Direct N-alkylation of amines with alcohols using AlCl3 as a Lewis acid

Article abstract of DOI:10.1016/j.cclet.2014.07.006

A substitution reaction of amines with alcohols for N-alkylated amines has been developed using inexpensive AlCl₃ without any ligand or additive. Either aromatic or aliphatic amines and primary or secondary alcohols perform the AlCl₃-mediated reaction smoothly to afford various N-alkylated amines in satisfactory yields.

Full text of DOI:10.1016/j.cclet.2014.07.006

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CCLET-3068; No. of Pages 5
Chinese Chemical Letters xxx (2014) xxx–xxx
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Chinese Chemical Letters
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Original article
Direct N-alkylation of amines with alcohols using AlCl3 as a Lewis acid
Ya-Qiong Li a, Yun-Bin Chen b, Zhi-Zhen Huang a,c,
*
a Department of Chemistry, Zhejiang University, Hangzhou 310028, China
b Zhejiang Jianye Chemical Co., Ltd., Hangzhou 311604, China
c State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China
A R T I C L E I N F O
A B S T R A C T
Article history:
A substitution reaction of amines with alcohols for N-alkylated amines has been developed using
inexpensive AlCl3 without any ligand or additive. Either aromatic or aliphatic amines and primary or
secondary alcohols perform the AlCl3-mediated reaction smoothly to afford various N-alkylated amines
in satisfactory yields.
Received 4 May 2014
Received in revised form 26 June 2014
Accepted 27 June 2014
Available online xxx
ß 2014 Zhi-Zhen Huang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights
reserved.
Keywords:
Amine
Alcohol
N-Alkylated amine
Lewis acid
Synthesis
1. Introduction
it was reported that under vapor phase conditions, aniline reacted
with methanol, ethanol, or propanol to form corresponding N-
N-Alkylated amines are very important intermediates in the
pharmaceutical, agrochemical, and fine chemical industries [1].
The most common method for the synthesis of N-alkylated amines
is the nucleophilic substitution reaction of amines or ammonia
with alkyl halides, sulfonates, etc. [2]. The reductive amination of
aldehydes or ketones is another reaction scheme to synthesize N-
alkylated amines. Using alcohols as starting materials, which are
readily available and less hazardous, is more attractive in the
preparation of N-alkylated amines, because the process is more
atom economical and environmentally friendly, owing to the
generation of water as a side-product. Recently, ‘‘borrowing
hydrogen’’ methodology for the synthesis of N-alkylated amines
from alcohols was developed by using transition metal complexes
[3]. Directly using alcohols instead of alkyl halides or sulfonates to
react with amines for N-alkylated amines has been realized by
using hydrochloric acid as a Brønsted acid [4], and montmoril-
lonite [5a] or sulfated tungstate [5b] as a solid Brønsted acid to
activate the hydroxyl group of alcohols. Furthermore, Lewis acids
have a lot of advantages and have been widely applied in modern
organic synthesis [6]. They activate hydroxyl groups in alcohols,
creating suitable substrates for substitution reactions. From 1924,
alkylated amines at high temperature (300–500 8C) catalyzed by
SiO2 [7] or mediated by Al2O3 [8]. In 2011, Saito et al. disclosed that
FeBr3 was employed as a Lewis acid and 1,2,3,4,5-pentamethyl-
cyclopenta-1,3-diene as a ligand to catalyze the N-alkylation of
anilines or benzyl amines at 160–200 8C [9]. Very recently, Ji et al.
developed In(OTf)3-catalyzed N-benzylation of amines with
benzyl alcohols [10]. However, these methods suffer from limited
scope in alcohols or amines. Herein, we wish to present our recent
results on the reaction of various amines with a broad range of
alcohols for the synthesis of N-alkylated amines using inexpen-
sive AlCl3 as a Lewis acid.
2. Experimental
2.1. The AlCl3-mediated reaction of aromatic amines 1a–d with
alcohols 2a–e for N-alkylated amines 3a–h
A mixture of aromatic amines 1a–d (3.28 mmol, 2.0 equiv.),
alcohols 2a–e (1.64 mmol) and AlCl3 (436 mg, 3.28 mmol,
2.0 equiv.) in mesitylene (2 mL) was stirred for 4 h at 166 8C.
Then, ethyl acetate (50 mL) was added. The mixture was washed
with aqueous NaOH (1 mol/L, 50 mL) and brine (50 mL) and dried
over Na2SO4. After evaporation, the residue was purified by
column chromatography (silica gel, petroleum ether/ethyl
acetate (100/1, v/v) as eluent) to give the desired N-alkylated
amines 3a–h.
*
Corresponding author at: Department of Chemistry, Zhejiang University,
Hangzhou 310028, China.
E-mail address: huangzhizhen@zju.edu.cn (Z.-Z. Huang).
http://dx.doi.org/10.1016/j.cclet.2014.07.006
1001-8417/ß 2014 Zhi-Zhen Huang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Please cite this article in press as: Y.-Q. Li, et al., Direct N-alkylation of amines with alcohols using AlCl3 as a Lewis acid, Chin. Chem. Lett.
(2014), http://dx.doi.org/10.1016/j.cclet.2014.07.006

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CCLET-3068; No. of Pages 5
2
Y.-Q. Li et al. / Chinese Chemical Letters xxx (2014) xxx–xxx
N-(2-Phenylethyl)aniline 3a [11]: Yield 80%, colorless oil.
1H NMR (400 MHz, CDCl3):
7.32–7.27 (m, 2H), 7.24–7.15 (m,
gel, dichloromethane/methanol (50/1, v/v) as eluent) to give the
desired N-alkylated amines 3j–l.
d
5H), 6.70 (t, 1H, J = 7.4 Hz), 6.59 (d, 2H, J = 8.0 Hz), 3.64 (brs, 1H),
3.37 (t, 2H, J = 7.2 Hz), 2.89 (t, 2H, J = 7.2 Hz), MS (EI): m/z 197 (M+),
133, 106, 91, 77, 65.
N-(3-Phenylpropyl)aniline 3b [12]: Yield 84%, colorless oil.
1H NMR (400 MHz, CDCl3):
d 7.29–7.25 (m, 2H), 7.20–7.13 (m, 5H),
N-Octyl-2-phenylethylamine 3j [16]: Yield 40%, colorless oil.
1H NMR (400 MHz, CDCl3):
d 7.30–7.27 (m, 2H), 7.21–7.17 (m, 3H),
2.89–2.79 (m, 4H), 2.60 (t, 2H, J = 7.4 Hz), 1.47–1.44 (m, 2H), 1.30–
1.26 (m, 10H), 0.88 (t, 3H, J = 6.8 Hz), MS (EI): m/z 234 (M+H)+, 91,
65, 43, 29.
6.67 (t, 1H, J = 7.4 Hz), 6.55 (d, 2H, J = 8.4 Hz), 3.54 (brs, 1H), 3.11 (t,
2H, J = 7.0 Hz), 2.70 (t, 2H, J = 7.6 Hz), 1.95–1.88 (m, 2H), MS (EI):
m/z 211 (M+), 118, 106, 91, 77, 65.
N-Octyl-3-phenylpropylamine 3k [17]: Yield 62%, colorless oil.
1H NMR (400 MHz, CDCl3):
d 7.29–7.25 (m, 2H), 7.19–7.15 (m, 3H),
2.67–2.56 (m, 6H), 1.86–1.78 (m, 2H), 1.48–1.43 (m, 2H), 1.30–1.25
(m, 10H), 0.88 (t, 3H, J = 6.8 Hz), MS (EI): m/z 248 (M+H)+, 148, 142,
91, 57, 44.
N-Butylaniline 3c [12]: Yield 55%, colorless oil. 1H NMR
(400 MHz, CDCl3):
d 7.18–7.14 (m, 2H), 6.67 (t, 1H, J = 7.4 Hz),
6.58 (d, 2H, J = 7.6 Hz), 3.52 (brs, 1H), 3.09 (t, 2 H, J = 7.2 Hz), 1.62–
1.55 (m, 2H), 1.46–1.37 (m, 2H), 0.95 (t, 3H, J = 7.4 Hz), MS (EI): m/z
149 (M+), 106, 77, 65, 41.
N-(2-Phenylethyl)-3-phenylpropylamine 3l [18]: Yield 66%,
colorless oil. 1H NMR (400 MHz, CDCl3):
d 7.30–7.13 (m, 10H),
2.88–2.77 (m, 4H), 2.65–2.59 (m, 4H), 1.83–1.75 (m, 2H), MS (EI):
m/z 240 (M+H)+, 148, 91, 65, 44.
N-Pentylaniline 3d [13]: Yield 41%, colorless oil. 1H NMR
(400 MHz, CDCl3): d 7.18–7.14 (m, 2H), 6.67 (t, 1H, J = 7.4 Hz), 6.59
(d, 2H, J = 7.6 Hz), 3.55 (brs, 1H), 3.09 (t, 2H, J = 7.2 Hz), 1.64–1.57
(m, 2H), 1.39–1.35 (m, 4H), 0.92 (t, 3H, J = 7.0 Hz), MS (EI): m/z 163
(M+), 106, 77, 29.
2.4. The AlCl3-mediated reaction of butyl amine 1g with 3-
phenylpropanol 2b for N-alkylated amine 3m
N-Hexylaniline 3e [12]: Yield 58%, colorless oil. 1H NMR
A mixture of butyl amine 1g (359 mg, 4.92 mmol, 3.0 equiv.), 3-
phenylpropanol 2b (223 mg, 1.64 mmol) and AlCl3 (436 mg,
3.28 mmol, 2.0 equiv.) in mesitylene (2 mL) was stirred for 20 h
at 176 8C. The similar work-up to that for 3j–l led to N-butyl-3-
phenylpropylamine 3m.
(400 MHz, CDCl3):
d 7.18–7.13 (m, 2H), 6.69–6.65 (m, 1H), 6.59–
6.56 (m, 2H), 3.56 (brs, 1H), 3.08 (t, 2H, J = 7.2 Hz), 1.63–1.56 (m,
2H), 1.42–1.26 (m, 6H), 0.90 (t, 3H, J = 7.0 Hz), MS (EI): m/z 177
(M+), 106, 77, 41, 29.
N-(m-Chlorophenyl)-3-phenylpropylamine 3f: Yield 76%, col-
N-Butyl-3-phenylpropylamine 3m [19]: Yield 83%, yellow oil.
1H NMR (400 MHz, CDCl3):
d 7.29–7.25 (m, 2H), 7.19–7.15 (m, 3H),
orless oil. 1H NMR (400 MHz, CDCl3):
d
7.32–7.28 (m, 2H), 7.22–
7.18 (m, 3H), 7.04 (t, 1H, J = 8.0 Hz), 6.64 (ddd, 1H, J1 = 0.8 Hz,
J2 = 1.6 Hz, J3 = 7.6 Hz), 6.52 (t, 1H, J = 2.2 Hz), 6.41 (ddd, 1H,
J1 = 0.8 Hz, J2 = 2.0 Hz, J3 = 8.0 Hz), 3.67 (brs, 1H), 3.12 (t, 2H,
J = 6.8 Hz), 2.72 (t, 2H, J = 7.4 Hz), 1.98–1.90 (m, 2H), MS (EI): m/z
245 (M+), 140, 91, 77.
2.67–2.56 (m, 6H), 1.85–1.78 (m, 2H), 1.49–1.42 (m, 2H), 1.37–1.28
(m, 2H), 0.91 (t, 3H, J = 7.2 Hz), MS (EI): m/z 192 (M+H)+, 148, 91,
86, 57, 44.
2.5. The AlCl3-mediated reaction of aniline 1a with secondary alcohol
2g for N-alkylated amine 3n
N-(m-Tolyl)-3-phenylpropylamine 3g [14]: Yield 66%, color-
less oil. 1H NMR (400 MHz, CDCl3):
d 7.29–7.26 (m, 2H), 7.20–
7.15 (m, 3H), 7.06–7.02 (m, 1H), 6.50 (d, 1H, J = 7.6 Hz), 6.38–6.36
(m, 2H), 3.51 (brs, 1H), 3.10 (t, 2H, J = 7.0 Hz), 2.70 (t, 2H,
J = 7.6 Hz), 2.25 (s, 3H), 1.95–1.87 (m, 2H), MS (EI): m/z 225 (M+),
120, 91, 77, 65.
A mixture of aniline 1a (762 mg, 8.20 mmol, 5.0 equiv.),
secondary alcohol 2g (246 mg, 1.64 mmol) and AlCl3 (436 mg,
3.28 mmol, 2.0 equiv.) in mesitylene (2 mL) was stirred for 4 h at
166 8C. The similar work-up to that for 3a–h led to N-phenyl-4-
phenyl-2-butylamine 3n.
N-Phenyl-4-phenyl-2-butylamine 3n [20]: Yield 51%, yellow
oil. 1H NMR (400 MHz, CDCl3):
d 7.28–7.25 (m, 2H), 7.19–7.11 (m,
5H), 6.65 (t, 1H, J = 7.4 Hz), 6.52–6.50 (m, 2H), 3.51–3.43 (m, 1H),
3.38 (brs, 1H), 2.71 (t, 2H, J = 8.0 Hz), 1.90–1.81 (m, 1H), 1.79–1.70
(m, 1H), 1.19 (d, 3H, J = 6.4 Hz), MS (EI): m/z 225 (M+), 210, 134,
120, 106, 91, 77.
N-(p-Tolyl)-3-phenylpropylamine 3h [15]: Yield 64%, colorless
oil. 1H NMR (400 MHz, CDCl3):
d
7.29–7.26 (m, 2H), 7.20–7.16 (m,
3H), 6.96 (d, 2H, J = 8.0 Hz), 6.51–6.47 (m, 2H), 3.43 (brs, 1H), 3.10
(t, 2H, J = 7.0 Hz), 2.71 (t, 2H, J = 7.6 Hz), 2.22 (s, 3H), 1.95–1.88 (m,
2H), MS (EI): m/z 225 (M+), 120, 91, 77, 65.
2.2. The AlCl3-mediated reaction of aniline 1a with benzyl alcohol 2f
for N-alkylated amine 3i
2.6. The AlCl3-mediated reaction of diethyl amine 1h with benzyl
alcohol 2f for N-alkylated amine 3o
A mixture of aniline 1a (305 mg, 3.28 mmol, 2.0 equiv.), benzyl
alcohol 2f (177 mg, 1.64 mmol) and AlCl3 (218 mg, 1.64 mmol,
1.0 equiv.) in mesitylene (2 mL) was stirred for 12 h at 100 8C. The
similar work-up to that for 3a–h led to N-benzylaniline 3i.
N-Benzylaniline 3i [11]: Yield 57%, colorless oil. 1H NMR
A mixture of diethyl amine 1h (359 mg, 4.92 mmol, 3.0 equiv.),
benzyl alcohol 2f (177 mg, 1.64 mmol) and AlCl3 (436 mg,
3.28 mmol, 2.0 equiv.) in toluene (2 mL) was stirred for 12 h at
100 8C. The similar work-up to that for 3j–l led to N,N-
diethylbenzylamine 3o.
(400 MHz, CDCl3): d 7.37–7.15 (m, 7H), 6.71 (t, 1H, J = 7.4 Hz), 6.63
(d, 2H, J = 8.0 Hz), 4.32 (s, 2H), 3.98 (brs, 1H), MS (EI): m/z 183 (M+),
106, 91, 77, 65.
N,N-Diethylbenzylamine 3o [21]. Yield 51%, yellow oil. 1H NMR
(400 MHz, CDCl3):
d 7.34–7.27 (m, 4H), 7.24–7.20 (m, 1H), 3.56 (s,
2.3. The AlCl3-mediated reaction of aliphatic amines 1e–f with
alcohols 2a–b for N-alkylated amines 3j–l
2H), 2.52 (q, 4H, J = 7.2 Hz), 1.04 (t, 6H, J = 7.0 Hz), MS (EI): m/z 163
(M+), 148, 91, 86, 29.
1H NMR and MS (EI) spectra of some N-alkylated amines 3 can
be found in Supporting information.
A mixture of aliphatic amines 1e–f (3.28 mmol, 2.0 equiv.),
alcohols 2a–b (1.64 mmol), diethyl amine (478 mg, 6.56 mmol,
4.0 equiv.) and AlCl3 (436 mg, 3.28 mmol, 2.0 equiv.) in mesitylene
(2 mL) was stirred for 20 h at 176 8C. Then ethyl acetate (50 mL)
was added. The mixture was washed with aqueous NaOH (1 mol/L,
50 mL) and brine (50 mL) and dried over Na2SO4. After evapora-
tion, the residue was purified by column chromatography (silica
3. Results and discussion
Initially, aniline 1a and phenylethanol 2a were chosen as model
substrates to explore and optimize their reaction for N-alkylated
amine 3a. It was found that when AlCl3 was employed as a Lewis
Please cite this article in press as: Y.-Q. Li, et al., Direct N-alkylation of amines with alcohols using AlCl3 as a Lewis acid, Chin. Chem. Lett.
(2014), http://dx.doi.org/10.1016/j.cclet.2014.07.006

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3
Table 1
Optimizing reaction of amine 1a with alcohol 2a for N-alkylated amine 3a.a
Entry
Lewis acid
Equiv. of Lewis acid
Solvent
Temperature (8C)
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
AlCl3
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
2.0
Chlorobenzene
Chlorobenzene
Chlorobenzene
Chlorobenzene
Chlorobenzene
Xylene
140
140
140
140
140
140
140
166
176
166
10
–
BF3ÁEt2O
ZnCl2
BiCl3
–
–
Al2(SO4)3
AlCl3
Trace
13
21
36
34
80
AlCl3
Mesitylene
AlCl3
Mesitylene
AlCl3
Mesitylene
AlCl3
Mesitylene
a
The mixture of 1a (3.28 mmol), 2a (1.64 mmol) and Lewis acid in solvent (2 mL) was stirred for 4 h.
b
Isolated yield.
Table 2
AlCl3-mediated reaction of amine 1 with alcohol 2 for N-alkylated amine 3.
Entry
R
Alkyl
Amine 3
Yielda (%)
1b
Ph
1a
1a
1a
1a
1a
1b
1c
1d
1a
1e
1e
1f
Ph(CH2)2
Ph(CH2)3
CH3(CH2)3
CH3(CH2)4
CH3(CH2)5
Ph(CH2)3
Ph(CH2)3
Ph(CH2)3
PhCH2
2a
2b
2c
2d
2e
2b
2b
2b
2f
PhNH(CH2)2Ph
PhNH(CH2)3Ph
PhNH(CH2)3CH3
PhNH(CH2)4CH3
PhNH(CH2)5CH3
3a
3b
3c
3d
3e
3f
80
84
55
41
58
76
66
64
57
40
62
66
83
51
2b
Ph
3b
Ph
4b
Ph
5b
Ph
6b
3-ClC6H4
3-CH3C6H4
4-CH3C6H4
Ph
3-ClC6H4NH(CH2)3Ph
3-CH3C6H4NH(CH2)3Ph
4-CH3C6H4NH(CH2)3Ph
PhNHCH2Ph
7b
3g
3h
3i
8b
9c
10d
11d
12d
13e
14f
CH3(CH2)7
CH3(CH2)7
Ph(CH2)2
CH3(CH2)3
Ph
Ph(CH2)2
Ph(CH2)3
Ph(CH2)3
Ph(CH2)3
2a
2b
2b
2b
2g
CH3(CH2)7NH(CH2)2Ph
CH3(CH2)7NH(CH2)3Ph
Ph(CH2)2NH(CH2)3Ph
CH3(CH2)3NH(CH2)3Ph
3j
3k
3l
1g
1a
3m
3n
a
Isolated yields.
b
c
d
e
f
2.0 equiv. AlCl3, 2.0 equiv. 1a–d, mesitylene, 166 8C, 4 h.
1.0 equiv. AlCl3, 2.0 equiv. 1a, mesitylene, 100 8C, 12 h.
2.0 equiv. AlCl3, 2.0 equiv. 1e–f, 4.0 equiv. diethylamine, mesitylene, 176 8C, 20 h.
2.0 equiv. AlCl3, 3.0 equiv. 1 g, mesitylene, 176 8C, 20 h.
2.0 equiv. AlCl3, 5.0 equiv. 1a, mesitylene, 166 8C, 4 h.
acid, the desired N-alkylated amine 3a was obtained in 10% yield
using chlorobenzene as a solvent at 140 8C (Table 1, entry 1).
Encouraged by this result, other Lewis acids were tested. BF3ÁEt2O,
ZnCl2, and BiCl3 did not initiate the reaction, and Al2(SO4)3 led to
only a trace amount of 3a (Table 1, entries 2–5). When xylene was
employed as a solvent, a similar yield of 3a was obtained (Table 1,
entry 6). Using mesitylene as a solvent resulted in the improve-
ment of the yield (Table 1, entry 7; also see Table S1 in Supporting
Information). When the reaction temperature was raised to 166 8C,
the yield of 3a was increase to 36% (Table 1, entry 8). However,
further raising the reaction temperature to 176 8C had no favorable
effect on the yield of 3a (Table 1, entry 9). To our delight, when
loading of AlCl3 was increased to 2 equiv., the yield of 3a was
remarkably improved to 80% (Table 1, entry 10). Thus, the
optimized reaction should be performed in the presence of AlCl3
(2 equiv.) using mesitylene as a solvent under 166 8C.
amines 3a–h (Table 2, entries 1–8). Probably due to the better
activity of the hydroxyl group in benzyl alcohol 2f as compared to
the alcohols 2a–e, its substitution reaction with aniline 1a
proceeded at a lower temperature (Table 2, entry 9). Under the
same reaction conditions, switching arylamines 1a–d to aliphatic
amines 1e–f led to no desired N-alkylated product. This may be
because aliphatic amines 1e–f, which has stronger basicity as
compared to aryl amines 1a–d, bound more tightly with AlCl3.
Gratifyingly, when an excess of diethylamine was added, the
substitution reactions of aliphatic amines 1e–f with alcohols 2a–b
were able to occur at 176 8C, affording the desired N-alkylated
amines 3j–l (Table 2, entries 10–12). Diethylamine itself as a
secondary amine did not perform the N-alkylation reaction readily
with alcohols 2a–b under the same conditions. Therefore,
After we established the optimized reaction conditions, various
amines 1 and alcohols 2 were probed to evaluate the generality of
the N-alkylation reaction. It was found that in the presence of AlCl3,
various arylamines 1a–d underwent the substitution reaction
readily with alcohols 2a–e at 166 8C to give the desired N-alkylated
Scheme 1. AlCl3-mediated reaction of diethylamine 1h with benzyl alcohol 2f for N-
alkylated amine 3o.
Please cite this article in press as: Y.-Q. Li, et al., Direct N-alkylation of amines with alcohols using AlCl3 as a Lewis acid, Chin. Chem. Lett.
(2014), http://dx.doi.org/10.1016/j.cclet.2014.07.006

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Scheme 2. The possible mechanism of amines 1 with alcohols 2 for N-alkylated amines 3.
diethylamine in this reaction may displace aliphatic amines 1e–f in
AlCl3–amine complexes 4c to form AlCl3–diethylamine complex
4d, which may more easily release diethylamine and regenerate
AlCl3 due to its lower boiling point. For n-butyl amine 1g, which
has a low boiling point as well, its substitution reaction with
alcohol 2b proceeded smoothly in the absence of diethylamine,
affording the expected amine 3m in a high yield (Table 2, entry 13).
It was also found that, similar to the above primary alcohols,
secondary alcohol 2g could also react expediently with aniline 1a
to afford the N-alkylated amine 3n at 166 8C (Table 2, entry 14).
Although primary amines 1a–d underwent the substitution
(Nos. 21072091 and 21372195) and the Low Carbon Fatty Amine
Engineering Research Center of Zhejiang Province (No.
2012E10033) are gratefully acknowledged.
Appendix A. Supplementary data
Supplementary data associated with this article can be found,
in the online version, at http://dx.doi.org/10.1016/j.cclet.2014.07.
006.
reaction with various alcohols 2a–f, diethylamine 1h as
a
References
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2f as an active alcohol to furnish the desired alkyl amine 3o
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The possible mechanism of the N-alkylation reaction of amines
1 with alcohols 2 is outlined in Scheme 2. First, amines 1a–d, 1g, or
1e–f may combine with AlCl3 to form the corresponding
complexes 4a, 4b or 4c, respectively. Because arylamines 1a–d
are weaker bases, their binding with AlCl3 in 4a is not fast. Thus
complex 4a is easily decomposed into amines 1a–d and AlCl3 by
heating. For complex 4b, heating may lead to its release of low
boiling point amine 1g and regenerate AlCl3. Because the basicity
of diethylamine as a secondary aliphatic amine is stronger than
that of primary aliphatic amine, diethylamine may replace primary
aliphatic amines 1e–f in complex 4c to form complex 4d, which
then releases diethylamine with regenerating AlCl3 by heating.
Subsequently, alcohol 2 combines with AlCl3 to form complex 5,
activating the C–O bond. Finally, amine 1 nucleophilically attacks
complex 5 to produce N-alkylated amine 3.
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4. Conclusion
In conclusion, we have developed an N-alkylation reaction of
amines 1 with alcohols 2 using inexpensive AlCl3 without any
ligand or additive. Either aromatic or aliphatic amines and primary
or secondary alcohols perform the AlCl3-mediated reaction
smoothly to afford various N-alkylated amines.
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Acknowledgments
Financial supports from MOST of China (973 program, No.
2011CB808600), National Natural Science Foundation of China
Please cite this article in press as: Y.-Q. Li, et al., Direct N-alkylation of amines with alcohols using AlCl3 as a Lewis acid, Chin. Chem. Lett.
(2014), http://dx.doi.org/10.1016/j.cclet.2014.07.006

G Model
CCLET-3068; No. of Pages 5
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Please cite this article in press as: Y.-Q. Li, et al., Direct N-alkylation of amines with alcohols using AlCl3 as a Lewis acid, Chin. Chem. Lett.
(2014), http://dx.doi.org/10.1016/j.cclet.2014.07.006