100 °C for 24 h); the products were isolated by
silica gel column chromatography after workup. The re-
sults are listed in Table 2 (compounds 1a – 1g). High yields
were observed. However, steric and electronic effects were
observed for the reaction of 3,5-dimethoxybenzyl alcohol
(1g): the corresponding sec-amine was isolated with a 42%
yield. To our delight, when the reaction was performed at
120 °C, the yield dramatically increased from 42% to 93%.
A para-substituent on benzyl alcohol with an electron-
withdrawing group such as fluoro resulted in a reduced
yield (31%; 1f). Fortunately, the diminished yield was
solved by increasing the reaction temperature to 120 °C
(81%). Next, we examined the reaction of 4-methylbenzyl
alcohol with substituted anilines (Table 2, 1i – 1k). It was
observed that acceptable yields (1h and 1i, 81% and 90%)
were observed for electron-donating substituents such as
All yields are isolated yields. Reaction conditions for 2o amine:
o
Co2Rh2 5 mol% (45 mg), 100 C, 24 h, N2. Reaction conditions
for 3o amine: Co2Rh2 10 mol% (90 mg), 140 oC, 24 h, N2. a)120
oC
Encouraged by the above observation, we decided to
study the alkylation of aniline with aliphatic alcohols. We
optimized the reaction conditions for the alkylation of ani-
line with 1-decanol (see SI). The optimum reaction condi-
tions were as follows: for monoalkylation,
5 mol%
Co2Rh2/C at 130 °C for 24 h and for dialkylation, 10 mol%
Co2Rh2/C at 165 °C for 24 h. First, we examined the reac-
tions of aniline with different aliphatic alcohol derivatives
under optimized reaction conditions (5 mol% Co2Rh2/C at
130 °C for 24 h) (Table 3). Aliphatic alcohols underwent
the N-alkylation reactions with aniline smoothly, affording
the desired products in high yields (2a – 2g; 56–94%).
Peculiarly, a dramatic decrease in the yield was observed
for 4-phenyl-2-butanol (2f, 27%) when compared to 1-
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The Journal of Organic Chemistry
o
Co2Rh2 5 mol% (45 mg), 130 C, 24 h. Reaction conditions for
phenylethan-1-ol (2e, 91%). However, increasing the reac-
3o amine: Co2Rh2 10 mol% (90 mg), 165 C, 24 h. a) 150 C
120 oC, alcohol 3 mL Co2Rh2 10 mol% (90 mg), 180 C, 36 h,
o
o
b)
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tion temperature to 150 °C solved this problem (81%). In
iridium-catalyzed reactions,[15] 4-phenyl-2-butanol and 1-
phenylethan-1-ol displayed reduced activity (19% and
38%, respectively), even with a greater catalyst loading
and longer reaction time. In other heterogeneous catalysts,
no reaction or poor yields of the corresponding secondary
amines were observed with long chain aliphatic alcohols.
In the presence of the nanosized zeolite beta,16 1-hexanol
and 1-octanol provided the respective mono-N-alkylated
products in 41% and 10% yields, respectively; no reaction
was observed with 1-decanol. Ethanol was also an ac-
ceptable substrate (2g - 89%). Unfortunately, methanol
was not an acceptable substrate8a,15 under identical reac-
tion conditions (5 mol% Co2Rh2/C at 130 °C for 24 h).
However, when 3,5-dimethylaniline was methylated at
180 °C in the presence of 5 mol% Co2Rh2/C, the mono-
methylated 3,5-dimethylaniline product was isolated with
a 38% yield. Lengthening the reaction time to 36 h in the
presence of 10 mol% Co2Rh2/C at 180 °C afforded the
mono-methylated 3,5-dimethylaniline at a 70% yield (2h).
Next, we tested the reaction of 1-decanol with substituted
aniline derivatives (2i – 2k). The treatment of aniline with
cyclohexanol, a secondary alcohol, at 140 °C resulted in N-
cyclohexylaniline (2l) with a 97% yield. Compared to
Zhang’s recent study,17 our result was remarkable. They
reported that the same reaction in the presence of a co-
balt(II) catalyst based on a pincer PNP ligand afforded a
mixture of N-cyclohexylaniline, N-phenylcyclohexanimine,
and cyclohexanone after 48 h, with the expected N-
cyclohexylaniline being the major product (48% GC yield).
Under the reaction conditions of formation of tert-amines
(10 mol% Co2Rh2/C at 165 °C for 24 h), the corresponding
tertiary amines could be obtained with 84–91% yields
(2aa – 2ee).
c)
o
alcohol 3 mL. d) 140 oC
Next, we studied the alkylation of aliphatic amines with
benzyl alcohols (Table 4). We optimized the reaction con-
ditions for the N-alkylation of decyl amine with 4-
methylbenzyl alcohol (see SI). Alkyl amines have a high
nucleophilicity compared to those of aryl amines and rela-
tive reduced temperatures were required to perform the
N-alkylation reactions. Thus, the optimum reaction condi-
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tions were as follows: for monoalkylation,
5 mol%
Co2Rh2/C at 80 °C for 24 h and for dialkylation, 5 mol%
Co2Rh2/C at 120 °C for 24 h. First, we tested the reactions
of 1-decyl amine with substituted benzyl alcohol deriva-
tives under optimized reaction conditions (Co2Rh2/C at
80 °C for 24 h). The results are listed in Table 4 (3a – 3e).
Sec-amines with a long alkyl chain were isolated in ac-
ceptable yields except for 3e. In the case of 3,5-
dimethoxybenzyl alcohol, the corresponding sec-amine
was isolated at a 48% yield (3e). However, increasing the
reaction temperature to 100 °C solved the problem (3,5-
dimethoxybenzyl alcohol: 84%). We next investigated the
reaction between 4-methylbenzyl alcohol with different
aliphatic amines (Table 4, 3f – 3k). N-alkylation produced
a secondary amine in high to excellent yield (66–98%),
depending upon the amine used. Cyclohexyl amine and 4-
methoxybenzyl amine were excellent substrates. Interest-
ingly, in the literature, the alkylation of cyclohexylamine
was a challenging reaction.18 For example, the treatment of
cyclohexylamine with benzyl alcohol in the presence of an
iridium NHC catalyst afforded
a 35% yield of N-
benzylcyclohexylamine.18a In the reaction with hexyl alco-
hol in the presence of [Cp*Ir(prolinato)Cl] at 150 °C for 72
h, the formation of N-benzylcyclohexylamine was observed
with a 27% yield.18b However, when cyclohexyl amine was
reacted with decanol under our reaction conditions, N-
decylcyclohexanamine was isolated at 93% (3l). Under the
reaction conditions of the formation of tert-amines (5 mol%
Co2Rh2/C at 120 °C for 24 h), the corresponding tertiary
amines could be obtained with 84–91% yields (3aa – 3ee).
Table 3. Reaction of Anilines with Aliphatic Alcohols
Table 4. Reaction of Aliphatic Amines
All yields are isolated yields. Reaction conditions for 2o amine:
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R
R
a Isolated yields.
OH
N
Co2Rh2/C 5 mol%,
24 h, 80~120 oC, N2
N
R
NH2
+
+
H
X
X
1
X
X
0.5 mmol
0.7 mL
To investigate the substitution effects of different
functional groups, competitive reactions of 4-methylbenzyl
alcohol, 4-fluorobenzylalcohol, and 4-ethoxybenzylalcohol
with aniline were performed (Scheme 3). Based on GC-MS
analysis, the yields of the corresponding sec-anilines were
22%, 13%, and 63%, respectively. Thus, the electron-rich
group on the aromatic ring of benzyl alcohols remarkably
enhanced the coupling reaction.
2
3
4
5
6
7
8
9
n-Decyl
n-Decyl
n-Decyl
n-Decyl
N
N
H
N
H
N
H
H
EtO
3d-91%
3b-96%
3c-81%
3a-92%
MeO
n-Decyl
N
n-Hexyl
N
H
n-Dodecyl
H
N
H
N
H
OMe
OMe
3i-98%
O
3g-84%
3e-84%a)
3f-83%
N
H
N
H
N
H
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3k-95%
N
3j-97%
3h-66%
n-Decyl
n-Decyl
n-Decyl
N
N
EtO
OEt
3cc-86%
3bb-84%
N
3aa-88%
n-Hexyl
N
O
H
N
n-Decyl
3l-93%a)
3ee-93%
3dd-91%
All yields are isolated yields. Reaction conditions for 2o amine:
Co2Rh2 5 mol% (45 mg), 80 oC, 24 h. Reaction conditions for 3o
amine: Co2Rh2 5 mol% (45 mg), 120 oC, 24 h. a) 100 oC
Scheme 3. Competitive Reaction
To illustrate the synthetic utility of our catalytic system,
our reaction conditions were applied to benzyl alcohol and
optically active 1-phenylethan-1-amines (eq 2). Secondary
amines were isolated in high yields (84 ~87%) with an
We performed additional experiments to further assess
the ability of Co2Rh2/C to promote the reactions of other
types of substrates (Scheme 1). Tryptamine, containing an
indole ring joined to an amino (NH2) group via an ethyl
(−CH2–CH2−) sidechain, is the common functional group in
a
set of compounds termed collectively serotonin
analogues. Under our reaction conditions, mono and di-
alkylation of an amino group were observed with high
yields: 92% for the mono-benzylation, and 89% and 83%
for the mono and bis-heptylation, respectively.
We also examined the reaction of cyclic amines with 4-
methylbenzyl alcohol in the presence of 5 mol% Co2Rh2/C
at 100 °C for 24 h (Scheme 2). High yields were observed
for morpholine (5a-92%), piperazine (5c-89%), and
1,2,3,4-tetrahydroisoquinoline (5b-98%). Interestingly, a
two-N-alkylation was observed in the case of piperazine.
excellent enantiomeric excess (ee >94%).
In the literature, the reaction of aliphatic alcohol with
aliphatic amines by heterogeneous catalysts is rare.
However, our results suggest that Co2Rh2/C demonstrated
high catalytic activities for the coupling of benzylic and
aliphatic alcohols, and aliphatic and aromatic amines to
produce secondary and tertiary amines selectively under
base and ligand-free conditions.
Scheme 1. Reaction of Tryptamine
R
NH2
HN
R
N
R
To verify the practicality of the developed method, a
gram scale reaction was performed (eq 3): a reaction of 6.5
mmol of benzyl alcohol (R = Me, 0.78 g; R = iPr, 0.96 g)
with 6 mmol of aniline afforded high yields of the corre-
sponding secondary amine (R = Me, 98%; 1.16 g; R = iPr,
91%; 1.23 g). Thus, secondary amines can be synthesized
Co2Rh2 5 mol%
24 h, N2
R
OH
+
+
N
H
N
N
H
H
0.7 mL
0.5 mmol
n-Heptyl
HN
HN n-Heptyl
N
n-Heptyl
N
N
H
N
H
H
4c-83%c)
4b-89%b)
4a-92%a)
All yields are isolated yields. a) 80 oC. b) 100 oC. c) 130 oC.
Scheme 2. Reaction of Cyclic Aminesa
OH
X
NH
Co2Rh2 5 mol%
100 oC, 24 h, N2
N
X
X
+
X
R
R
by the alkylation of amine with virtually a theoretical
equivalent of primary alcohols.
0.7 mL
N
0.5 mmol
To demonstrate the usefulness of the present system, we
explored the synthesis of unsymmetrically substituted
tertiary amines. When aniline, 4-ethoxybenzyl alcohol, and
1-decanol in a mole ratio of 1:1:1.5 were reacted in a one-
N
N
N
O
5a-92%
5c-89%
5b-98%
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N-decyl-N-(4- 1). Then, the metal complex transforms into a metal-
step
and
one-pot
reaction,
1
ethoxybenzyl)aniline and N,N-decylaniline were isolated in
64% and 34% yields, respectively, with a trace amount of
N,N-bis(4-ethoxybenzyl)aniline (eq 4).
dihydride and an aldehyde by a β-hydride elimination
(step 2). An amine readily forms an imine with the
aldehyde (step 3). Finally, a hydrogen transfer from the
metal dihydride to the imine intermediate proceeds to
afford a desired secondary amine (step 4). Tertiary amine
formation should proceed through similar sequential
processes.
2
3
4
OH
NH2
N
(4)
Co2Rh2 10 mol%
165 oC, 24 h, N2
5
Decyl
+
+
EtO
N
Decyl
EtO
Decyl
6
Decanol
64 %
34 %
7
8
9
Thus, the attempt was a “half way” to success. Then, a two-
step reaction was employed for the synthesis of unsym-
metrically substituted tertiary amines: aniline was treated
with an alcohol to obtain a secondary amine. Then, the
synthesized secondary amine was reacted with another
alcohol to produce unsymmetrically substituted tertiary
amines. After workup, the corresponding tertiary amines
(N-heptyl-N-(4-isopropylbenzyl)aniline), (N-heptyl-N-(3-
Scheme 4. Proposed Catalytic Cycle
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phenylpropyl)aniline),
(N-decyl-N-heptylaniline),
(N-
decyl-N-methylaniline), and (N-heptyl-N-methylaniline)
from their corresponding alcohol, were isolated in excel-
lent yields(6a-93%, 6b-99%, 6c-99%, 6d-99%, and 6e-
99%),
respectively
(eq
5).
R
N
H
N
Co2Rh2 10 mol%
140 oC, 24 h, N2
R'
R'
R
OH
+
(5)
4-isopropylbenzyl
3-phenyl-1-propyl
1-decyl
1-decyl
1-heptyl
R=
R'= heptyl
heptyl
6a- 93%
6b- 99%
6c- 99%
6d- 99%
6e- 99%
Conclusion
heptyl
methyl
methyl
In summary, a chemoselective method for the prepara-
tion of secondary or tertiary amines from primary amines
with alcohols was successfully realized with a heterogene-
ous bimetallic Co2Rh2/C catalyst through a borrowing hy-
drogen strategy. The catalyst exhibited excellent catalytic
activity and selectivity and could be readily recycled. The
advantages of this method are the general applicability
with different amines and alcohols in high yields and the
observed selectivity, which provide an attractive and use-
ful methodology for secondary and tertiary amine synthe-
sis. The present protocol provides a green and concise be-
nign method to access higher-order amines.
The reusability of Co2Rh2/C was investigated by per-
forming the alkylation of aniline with 4-methylbenzyl al-
cohol (Table 5). A high level of activity (97–99%) was
maintained even after ten cycles of reuse. The catalytic
system demonstrated an excellent capability of reuse and a
significant air-stability under the reaction conditions.
Table 5. Recycle test
EXPERIMENTAL SECTION
Run
Yield (%)a)
General Information. Workup procedures were done in air.
Toluene was used after purification. The other solvents were used
without further purification. Unless otherwise noted, all commer-
cial materials were used without purification. Commercial availa-
ble reagents were used as received. High purity Ar (99.999%) was
used. TLC analysis of reaction mixtures was performed on Merck
silica gel 60 F254 TLC plates. TLC plates were visualized by ultra-
violet light and treated with KMnO4 stain followed by gentle heat-
ing. Flash column chromatography was carried out on Merck 60
silica gel (230 – 400 mesh). 1H and 13C{1H} NMR spectra were
recorded with Agilent 400-MR DD2 (400 MHz and 100 MHz, re-
spectively) and Varian (500 MHz and 125 MHz, respectively)
1a
99
99
98
99
97
98
98
99
97
99
1
2
3
4
5
6
7
1
spectrometer. H NMR spectra were taken in CDCl3 and were ref-
erenced to residual TMS (0 ppm) and reported as follows: chemi-
cal shift (δ ppm), multiplicity (s = singlet, d= doublet, t = triplet, q
= quartet, m = multiplet), coupling constant (Hz), and integration.
Chemical shifts of the 13C{1H} NMR spectra were measured rela-
tive to CDCl3 (77.16 ppm). High-Resolution Mass Spectra were
obtained at the Korea Basic Science Institute (Daegu, South Korea)
on a Jeol JMS 700 high resolution mass spectrometer. All reac-
tants are commercially available compounds.
8
9
10
a) Isolated yields.
The Co2Rh2/C-catalyzed dehydrogenative N-alkylation of
amines with alcohols may proceed through a number of
sequential reactions. (Scheme 4) An alcohol coordinates to
a metal with the formation of a metal-hydride species (step
Synthesis of Co/Rh Nanoparticles on Charcoal To a two-
neck flask were added o-dichlorobenzene (10 mL), oleic acid (0.2
mL), and trioctylphosphine oxide (0.4 g). While the solution was
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 10
heated at 180°C, a solution of metal carbonyl Co2Rh2(CO)12 (0.8 g)
silica gel column eluting with hexane and ethyl acetate (silica,
in 25 mL of o-dichlorobenzene was injected into the flask. The
resulting solution was heated to 180°C for 2 h and then concen-
trated to a volume of 5 mL. The concentrated solution was cooled
to room temperature. To the cooled solution was added 30 mL of
THF. After the solution was well stirred for 10 min, flame-dried
charcoal (1.6 g) was added to the solution. After the resulting
solution had been refluxed for 12 h, the precipitates were filtered
and washed with diethyl ether (20 mL), dichloromethane (20 mL),
acetone (20 mL), and methanol (20 mL). Vacuum dry gave a black
solid.
1
2
3
4
5
6
7
8
1/100 EtOAc/hexane).
Gram scale experiment Reactions were performed in a 20
mL schlenk flask equipped with a stirring bar and the follow-
ings were place in the schlenk flask in the order: aniline (6
mmol), alcohol (6.5 mmmol) and 5 mol% Co2Rh2 (540 mg of
the immobilized Co2Rh2/C). The flask was purged with Ar gas
o
and heated at 100 C for 24 h. After the reactor was cooled to
room temperature, the solution was filtered and concentrated,
and the product was isolated by chromatography on a silica
gel column eluting with hexane and ethyl acetate (silica, 1/100
EtOAc/hexane).
9
General Procedure for Synthesis and Characterization
for reaction of Anilines Reactions were performed in a 20 mL
Schlenk flask equipped with a stirring bar and the followings
were placed in the Schlenk flask in the order: amine (0.5 mmol),
alcohol (0.7 mL) and 5 mol% ~ 10 mol% Co2Rh2 (45 mg ~ 90 mg
of the immobilized Co2Rh2/C). The flask was purged with N2 gas,
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N-(4-Methylbenzyl)aniline (1a). Colorless oil (98 mg, 99%). 1H
NMR (500 MHz, CDCl3) δ 7.12 (d, J = 7.7 Hz, 2 H), 7.04 (m, 4 H),
6.59 (t, J = 7.3 Hz, 1 H), 6.48 (d, J = 7.9 Hz, 2 H), 4.11 (s, 2 H), 3.79
(s, 1 H), 2.27 – 2.18 (m, 3 H); 13C{1H} NMR (125 MHz, CDCl3) δ
148.3, 136.8, 136.5, 129.33, 129.27, 127.5, 117.5, 112.9, 48.1, 21.1;
HRMS (EI+): m/z M+ calcd for [C14H15N]+: 197.1204, found
197.1205.
o
o
and heated at 100 C~165 C for 24 h. After the flask was cooled
to room temperature, the solution was filtered and the product
was isolated by chromatography on a silica gel column eluting
N-(4-Isopropylbenzyl)aniline (1c). Colorless oil (112 mg, 99%).
1H NMR (500 MHz, CDCl3) δ 7.21 (d, J = 8.1 Hz, 2 H), 7.14 – 7.04
(m, 4 H), 6.62 (t, J = 7.3 Hz, 1 H), 6.55 (d, J = 7.6 Hz, 2 H), 4.18 (s, 2
H), 3.86 (s, 1 H), 2.81 (m, 1H), 1.17 (d, J = 6.9 Hz, 6 H); 13C{1H}
NMR (125 MHz, CDCl3) δ 148.39, 148.07, 136.86, 129.36, 127.75,
126.79, 117.58, 112.92, 48.22, 33.94, 24.16; HRMS (EI+): m/z M+
calcd for [C16H19N]+: 225.1517, found 225.1518.
with hexane and ethyl acetate (silica, 1/80
EtOAc/hexane).
–
1/150
General Procedure for Synthesis and Characterization
for reaction of Aliphatic amines Reactions were performed
in a 20 mL Schlenk flask equipped with a stirring bar and the
followings were placed in the Schlenk flask in the order:
amine (0.5 mmol), alcohol (0.7 mL) and 5 mol% Co2Rh2 (45
mg of the immobilized Co2Rh2/C). The flask was purged with
N2 gas, and heated at 80 oC~120 oC for 24 h. After the flask
was cooled to room temperature, the solution was filtered and
the product was isolated by chromatography on a silica gel
column eluting with hexane and ethyl acetate for 3aa-3ee (silica,
1/100 EtOAc/hexane), dichloromethane and methanol for 3a-3l
(silica, 1/100 CH2Cl2/MeOH) .
N-(4-(tert-Butyl)benzyl)aniline (1d). White solid(107 mg, 89%);
o
1
m.p. 38.7 C. H NMR (500 MHz, CDCl3) δ 7.28 (d, J = 8.3 Hz, 2 H),
7.21 (d, J = 8.2 Hz, 2 H), 7.08 (m, 2 H), 6.62 (t, J = 7.3 Hz, 1 H), 6.55
(d, J = 7.7 Hz, 2 H), 4.19 (s, 2 H), 3.86 (s, 1 H), 1.23 (s, 9 H); 13C{1H}
NMR (125 MHz, CDCl3) δ 150.6, 148.4, 136.5, 129.4, 127.5, 125.7,
117.6, 112.9, 48.1, 34.6, 31.5; HRMS (EI+): m/z M+ calcd for
[C17H21N]+: 239.1674, found 239.1672.
N-(4-Ethoxybenzyl)aniline (1e). Colorless oil (112 mg, 99%). 1H
NMR (500 MHz, CDCl3) δ 7.18 (d, J = 7.6 Hz, 2 H), 7.08 (t, J = 7.3 Hz,
2 H), 6.78 (d, J = 7.3 Hz, 2 H), 6.62 (t, J = 7.2 Hz, 1 H), 6.54 (d, J =
7.8 Hz, 2 H), 4.14 (s, 2 H), 3.92 (q, J = 6.9 Hz, 2 H), 3.83 (s, 1 H),
1.31 (m, 3 H); 13C{1H} NMR (125 MHz, CDCl3) δ 158.3, 148.6,
131.4, 129.3, 128.9, 117.6, 114.7, 112.9, 63.6, 47.9, 14.97; HRMS
(EI+): m/z M+ calcd for [C15H17NO]+: 227.1310, found 227.1312.
N-(4-Fluorobenzyl)aniline (1f). Yellow oil (82 mg, 81%). 1H
NMR (400 MHz, CDCl3) δ 7.31 – 7.22 (m, 2 H), 7.10 (t, J = 7.3 Hz, 2
H), 6.95 (t, J = 8.0 Hz, 2 H), 6.65 (t, J = 7.0 Hz, 1 H), 6.55 (d, J = 8.2
Hz, 2 H), 4.23 (s, 2 H), 3.94 (s, 1 H); 13C{1H} NMR (101 MHz, CDCl3)
δ 163.4, 161.0, 148.0, 135.24, 135.21, 129.4, 129.18, 129.10, 117.9,
115.7, 115.5, 113.0, 47.8; HRMS (EI+): m/z M+ calcd for
[C13H12NF]+: 201.0954, found 201.0952.
General Procedure for Synthesis and Characterization
for reaction of cyclic amines Reactions were performed in a
20 mL Schlenk flask equipped with a stirring bar and the fol-
lowings were placed in the Schlenk flask in the order: amine
(0.5 mmol), alcohol (0.7 mL) and 5 mol% Co2Rh2 (45 mg of
the immobilized Co2Rh2/C). The flask was purged with N2 gas,
and heated at 100 oC for 24 h. After the flask was cooled to
room temperature, the solution was filtered and the product
was isolated by chromatography on a silica gel column eluting
with dichloromethane and methanol (silica, 1/100 CH2Cl2/MeOH).
General Procedure for Synthesis and Characterization
for methylation and ethylation of aniline Reactions were
performed in a 30 mL stainless steel autoclave equipped with a
stirring bar and the followings were place in the autoclave in the
order: amine (0.5 mmol), alcohol (3 mL) and 5 mol% for ethyla-
tion ~ 10 mol% for methylation Co2Rh2 (45 mg~ 90 mg of the
immobilized Co2Rh2/C). The reactor was purged with Ar gas, and
N-(3,5-Dimethoxybenzyl)aniline (1g). Colorless oil (101 mg,
1
83 %). H NMR (400 MHz, CDCl3) δ 7.09 (t, J = 7.6 Hz, 2 H), 6.64 (t,
J = 7.2 Hz, 1 H), 6.55 (d, J = 7.9 Hz, 2 H), 6.46 (s, 2 H), 6.30 (s, 1 H),
4.19 (s, 2 H), 3.95 (s, 1 H), 3.70 (s, 6 H); 13C{1H} NMR (100 MHz,
CDCl3) δ 161.2, 148.3, 142.2, 129.4, 117.8, 113.0, 105.4, 99.2, 55.5,
48.7; HRMS (EI+): m/z M+ calcd for [C15H17NO2]+: 243.1259, found
243.1261.
o
charged with 1 atm of Ar and heated at (ethylation: 120 C for 24
o
h) or (methylation: 180 C for 48 h). After the reactor was cooled
to room temperature, the solution was filtered and concentrated,
and the product was isolated by chromatography on a silica gel
column eluting with hexane and ethyl acetate. (silica, 1/150
EtOAc/hexane)
1
N-Benzylaniline (1b). Colorless oil (90 mg, 99%). H NMR (400
MHz, CDCl3) δ 7.28 (m, 4 H), 7.19 (m, 1 H), 7.10 (t, J = 7.6 Hz, 2 H),
6.64 (t, J = 7.3 Hz, 1 H), 6.57 (d, J = 8.5 Hz, 2 H), 4.25 (s, 2 H), 4.06
(s, 1 H); 13C{1H} NMR (100 MHz, CDCl3) δ 148.2, 139.5, 129.4,
128.8, 127.7, 127.4, 117.8, 113.1, 48.5; HRMS (EI+): m/z M+ calcd
for [C13H13N]+: 183.1048, found 183.1049.
General Procedure for Synthesis and Characterization
for reaction of asymmetric tertiary amine(eq5) Reactions
were performed in a 20 mL schlenk flask equipped with a
stirring bar and the followings were placed in the schlenk
flask in the order: amine (0.5 mmol), alcohol (0.7 mL) and 10
mol% Co2Rh2 (90 mg of the immobilized Co2Rh2/C). The flask
4-(tert-Butyl)-N-(4-methylbenzyl)aniline (1h). Off-white solid
o
1
(103 mg, 81 %); m.p. 42 - 44 C. H NMR (500 MHz, CDCl3) δ 7.15
(d, J = 7.8 Hz, 2 H), 7.10 (d, J = 8.4 Hz, 2 H), 7.04 (d, J = 7.8 Hz, 2 H),
6.48 (d, J = 8.5 Hz, 2 H), 4.14 (s, 2 H), 3.74 (s, 1 H), 2.23 (s, 3 H),
1.18 (s, 9 H); 13C{1H} NMR (125 MHz, CDCl3) δ 146.0, 140.3,
136.84, 136.75, 129.4, 127.7, 126.1, 112.7, 48.5, 34.0, 31.7, 21.2;
HRMS (EI+): m/z M+ calcd for [C18H23N]+: 253.1830, found
253.1832.
o
was purged with N2 gas, and heated at 140 C for 24 h. After
the flask was cooled to room temperature, the solution was
filtered and the product was isolated by chromatography on a
ACS Paragon Plus Environment

Page 7 of 10
The Journal of Organic Chemistry
N-(4-Methylbenzyl)-4-phenoxyaniline (1i). Colorless to yellow
oil (130 mg, 90 %). 1H NMR (500 MHz, CDCl3) δ 7.12 (m, 4 H),
7.02 (d, J = 7.8 Hz, 2 H), 6.85 (t, J = 7.3 Hz, 1 H), 6.77 (m, 4 H), 6.45
(d, J = 8.8 Hz, 2 H), 4.09 (s, 2 H), 3.74 (s, 1 H), 2.21 (s, 3 H); 13C{1H}
NMR (125 MHz, CDCl3) δ 159.2, 147.7, 145.0, 136.9, 136.4, 129.5,
129.4, 127.6, 122.0, 121.3, 117.2, 113.9, 48.6, 21.2; HRMS (EI+):
m/z M+ calcd for [C20H19NO]+: 289.1467, found 289.1468.
N-Tetradecylaniline (2c). White solid (110 mg, 76 %); m.p. 32.3
1
oC. H NMR (500 MHz, CDCl3) δ 7.12 – 7.05 (m, 2 H), 6.60 (t, J = 7.3
1
2
3
4
5
6
7
8
Hz, 1 H), 6.53 – 6.50 (m, 2 H), 3.50 (s, 1 H), 3.02 (t, J = 7.1 Hz, 2 H),
1.53 (m, 2 H), 1.37 – 1.13 (m, 22 H), 0.81 (t, J = 6.9 Hz, 3 H); 13C{1H}
NMR (125 MHz, CDCl3) δ 148.7, 129.3, 117.2, 112.8, 44.2, 32.1,
29.82, 29.75, 29.6, 29.5, 27.3, 22.9, 14.3; HRMS (EI+): m/z M+ calcd
for [C20H35N]+: 289.2770, found 289.2767.
N-(3-Phenylpropyl)aniline (2d). Colorless oil (60 mg, 56 %). 1H
NMR (500 MHz, CDCl3) δ 7.24 – 7.15 (m, 2 H), 7.09 (m, 5 H), 6.60
(t, J = 7.3 Hz, 1 H), 6.48 (d, J = 7.7 Hz, 2 H), 3.49 (s, 1 H), 3.05 (t, J =
7.0 Hz, 2 H), 2.64 (t, J = 7.6 Hz, 2 H), 1.85 (m, 2 H); 13C{1H} NMR
(125 MHz, CDCl3) δ 148.4, 141.7, 129.3, 128.49, 128.46, 126.0,
117.3, 112.8, 43.5, 33.5, 31.1; HRMS (EI+): m/z M+ calcd for
[C15H17N]+: 211.1361, found 211.1362.
N-(1-Phenylethyl)aniline (2e). Colorless oil (90 mg, 91 %). 1H
NMR (500 MHz, CDCl3) δ 7.32 – 7.19 (m, 4 H), 7.13 (t, J = 7.2 Hz, 1
H), 7.00 (t, J = 7.3 Hz, 2 H), 6.56 (t, J = 7.3 Hz, 1 H), 6.42 (d, J = 7.8
Hz, 2 H), 4.40 (q, J = 6.5 Hz, 1 H), 3.92 (s, 1 H), 1.42 (d, J = 6.7 Hz, 3
H); 13C NMR (125 MHz, CDCl3) δ 147.4, 145.3, 129.2, 128.7, 127.0,
126.0, 117.4, 113.4, 53.6, 25.1; HRMS (EI+): m/z M+ calcd for
[C14H15N]+: 197.1204, found 197.1207.
N-(4-Phenylbutan-2-yl)aniline (2f). Colorless oil (91 mg, 81 %).
1H NMR (500 MHz, CDCl3) δ 7.18 (t, J = 7.6 Hz, 2 H), 7.14 – 7.03 (m,
5 H), 6.57 (t, J = 7.3 Hz, 1 H), 6.43 (d, J = 8.6 Hz, 2 H), 3.39 (m, 1 H),
3.32 (s, 1 H), 2.63 (t, J = 7.9 Hz, 2 H), 1.77 (m, 1 H), 1.67 (m, 1 H),
1.11 (d, J = 6.3 Hz, 3 H); 13C{1H} NMR (125 MHz, CDCl3) δ 147.7,
142.1, 129.3, 128.53, 128.48, 125.9, 117.0, 113.3, 48.0, 38.9, 32.6,
21.0; HRMS (EI+): m/z M+ calcd for [C16H19N]+: 225.1517, found
225.1516.
4-(tert-Butyl)-N-decylaniline (2i). Colorless to red oil (142 mg,
89 %). 1H NMR (500 MHz, CDCl3) δ 7.11 (d, J = 8.4 Hz, 2 H), 6.47
(d, J = 8.2 Hz, 2 H), 3.40 (s, 1 H), 3.00 (t, J = 7.0 Hz, 2 H), 1.57 – 1.46
(m, 2 H), 1.37 – 1.12 (m, 23 H), 0.81 (t, J = 6.4 Hz, 3 H); 13C{1H}
NMR (125 MHz, CDCl3) δ 146.4, 139.9, 126.1, 112.5, 44.4, 33.9,
32.0, 31.7, 29.84, 29.76, 29.72, 29.6, 29.5, 27.4, 22.8, 14.3; HRMS
(EI+): m/z M+ calcd for [C20H35N]+: 289.2770, found 289.2771.
N-Decyl-4-phenoxyaniline (2j). Colorless oil (140 mg, 86 %). 1H
NMR (500 MHz, CDCl3) δ 7.17 (t, J = 7.2 Hz, 2 H), 6.90 (t, J = 7.3 Hz,
1 H), 6.86 – 6.73 (m, 4 H), 6.50 (d, J = 7.8 Hz, 2 H), 3.44 (s, 1 H),
3.00 (t, J = 6.9 Hz, 2 H), 1.53 (m, 2 H), 1.25 (m, 14 H), 0.80 (t, J =
6.2 Hz, 3 H); 13C{1H} NMR (125 MHz, CDCl3) δ 159.4, 147.6, 145.4,
129.6, 122.0, 121.4, 117.2, 113.8, 44.8, 32.1, 29.81, 29.75, 29.71,
29.6, 29.5, 27.4, 22.8, 14.2; HRMS (EI+): m/z M+ calcd for
[C22H31NO]+: 325.2406, found 325.2408.
N-Decyl-3,5-dimethylaniline (2k). Colorless to yellow oil (109
mg, 83 %). 1H NMR (500 MHz, CDCl3) δ 6.43 (s, 1 H), 6.32 (s, 2 H),
3.55 (s, 1 H), 3.15 (t, J = 7.1 Hz, 2 H), 2.32 (s, 6 H), 1.66 (m, 2 H),
1.50 – 1.29 (m, 14 H), 0.97 (t, J = 6.9 Hz, 3 H); 13C{1H} NMR (125
MHz, CDCl3) δ 148.8, 138.9, 119.2, 110.8, 44.2, 32.0, 29.79, 29.76,
29.72, 29.6, 29.5, 27.3, 22.8, 21.6, 14.2; HRMS (EI+): m/z M+ calcd
for [C18H31N]+: 261.2457, found 261.2459.
N-3,5-Trimethylaniline (2h). Colorless to yellow oil (47 mg,
70 %). 1H NMR (500 MHz, CDCl3) δ 6.33 (s, 1 H), 6.22 (s, 2 H),
2.76 (s, 3 H), 2.19 (s, 6 H); 13C{1H} NMR (125 MHz, CDCl3) δ 139.0,
119.7, 110.7, 31.1, 21.6; HRMS (EI+): m/z M+ calcd for [C9H13N]+:
135.1048, found 135.1049.
N,N-Didecylaniline (2bb). Colorless oil (175 mg, 94 %). 1H NMR
(500 MHz, CDCl3) δ 7.30 (t, J = 8.0 Hz, 2 H), 6.81 – 6.64 (m, 3 H),
3.43 – 3.29 (m, 4 H), 1.68 (m, 4 H), 1.41 (m, 28 H), 1.08 – 0.97 (m,
6 H); 13C{1H} NMR (125 MHz, CDCl3) δ 148.3, 129.23, 115.2, 111.9,
51.2, 32.1, 29.8, 29.74, 29.71, 29.5, 27.42, 27.37, 22.8, 14.2; HRMS
(EI+): m/z M+ calcd for [C26H47N]+: 373.3709, found 373.3710 .
N,N-Diheptylaniline (2aa). Colorless oil (143 mg, 99 %). 1H
NMR (500 MHz, CDCl3) δ 7.19 – 7.07 (m, 2 H), 6.56 (m, 3 H), 3.24 –
3.10 (m, 4 H), 1.58 – 1.46 (m, 4 H), 1.24 (m, 16 H), 0.83 (t, J = 7.0
Hz, 6 H); 13C{1H} NMR (125 MHz, CDCl3) δ 148.6, 129.3, 115.2,
111.8, 51.2, 32.1, 29.4, 27.4, 27.3, 22.8, 14.2; HRMS (EI+): m/z M+
calcd for [C20H35N]+: 289.2770, found 289.2771.
3-Fluoro-N-(4-methylbenzyl)aniline (1j). Colorless to yellow oil
1
(77 mg, 71 %). H NMR (500 MHz, CDCl3) δ 7.30 (d, J = 7.9 Hz, 2
H), 7.22 (d, J = 7.8 Hz, 2 H), 7.14 (m, 1 H), 6.48 – 6.40 (m, 2 H),
6.36 (m, 1H), 4.30 (s, 2 H), 4.14 (s, 1 H), 2.41 (s, 3 H); 13C{1H} NMR
(125 MHz, CDCl3) δ 165.2, 163.3, 150.0, 137.2, 135.9, 130.4, 130.3,
129.5, 127.6, 108.8, 104.0, 103.9, 99.7, 99.5, 48.1, 21.2; 19F NMR
(376 MHz, cdcl3) δ -115.60, -115.62, -115.63, -115.64, -115.65, -
115.66, -115.68; HRMS (EI+): m/z M+ calcd for [C14H14NF]+:
215.1110, found 215.1107.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
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53
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3,5-Dimethyl-N-(4-methylbenzyl)aniline (1k). Colorless oil (94
1
mg, 83 %). H NMR (500 MHz, CDCl3) δ 7.13 (d, J = 7.9 Hz, 2 H),
7.03 (d, J = 7.8 Hz, 2 H), 6.28 (s, 1 H), 6.16 (s, 2 H), 4.12 (s, 2 H),
3.69 (s, 1 H), 2.23 (s, 3 H), 2.12 (s, 6 H); 13C{1H} NMR (125 MHz,
CDCl3) δ 148.5, 138.9, 136.8, 136.7, 129.3, 127.6, 119.6, 110.9,
48.2, 21.6, 21.2; HRMS (EI+): m/z M+ calcd for [C16H19N]+:
225.1517, found 225.1515.
N,N-bis(4-Methylbenzyl)aniline (1aa). Colorless oil (139 mg,
1
92 %). H NMR (500 MHz, CDCl3) δ 6.31 – 6.21 (m, 10 H), 5.87 (d, J
= 8.0 Hz, 2 H), 5.82 (t, J = 7.2 Hz, 1 H), 3.73 (s, 4 H), 1.47 (s, 6 H);
13C{1H} NMR (125 MHz, CDCl3) δ 136.6, 135.7, 129.4, 129.3,
126.82, 116.7, 112.7, 54.0, 21.2; HRMS (EI+): m/z M+ calcd for
[C22H23N]+: 301.1830, found 301.1833.
N,N-bis(4-Isopropylbenzyl)aniline (1bb). Colorless oil (173 mg,
1
97 %). H NMR (500 MHz, CDCl3) δ 7.14 – 7.05 (m, 10 H), 6.67 (d, J
= 8.0 Hz, 2 H), 6.61 (t, J = 7.3 Hz, 1 H), 4.54 (s, 4 H), 2.82 (m, 2 H),
1.17 (t, J = 6.8 Hz, 12 H); 13C{1H} NMR (125 MHz, CDCl3) δ 149.5,
147.6, 136.1, 129.3, 126.78, 126.75, 116.6, 112.5, 54.0, 33.9, 24.2;
HRMS (EI+): m/z M+ calcd for [C26H31N]+: 357.2457, found
357.2459.
3,5-Dimethyl-N,N-bis(4-methylbenzyl)aniline (1cc). Colorless oil
1
(153 mg, 93 %). H NMR (500 MHz, CDCl3) δ 7.05 (m, 8 H), 6.31
(m, 3 H), 4.47 (s, 4 H), 2.26 (s, 6 H), 2.13 (s, 6 H); 13C{1H} NMR
(125 MHz, CDCl3) δ 149.9, 138.9, 136.4, 135.9, 129.4, 126.9, 118.8,
110.4, 53.5, 21.9, 21.2; HRMS (EI+): m/z M+ calcd for [C24H27N]+:
329.2143, found 329.2141.
N,N-bis(4-Methylbenzyl)-4-phenoxyaniline (1dd). Yellow oil
1
(195 mg, 99 %). H NMR (400 MHz, CDCl3) δ 7.17 (m, 3 H), 7.06
(m, 7H), 6.95 – 6.74 (m, 5 H), 6.62 (m, 2 H), 4.49 (m, 4 H), 2.25 (s,
6 H); 13C{1H} NMR (100 MHz, CDCl3) δ 159.1, 147.3, 146.2, 136.6,
135.7, 129.6, 129.4, 126.8, 122.1, 121.0, 117.4, 113.8, 54.6, 21.2;
HRMS (EI+): m/z M+ calcd for [C28H27NO]+: 393.2093, found
393.2095.
4-(tert-Butyl)-N,N-bis(4-methylbenzyl)aniline (1ee). Colorless to
1
yellow oil (168 mg, 94 %). H NMR (500 MHz, CDCl3) δ 7.14 – 6.99
(m, 10 H), 6.58 (m, 2 H), 4.47 (s, 4 H), 2.23 (s, 6 H), 1.16 (m, 9 H);
13C{1H} NMR (125 MHz, CDCl3) δ 147.3, 139.2, 136.4, 136.0, 129.4,
126.9, 126.0, 112.2, 54.1, 33.9, 31.7, 21.2; HRMS (EI+): m/z M+
calcd for [C26H31N]+: 357.2457, found 357.2454.
N-Decylaniline (2a). Colorless oil (110 mg, 94 %). 1H NMR (500
MHz, CDCl3) δ 7.09 (m, 2 H), 6.60 (m, 1 H), 6.51 (d, J = 8.3 Hz, 2 H),
3.49 (s, 1 H), 3.01 (t, J = 7.1 Hz, 2 H), 1.53 (m, 2 H), 1.36 – 1.13 (m,
14 H), 0.81 (t, J = 6.7 Hz, 3 H); 13C{1H} NMR (125 MHz, CDCl3) δ
148.7, 129.3, 117.2, 112.8, 44.2, 32.0, 29.8, 29.7, 29.6, 29.5, 27.3,
22.8, 14.2; HRMS (EI+): m/z M+ calcd for [C16H27N]+: 233.2143,
found 233.2145.
1
N-Heptylaniline (2b). Colorless oil (86 mg, 90 %). H NMR (500
MHz, CDCl3) δ 7.08 (m, 2 H), 6.60 (m, 1 H), 6.51 (m, 2 H), 3.49 (s, 1
H), 3.07 – 2.95 (m, 2 H), 1.63 – 1.43 (m, 2 H), 1.26 (m, 8 H), 0.81
(m, 3 H); 13C{1H} NMR (125 MHz, CDCl3) δ 148.66, 129.31, 117.16,
112.79, 44.2, 31.9, 29.7, 29.3, 27.3, 22.8, 14.2; HRMS (EI+): m/z M+
calcd for [C13H21N]+: 191.1674, found 191.1672.
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The Journal of Organic Chemistry
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N,N-bis(3-Phenylpropyl)aniline (2cc). Colorless oil (161 mg,
Hz, 2 H), 7.14 (d, J = 8.0 Hz, 2 H), 3.74 (s, 2 H), 2.65 – 2.54 (m, 2 H),
98 %). 1H NMR (500 MHz, CDCl3) δ 7.18 (m, 4 H), 7.11 – 7.00 (m, 8
H), 6.53 (t, J = 7.2 Hz, 1 H), 6.47 (d, J = 8.6 Hz, 2 H), 3.22 – 3.12 (m,
4 H), 2.53 (t, J = 7.7 Hz, 4 H), 1.86 – 1.73 (m, 4 H); 13C{1H} NMR
(125 MHz, CDCl3) δ 148.2, 141.9, 129.3, 128.51, 128.47, 126.0,
115.8, 112.3, 50.7, 33.5, 28.9; HRMS (EI+): m/z M+ calcd for
[C24H27N]+: 329.2143, found 329.2147.
2.30 (s, 3 H), 1.58 – 1.49 (m, 2 H), 1.28 (m, 18 H), 0.89 (t, J = 7.0 Hz,
3 H); 13C{1H} NMR (125 MHz, CD3OD) δ 138.3, 136.1, 130.2, 129.7,
53.8, 49.6, 33.1, 30.8, 30.7, 30.7, 30.6, 30.5, 29.8, 28.3, 23.7, 21.3,
14.5; HRMS (EI+): m/z M+ calcd for [C20H35N]+: 289.2770, found
289.2766.
1
2
3
4
5
6
7
8
N-(4-Methylbenzyl)-4-phenylbutan-1-amine (3h). Yellow oil (84
1
N,N-Didecyl-3-fluoroaniline (2dd). Colorless oil (176 mg, 90 %).
1H NMR (500 MHz, CDCl3) δ 7.01 (d, J = 8.1 Hz, 1 H), 6.28 (d, J = 8.3
Hz, 1 H), 6.23 – 6.15 (m, 2 H), 3.24 – 3.03 (m, 4 H), 1.48 (m, 4 H),
1.21 (m, 28 H), 0.81 (t, J = 6.5 Hz, 6 H); 13C{1H} NMR (125 MHz,
CDCl3) δ 165.5, 163.6, 150.2, 150.1, 130.2, 130.1, 107.4, 101.7,
101.5, 98.8, 98.5, 51.3, 32.1, 29.8, 29.74, 29.69, 29.5, 27.4, 27.3,
22.8, 14.2; 19F NMR (376 MHz, CDCl3) δ -112.80, -112.82, -112.83,
-112.84, -112.85, -112.87; HRMS (EI+): m/z M+ calcd for
[C26H46FN]+: 391.3614, found 391.3611.
4-(tert-Butyl)-N,N-didecylaniline (2ee). Colorless oil (208 mg,
97 %). 1H NMR (500 MHz, CDCl3) δ 7.14 (d, J = 8.5 Hz, 2 H), 6.50 (d,
J = 8.5 Hz, 2 H), 3.16 – 3.09 (m, 4 H), 1.46 (m, 4 H), 1.20 (m, 37 H),
0.80 (t, J = 6.8 Hz, 6 H); 13C{1H} NMR (125 MHz, CDCl3) δ 146.2,
137.8, 126.1, 111.5, 51.3, 33.8, 32.1, 31.7, 29.9, 29.8, 29.5, 27.5,
27.4, 22.9, 14.3; HRMS (EI+): m/z M+ calcd for [C30H55N]+:
429.4355, found 429.4332.
mg, 66 %). H NMR (500 MHz, CD3OD) δ 7.25 – 7.15 (m, 4 H), 7.12
(m, 5 H), 3.66 (s, 2 H), 2.56 (m, 4 H), 2.29 (s, 3 H), 1.55 (m, 4 H);
13C{1H} NMR (125 MHz, CD3OD) δ 143.4, 138.0, 136.8, 130.1,
129.6, 129.4, 129.3, 126.7, 53.9, 49.5, 36.6, 30.2, 29.6, 21.2; HRMS
(EI+): m/z M+ calcd for [C18H23N]+: 253.1830, found 253.1830.
N-(4-Methoxybenzyl)-1-(p-tolyl)methanamine (3i). Colorless oil
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
(118 mg, 98 %). H NMR (500 MHz, CD3OD) δ 7.22 (d, J = 8.7 Hz, 2
H), 7.19 (d, J = 8.0 Hz, 2 H), 7.13 (d, J = 7.9 Hz, 2 H), 6.87 (d, J = 8.7
Hz, 2 H), 3.76 (s, 3 H), 3.65 (s, 2 H), 3.64 (s, 2 H), 2.30 (s, 3 H);
13C{1H} NMR (125 MHz, CD3OD) δ 160.4, 137.9, 137.5, 132.6,
130.8, 130.1, 129.5, 114.9, 55.7, 53.2, 52.9, 21.1; HRMS (EI+): m/z
M+ calcd for [C16H19NO]+: 241.1467, found 241.1464.
N-(4-Methylbenzyl)cyclohexanamine (3j). Colorless oil (98 mg,
1
97 %). H NMR (500 MHz, CD3OD) δ 7.21 (d, J = 7.9 Hz, 2 H), 7.12
(d, J = 7.9 Hz, 2 H), 3.74 (s, 2 H), 2.50 (m, 1 H), 2.29 (s, 3 H), 1.99 –
1.90 (m, 2 H), 1.78 – 1.69 (m, 2 H), 1.62 (m, 1 H), 1.32 – 1.09 (m, 5
H); 13C{1H} NMR (125 MHz, CD3OD) δ 138.1, 136.8, 130.2, 129.6,
57.1, 50.8, 33.3, 27.1, 26.1, 21.2; HRMS (EI+): m/z M+ calcd for
[C14H21N]+: 203.1674, found 203.1676.
N-(4-Methylbenzyl)decan-1-amine (3a). Colorless oil (120 mg,
1
92 %). H NMR (500 MHz, CD3OD) δ 7.20 (d, J = 7.9 Hz, 2 H), 7.13
(d, J = 7.9 Hz, 2 H), 3.70 (s, 2 H), 2.62 – 2.50 (m, 2 H), 2.31 (s, 3 H),
1.59 – 1.45 (m, 2 H), 1.30 (m,14 H), 0.89 (t, J = 6.9 Hz, 3 H); 13C{1H}
NMR (125 MHz, CD3OD) δ 138.0, 137.0, 130.1, 129.6, 54.0, 49.8,
33.0, 30.7, 30.6, 30.4, 30.1, 28.4, 23.7, 21.2, 14.5; HRMS (EI+): m/z
M+ calcd for [C18H31N]+: 261.2457, found 261.2457.
3-Isopropoxy-N-(4-methylbenzyl)propan-1-amine (3k). Colorless
1
oil (105 mg, 95 %). H NMR (500 MHz, CD3OD) δ 7.20 (d, J = 8.0
Hz, 2 H), 7.12 (d, J = 8.0 Hz, 2 H), 3.71 (s, 2 H), 3.59 – 3.49 (m, 1 H),
3.46 (t, J = 6.1 Hz, 2 H), 2.68 (t, J = 7.1 Hz, 2 H), 2.29 (s, 3 H), 1.80 –
1.70 (m, 2 H), 1.09 (d, J = 6.2 Hz, 6 H); 13C{1H} NMR (125 MHz,
CD3OD) δ 138.1, 136.6, 130.1, 129.6, 72.9, 67.8, 54.0, 47.7, 30.3,
22.4, 21.2; HRMS (EI+): m/z M+ calcd for [C14H23NO]+: 221.1780,
found 221.1783.
N-(4-Isopropylbenzyl)decan-1-amine (3b). Colorless oil (138 mg,
1
96 %). H NMR (500 MHz, CD3OD) δ 7.26 (d, J = 8.1 Hz, 2 H), 7.19
(d, J = 8.1 Hz, 2 H), 3.75 (s, 2 H), 2.94 – 2.81 (m, 1 H), 2.66 – 2.55
(m, 2 H), 1.61 – 1.49 (m, 2 H), 1.36 – 1.25 (m, 14 H), 1.23 (d, J = 7.0
Hz, 6 H), 0.89 (t, J = 6.9 Hz, 3 H); 13C{1H} NMR (125 MHz, CD3OD) δ
149.2, 136.8, 129.7, 127.5, 53.9, 49.7, 35.0, 33.0, 30.6, 30.5, 30.4,
29.9, 28.3, 24.5, 23.7, 14.5; HRMS (EI+): m/z M+ calcd for
[C20H35N]+: 289.2770, found 289.2767.
N-(4-(tert-Butyl)benzyl)decan-1-amine (3c). White solid (123
mg, 81 %); m.p. 73 - 75 oC. 1H NMR (500 MHz, CD3OD) δ 7.37 (d, J
= 8.1 Hz, 2 H), 7.26 (d, J = 8.1 Hz, 2 H), 3.74 (s, 2 H), 2.66 – 2.54 (m,
2 H), 1.55 (m, 2 H), 1.30 (m, 20 H), 0.90 (t, J = 6.7 Hz, 3 H); 13C{1H}
NMR (125 MHz, CD3OD) δ 151.4, 136.6, 129.4, 126.4, 53.9, 49.8,
35.3, 33.0, 31.9, 30.7, 30.6, 30.4, 30.0, 28.4, 23.7, 14.5; HRMS (EI+):
m/z M+ calcd for [C21H37N]+: 303.2926, found 303.2923.
N,N-bis(4-Methylbenzyl)decan-1-amine (3aa). Colorless oil (161
1
mg, 88 %). H NMR (500 MHz, CDCl3) δ 7.18 (m, 4 H), 7.04 (m, 4
H), 3.43 (s, 4 H), 2.35 – 2.28 (m, 2 H), 2.26 (s, 6 H), 1.46 – 1.39 (m,
2 H), 1.29 – 1.07 (m, 14 H), 0.82 (t, J = 7.0 Hz, 3 H); 13C{1H} NMR
(125 MHz, CDCl3) δ 137.2, 136.2, 128.91, 128.86, 58.0, 53.4, 32.1,
29.82, 29.77, 29.69, 29.5, 27.5, 27.1, 22.9, 21.2, 14.3; HRMS (EI+):
m/z M+ calcd for [C26H39N]+: 365.3083, found 365.3083.
N,N-bis(4-Isopropylbenzyl)decan-1-amine (3bb). Colorless oil
1
(177 mg, 84 %). H NMR (500 MHz, CDCl3) δ 7.20 (m, 4 H), 7.07
(m, 4 H), 3.43 (s, 4 H), 2.80 (m, 2 H), 2.38 – 2.25 (m, 2 H), 1.45 –
1.38 (m, 2 H), 1.15 (m, 26 H), 0.80 (t, J = 7.0 Hz, 3 H); 13C{1H} NMR
(125 MHz, CDCl3) δ 147.3, 137.6, 128.8, 126.2, 58.1, 53.6, 33.9,
32.1, 29.83, 29.79, 29.7, 29.5, 27.4, 27.2, 24.2, 22.9, 14.3; HRMS
(EI+): m/z M+ calcd for [C30H47N]+: 421.3709, found 421.3710.
N,N-bis(4-Isopropylbenzyl)decan-1-amine (3cc). Colorless oil
N-(4-Ethoxybenzyl)decan-1-amine (3d). Colorless oil (133 mg,
1
91 %). H NMR (500 MHz, CD3OD) δ 7.24 (d, J = 8.6 Hz, 2 H), 6.86
(d, J = 8.6 Hz, 2 H), 4.00 (q, J = 7.0 Hz, 2 H), 3.71 (s, 2 H), 2.63 –
2.55 (m, 2 H), 1.60 – 1.46 (m, 2 H), 1.36 (t, J = 7.0 Hz, 3 H), 1.28 (m,
14 H), 0.89 (t, J = 6.9 Hz, 3 H); 13C{1H} NMR (125 MHz, CD3OD) δ
159.9, 131.3, 131.0, 115.6, 64.5, 53.6, 49.6, 33.1, 30.7, 30.6, 30.4,
29.9, 28.4, 23.7, 15.2, 14.5; HRMS (EI+): m/z M+ calcd for
[C19H33NO]+: 291.2562, found 291.2563.
1
(182 mg, 86 %). H NMR (500 MHz, CDCl3) δ 7.13 (m, 4 H), 6.72
(m, 4 H), 3.89 (q, J = 7.0 Hz, 4 H), 3.35 (s, 4 H), 2.30 – 2.21 (m, 2 H),
1.41 – 1.34 (m, 2 H), 1.28 (t, J = 7.0 Hz, 6 H), 1.25 – 1.02 (m, 14 H),
0.79 (t, J = 7.0 Hz, 3 H); 13C{1H} NMR (125 MHz, CDCl3) δ 157.9,
132.1, 129.9, 114.2, 63.4, 57.6, 53.2, 32.1, 29.80, 29.75, 29.6, 29.5,
27.4, 27.1, 22.8, 15.0, 14.2; HRMS (EI+): m/z M+ calcd for
[C28H43NO2]+: 425.3294, found 425.3291.
N-(3,5-Dimethoxybenzyl)decan-1-amine (3e). Colorless oil (128
1
mg, 84 %). H NMR (500 MHz, CD3OD) δ 6.51 (d, J = 2.2 Hz, 2 H),
6.37 (t, J = 2.2 Hz, 1 H), 3.75 (s, 6 H), 3.67 (s, 2 H), 2.60 – 2.51 (m, 2
H), 1.56 – 1.48 (m, 2 H), 1.28 (m, 14 H), 0.89 (t, J = 6.9 Hz, 3 H);
13C{1H} NMR (125 MHz, CD3OD) δ 162.4, 142.5, 107.4, 100.2, 55.7,
54.5, 49.8, 33.0, 30.7, 30.6, 30.4, 30.2, 28.4, 23.7, 14.5; HRMS (EI+):
m/z M+ calcd for [C19H33NO2]+: 307.2511, found 307.2507.
N-(4-Methylbenzyl)hexan-1-amine (3f). Colorless oil (85 mg,
83 %). 1H NMR (500 MHz, CD3OD) δ 7.21 (d, J = 7.8 Hz, 2 H), 7.13
(d, J = 7.8 Hz, 2 H), 3.72 (s, 2 H), 2.64 – 2.52 (m, 2 H), 2.30 (s, 3 H),
1.58 – 1.44 (m, 2 H), 1.37 – 1.22 (m, 6 H), 0.89 (t, J = 6.7 Hz, 3 H);
13C{1H} NMR (125 MHz, CD3OD) δ 138.1, 136.6, 130.1, 129.6, 53.9,
49.8, 32.8, 30.0, 28.0, 23.6, 21.2, 14.4; HRMS (EI+): m/z M+ calcd
for [C14H23N]+: 205.1830, found 205.1829.
N,N-bis(4-Methylbenzyl)hexan-1-amine (3dd). Colorless oil
1
(140 mg, 91 %). H NMR (500 MHz, CDCl3) δ 7.14 (m, 4 H), 7.01 (s,
4 H), 3.40 (m, 4 H), 2.28 (t, J = 7.2 Hz, 2 H), 2.22 (s, 6 H), 1.46 –
1.32 (m, 2 H), 1.13 (m, 6 H), 0.75 (t, J = 7.1 Hz, 3 H); 13C{1H} NMR
(125 MHz, CDCl3) δ 137.1, 136.2, 128.90, 128.85, 58.0, 53.4, 31.9,
27.12, 27.11, 22.8, 21.2, 14.2; HRMS (EI+): m/z M+ calcd for
[C22H31N]+: 309.2457, found 309.2454.
3-Isopropoxy-N,N-bis(4-methylbenzyl)propan-1-amine
(3ee).
1
Colorless oil (151 mg, 93 %). H NMR (500 MHz, CDCl3) δ 7.14 (d,
J = 7.9 Hz, 4 H), 7.02 (d, J = 7.8 Hz, 4 H), 3.42 (s, 4 H), 3.38 – 3.32
(m, 1 H), 3.30 (t, J = 6.8 Hz, 2 H), 2.39 (t, J = 6.9 Hz, 2 H), 2.23 (s, 6
H), 1.72 – 1.63 (m, 2 H), 0.99 (d, J = 6.1 Hz, 6 H); 13C{1H} NMR (126
MHz, CDCl3) δ 136.9, 136.3, 128.8, 128.86, 71.4, 66.4, 58.0, 50.2,
N-(4-Methylbenzyl)dodecan-1-amine (3g). White sloid (121 mg,
84 %); m.p. 62 - 64 oC. 1H NMR (500 MHz, CD3OD) δ 7.22 (d, J = 8.0
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The Journal of Organic Chemistry
27.9, 22.2, 21.2; HRMS (EI+): m/z M+ calcd for [C22H31NO]+:
325.2406, found 325.2403.
N-Heptyl-N-(4-isopropylbenzyl)aniline (6a). Colorless oil (150
mg, 93 %). H NMR (500 MHz, CDCl3) δ 7.08 (m, 6 H), 6.57 (m, 3
1
1
2
3
4
5
6
7
8
N-Decylcyclohexanamine (3l). Colorless oil (111 mg, 93 %). 1H
NMR (500 MHz, CD3OD) δ 2.59 – 2.53 (m, 2 H), 2.42 (m, 1 H), 1.94
– 1.85 (m, 2 H), 1.78 – 1.71 (m, 2 H), 1.66 – 1.59 (m, 1 H), 1.52 –
1.44 (m, 2 H), 1.35 – 1.22 (m, 16 H), 1.22 – 1.13 (m, 1 H), 1.13 –
1.02 (m, 2 H), 0.88 (t, J = 7.0 Hz, 3 H); 13C{1H} NMR (125 MHz,
CD3OD) δ 58.1, 47.6, 33.7, 33.1, 30.71, 30.68, 30.63, 30.5, 28.5,
27.2, 26.2, 23.7, 14.5; HRMS (EI+): m/z M+ calcd for [C16H33N]+:
239.2613, found 239.2610.
H), 4.42 (s, 2 H), 3.33 – 3.23 (m, 2 H), 2.86 – 2.73 (m, 1 H), 1.58 (m,
2 H), 1.30 – 1.11 (m, 14 H), 0.80 (t, J = 6.7 Hz, 3 H); 13C{1H} NMR
(125 MHz, CDCl3) δ 148.8, 147.4, 136.6, 129.3, 126.7, 126.6, 115.9,
112.2, 54.3, 51.4, 33.9, 32.0, 29.3, 27.3, 27.2, 24.2, 22.7, 14.2;
HRMS (EI+): m/z M+ calcd for [C23H33N]+: 323.2613, found
323.2611.
N-Heptyl-N-(3-phenylpropyl)aniline (6b). Colorless oil (153 mg,
1
99 %). H NMR (500 MHz, CDCl3) δ 7.17 (t, J = 7.4 Hz, 2 H), 7.08 (t,
2-(1H-Indol-3-yl)-N-(4-methylbenzyl)ethan-1-amine (4a). Color-
J = 7.2 Hz, 5 H), 6.52 (m, 3 H), 3.22 – 3.15 (m, 2 H), 3.15 – 3.09 (m,
2 H), 2.54 (t, J = 7.7 Hz, 2 H), 1.81 (m, 2 H), 1.52 – 1.39 (m, 2 H),
1.19 (m, 8 H), 0.80 (t, J = 6.5 Hz, 3 H); 13C{1H} NMR (125 MHz,
CDCl3) δ 148.2, 141.9, 129.3, 128.5, 128.4, 126.0, 115.5, 112.0,
51.2, 50.6, 33.5, 32.0, 29.3, 28.9, 27.4, 27.3, 22.7, 14.2; HRMS (EI+):
m/z M+ calcd for [C22H31N]+: 309.2457, found 309.2457.
N-Decyl-N-heptylaniline (6c). Colorless oil (164 mg, 99 %). 1H
NMR (500 MHz, CDCl3) δ 7.16 – 7.08 (m, 2 H), 6.54 (m, 3 H), 3.20 –
3.11 (m, 4 H), 1.50 (m, 4 H), 1.31 – 1.09 (m, 22 H), 0.81 (m, 6 H);
13C{1H} NMR (125 MHz, CDCl3) δ 148.4, 129.3, 115.2, 111.9, 51.2,
32.1, 29.8, 29.74, 29.72, 29.5, 29.4, 27.42, 27.37, 27.35, 22.8, 22.8,
14.3; HRMS (EI+): m/z M+ calcd for [C23H41N]+: 331.3239, found
331.3237.
9
1
less oil (121 mg, 92 %). H NMR (500 MHz, CD3OD) δ 7.50 (d, J =
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
7.9 Hz, 1 H), 7.33 (d, J = 8.1 Hz, 1 H), 7.15 – 7.03 (m, 5 H), 6.99 (m,
2 H), 3.68 (s, 2 H), 2.96 (t, J = 6.9 Hz, 2 H), 2.89 (t, J = 6.7 Hz, 2 H),
2.27 (s, 3 H); 13C{1H} NMR (125 MHz, CD3OD) δ 138.21, 138.16,
136.3, 130.1, 129.5, 128.6, 123.5, 122.4, 119.6, 119.3, 113.0, 112.3,
53.7, 50.0, 25.7, 21.1; HRMS (EI+): m/z M+ calcd for [C18H20N2]+:
264.1626, found 264.1629.
2-(1H-Indol-3-yl)-N-(4-methylbenzyl)ethan-1-amine (4b). White
solid (115 mg, 89 %); m.p. 166 - 168 oC. 1H NMR (400 MHz,
CD3OD) δ 7.58 (d, J = 7.9 Hz, 1 H), 7.36 (d, J = 8.1 Hz, 1 H), 7.16 (s,
1 H), 7.12 (t, J = 7.6 Hz, 1 H), 7.04 (t, J = 7.0 Hz, 1 H), 3.25 – 3.17 (m,
2 H), 3.17 – 3.09 (m, 2 H), 2.97 – 2.87 (m, 2 H), 1.70 – 1.57 (m, 2
H), 1.44 – 1.17 (m, 8 H), 0.90 (t, J = 6.8 Hz, 3 H); 13C{1H} NMR (100
MHz, CD3OD) δ 138.3, 128.2, 124.1, 122.7, 120.0, 119.0, 112.5,
110.7, 49.6, 32.8, 29.9, 27.70, 27.65, 23.8, 23.6, 14.4; HRMS (EI+):
m/z M+ calcd for [C17H26N2]+: 258.2096, found 258.2093.
1
N-Decyl-N-methylaniline (6d). Colorless oil (123 mg, 99 %). H
NMR (500 MHz, CDCl3) δ 7.15 (t, J = 8.0 Hz, 2 H), 6.61 (m, 3 H),
3.26 – 3.18 (m, 2 H), 2.85 (s, 3 H), 1.57 – 1.43 (m, 2 H), 1.31 – 1.16
(m, 14 H), 0.83 (t, J = 6.9 Hz, 3 H); 13C{1H} NMR (125 MHz, CDCl3)
δ 149.5, 129.2, 115.9, 112.2, 53.0, 38.4, 32.0, 29.8, 29.73, 29.71,
29.5, 27.3, 26.8, 22.8, 14.3; HRMS (EI+): m/z M+ calcd for
[C17H29N]+: 247.2300, found 247.2301.
N-Heptyl-N-methylaniline (6e). Colorless oil (123 mg, 99 %). 1H
NMR (500 MHz, CDCl3) δ 7.22 – 7.11 (m, 2 H), 6.62 (m, 3 H), 3.25 –
3.17 (m, 2 H), 2.85 (s, 3 H), 1.57 – 1.44 (m, 2 H), 1.25 (m, 8 H),
0.83 (t, J = 6.9 Hz, 3 H); 13C{1H} NMR (125 MHz, CDCl3) δ 149.5,
129.2, 115.9, 112.2, 53.0, 38.4, 32.0, 29.4, 27.3, 26.8, 22.8, 14.2;
HRMS (EI+): m/z M+ calcd for [C17H23N]+: 205.1830, found
205.1832.
N-(2-(1H-Indol-3-yl)ethyl)-N-heptylheptan-1-amine (4c). Color-
1
less oil (147 mg, 83 %). H NMR (500 MHz, CD3OD) δ 7.52 (d, J =
7.9 Hz, 1 H), 7.34 (d, J = 8.1 Hz, 1 H), 7.08 (m, 2 H), 7.03 – 6.97 (m,
1 H), 2.93 (m, 4 H), 2.72 – 2.60 (m, 4 H), 1.59 – 1.45 (m, 4 H), 1.32
(m, 16 H), 0.92 (t, J = 7.0 Hz, 6 H); 13C{1H} NMR (125 MHz, CD3OD)
δ 138.2, 128.6, 123.3, 122.4, 119.6, 119.1, 113.3, 112.4, 55.5, 55.0,
33.0, 30.3, 28.5, 27.0, 23.7, 22.9, 14.4; HRMS (EI+): m/z M+ calcd
for [C24H40N2]+: 356.3191, found 356.3187.
1
N-Cyclohexylaniline (2l). Colorless oil (81 mg, 93 %). H NMR
(500 MHz, CDCl3) δ 7.10 – 7.04 (m, 2 H), 6.58 (t, J = 7.3 Hz, 1 H),
6.50 (d, J = 7.7 Hz, 2 H), 3.42 (s, 1 H), 3.17 (m, 1 H), 2.03 – 1.92 (m,
2 H), 1.74 – 1.64 (m, 2 H), 1.64 – 1.52 (m, 1 H), 1.37 – 1.25 (m, 2
H), 1.20 – 0.97 (m, 4 H); 13C{1H} NMR (125 MHz, CDCl3) δ 147.5,
129.3, 116.9, 113.2, 51.8, 33.6, 26.1, 25.1; HRMS (EI+): m/z M+
calcd for [C12H17N]+: 175.1361, found 175.1363.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge
on the ACS Publications website. Additional experimental
data and copies of 1H, 13C, or 19F spectra for compounds
and HPLC chromatograms (PDF).
2-(4-Methylbenzyl)-1,2,3,4-tetrahydroisoquinoline (5b). Color-
1
less oil (116 mg, 98 %). H NMR (500 MHz, CDCl3) δ 7.18 (d, J =
7.9 Hz, 2 H), 7.03 (d, J = 7.9 Hz, 2 H), 7.01 – 6.95 (m, 3 H), 6.86 (d, J
= 7.1 Hz, 1 H), 3.52 (m, 4 H), 2.78 (t, J = 5.9 Hz, 2 H), 2.61 (t, J = 5.9
Hz, 2 H), 2.24 (s, 3 H); 13C{1H} NMR (125 MHz, CDCl3) δ 136.7,
135.4, 135.1, 134.5, 129.11, 129.05, 128.7, 126.7, 126.1, 125.6,
62.6, 56.2, 50.7, 29.3, 21.2; HRMS (EI+): m/z M+ calcd for
[C17H19N]+: 237.1517, found 237.1516.
4-(4-Methylbenzyl)morpholine (5a). Colorless oil (88 mg, 92 %).
1H NMR (500 MHz, CD3OD) δ 7.19 (d, J = 8.0 Hz, 2 H), 7.12 (d, J =
7.9 Hz, 2 H), 3.69 – 3.61 (m, 4 H), 3.44 (s, 2 H), 2.41 (d, J = 4.1 Hz, 4
H), 2.30 (s, 3 H); 13C{1H} NMR (125 MHz, CD3OD) δ 138.1, 135.0,
130.6, 129.9, 67.7, 64.1, 54.5, 21.2; HRMS (EI+): m/z M+ calcd for
[C12H17NO]+: 191.1310, found 191.1310.
1,4-bis(4-Isopropylbenzyl)piperazine (5c). White solid (156 mg,
89 %); m.p. 58 - 60 oC. 1H NMR (500 MHz, CD3OD) δ 7.21 (d, J = 8.2
Hz, 4 H), 7.17 (d, J = 8.1 Hz, 4 H), 3.48 (s, 4 H), 2.87 (m, 2 H), 2.48
(s, 8 H), 1.23 (m, 12 H); 13C{1H} NMR (125 MHz, CD3OD) δ 149.3,
135.4, 130.8, 127.3, 63.6, 53.6, 35.1, 24.4; HRMS (EI+): m/z M+
calcd for [C24H34N2]+: 350.2722, found 350.2719.
N-Benzyl-1-phenylethan-1-amine (eq2). Colorless oil (D-form 93
mg, 88 %) (L-form 92 mg, 87%)). 1H NMR (400 MHz, CD3OD) δ
7.29 – 7.06 (m, 10 H), 3.66 (q, J = 6.7 Hz, 1 H), 3.45 (m, 2 H), 1.27
(d, J = 6.7 Hz, 3 H); 13C{1H} NMR (101 MHz, CD3OD) δ 145.9, 140.8,
129.6, 129.4, 128.2, 128.1, 128.0, 58.5, 52.2, 23.8; HRMS (EI+):
m/z M+ calcd for [C15H17N]+: 211.1361, found D-form - 211.1360
L-form – 211.1362.
ACKNOWLEDGMENT
This work was supported by a National Research
Foundation of Korea (NRF) grant funded by the Korean
government (2014R1A5A1011165 and 2007-0093864).
HC is a recipient of BK21 plus Fellowship.
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