Amination of alcohols catalyzed by copper-aluminium Hydrotalcite: A green synthesis of amines

Article abstract of DOI:10.1002/ejoc.200900628

Copper-aluminium hydrotalcite (CuAl-HT)/K₂CO₃ has been employed in the activation of various benzyl alcohols with benzylamines to afford the corresponding amines in good to high yields. Experimentation showed that the reaction takes place through sequential transformations: the oxidation of alcohols into carbonyl compounds, imine formation between amines and carbonyl compounds, and then reduction of imines to amines, heterogeneously catalyzed by non-noble Cu-Al HT catalyst in a one-pot and straightforward fashion. The process was further extended to amination of alcohols with anilines, which are often resistant to alkylation reactions when substituted with strong electron-withdrawing groups.

Full text of DOI:10.1002/ejoc.200900628

FULL PAPER
DOI: 10.1002/ejoc.200900628
Amination of Alcohols Catalyzed by Copper-Aluminium Hydrotalcite:
A Green Synthesis of Amines
[a]
[a]
[a]
Pravin R. Likhar,* Racha Arundhathi, Mannepalli Lakshmi Kantam, and
Parvathaneni Sai Prathima[
a]
Keywords: Heterogeneous catalysis / Hydrotalcite / Amines / Amination / Alcohols / Anilines
Copper-aluminium hydrotalcite (CuAl-HT)/K
2
CO
3
has been
imines to amines, heterogeneously catalyzed by non-noble
Cu-Al HT catalyst in a one-pot and straightforward fashion.
The process was further extended to amination of alcohols
with anilines, which are often resistant to alkylation reactions
when substituted with strong electron-withdrawing groups.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
employed in the activation of various benzyl alcohols with
benzylamines to afford the corresponding amines in good to
high yields. Experimentation showed that the reaction takes
place through sequential transformations: the oxidation of
alcohols into carbonyl compounds, imine formation between
amines and carbonyl compounds, and then reduction of Germany, 2009)
Introduction
mediate that readily react with amines to form imine or
iminium species and then reduce to amines with concomi-
tant formation of water (Scheme 1).
Formation of carbon–nitrogen bonds is of broad interest
to synthetic organic chemists because nitrogen-containing
compounds, particularly amines and their derivatives, are
versatile building blocks for various organic molecules and
precursors to a variety of biologically active com-
[
1–4]
pounds.
Scheme 1. Catalytic amination of alcohols with amines.
With this growing repertoire of applications, the develop-
ment of efficient methods for the synthesis of amines con-
tinues to be a challenging and active area of research. The
usual synthetic methods for the synthesis of amines are
Several catalytic systems for the amination of alcohols
have been studied for this oxidation/imination/reduction se-
[21]
[22–39]
[40]
quence,
num,
based on ruthenium,
rhodium,
plati-
[5–7]
amination of aryl/alkyl halides
and reductive amination
However, these methods have
[41]
[42,43]
and iridium catalysts
under homogeneous
of carbonyl compounds.[
8–11]
conditions. Although the reported catalysts are active for
this reaction, they are significantly more expensive and non-
recoverable. Furthermore, most of the reactions are restric-
ted to the use of primary alcohols at very high reaction
temperatures.
The development of heterogeneous catalysts for the syn-
thesis of fine chemicals has become a major area of re-
search, because the potential advantages of these materials
some drawbacks, such as the need for activation of aryl/
alkyl halides, the toxicities of the alkylating agents, and the
use of strong reducing reagents, which are undesirable from
an environmental point of view. Alternatively, in recent
[
12–16]
years a number of reports on the hydroamination
or
for the
hydroamino-methylation of olefins or alkynes[
synthesis of amines have appeared.
17–20]
The catalytic amination of alcohols is an atom-economi-
cal and environmentally attractive method for the synthesis
of amines, thanks to the ubiquitous availability of alcohols.
One of the attractive features of this method is the replace-
ment of aryl/alkyl halides by alcohols as alkylating agents;
these undergo loss of hydrogen to provide carbonyl inter-
(
simplified recovery and reusability, the potential for incor-
poration in continuous reactors and microreactors) over
homogeneous systems could have major positive environ-
mental consequences.
systems have recently been employed for the amination of
[44,45]
In this context, heterogeneous
[46,47]
alcohols.
In our earlier study we reported the preparation of recy-
clable heterogeneous Cu-exchanged fluoroapatite and tert-
butoxyapatite catalysts, through the incorporation of the
[
a] Inorganic and Physical Chemistry Division, Indian Institution
of Chemical Technology,
–
–
Uppal Road, Tarnaka Hyderabad 500670, India
Fax: +91-40-27160921
basic species F /tBuO in apatite in situ by co-precipitation
II
and subsequent exchange with Cu for the N-arylation of
E-mail: plikhar@iict.res.in
imidazoles and other heterocycles with chloroarenes and
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.200900628.
[
48,49]
fluoroarenes, with good to excellent yields,
together
5383
Eur. J. Org. Chem. 2009, 5383–5389
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

P. R. Likhar, R. Arundhathi, M. L. Kantam, P. S. Prathima
FULL PAPER
with the CuAl-HT-catalyzed[50] (CuAl-HT: copper-alumin- served that electron-donating substituents facilitated the
ium hydrotalcite) amination of aryl chlorides with benzyl- amination reaction, to afford excellent yields (Table 2, En-
amines and cycloalkylamines.[
51,52]
Here we report a practi- tries 1 and 2), whereas lower yields were obtained with elec-
cal and atom-economic synthesis of secondary and tertiary tron-withdrawing substituents (Table 2, Entries 3–6). The
amines by amination of alcohols (primary and secondary ortho-substituted benzyl alcohols gave lower yields than the
alcohols) with the aid of copper-aluminium hydrotalcite as para-substituted benzyl alcohols because of steric hindrance
a catalyst in the presence of base under solvent-free condi- at the ortho-position (Table 2, Entries 4 and 6). In the case
tions.
of amination of benzyl alcohol with benzylamine, the de-
sired coupling product, dibenzylamine, was isolated in 72%
yield at a relatively low temperature after 14 h (Table 2, En-
try 7). Long-chain (C7, C8, and C12) aliphatic alcohols
were also aminated with benzylamine and it was observed
that the yields of the products decreased with increasing
carbon chain length (Table 2, Entries 8–10). Further, at-
Results and Discussion
Initially we studied the amination of p-methoxybenzyl
alcohol with benzylamine in the presence of CuAl-HT and
base. Subsequent work was focused on the optimization of
this reaction in terms of various reaction parameters such
as base, temperature, and time (see the Supporting Infor-
mation for optimization conditions). Of the various bases Table 2. Amination of substituted benzyl alcohols and aliphatic
screened for this reaction, K CO gave the best results. We alcohols with benzylamine.[
a]
2
3
also studied the catalytic activities of the various copper
catalysts under the optimized reaction conditions, and the
results are summarized in Table 1. It was observed that Cu-
(
HAP) and Cu(FAP) catalysts, which have been shown to
[46]
be highly active in N-arylation of imidazoles,
were inef-
fective for this reaction. Out of the CuAl-HT catalysts with
different Cu/Al ratios (Cu/Al-HT1 3:1), (Cu/Al-HT2 2.5:1)
and (Cu/Al-HT3 2:1), Cu/Al-HT2 catalyst was found to be
the most effective catalyst for the amination of p-meth-
oxybenzyl alcohol with benzylamine.
Table 1. Screening of various copper catalysts for amination of p-
methoxybenzyl alcohol with benzylamine.[
a]
[
4
4
a] Reaction conditions: p-methoxybenzyl alcohol (0.6 g,
.62 mmol), benzylamine (0.76 mL, 6.93 mmol), catalyst (Cu,
.0 mol-%), K CO (0.8 g, 5.8 mmol), 160 °C, 9 h, under air. De-
2
3
[
(
5
a] Reaction conditions: alcohols (4.62 mmol), benzylamine
0.76 mL, 6.93 mmol), catalyst (Cu, 4.0 mol-%), K CO (0.8 g,
.8 mmol), 160 °C, 9 h, under air. [b] All products were charac-
grees of conversion are based on alcohol. [b] Isolated yield.
2
3
Various benzyl and aliphatic alcohols were allowed to
react with benzylamine under optimized conditions; the re-
terized by NMR and mass spectroscopy (see the Supporting Infor-
mation). [c] Isolated yield. [d] Yield after fifth cycle. [e] Reaction
sults are summarized in Table 2, from which it can be ob- temperature 150 °C and reaction time 14 h under air.
5
384 Eur. J. Org. Chem. 2009, 5383–5389
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

A Green Synthesis of Amines
tempted amination of aliphatic secondary alcohols (open- amination of alcohols is usually unsuccessful, especially
chain or cyclic) with benzylamine resulted in no product with anilines possessing strongly electron-withdrawing
formation (Table 2, Entries 11 and 12), but the reaction be- groups (p-nitroaniline), which are often resistant to alky-
tween benzhydrol and benzylamine proceeded well to afford lation reactions. We were delighted to observe that the
the corresponding secondary amine in excellent yields CuAl-HT2/K CO combination was successful for the for-
2
3
(
Table 2, Entry 13). It is clear from the results that this cata- mation of a range of N-phenylamines (Table 4, Entries 1–9).
lyst system is better suited for arylalkyl secondary alcohols All the catalytic reactions were attempted under the same
rather than simple aliphatic secondary alcohols. optimal reaction conditions to allow observation of the ef-
We also examined the amination of benzyl alcohols with fects of steric and electronic parameters. The electron-rich
primary and secondary amines, benzylamines, and long- 4-methoxyaniline and 3,5-dimethoxyaniline gave excellent
chain aliphatic amines. The results are summarized in yields (Table 4, Entries 2 and 3), whereas anilines with elec-
Table 3, from which it can be seen that benzylamines con- tron-withdrawing substituents (Table 4, Entries 4–9) were
taining either electron-donating groups (Table 3, Entry 1) N-alkylated in yields ranging from moderate to excellent.
or electron-withdrawing groups (Table 3, Entry 2) displayed The ortho-substituted anilines gave lower yields than their
similar reactivity patterns, thus implying that the electronic para-substituted counterparts (Table 4, Entries 6 vs. 7 and
nature of the substituent on benzylamine does not have any 8 vs. 9), which might be due to the steric hindrance of the
noticeable influence on the reaction. Amination of benzyl substituent at the ortho-position.
alcohol with decylamine also afforded the corresponding
aminated product but in diminished yields (Table 3, En-
try 4). When the secondary amine dibenzylamine was em-
ployed in the reaction, tribenzylamine was obtained in ex-
cellent yields (Table 3, Entry 5) within 5 h.
Table 4. Amination of benzyl alcohols with anilines.[a]
Table 3. Amination of benzyl alcohols with various amines.[a]
[
(
1
a] Reaction conditions: benzyl alcohol (0.5 g, 4.62 mmol), amines
6.93 mmol), catalyst (Cu, 4.0 mol-%), K CO (0.8 g, 5.8 mmol),
60 °C, 9 h, under air. [b] Isolated yield. [c] Reaction time 5 h.
2
3
[
(
1
a] Reaction conditions: benzyl alcohol (0.5 g, 4.62 mmol), anilines
6.93 mmol), catalyst (Cu, 4.0 mol-%), K CO (0.8 g, 5.8 mmol),
60 °C, 9 h, under air. [b] All products are characterized by NMR
and mass spectroscopy (see the Supporting Information). [c] Iso-
Later, we successfully extended the scope of the method-
ology by using anilines as coupling partners under similar
reaction conditions, to produce amines useful in the fine
2
3
chemicals industries (Table 4). The use of anilines in the lated yield. [d] Yield after fifth cycle.
Eur. J. Org. Chem. 2009, 5383–5389
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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5385

P. R. Likhar, R. Arundhathi, M. L. Kantam, P. S. Prathima
Further, to verify the role of CuAl-HT in the reduction
FULL PAPER
Although this methodology requires relatively high reac-
tion temperatures and excesses of amines, it offers several of imines to amines, we conducted a separate reaction be-
advantages such as the use of the cheap heterogeneous cata- tween PAA and BA at 160 °C in the presence of CuAl-HT2
lyst Cu-Al hydrotalcite in place of expensive and non-recov- with monitoring for 9 h. We observed no formation of the
erable homogeneous catalysts, its applicability for a wide N-alkylated amine during the course of the reaction. From
range of alcohols in combination with benzyl and aromatic this study, it is clear that the reaction proceeds through an
[
21]
amines, and the easy separation and recovery of the cata- oxidation/imination/reduction sequence with in situ gen-
lyst. eration of metal hydride species and their subsequent par-
In order to examine the role of base in the aminations of ticipation in reduction of imine, which indicated no net hy-
the alcohols, we performed the reactions in the absence of drogen loss or gain at the end of the catalytic cycle. This
base and no products were observed. We thus speculated was further confirmed by an X-ray photoelectron spectro-
II
that the oxidation step may possibly proceed through the scopic study (see Figure 2, XPS spectra for Cu ) in which
formation of an alkoxide by the abstraction of a proton the XPS spectra for the fresh CuAl-HT2 and for the reco-
from the alcohol in the presence of base and binding to the vered catalyst each show a 2p peak at 936.3 eV correspond-
II
copper atom in the hydrotalcite. The copper alkoxide could ing to Cu in the +2 oxidation state (no reduction of Cu
be transformed into the aldehyde through β-hydride elimi- was observed).
nation, which could result in the concomitant formation of
mono(hydrido)copper. The condensation of the aldehyde
with the amine could result in the imine, which could be
reduced by the mono(hydrido)copper[
53,54]
to form an
(amido)copper species. Ligand exchange between the cop-
per amide and the alcoholic substrate (or alkoxide) could
afford the desired amination product. To obtain an insight
into the reaction pathway, we monitored the amination of
p-methoxybenzyl alcohol (PMBA) with benzylamine (BA)
in the presence of CuAl-HT2 and K CO at 160 °C for 9 h
2
3
by GC analysis and plotted the assessment of reactant and
product over time. As shown in Figure 1, in the first part
of the reaction, p-anisaldehyde (PAA) was rapidly generated
from the copper alkoxide with a subsequent β-hydride eli-
mination process. The formation of PAA was at its maxi-
mum at 2 h. Subsequently, the yield of PAA decreased, and
the yield of N-alkylated product increased.
Figure 2. High-resolution XPS narrow scans of Cu 2p for (a) fresh
CuAl-HT2, and (b) recovered catalyst after the 5 cycle.
th
The CuAl-HT2 catalyst was readily separated from the
reaction mixture by simple filtration. The recovered cata-
lyst, after washing with acetone followed by drying at 65 °C,
was used in the next run and consistent activity was ob-
served (Table 4, Entry 9, first cycle 98%; fifth cycle 97%).
In order to examine whether CuAl-HT2-catalyzed amin-
ation of alcohols with amines is heterogeneous, we termin-
ated the reaction between o-nitroaniline and benzyl alcohol
after 45 min at 20% conversion and the catalyst was filtered
hot. The reaction was continued with the filtrate for 9 h and
no change in the conversion of o-nitroaniline was observed.
Further, the filtrate was tested by AAS analysis for metal
content and no copper was found in the filtrate.
We also studied the XRD patterns of fresh CuAl-HT2
catalyst and of recovered catalyst from the fifth reaction
cycle (see the Supporting Information), which suggested
that there is no difference between the XRD patterns of
the fresh catalyst and of the recovered catalyst. This study
illustrates that the catalyst is very robust and efficient and
works purely heterogeneously.
Figure 1. PAA and N-alkylated product over time in the CuAl-
HT2/K CO -catalyzed amination of PMBA with BA (160 °C, 9 h).
2 3
However, we could not detect the imine species, the con-
densation product of PAA and BA, during the course of
the reaction. The sequential conversion of PMBA into PAA
and the formation of the product was almost constant in
the second part of the reaction. The above observation
clearly suggests the possible intermediacy of the aldehyde
derived from the alcohol in the N-alkylation reaction. In-
deed, in a separate experiment, using only PMBA in the
presence of catalyst and base at 160 °C for 2.5 h, we ob-
tained PAA in 98% isolated yield.
Conclusions
In conclusion, we have developed an efficient and inex-
pensive CuAl-HT2/K CO3 catalyst system for the amin-
2
5386
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Eur. J. Org. Chem. 2009, 5383–5389

A Green Synthesis of Amines
3
ation of various alcohols. The catalyst system shows excel- CDCl ): δ = 7.35–7.20 (m, 5 H), 6.81–6.71 (m, 3 H), 3.87 (s, 4 H),
1
3
3
.72 (s, 6 H), 2.20 (br. s, 1 H) ppm. C NMR (75 MHz, CDCl
3
):
lent selectivity and good to high yields in the amination of
benzyl alcohols with aliphatic/aromatic amines, including
anilines, to provide the corresponding amines. Moreover,
the catalyst can be easily separated by simple filtration and
reused for several cycles with consistent activity.
δ = 154.0, 153.8, 128.4, 127.9, 126.9, 123.8, 114.8, 114.4, 113.5,
+
5
(
5
7.9, 57.7, 57.5, 50.3 ppm. EI-MS: m/z = 257 [M] . C16
257.33): calcd. C 74.68, H 7.44, N 5.44; found C 75.05, H 7.45, N
.42.
H19NO
2
Benzyl(4-nitrobenzyl)amine: See Table 2, Entry 3; yellow solid
0.7490 g, 3.0954 mmol, 67%); m.p. 246–249 °C.
1
(
H NMR
(
300 MHz, CDCl ): δ = 8.15 (d, J = 8.4 Hz, 2 H), 7.41–7.20 (m, 5
3
Experimental Section
H), 6.61 (d, J = 8.4 Hz, 2 H), 4.75 (br. s, 1 H), 4.41 (s, 4 H) ppm.
1
3
General: All chemicals were purchased from Aldrich and were used
as received. All solvents used were of analytical grade and were
used as received from Merck India Pvt. Ltd. X-ray powder diffrac-
tion (XRD) data were collected with a Simens/D-5000 dif-
C NMR (75 MHz, CDCl
3
): δ = 148.2, 144.0, 137.5, 129.0, 128.4,
+
128.1, 123.6, 56.1 ppm. EI-MS: m/z = 242 [M] . C14
(242.28): calcd. C 69.41, H 5.82, N 11.56; found C 70.01, H 6.00,
N 11.61.
14 2 2
H N O
fractometer with use of Cu-K
corded with a Kratos AXIS 165 apparatus with a dual anode (Mg
and Al) with use of the Mg K anode. The pressure in the spectrom-
eter was about 10–9 Torr. For energy calibration we used the carbon
s photoelectron line. The carbon 1s binding energy was taken to
α
radiation. XPS spectra were re-
Benzyl(2-nitrobenzyl)amine: See Table 2, Entry 4; yellow solid
1
(
0.3913 g, 1.617 mmol, 35%). H NMR (300 MHz, CDCl
3
): δ =
α
8
7
.35 (br. s, 1 H), 8.15 (dd, J = 10.19, 8.7 Hz, 1 H), 7.72 (t, J = 8.7,
.9 Hz, 1 H), 7.57 (d, J = 8.8 Hz, 1 H), 7.44–7.36 (m, 6 H), 4.50
1
13
(
s, 4 H) ppm. C NMR (75 MHz, CDCl
3
): δ = 148.2, 137.2, 134.6,
be 285.0 eV. Spectra were deconvoluted with the aid of the Sun
Solaris-based Vision 2 curve resolver. The location and the full
width at half maximum (FWHM) for a species were first deter-
mined from the spectrum of a pure sample, and the locations and
FWHMs of the products not obtained as pure species were ad-
justed until the best fits were obtained. Symmetric Gaussian shapes
were used in all cases. The Cu/Al ratio was determined by Induc-
tively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES).
GC analysis was performed with a Shimadzu GC-2010 instrument
and a ZB-5 capillary column. 1H and C spectra were recorded
1
32.4, 129.0, 128.4, 128.1, 127.8, 127.3, 123.1, 57.0, 46.4 ppm. EI-
H N O (242.28): calcd. C 69.41, H
14 2 2
.82, N 11.56; found C 68.99, H 5.79, N 11.54.
+
MS: m/z = 243 [M + H] . C14
5
Benzyl(4-chlorobenzyl)amine: See Table 2, Entry 5; colorless liquid
1
(0.8449 g, 3.6498 mmol, 79%). H NMR (300 MHz, CDCl
7.29–7.21 (m, 4 H), 7.19–6.98 (m, 5 H), 3.73 (s, 4 H) ppm.
NMR (75 MHz, CDCl ): δ = 137.3, 135.2, 132.0, 131.3, 128.7,
128.4, 128.1, 126.8, 55.6 ppm. EI-MS: m/z = 232 [M] . C14
(231.72): calcd. C 72.57, H 6.09, N 6.04; found C 72.67, H 5.92, N
5.99.
3
): δ =
1
3
C
3
+
H
14ClN
13
1
13
with a Bruker Avance 300 (300 MHz H and C) spectrometer at
1
13
room temperature with respect to TMS and CDCl
3
for H and
C
Benzyl(2-chlorobenzyl)amine: See Table 2, Entry 6; pale yellow li-
quid (0.3422 g, 1.4784 mmol, 32%). H NMR (300 MHz, CDCl
δ = 8.25–8.15 (m, 2 H), 7.61–7.50 (m, 7 H), 4.95 (d, J = 5.7 Hz, 2
H) ppm. C NMR (75 MHz, CDCl
NMRs, respectively. Chemical shifts are reported in ppm relative
1
3
):
1
3 3
to residual CHCl or to CDCl (δ = 7.28 ppm for H; δ = 77.0 ppm
for 13C). Coupling constants (J) are reported in Hertz. The copper-
aluminium hydrotalcite catalysts CuAl-HT1, CuAl-HT2, and
CuAl-HT3 were prepared by the literature procedure.[
13
3
): δ = 137.8, 136.9, 134.0,
129.4, 128.8, 128.4, 128.1, 126.9, 57.3, 46.4 ppm. EI-MS: m/z = 232
48]
+
[M] . C14H14ClN (231.72): calcd. C 75.57, H 6.09, N 6.04; found
General Procedure for the Amination of Alcohols with Amines: Ben- C 75.90, H 6.05, N 6.05.
zylamine (0.76 mL, 6.93 mmol), p-methoxybenzyl alcohol (0.6 g,
Dibenzylamine: See Table 2, Entry 7; colorless liquid (0.8919 g,
4
.62 mmol), Cu/Al-HT2 (4 mol-%), and K
2
CO
3
(0.8 g, 5.8 mmol)
1
4
1
1
.53 mmol, 72%). H NMR (300 MHz, CDCl
0 H), 3.73 (s, 4 H) ppm. C NMR (75 MHz, CDCl ): δ = 128.4,
28.2, 127.0, 53.0 ppm. GC-MS: m/z = 197 [M] . C14H N
15
3
): δ = 6.12–5.90 (m,
were placed in a 50 mL round-bottomed flask containing a Teflon-
coated magnetic stirring bead and introduced into a pre-heated oil
bath at 160 °C. The mixture was stirred for 9 h. The progress of
the reaction was monitored by TLC, and on completion of the
reaction the reaction mixture was centrifuged to separate the cata-
lyst, the solid residue was washed with EtOAc (1ϫ5 mL) to make
the catalyst free of organic matter, and the reaction mixture was
diluted with water (20 mL) and then extracted with EtOAc
13
3
+
(
7
197.28): calcd. C 85.24, H 7.66, N 7.10; found C 85.12, H 7.75, N
.12.
N-Benzylheptan-1-amine: See Table 2, Entry 8; colorless liquid
1
(0.8904 g, 4.0656 mmol, 88%). H NMR (300 MHz, CDCl
3
): δ =
7.43–6.67 (m, 5 H), 3.52–3.40 (m, 2 H), 3.85 (s, 4 H), 2.84 (br. s, 2
3ϫ10 mL). The combined organic layers were washed with brine H), 1.36–1.16 (m, 10 H), 0.88 (t, J = 6.8 Hz, 3 H) ppm. 1 C NMR
3
(
(
10 mL) and dried with anhydrous Na
2
SO
4
. The solvent was evapo-
(75 MHz, CDCl
3
): δ = 137.8, 128.1, 127.2, 126.6, 54.5, 42.0, 32.9,
+
rated under reduced pressure to yield the crude product. This was
31.6, 29.1, 26.6, 22.5, 13.9 ppm. EI-MS: m/z = 206 [M] . C14H N
23
then purified by flash chromatography over silica gel (100–
(205.34): calcd. C 81.89, H 11.29, N 6.82; found C 81.60, H 11.25,
N 6.85.
200 mesh) with hexane/ethyl acetate (98:2 v/v) as eluent to afford
the pure product.
N-Benzyloctan-1-amine: See Table 2, Entry 9; colorless liquid
1
Benzyl(4-methoxybenzyl)amine: See Table 2, Entry 1; yellow solid
(0.7643 g, 3.2802 mmol, 71%). H NMR (300 MHz, CDCl
3
): δ =
1
(
(
3
1
0.9648 g, 4.2504 mmol, 92%); m.p. 192–194 °C.
300 MHz, CDCl
H
NMR 7.50–6.80 (m, 5 H), 3.47 (d, J = 5.6 Hz, 2 H), 2.80 (br. s, 1 H),
): δ = 7.61–7.10 (m, 9 H), 3.85 (s, 4 H), 3.76 (s, 1.55–1.36 (m, 2 H), 1.35–1.14 (m, 12 H), 0.88 (t, J = 6.8 Hz, 3
3
H), 1.75 (br. s, 1 H) ppm. 13C NMR (75 MHz, CDCl
): δ = 160.1,
13
H) ppm. C NMR (75 MHz, CDCl
3
): δ = 140.8, 128.2, 127.2,
3
39.6, 130.2, 128.8, 128.7, 128.5, 126.8, 57.9, 57.1 ppm. GC-MS:
126.7, 54.5, 41.4, 32.9, 31.6, 29.9, 26.6, 22.5, 13.9 ppm. EI-MS: m/z
+
+
m/z = 228 [M + H] . C15
H
17NO (227.31): calcd. C 79.26, H 7.54,
= 219 [M] . C15H25N (219.37): calcd. C 82.13, H 11.49, N 6.39;
N 6.16; found C 79.29, H 7.55, N 6.20.
found C 82.09, H 11.33, N 6.38.
Benzyl(2,5-dimethoxybenzyl)amine: See Table 2, Entry 2; yellow
semisolid (0.9854 g, 3.835 mmol, 83%). H NMR (300 MHz, (0.8258 g, 3.003 mmol, 65%). H NMR (300 MHz, CDCl
N-Benzyldodecan-1-amine: See Table 2, Entry 10; colorless liquid
1
1
3
): δ =
Eur. J. Org. Chem. 2009, 5383–5389
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5387

P. R. Likhar, R. Arundhathi, M. L. Kantam, P. S. Prathima
FULL PAPER
7
1
.40–7.08 (m, 5 H), 3.49 (d, J = 5.7 Hz, 2 H), 3.05 (br. s, 1 H), 13C NMR (75 MHz, CDCl
3
): δ = 170.3, 153.1, 138.2, 137.3, 130.2,
.68–1.48 (m, 2 H), 1.40–1.20 (m, 20 H), 0.90 (t, J = 6.0 Hz, 3 128.9, 127.2, 126.3, 117.4, 111.2, 47.5 ppm. EI-MS: m/z = 228 [M
13
+
H) ppm. C NMR (75 MHz, CDCl
3
): δ = 140.7, 128.1, 127.1,
2
+ H] . C14H13NO (227.26): calcd. C 73.99, H 5.77, N 6.16; found
1
26.7, 54.4, 42.4, 32.3, 31.7, 29.4, 29.2, 29.1, 25.5, 13.9 ppm. EI-
H33N (275.48): calcd. C 82.84, H
2.07, N 5.08; found C 82.73, H 12.11, N 4.94.
C 74.00, H 5.55, N 6.20.
+
MS: m/z = 276 [M + H] . C19
1
Benzyl(4-chlorophenyl)amine: See Table 4, Entry 5; light yellow li-
quid (0.8742 g, 4.0197 mmol, 87%). H NMR (300 MHz, CDCl
1
3
):
N-Benzyldiphenylmethanamine: See Table 2, Entry 13; yellow solid
δ = 8.10 (br. s, 1 H), 7.41–7.34 (m, 5 H), 6.62 (d, J = 8.4 Hz, 2 H),
1
13
(
7
1.0972 g, 4.0914 mmol, 87%). H NMR (300 MHz, CDCl
3
): δ = 6.32 (d, J = 8.4 Hz, 2 H), 3.45 (s, 2 H) ppm. C NMR (75 MHz,
.35–7.10 (m, 15 H), 5.65 (s, 1 H), 3.75 (s, 2 H) ppm. 1 C NMR
3
CDCl ): δ = 144.4, 140.4, 128.4, 127.8, 126.8, 122.5, 116.1,
3
+
(
4
75 MHz, CDCl
5.8 ppm. EI-MS: m/z = 273 [M] . C20
3
): δ = 143.7, 140.6, 128.2, 127.2, 126.8, 126.4, 64.6,
45.8 ppm. EI-MS: m/z = 218 [M + H] . C H ClN (217.70): calcd.
1
3
12
+
H
19N (273.38): calcd. C
C 71.72, H 5.56, N 6.43; found C 71.80, H 5. 55, N 6.39.
8
7.87, H 7.01, N 5.12; found C 87.84, H 6.98, N 4.99.
2
-(Benzylamino)benzonitrile: See Table 4, Entry 6; white solid
1
N-Benzyl-2-phenylethanamine: See Table 3, Entry 3; colorless liquid
0.7117 g, 3.373 mmol, 73%). 1H NMR (300 MHz, CDCl
): δ = 8.10 (br. s, 1 H), 7.7 (d, J = 8.5 Hz, 1 H), 7.40–7.20 (m, 7 H), 6.66
.33–7.12 (m, 10 H), 4.45 (s, 2 H), 2.85 (s, 2 H), 2.55 (s, 2 H) ppm.
3
(0.3939 g, 1.8942 mmol, 41%). H NMR (300 MHz, CDCl ): δ =
(
7
3
1
3
(d, J = 8.5 Hz, 1 H), 4.40 (s, 2 H) ppm. C NMR (75 MHz,
3
): δ = 140.5, 138.2, 128.5, 127.9, 126.9, CDCl ): δ = 148.2, 147.1, 134.0, 133.1, 128.5, 126.9, 117.4, 116.3,
1
3
C NMR (75 MHz, CDCl
26.5, 125.8, 54.0, 48.8, 38.5 ppm. EI-MS: m/z = 211 [M] .
17N (211.31): calcd. C 85.26, H 8.11, N 6.63; found C 85.37,
3
+
+
1
C
14 12 2
113.9, 95.4, 43.8 ppm. GC-MS: m/z = 208 [M] . C H N (208.26):
calcd. C 80.74, H 5.81, N 13.45; found C 81.02, H 5.85, N 14.20.
15
H
H 8.99, N 6.56.
4
-(Benzylamino)benzonitrile: See Table 4, Entry 7): Yellow solid
1
N-Benzyldecan-1-amine: See Table 3, Entry 4; colorless liquid
(0.6631 g, 3.187 mmol, 69%); m.p. 80 °C. H NMR (300 MHz,
1
(0.7430 g, 3.003 mmol, 65%). H NMR (300 MHz, CDCl
3
): δ = CDCl ): δ = 8.32 (d, J = 8.4 Hz, 2 H), 7.36–7.28 (m, 5 H), 6.53 (d,
3
1
3
7
1
.23 (d, J = 9.8 Hz, 2 H), 7.15–7.10 (m, 3 H), 3.91 (s, 2 H), 1.40– J = 8.4 Hz, 2 H), 4.85 (s, 2 H) ppm. C NMR (75 MHz, CDCl3):
.21 (m, 16 H), 0.90 (t, J = 6.8, 6.0 Hz, 3 H) ppm. 1 C NMR δ = 148.2, 143.7, 133.1, 129.0, 126.9, 126.0, 117.0, 113.9, 99.9,
3
+
(75 MHz, CDCl
3
): δ = 138.6, 130.8, 130.5, 127.1, 55.8, 50.9, 33.8,
45.8 ppm. GC-MS: m/z = 209 [M + H] . C H N (208.26): calcd.
C 80.74, H 5.81, N 13.45; found C 81.72, H 5.88, N 13.90.
1
4
12
2
+
32.7, 31.0, 30.9, 29.3, 24.7, 14.3 ppm. EI-MS: m/z = 247 [M] .
17
C H
29N (247.42): calcd. C 82.52, H 11.81, N 5.66; found C 82.63,
H 12.11, N 5.69.
Benzyl(2-nitrophenyl)amine: See Table 4, Entry 8; orange crystalline
solid (0.7374 g, 3.234 mmol, 70%); m.p. 76–78 °C. H NMR
1
Tribenzylamine: See Table 3, Entry 5; white crystalline solid
(300 MHz, CDCl ): δ = 8.46 (br. s, 1 H), 8.21 (dd, J = 8.3, 1.5 Hz,
3
1
(1.2994 g, 4.5276 mmol, 98%); m.p. 92–93 °C. H NMR (300 MHz,
1 H), 7.42–7.31 (m, 6 H), 6.80 (d, J = 8.3 Hz, 1 H), 6.68 (t, J =
1
3
3
CDCl ): δ = 7.36 (d, J = 7.6 Hz, 6 H), 7.27 (t, J = 7.6, 6.8 Hz, 6 7.6 Hz, 1 H), 4.57 (d, J = 6.0 Hz, 2 H) ppm. C NMR (75 MHz,
13
H), 7.17 (t, J = 7.6, 6.8 Hz, 3 H), 3.55 (s, 6 H) ppm. C NMR CDCl ): δ = 145.2, 137.3, 136.2, 128.9, 127.6, 127.0, 125.1, 116.3,
3
+
(
75 MHz, CDCl
MS: m/z = 288 [M + H] . C21
.36, N 4.87; found C 87.77, H 7.39, N 4.76.
3
): δ = 139.6, 128.7, 128.1, 126.8, 57.8 ppm. GC-
114.1, 47.0 ppm. EI-MS: m/z = 228 [M] . C H N O (228.25):
1
3
12
2
2
+
H
21N (287.40): calcd. C 87.76, H
calcd. C 68.41, H 5.30, N 12.27; found C 68.59, H 5.25, N 12.25.
7
Benzyl(4-nitrophenyl)amine: See Table 4, Entry 9; orange solid
1
N-Benzylbenzenamine: See Table 4, Entry 1; colorless liquid
(1.0323 g, 4.5276 mmol, 98%); m.p. 146–148 °C.
H NMR
1
(
0.7693 g, 4.2042 mmol, 91%). H NMR (300 MHz, CDCl
3
): δ = (300 MHz, CDCl ): δ = 8.17 (dd, J = 9.8, 8.3 Hz, 2 H), 8.12 (br.
3
7
4
1
.49–7.35 (m, 5 H), 6.85–6.70 (m, 5 H), 4.50 (d, J = 5.6 Hz, 2 H), d, J = 6.8 Hz, 1 H), 7.38 (t, J = 8.3, 7.6 Hz, 2 H), 6.85 (d, J =
.00 (br. s, 1 H) ppm. 13C NMR (75 MHz, CDCl
13
3
): δ = 145.7, 9.1 Hz, 2 H), 6.60 (t, J = 8.3, 7.6 Hz, 3 H), 3.55 (s, 2 H) ppm.
C
40.6, 128.6, 127.7, 126.6, 126.3, 117.9, 114.8, 53.7 ppm. EI-MS:
NMR (75 MHz, CDCl ): δ = 156.4, 145.2, 136.2, 128.9, 127.7,
3
+
+
m/z = 183 [M] . C13
H
13N (183.25): calcd. C 85.21, H 7.15, N 7.64;
127.0, 122.5, 114.1, 47.1 ppm. GC-MS: m/z
=
228 [M] .
found C 85.07, H 7.19, N 7.55.
13 12 2 2
C H N O (228.25): calcd. C 68.41, H 5.30, N 12.27; found C
6
8.30, H 5.25, N 12.25.
Benzyl(4-methoxyphenyl)amine: See Table 4, Entry 2; pale yellow
solid (0.9545 g, 4.4814 mmol, 97%); m.p. 48–50 °C. H NMR
1
Supporting Information (see also the footnote on the first page of
(
300 MHz, CDCl
3
): δ = 7.35 (d, J = 7.9 Hz, 2 H), 6.88–6.76 (m, 5
this article): General remarks, preparation of catalysts, experimen-
1
H), 6.56 (d, J = 7.9 Hz, 2 H), 4.22 (d, J = 5.6 Hz, 2 H), 4.0 (br. s, tal procedures, optimization of reaction conditions, H NMR and
1
1
H), 3.75 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl
41.5, 135.8, 128.4, 126.9, 126.4, 114.4, 113.9, 56.9, 56.5 ppm. GC- cyclability chart, GC spectra for the sequential formation of p-anis-
13
3
): δ = 148.1,
C NMR, XRD spectra of fresh and reused catalyst, catalyst re-
+
MS: m/z = 214 [M + H] . C14
H15NO (213.28): calcd. C 78.84, H aldehyde and benzyl(4-methoxybenzyl)amine in the amination of
7.09, N 6.57; found C 79.19, H 7.05, N 6.60.
p-methoxybenzyl alcohol with benzylamine, references.
Benzyl(3,5-dimethoxyphenyl)amine: See Table 4, Entry 3; yellow li-
1
3
quid (1.1002 g, 4.5276 mmol, 98%). H NMR (300 MHz, CDCl ):
Acknowledgments
δ = 6.85–6.60 (m, 5 H), 5.51–5.24 (m, 3 H), 4.15 (d, J = 5.6 Hz, 2
H), 4.00 (br. s, 1 H), 3.75 (s, 6 H) ppm. 13C NMR (75 MHz,
R. A. wishes to thank the Department of Science and Technology
CDCl
7.0, 56.1 ppm. GC-MS: m/z = 243 [M] . C15
calcd. C 74.05, H 7.04, N 5.76; found C 74.19, H 7.05, N 6.01.
3
): δ = 165.1, 145.1, 143.3, 127.9, 126.9, 126.5, 90.1, 87.7,
(
DST), India (GAP-0152) for a research fellowship.
+
5
2
H17NO (243.30):
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Received: June 9, 2009
Published Online: September 22, 2009
Eur. J. Org. Chem. 2009, 5383–5389
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5389