Sulfonic acid supported on hydroxyapatite-encapsulated-γ-Fe 2O3 nanocrystallites as a magnetically separable catalyst for one-pot reductive amination of carbonyl compounds

Article abstract of DOI:10.1039/c1gc15470b

A novel, environmentally friendly procedure has been developed for the preparation of secondary or tertiary amines by one-pot reductive amination of carbonyl compounds using sodium borohydride in the presence of a magnetically recoverable sulfonic acid supported on hydroxyapatite-encapsulated-γ- Fe₂O₃ [γ-Fe₂O₃@HAP-SO ₃H] at room temperature. The catalyst was easily separated from the reaction mixture by applying an external magnet and reused for six cycles without significant loss of catalytic activity.

Full text of DOI:10.1039/c1gc15470b

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PAPER
Sulfonic acid supported on hydroxyapatite-encapsulated-c-Fe2O3
nanocrystallites as a magnetically separable catalyst for one-pot reductive
amination of carbonyl compounds†
Jia Deng, Li-Ping Mo, Fei-Yang Zhao, Lan-Lan Hou, Li Yang and Zhan-Hui Zhang*
Received 28th April 2011, Accepted 6th July 2011
DOI: 10.1039/c1gc15470b
A novel, environmentally friendly procedure has been developed for the preparation of secondary
or tertiary amines by one-pot reductive amination of carbonyl compounds using sodium
borohydride in the presence of a magnetically recoverable sulfonic acid supported on
hydroxyapatite-encapsulated-g-Fe2O3 [g-Fe2O3@HAP-SO3H] at room temperature. The catalyst
was easily separated from the reaction mixture by applying an external magnet and reused for six
cycles without significant loss of catalytic activity.
Amine formation is one of most important transformations
Introduction
in organic synthesis. Amides are also found in numerous natural
Currently, the development of novel, non-toxic, low cost, eco-
products and also serve as building blocks for pharmaceuticals,
friendly, recyclable catalytic systems with high efficiency has
agrochemicals, dyes, resins, fine chemicals, solvents, textile addi-
received a great deal of research attention in organic synthe-
tives, disinfectants, rubber stabilizers, corrosion inhibitors, in the
sis for environmental and economic reasons. In this regard,
manufacture of detergents and plastics, bases for many synthetic
nanoparticles (NPs) have emerged as viable and appealing
transformations, and ligands in coordination chemistry.4 As
candidates and are considered to be a bridge between homo-
a consequence, various methods for the efficient formation
geneous and heterogeneous catalysts.1 NPs-supported catalysts
of C–N bond have been widely investigated. Among all the
mimic their homogeneous counterparts and can be employed
available methods, direct reductive amination (DRA) is one of
in a quasi-homogeneous phase or serve as precursors for
the oldest, but the most powerful and widely used synthetic
heterogeneous catalysts since they readily disperse in reaction
transformations, which allows creation of a new C–N bond by
medium through forming stable suspensions, thus display highly
coupling diverse carbonyl compounds with amine-containing
accessible surface catalytic sites. Despite their distinct catalytic
fragments in one vessel without isolation of the intermediary
activities, difficulties in recovering the catalyst from the reaction
imines or hydroxyamines.5
mixture, due to their small diameter, severely limit their wide
A variety of methods have been reported to accomplished
applications. To further address the issues of recyclability and
this transformation including hydrogenation in the presence
reusability, magnetic nanoparticles (MNPs) are particularly
of Pd/C, iridium complex or FeII/EDTA complex,6 transfer
attractive since their paramagnetic nature enables trouble-free
hydrogenation,7 or using a reducing agent such as sodium
separation of the catalyst from the reaction mixture using an
cyanoborohydride,8 sodium triacetoxyborohydride,9 zinc
external magnet. Thus eliminating the necessity for tedious
borohydride,10 N-methyl piperidine zinc borohydride,11
centrifugation, filtration, or membrane separation.2 Meanwhile,
pyridine-BH3,12 zirconium borohydride-piperazine complexes,13
tandem catalysis that enables multi-step reactions in one-pot has
organosilane,14 poly(methylhydrosiloxane (PMHS),15 tin
the great advantage over multiple-step synthesis, of eliminating
hydride
complex16
1,2,3-triazole-borane
complexes,17
isolation of unstable intermediates and reducing the number of
chemical steps and waste production.3 Design of a recyclable
catalytic system that promotes efficient one-pot synthesis has
become an important research area in organic chemistry.
aminoboranes,18 and Al.19 However, consideration of functional
group tolerance, and side reactions, most of these reagents
may have one or more drawbacks. For example, catalytic
hydrogenation methods, are efficient for DRAs, but are
not compatible with compounds containing other reducible
functional groups such as carbon–carbon double or triple
bonds, cyano, and nitro groups, and require expensive metals as
catalysts. Cyanoborohydride and organotin are highly toxic and
resulted in contamination of the product with toxic by-products
such as HCN, NaCN or organotin compounds. Pyridine-BH3 is
Key Laboratory of Inorganic Nanomaterial of Hebei Province, The
College of Chemistry & Material Science, Hebei Normal University,
Shijiazhuang, 050016, China. E-mail: zhanhui@mail.nankai.edu.cn
† Electronic supplementary information (ESI) available: XRD, IR and
TEM data of the catalyst, and H NMR and 13C NMR spectra of all
1
new compounds. See DOI: 10.1039/c1gc15470b
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Table 1 Influence of different catalysts on the reductive condensation
of 2-nitrobenzaldehyde with anilinea
quite unstable to heat and must be handled with extreme care.
Triacetoxyborohydride is flammable, water-reactive, and poorly
soluble in most organic solvents.
Sodium borohydride is a relatively inexpensive, mild, safe,
water tolerant agent for applications in a wide range of reduction
processes.20 Although sodium borohydride has been used in
combination with some catalysts such as Ti(O-i-Pr)4,21 ZrCl4,22
NiCl2,23 H3BO3,24 H3PW12O40,25 guanidine hydrochloride,26 silica
phosphoric acid,27 Amberlyst-15,28 silica chloride,29 wet clay,30
and cellulose sulfric acid31 or in 2,2,2-trifluoroethanol32 for
DRAs, in some cases catalyst can not be recovered or high
temperature was required. Therefore, the search continues for
better methods for reductive amination of carbonyl compounds
with mild reaction conditions, economic viability and environ-
mentally benignity.
Entry
Catalyst
Time (min)
Isolated yield (%)
1
2
3
4
5
6
7
8
9
No
p-TSA
Chlorosulfonic acid
LiCl
HClO4/SiO2
Silicotungstic acid
Nano Fe3O4
Nano g- Fe2O3
g-Fe2O3@HAP-SO3H
180
60
40
60
60
60
60
180
45
Trace
77
39
61
80
62
42
25
95
Very recently, we have discovered that magnetic Fe3O4
nanoparticles are excellent catalysts for the synthesis of
quinoxalines33 and 2,3-dihydroquinazolin-4(1H)-ones.34 As a
continuation of our interest in developing efficient and environ-
mental benign synthetic methodologies,35 we report here a new,
green, and practical method for one-pot reductive amination
of carbonyl compounds using NaBH4 in the presence of g-
Fe2O3@HAP-SO3H as an highly efficient, inexpensive, and
reusable catalyst (Scheme 1).
a Reaction conditions: 2-nitrobenzaldehyde (1 mmol), aniline (1 mmol),
NaBH4 (1 mmol), catalyst (10 mmol%), EtOH (5 ml).
Table 2 Optimisation of reaction conditionsa
Entry Catalyst (mol%) Solvent
Time (min) Isolated yield (%)
1
2
3
4
5
6
7
8
9
10
10
10
10
10
10
5
No
CH2Cl2
CH3CN 60
AcOEt
H2O
MeOH
EtOH
EtOH
EtOH
60
60
78
65
73
61
90
94
81
95
96
60
45
45
60
45
45
10
15
Scheme 1 Reductive amination of carbonyl compounds by NaBH4-[g-
Fe2O3@HAP-SO3H].
a Reaction conditions: 2-nitrobenzaldehyde (1 mmol), aniline (1 mmol),
NaBH4 (1 mmol), solvent (5 ml).
Results and discussion
results indicated that different solvents affected the efficiency
of the reaction (Table 2). Based on the reaction yields and
environmental consideration, ethanol was proved to be superior
to others such as dichloromethane, acetonitrile, ethyl acetate,
methanol, and water. Moreover, we found that the yields were
obviously affected by the loading of g-Fe2O3@HAP-SO3H.
When 5 mol%, 10 mol% and 15 mol% of g-Fe2O3@HAP-SO3H
were used, the yields were 81%, 95%, and 96%, respectively
(Table 2, entries 7–9). Therefore, 10 mol% of g-Fe2O3@HAP-
SO3H was sufficient for this DRA.
To evaluate the scope and limitations of this methodology, we
extended our studies to various structurally different carbonyl
compounds and amines. Firstly, we examined the reactions of
aniline with different aldehydes and the results are summarized
in Table 3. It was found that there was no remarkable electron
and position effects from the aromatic aldehydes for this DRA,
since benzaldehydes with o-, m, and p-substituents (Table 3,
entries 14–16) resulted in the corresponding alkylated anilines
in excellent yields, while both 4-methoxybenzaldehyde (Table 3,
entry 5) and 4-nitrobenzaldehyde (Table 3, entry 21) were compe-
tent substrates in this procedure. It is important to note that acid-
sensitive aldehydes such as furan-2-carbaldehyde, thiophene-
2-carbaldehyde, and nicotinaldehyde (Table 3, entries 26–28)
were suitable substrates, affording the corresponding products
in high yields without the formation of any side products.
Furthermore, this procedure is applicable to reductive amination
Initially, 2-nitrobenzaldehyde and aniline were used as model
substrates to study the activity of various catalysts, including
protic acids such as toluenesulfonic acid, Lewis acids such as
LiCl, solid acid such as HClO4/SiO2, heteropoly acids such as
silicotungstic acid, and nanocrystalline metal oxides such as
nano Fe3O4 and g-Fe2O3 (Table 1).
In a typical reaction, 2-nitrobenzaldehyde and aniline were
mixeded in EtOH and catalyst was then added. After completion
of the imine formation, NaBH4 was added. The mixture was
stirred at room temperature. It was observed that all of the
investigated catalysts were able to catalyze this DRA and
furnished the corresponding product in moderate to high yields,
while the reaction performed in the absence of catalyst, only
resulted in the formation of trace amount of the desired
product. In order to further improve this procedure and recover
the heterogeneous catalyst, we decided to prepare the sul-
fonic acid supported on hydroxyapatite-encapsulated-g-Fe2O3
[g-Fe2O3@HAP-SO3H] according to a previously reported pro-
cedure with some modifications.36 The prepared catalyst was
characterized by XRD, SEM, TEM, and FT-IR (ESI†, Fig. S1–
4). We examined the use of g-Fe2O3@HAP-SO3H as a catalyst
and observed that this reaction proceeded well and afforded the
alkylated aniline in 95% yield.
In the following studies, the above reaction was conducted in
the presence of g-Fe2O3@HAP-SO3H with various solvents. The
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Table 3 Direct reductive amination of carbonyl compounds using NaBH4-[g-Fe2O3@HAP-SO3H]
Entry
Carbonyl compound
Amine
Product
Time (min)
Yield (%)a
Ref.
1
2
3
4
5
6
7
8
PhCHO
PhNH2
PhNH2
PhNH2
PhNH2
PhNH2
PhNH2
PhNH2
PhNH2
PhNH2
PhNH2
PhNH2
PhNH2
PhNH2
PhNH2
PhNH2
PhNH2
PhNH2
PhNH2
PhNH2
PhNH2
PhNH2
PhNH2
PhNH2
PhNH2
PhNH2
3a
3b
3c
3d
3e
3f
3g
3h
3i
40
40
40
35
20
30
30
30
30
45
35
45
35
40
35
35
35
60
45
40
40
80
80
60
100
94
93
92
93
94
93
93
91
90
92
93
92
93
91
92
94
93
85
95
93
94
91
90
94
85
14a
37
31
37
14a
3-CH3C6H4CHO
4-CH3C6H4CHO
2-OCH3C6H4CHO
4-OCH3C6H5CHO
2,3,4-(OMe)3C6H2CHO
2-OHC6H4CHO
3-OMe-2-OHC6H3CHO
4-OMe-2-OHC6H3CHO
5-F-2-OHC6H3CHO
5-Br-2-OHC6H3CHO
5-NO2-2-OHC6H3CHO
4-FC6H4CHO
30
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
3j
3k
3l
38
39
31
32
31
14a
3m
3n
3o
3p
3q
3r
3s
3t
3u
3v
3w
3x
3y
2-ClC6H4CHO
3-ClC6H4CHO
4-ClC6H4CHO
4-BrC6H4CHO
4-IC6H4CHO
2-NO2C6H4CHO
3-NO2C6H4CHO
4-NO2C6H4CHO
3-CF3C6H4CHO
4-CNC6H4CHO
PhCH CHCHO
31
15a
14a
14a
14a
14a
39
26
27
28
PhNH2
PhNH2
PhNH2
3z
40
60
40
95
95
90
15a
15a
15b
3aa
3ab
29
30
PhNH2
PhNH2
3ac
3ad
60
45
81
93
36
15b
31
32
33
34
35
36
37
38
39
40
41
42
43
CH3CHO
PhNH2
PhNH2
PhNH2
PhNH2
PhNH2
PhNH2
4-OCH3C6H5NH2
4-OEtC6H5NH2
4-CH3C6H4NH2
4-ClC6H4NH2
4-ClC6H4NH2
4-BrC6H4NH2
4-NO2C6H4NH2
3ae
3af
3ag
3ah
3ai
40
40
60
50
60
60
20
25
30
75
70
100
180
88
90
92
91
94
85
95
94
93
90
89
91
89
40
35e
27
15a
24
41
32
31
31
37
CH3CH2CHO
CH3(CH2)2CHO
CH3(CH2)4CHO
CH3(CH2)7CHO
PhCH2CHO
PhCHO
PhCHO
PhCHO
PhCHO
PhCHO
3aj
3ak
3al
3am
3an
3ao
3ap
3aq
31
15a
31
PhCHO
PhCHO
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Table 3 (Contd.)
Entry
44
Carbonyl compound
Amine
Product
Time (min)
2
Yield (%)a
90
Ref.
15a
PhCHO
PhCHO
PhCHO
3ar
45
46
3as
3at
1
93
82
42
32
120
47
48
49
50
51
PhCHO
PHCHO
PHCHO
PhCHO
PhCHO
PhCH2NH2
MeNH2
EtNH2
3au
3av
3aw
3ax
3ay
5
2
2
1
92
90
88
91
91
31
43
44
19
45
CH3(CH2)3NH2
10
52
53
PhCHO
CH2 CHCH2NH2
4-OCH3C6H5NH2
3az
3ba
1
30
90
92
27
26
54
55
56
4-ClC6H4NH2
4-BrC6H4NH2
3bb
3bc
3bd
40
91
88
81
46
44
37
60
180
57
58
59
60
61
CH3(CH2)3NH2
4-OCH3C6H5NH2
4-ClC6H4NH2
3be
3bf
3bg
3bh
3bi
1
94
92
90
95
80
47
46
37
45
45
1
120
62
63
CH3(CH2)3NH2
4-CH3C6H5NH2
3bj
1
96
92
47
46
3bk
60
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Table 3 (Contd.)
Entry
64
Carbonyl compound
Amine
Product
Time (min)
1
Yield (%)a
Ref.
48
3bl
93
65
CH3(CH2)3NH2
PhCH2NH2
3bm
1
94
66
67
3bn
3bo
5
2
94
93
24
68
69
70
71
PhCH CHCHO
PhCH CHCHO
PhCH CHCHO
PhCH CHCHO
4-CH3C6H5NH2
4-OCH3C6H5NH2
4-ClC6H4NH2
3bp
3bq
3br
3bs
40
35
45
140
90
91
88
82
49
49
49
72
73
PhCHO
PhCHO
3bt
7
5
89
90
31
31
3bu
74
75
PhNH2
PhNH2
3bv
40
40
87
87
50
31
3bw
76
77
78
79
CH3(CH2)3NH2
CH2 CHCH2NH2
PhNH2
3bx
3by
3bz
3ca
5
92
93
88
89
19
19
51
50
5
45
45
PhNH2
80
81
PhNH2
PhNH2
3cb
3cc
35
45
91
87
52
53
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Table 3 (Contd.)
Entry
82
Carbonyl compound
Amine
PhNH2
Product
Time (min)
40
Yield (%)a
90
Ref.
3cd
83
PhNH2
3ce
35
92
54
84
85
PhCHO
3cf
40
60
88b
89c
55
56
PhNH2
3cg
a Isolated yield. b Two equivalents of benzaldehyde were used. c Two equivalents of amines were used.
of aliphatic and a,b-unsaturated aldehydes. In addition to
aldehydes, some ketones were also selected to carry out this
DRA. For the aliphatic ketones like cyclohexanone, cyclodo-
decanone, bicyclo[2.2.1]heptan-2-one, 1H-inden-2(3H)-one and
adamantan-2-one, the desired products were smoothly obtained
in high yield through this catalytic system. Unfortunately, only
a trace amount of the target product was isolated, when less
reactive aromatic ketones like acetophenone was aminated with
the aromatic and aliphatic amines under the same reaction
conditions.
The reactivities of amines in this DRA were then tested. Aro-
matic amines with electron-withdrawing groups such as a nitro
group showed slightly weaker reactivity than those containing
electron-neutral or electron-donating groups (Table 3, entry 43).
Besides, heteroaromatic amines like pyridin-2-amine acted as a
suitable candidate for this reaction. Aliphatic amines and allylic
amine were reactive and underwent the title reaction in a shorter
reaction time compared to aromatic amines. It is noteworthy that
optically active plenylglycinol underwent reductive amination
successfully to give the corresponding amine (3ay) without any
racemization or inversion as determined by measurement of
optical rotation. The reactions worked also well when secondary
amines like piperidine and morpholine were utilized.
Encouraged by the above interesting results, we also attempted
to prepare bis-alkylated amines to further broaden the scope. To
our delight, the reaction of p-phenylenediamine with 2 equiv. of
benzaldehyde resulted in the desired product (3cf) in high yield.
Similarly, terephthaldicarboxaldehyde also underwent reductive
amination smoothly to afford the target product 3cg in 89% yield
(Scheme 2). Moreover, the model reaction was carried out in a
scale of 100 mmol. As expected, the reaction proceeded nicely
to afford the desired product in 93% yield in 50 min.
Scheme 2 Synthesis of bis-alkylated amines.
cyanide, ethers, carbon-carbon double bond under the reaction
conditions. Furthermore, the reaction was clean and no side
products were observed.
From the view point of green chemistry, good recovery
and reusability of the catalyst are highly preferable. In this
work, we examined the possibility of recovery and reuse of
g-Fe2O3@HAP-SO3H. After completion of the reaction of
nitrobenzaldehyde and amine, the catalyst was recovered from
the reaction mixture simply by applying an external magnet.
Then the recovered catalyst was first washed with water and
then with diethyl ether, and dried at room temperature. The
recovered catalyst was added to fresh reaction mixture under
same conditions for six runs without significant drop in yield and
its catalytic activity (Fig. 1). No quantifiable amount of leached
Fe was detected in the filtrates as determined by inductively
coupled plasma atomic emission spectroscopy (ICP-AES). To
determine of the percent leaching of the acid, the model reaction
was carried out in the presence of g-Fe2O3@HAP-SO3H for
20 min and at that point the catalyst was removed by external
magnet. The residual solution was then allowed to react, but
no significant progress was observed after 1 h. Therefore, these
experiments are a further testimony to the heterogeneous nature
of the catalytic system.57 Furthermore, the SEM images of the
used catalyst showed that the shape and size of catalyst particles
remained almost the same after six-run reuse, which proved its
robustness (ESI†).
An important feature of this procedure is the tolerance of a
variety of function groups such as fluoro, chloro, iodine, nitro,
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chromatography on silica gel using ethyl acetate/petroleum
ether as the eluent.
N-(2,3,4-Trimethoxybenzyl)aniline (3f). Viscous liquid; IR
(neat): 3408, 2935, 1602, 1494, 1506, 1463, 1431, 1415, 1271,
1197, 1178, 1093, 1016, 904, 800, 750 cm-1; 1H NMR (500 MHz,
CDCl3) d: 3.82 (s, 3H), 3.87 (s, 3H), 3.91 (s, 3H), 3.98 (br s, 1H,
NH), 4.25 (s, 2H), 6.60 (d, J = 8.0 Hz, 1H), 6.64 (d, J = 7.5 Hz,
2H), 6.68 (t, J = 7.5 Hz, 1H), 6.70 (d, J = 8.0 Hz, 1H), 7.15 (t,
J = 7.5 Hz, 2H); 13C NMR (125 MHz, CDCl3) d: 43.3, 53.0,
60.9, 61.2, 107.2, 113.1, 117.4, 123.5, 125.1, 129.2, 142.3, 148.4,
151.3, 153.2; Anal. Calcd for C16H19NO3: C, 70.31; H, 7.01; N,
5.12. Found: C, 70.12; H, 6.88; N, 4.98.
Fig. 1 The catalytic activity of g-Fe2O3@HAP-SO3H in six cycles for
the model reaction.
2-Methoxy-6-((phenylamino)methyl)phenol
(3h). White
◦
solid, Mp: 62–64 C; IR (KBr): 3311, 3012, 1601, 1500, 1477,
1440, 1429, 1356, 1269, 1247, 1224, 1168, 1083, 1051, 925 cm-1;
1H NMR (500 MHz, CDCl3) d: 3.78 (s, 3H), 4.36 (s, 2H), 6.44
(dd, J = 8.5, 2.5 Hz, 1H), 6.48 (d, J = 2.5 Hz, 1H), 6.85 (d, J =
8.0 Hz, 2H), 6.92 (t, J = 7.5 Hz, 1H), 7.04 (d, J = 8.0 Hz, 1H),
7.23–7.26 (m, 2H); 13C NMR (125 MHz, CDCl3) d: 44.2, 56.1,
110.0, 113.7, 118.2, 119.6, 121.2, 124.7, 129.2, 144.1, 146.8,
148.1; Anal. Calcd for C14H15NO2: C, 73.34; H, 6.59; N, 6.11.
Found: C, 73.15; H, 6.76; N, 5.98.
Conclusions
In conclusion, we have developed a highly efficient and eco-
friendly method for one-pot reductive amination of carbonyl
compounds using magnetically separable sulfonic acid sup-
ported on hydroxyapatite-encapsulated-g-Fe2O3 as the catalyst
under mild conditions. This protocol can be used to generate a
diverse range of secondary or tertiary amines in high to excellent
yields. The catalyst is completely magnetically recoverable and
the efficiency of the catalyst remains unaltered even after six
cycles. These advantages make this methodology attractive for
large-scale synthesis.
4-Methoxy-2-((phenylamino)methyl)phenol
(3i). White
solid, Mp: 137–139 ◦C; IR (KBr): 3254, 2960, 1614, 1593, 1516,
1445, 1437, 1421, 1325, 1282, 1232, 1107, 954 cm-1; H NMR
1
(500 MHz, CDCl3) d: 3.89 (s, 3H), 4.38 (s, 2H), 6.70–6.76 (m,
3H), 6.81 (d, J = 5.0 Hz, 2H), 6.89 (t, J = 5.0 Hz, 1H), 7.18 (t,
J = 7.5 Hz, 2H); 13C NMR (125 MHz, CDCl3) d: 48.4, 55.3,
102.2, 106.0, 115.1, 116.0, 120.9, 129.3, 129.4, 147.2, 157.9,
160.7; Anal. Calcd for C14H15NO2: C, 73.34; H, 6.59; N, 6.11.
Found: C, 73.50; H, 6.41; N, 6.30.
Experimental
IR spectra were recorded with a Shimadzu FTIR-8900 spec-
1
trometer. The H NMR (500 MHz) and 13C NMR (125 MHz)
spectra were recorded on a Bruker DRX-500 spectrometer using
CDCl3 as solvent and TMS as internal standard. Elemental
analyses were carried out on a Vario EL III CHNOS elemental
analyzer. Commercially available reagents were used without
further purification.
4-Fluoro-2-((phenylamino)methyl)phenol (3j). White solid,
Mp: 107–109 ◦C; IR (KBr): 3300, 1601,1498, 1438, 1252, 1230,
1201, 1078, 898, 825 cm-1; 1H NMR (500 MHz, CDCl3) d: 4.39
(s, 2H), 6.80–6.84 (m, 3H), 6.87–6.95 (m, 3H), 7.23–7.26 (m,
2H); 13C NMR (125 MHz, CDCl3) d: 48.6, 114.9 (d, 2JFC = 23.4
Preparation of c-Fe2O3@HAP-SO3H36
2
3
Hz), 115.3 (d, JFC = 22.6 Hz), 115.9, 117.4 (d, JFC = 7.6 Hz),
To g-Fe2O3@HAP (1 g), chlorosulfonic acid (1 g, 9 mmol)
was added dropwise at room temperature during 15 min. After
completion of the addition, the mixture was mechanically stirred
for 6 h until HCl was removed from reaction vessel. Then the
mixture was washed with CH2Cl2 (10 ml), resulted magnetic
nanoparticles were separated by an external magnet device and
washed with distilled water until neutral, then dried under
vacuum at room temperature to obtain g-Fe2O3@HAP-SO3H
as brown powder. The number of H+ site (0.9 mmol SO3H/g) of
g-Fe2O3@HAP-SO3H was determined by acid–base titration.
3
121.1, 123.9 (d, JFC = 6.9 Hz), 129.4, 146.9, 152.7, 156.5 (d,
1JFC = 236.1 Hz); Anal. Calcd for C13H12FNO: C, 71.87; H, 5.57;
N, 6.45. Found: C, 71.92; H, 5.75; N, 6.28.
4-Bromo-2-((phenylamino)methyl)phenol (3k). White solid,
Mp: 114–116 ◦C; IR (KBr): 3267, 2974, 1602, 1489, 1456, 1355,
1290, 1251, 1218, 1182, 1126, 1089, 1055, 864, 827, 804 cm-1; 1H
NMR (500 MHz, CDCl3) d: 4.39 (s, 2H), 6.76 (d, J = 8.5 Hz, 1H),
6.84(d, J = 8.0 Hz, 2H), 6.95 (t, J = 7.5 Hz, 1H), 7.24–7.32 (m,
4H); 13C NMR (125 MHz, CDCl3) d: 48.6, 111.8, 116.1, 118.5,
121.3, 124.9, 129.5, 131.1, 131.9, 146.7, 156.1; Anal. Calcd for
C13H12BrNO: C, 56.14; H, 4.35; N, 5.04. Found: C, 55.98; H,
4.26; N, 4.88.
General procedure for the reductive amination of carbonyl
compounds
Carbonyl compound (1 mmol) and amine (1 mmol) were mixed
in EtOH (5 ml) and then g-Fe2O3@HAP-SO3H (0.1 mmol)
was added. After completion of the imine formation, NaBH4
(1 mmol) was added. The progress of reaction was monitored
by TLC or GC. After completion of the reaction, the catalyst
was separated with the aid of an external magnet. Ethanol was
evaporated and the crude product was purified by short column
N-(4-Iodobenzyl)aniline (3r). White solid, Mp: 53–55 ◦C; IR
(KBr): 3429, 1593, 1504, 1492, 1436, 1448, 1398, 1375, 1325,
1292, 1271, 1153, 1124, 1058, 1028, 985, 806, 732 cm-1; 1H NMR
(500 MHz, CDCl3) d: 4.06 (br s, 1H, NH), 4.27 (s, 2H), 6.38 (d,
J = 9.0 Hz, 2H), 7.25–7.28 (m, 1H) 7.32–7.33 (m, 4H), 7.38
(d, J = 9.0 Hz, 2H); 13C NMR (125 MHz, CDCl3) d: 47.92,
78.03, 115.0, 127.3, 128.6, 137.7, 138.7, 147.5; Anal. Calcd for
2582 | Green Chem., 2011, 13, 2576–2584
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C13H12IN: C, 50.51; H, 3.91; N, 4.53. Found: C, 50.33; H, 7.05;
N, 4.70.
1H); 13C NMR (125 MHz, CDCl3) d: 44.3, 106.9, 113.2, 126.4,
126.7, 127.5, 128.6, 131.4, 136.8, 137.5, 148.2, 158.5; Anal. Calcd
for C14H14N2: C, 79.97; H, 6.71; N, 13.32. Found: C, 80.09; H,
6.88; N, 13.16.
(S)-2-(Benzylamino)-2-phenylethanol (3ay). White solid,
Mp: 86–87 ◦C; [a]D20 = +82.6 (c 1.08 in CHCl3), Lit.45 [a]D28 = +83.2;
IR (KBr): 3251, 2920, 1569, 1496, 1488, 1452, 1328, 1234, 1099,
N-Phenylcyclododecanamine (3cd). Yellow solid, Mp: 75–
77 ◦C; IR (KBr): 3401, 3043, 1601, 1503, 1440, 1435, 1316, 1260,
1
1055, 1014, 920, 877, 756 cm-1; H NMR (500 MHz, CDCl3)
1
1185, 1145, 1110, 745, 690 cm-1; H NMR (500 MHz, CDCl3)
d: 3.64 (d, J = 13.5 Hz, 1H), 3.70–3.76 (m, 2H), 3.85 (d, J =
13.5 Hz, 1H), 3.88–3.91 (m, 1H), 7.28–7.40 (m, 10H); 13C NMR
(125 MHz, CDCl3) d: 51.1, 63.8, 66.7, 127.1, 127.3, 127.7, 128.2,
128.5, 128.7, 139.9, 140.3; Anal. Calcd for C15H17NO: C, 79.26;
H, 7.54; N, 6.16. Found: C, 79.08; H, 7.70; N, 5.98.
d: 1.28–1.72 (m, 22H), 2.47 (t, J = 6.0 Hz, 1H), 3.51 (br s, 1H),
6.58 (d, J = 7.5 Hz, 2H), 6.65 (t, J = 7.5 Hz, 1H), 7.15 (t, J =
7.5 Hz, 2H); 13C NMR (125 MHz, CDCl3) d: 21.3, 22.4, 22.6,
23.3, 24.0, 24.3, 24.4, 24.7, 24.8, 29.8, 40.4, 49.5, 113.1, 116.7,
129.3, 147.9; Anal. Calcd for C18H29N: C, 83.33; H, 11.27; N,
5.40. Found: C, 83.15; H, 11.08; N, 5.56.
4-Methoxy-N-(thiophen-2-ylmethyl)aniline
solid, Mp: 64–66 C; IR (KBr): 3393, 2831, 1512, 1460, 1440,
1406, 1311, 1298, 1267, 1236, 1178, 1116, 1035, 850 cm-1; H
(3bf). White
◦
1
N,N¢-Dibenzyl-p-phenylenediamine (3cf). White solid, Mp:
125–127 ◦C; IR (KBr): 3294, 1600, 1508, 1494, 1452, 1357,
NMR (500 MHz, CDCl3) d: 3.74 (s, 3H), 4.46 (s, 1H), 6.64 (d,
J = 9.0 Hz, 2H), 6.78 (d, J = 9.0 Hz, 2H), 6.95 (t, J = 5.0 Hz,
1H), 6.99 (d, J = 3.0 HZ, 1H) 7.20 (dd, J = 5.0 HZ, 1.0 Hz, 1H);
13C NMR (125 MHz, CDCl3) d: 44.5, 55.8, 114.6, 114.9, 124.5,
124.9, 126.9, 141.9, 143.4, 152.6; Anal. Calcd for C12H13NOS:
C, 65.72; H, 5.97; N, 6.39. Found: C, 65.90; H, 6.15; N, 6.58.
1
1294, 1244, 1217, 1132, 1068, 1029, 817, 698 cm-1; H NMR
(500 MHz, CDCl3) d: 4.26 (s, 4H), 6.60 (s, 4H), 7.24–7.27 (m,
2H), 7.32 (t, J = 7.5 Hz, 4H), 7.36 (d, J = 7.5 Hz, 4H); 13C NMR
(125 MHz, CDCl3) d: 49.6, 114.9, 127.1, 127.7, 128.5; Anal.
Calcd for C20H20N2: C, 83.30; H, 6.99; N, 9.71. Found: C, 83.45;
H, 6.82; N, 9.90.
1-(Furan-2-yl)-N-(thiophen-2-ylmethyl)methanamine (3bh).
Yellow oil; IR (neat): 3448, 1541, 1382, 1147, 1078, 1008, 734,
700 cm-1; 1H NMR (500 MHz, CDCl3) d: 3.81 (s, 2H), 3.97 (s,
2H), 6.19 (d, J = 3.0 Hz, 1H), 6.32 (dd, J = 3.0, 1.0 Hz, 1H),
6.92–6.96 (m, 2H), 7.22 (dd, J = 5.0, 1.0 Hz, 1H, ArH), 7.37 (d,
J = 1.0 Hz, 1H); 13C NMR (125 MHz, CDCl3) d: 44.9, 47.2,
107.3, 110.1, 124.6, 125.2, 126.7, 141.9, 143.6, 153.5; Anal.
Calcd for C10H11NOS: C, 62.15; H, 5.74; N, 7.25. Found: C,
61.96; H, 5.92; N, 7.08.
N-(4-((Phenylamino)methyl)benzyl)benzenamine
(3cg).
White solid, Mp: 105–107 ◦C; IR (KBr): 3423, 1604, 1508, 1490,
1319, 1276, 1178, 1151, 1122, 1089, 1072, 983, 750 cm-1; H
1
NMR (500 MHz, CDCl3) d: 4.02 (br s, 2H), 4.32 (s, 4H), 6.63
(d, J = 7.5 Hz, 4H), 6.72 (t, J = 7.5 Hz, 2H), 7.17 (t, J = 7.5 Hz,
4H), 7.35 (s, 4H); 13C NMR (125 MHz, CDCl3) d: 48.0, 112.8,
117.6, 127.8, 129.3, 138.5, 148.1; Anal. Calcd for C20H20N2: C,
83.30; H, 6.99; N, 9.71. Found: C, 83.16; H, 7.18; N, 9.53.
N-(Pyridin-3-ylmethyl)butan-1-amine (3bm). Yellow oil; IR
(neat): 3442, 2956, 2927, 1577, 1560, 1477, 1458, 1423, 1382,
1120, 1028, 785, 713 cm-1; 1H NMR (500 MHz, CDCl3) d: 0.91
(t, J = 7.5 Hz, 3H), 1.35 (sext, J = 7.5 Hz, 2H), 1.49 (quin, J =
7.5 Hz, 2H), 2.63 (t, J = 7.5 Hz, 2H), 3.80 (s, 2H), 7.25 (dd,
J = 7.5, 5.0 Hz, 1H), 7.67 (d, J = 7.5 Hz, 1H), 8.49 (dd, J =
5.0, 1.5 Hz, 1H), 8.56 (s, 1H); 13C NMR (125 MHz, CDCl3)
d: 14.0, 20.4, 32.2, 49.2, 51.3, 123.3, 135.7, 135.8, 148.4, 149.7;
Anal. Calcd for C10H16N2: C, 73.13; H, 9.82; N, 17.06. Found:
C, 72.96; H, 10.01; N, 16.90.
Acknowledgements
This work was supported financially by the National Natural
Science Foundation of China (20872025 and 21072042) and
Nature Science Foundation of Hebei Province (B2011205031).
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1
1157, 1147, 1124, 1080, 968, 767 cm-1; H NMR (500 MHz,
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7.5 Hz, 2H), 7.43 (td, J = 7.5, 2.0 Hz, 1H), 8.11 (d, J = 5.0 Hz,
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