Tri-n-butylphosphane catalyzed ring opening of aziridines with secondary amines

Article abstract of DOI:10.1016/j.cclet.2012.04.003

Ring opening of aziridine with dialkyl amine took place readily in the presence of catalytic amounts of tri-n-butylphosphane (10 mol%) in the mixture of CH₃CN/H₂O (10:1), giving corresponding vicinal diamines in mediate to high yield

Full text of DOI:10.1016/j.cclet.2012.04.003

Available online at www.sciencedirect.com
Chinese Chemical Letters 23 (2012) 657–660
www.elsevier.com/locate/cclet
Tri-n-butylphosphane catalyzed ring opening of
aziridines with secondary amines
*
Wan Xuan Zhang , Li Su, Wei Gang Hu, Jie Zhou
Ministry of Education Key Laboratory for the Synthesis and Application of Organic Functional Molecules,
Hubei University, Wuhan 430062, China
Received 12 January 2012
Available online 14 May 2012
Abstract
Ring opening of aziridine with dialkyl amine took place readily in the presence of catalytic amounts of tri-n-butylphosphane
(10 mol%) in the mixture of CH3CN/H2O (10:1), giving corresponding vicinal diamines in mediate to high yields (58–95%) with
good regioselectivitie, while aromatic secondary amine could not react under the same conditions. Tri-n-butylphosphane exhibited
different catalytic selectivity to amines from Lewis acid catalysts.
# 2012 Wan Xuan Zhang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Aziridines; Ring-opening reaction; Secondary amine; Tri-n-butylphosphane; Vicinal diamine
Vicinal diamines are medicinally, and synthetically important compounds [1]. Though the metal-mediated and
metal-catalyzed diamination of olefins presents an effective strategy to access vicinal diamines [2], the ring opening of
aziridines with amines is one of the most straightforward synthetic methods [3]. The reactions of aziridines with
secondary amines afford b-amino tertiary amines, which are also precursor of some biologically active compounds
and catalysts [1,4]. In contrast to ring opening of aziridines with primary amines, fewer methods are available for the
ring opening of aziridines with secondary amines. Tantalum (V) chloride [3c] and lithium perchlorate [5] have been
utilized as catalysts for ring opening of aziridines with secondary amines, but aliphatic amines failed to react with
aziridines in the presence of tantalum (V) chloride, while the behavior of acyclic dialkyl amines catalyzed by lithium
perchlorate were not disclosed. Ytterbium triflate [6] and bistrifluoromethanesulfonimidate (LiNTf2) [7] could
catalyze the reactions of aziridines with N-dialkyl amines respectively, but these methods have the limitations such as
precious catalysts and longer reaction times. The above catalysts used in the reactions are Lewis acids. Recently, we
found that tri-n-butyl phosphane (n-Bu3P), which is a Lewis base, can be used efficiently as a catalyst for the ring
opening of aziridines with aliphatic secondary amines in the mixture of CH3CN/H2O (10:1), while secondary aryl
amines did not react under the same conditions. In the reactions, both acyclic and cyclic diaylkyl amines led to
corresponding 1,2-diamines in good to high yields with high regioselectivities (Scheme 1).
* Corresponding author.
E-mail address: zhangwx@hubu.edu.cn (W.X. Zhang).
1001-8417/$ – see front matter # 2012 Wan Xuan Zhang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
http://dx.doi.org/10.1016/j.cclet.2012.04.003

658
W.X. Zhang et al. / Chinese Chemical Letters 23 (2012) 657–660
R2
R1
R1
TsHN
R2
10 mol % n-Bu3P
CH3CN/H2O
+ R'R''NH
N
NR'R''
Ts
R1 = alkyl, Ph; R2 = H, alkyl; R',R'' = alkyl
Scheme 1. The ring opening reaction of aziridines with aliphatic secondary amines.
1. Experimental
Melting points were determined on a WRS-1A apparatus, and uncorrected. IR spectra were recorded on a PE
(spectrum one) infrared spectrometer. 1H and 13C NMR spectra were recorded on varian unity INOVA 600 (600 MHz)
instruments in CDCl3. Mass spectra (EI-MS) were recorded on a HP 5989 mass spectrometer, and elemental analyses
were recorded on Vario EL III.
General procedure for the ring opening of aziridines with secondary amines: Aziridines 1 (0.5 mmol) and
secondary amines (0.75 mmol) were added to a stirred solution of n-Bu3P (10 mol%) in the mixture solvent of
acetonitrile (2 mL) and H2O (0.2 mL). The reaction mixture refluxed under an Ar atmosphere. After the reaction was
completed (monitored by TLC), the solvent was removed under reduced pressure, and the residue was purified by
chromatography on silica gel to afford pure products 3.
2. Results and discussion
The reaction conditions for the ring opening reaction catalyzed by n-Bu3P were investigated using N-tosycyclo-
hexeneimine (1a) and diethylamine as substrates (Scheme 2; Table 1). Benzene, 1,4-dioxane, CH3CN and the mixture
of CH3CN and water were used as solvents respectively in the reaction (Table 1, entries 1–7). The highest yield (83%)
of 3aAwas obtained in the mixture of CH3CN and water (CH3CN/H2O = 10:1) under reflux within 12 h (Table 1, entry
4). Increases in the amount of H2O in the solvent reduced the yield of 3aA, and 4a was obtained as a main side product,
which resulted from the water nucleophilic addition to 1a (Table 1, entries 4–6). Relatively low temperature was not
good for the reaction (Table 1, entry 7). These results showed that the presence of a minor amount of water in the
solvent CH3CN remarkably promoted the reaction. When the reaction was run in the mixture of acetonitrile and H2O
(10/1) without catalyst n-Bu3P under reflux, no conversion took place after 48 h.
Further investigation shown 10 mol% of n-Bu3P was sufficient in the reaction, so various aziridines and secondary
amines were tested in the mixture of acetonitrile and H2O (10/1) in the presence of 10 mol% n-Bu3P under reflux
(Table 2). It can be seen that all aziridines 1a–1e derived from cyclic or acyclic alkenes are suitable substrates to react
with diethylamine (2A), di-n-hexylamine (2B), pyrrolidine (2C) and piperidine (2D) respectively providing
corresponding 1,2-diamines in mediate to high yields (58–95%). Acyclic terminal aziridines 1c–1e gave highly
regioselective adducts from the attack at the less hindered carbon (entries 9–18 in Table 2). It is interesting that phenyl
aziridine 1c underwent cleavage in a regioselective manner with preferential attack at the terminal carbon as shown in
Table 2 (entries 9–11), which is opposite to that in the Lewis acid catalyzed reaction [6].
The reactivity of a secondary amine depends on its structure. Cyclic amine pyrrolidine 2C took the shortest time
(entries 3, 7, 10, 14, 17 in Table 2) to complete the reaction, whereas di-n-hexyl amine 2B took the longest time (entries
2, 6, 13, 16 in Table 2) when they reacted with a same aziridine. This might resulted from the different hindrance
between 2C and 2B. Aryl amines, such as N-methyl aniline and diphenyl amine, could not react with aziridines 1a due
to the low nucleophility of aryl amine in our investigation.
The mechanism of the ring opening might be the same as that reported in literature (Scheme 3) [8]. The reaction is
triggered by the attack for tributylphosphine to aziridine affording a phosphonium 5. The anion R0R00Nꢀ, which is
resulted from the deprotonation of R0R00NH by the phosphonium 5 or the ring-opened intermediate 7, acts as a
necleophile in the ring opening reaction of aziridine.
NHTs
NHTs
n-Bu3P
+
HN(C2H5)2
NTs
Solvent
OH
4a
N(C2H5)2
3aA
1a
2A
Scheme 2. The reaction of aziridine 1a with diethylamine.

W.X. Zhang et al. / Chinese Chemical Letters 23 (2012) 657–660
659
Table 1
Conditions for the reaction of 1a with diethylamine.a
Entry
Solvent
Temperature
Time (h)
Yield (%)b
1
2
3
4
5
6
7
Benzene
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
25 8C
36
80
24
12
10
10
48
Complex
55
1,4-Dioxane
CH3CN
63
CH3CN:H2O (10:1)
CH3CN:H2O (3:1)
CH3CN:H2O (1:3)
CH3CN:H2O (10:1)
83
71
48
Trace
a
15 mol% of n-Bu3P was added in the reaction.
b
Isolated yield.
Table 2
Bu3P catalyzed ring opening of aziridines with secondary amines.
Entrya
Aziridine
R0R00NHb
Product
Time (h)
Yield (%)c
1
2
3
4
2A
2B
2C
2D
3aA, R0 = R00 = Et
12
15
2
83
90
95
91
NHTs
3aB, R0 = R00 = n-hexyl
3aC, R0, R00 = -(CH2)4-
3aD, R0, R00 = -(CH2)5-
N
Ts
NR'R"
1a
4
5
6
7
8
2A
2B
2C
2D
3bA, R0 = R00 = Et
7
14
4
89
86
92
95
NHTs
NR'R"
3bB, R0 = R00 = n-hexylꢀ
N
Ts
3bC, R0, R00 = ꢀ(CH2)4
1b
ꢀ
3bD, R0, R00 = ꢀ(CH2)5
8
3cA, R0 = R00 = Et
5
4
5
58
78
91
TsHN
Ph
9
2A
2C
2D
ꢀ
ꢀ
3cC, R0, R00 = ꢀ(CH2)4
NTs
10
11
NR'R"
3cD, R0, R00 = ꢀ(CH2)5
1c
(CH2)3CH3
NHTs
12
13
14
2A
2B
2C
3dA, R0 = R00 = Et
3
4
1
91
82
89
TsN
"RR'N
3dB, R0 = R00 = n-hexylꢀ
3dC, R0, R00 = ꢀ(CH2)4
1d
(CH2)15CH3
NHTs
15
16
17
18
2A
2B
2C
2D
3eA, R0 = R00 = Et
2
94
71
83
78
TsN
R''R'N
3eB, R0 = R00 = n-hexylꢀ
4.5
1
(CH2)15CH3
3eC, R0, R00 = ꢀ(CH2)4
1e
ꢀ
3eD, R0, R00 = ꢀ(CH2)5
2
a
Reaction catalyzed by 10 mol% Bu3P in a mixture of CH3CN and H2O (v/v = 10/1) under reflux.
2A = diethylamine, 2B = di-n-hexylamine, 2C = pyrrolidine, 2D = piperidine.
Isolated yield [9].
b
c
R1
NTs
R2
R1
R1
R2
R1
R2
NTs
NTs
NTs
R'R''NH
R1
R2
7
R'R''N
PBu3
NR'R''
PBu3
NHTs
5
PBu3
R2
R1
R2
6
NHTs
NR'R''
R'R''NH
Scheme 3.

660
W.X. Zhang et al. / Chinese Chemical Letters 23 (2012) 657–660
We have demonstrated a simple, convenient and efficient procedure for the ring opening of N-tosyl aziridines with
dialkyl amines in the presence of Bu3P in the mixture of acetonitrile and H2O (10/1). Both cyclic and acyclic dialkyl
amines could react with aziridines affording b-amino tertiary amines in high yield with good regioselectivity. In
contrast to the Lewis acid catalysts, tri-n-butylphosphane exhibited different catalytic selectivity between dialkyl and
aromatic secondary amine in the reaction.
Acknowledgment
This research was financially supported by the National Natural Science Foundation of China (No. 20872031).
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[9] Spectral data of selected compounds: N-(2-Diethylaminocyclopentyl)-4-methylbenzenesulfonamide (3bA): mp 89.3–90.2 8C. 1H NMR
(600 MHz, CDCl3): d 7.75 (d, 2H, J = 7.2 Hz), 7.30 (br d, 2H, J = 7.2 Hz), 4.91 (br s, 1H), 2.85 (m, 1H, NCH), 2.75 (m, 1H, NCH), 2.43
(s, 3H), 2.29 (q, 4H, J = 3.6), 2.00 (m, 1H), 1.53–1.63 (m, 3H), 1.46 (m, 1H), 1.29 (m, 1H), 0.84 (t, 6H, J =6.9 Hz); IR (KBr) n: 3254, 1596, 1437,
1324, 1155, 1093 cmꢀ1. EI-MS: m/z (%) 310 (M+, 0.3), 155, 112 (100), 91, 44; Anal. calcd. for C16H26N2O2S: C, 61.90; H, 8.44; N, 9.02. Found:
C, 61.82; H, 8.24; N, 8. 90.;
N-(2-Dihexylaminocyclopentyl)-4-methylbenzenesulfonamide (3bB): Colorless oil. 1H NMR (600 MHz, CDCl3): d 7.71 (d, 2H, J = 8.4 Hz),
7.26 (br d, 2H, J = 8.4 Hz), 4.85 (br s, 1H), 2.75–2.79 (m, 1H, NCH), 2.68–2.73(m, 1H, NCH), 2.38 (s, 3H), 2.10–2.16 (m, 4H,), 1.98–2.01 (m,
1H), 1.48–1.60 (m, 5H), 1.02–1.31 (m, 16H), 0.85 (t, 6H, J = 7.2 Hz); IR (KBr) n: 3278, 1599, 1455, 1331, 1162, 1094 cmꢀ1. EI-MS: m/z (%)
422 (M+, 0.5), 224 (100), 155, 91, 44; Anal. calcd. for C24H42N2O2S: C, 68.20; H, 10.02; N, 6.63. Found: C, 68.32; H, 9.97; N, 6.64.;
4-Methyl-N-(2-pyrrolidin-1-yl-cyclopentyl)benzenesulfonamide (3bC): mp 98.5–99.2 8C. 1H NMR (600 MHz, CDCl3): d 7.73 (d, 2H,
J = 8.4 Hz), 7.27 (br d, 2H, J = 8.4 Hz), 4.62 (br s, 1H), 3.35 (q, 1H, J = 6.6 Hz, NCH), 2.43 (s, 3H), 2.33–2.42 (m, 4H), 2.14 (m, 1H),
1.29–1.84 (m, 10H); IR (KBr) n: 3253, 1598, 1449, 1322, 1160, 1094 cmꢀ1. EI-MS: m/z (%) 308 (M+, 0.6), 224, 155, 110 (100), 91, 44; Anal.
calcd. for C16H24N2O2S: C, 62.30; H, 7.84; N, 9.08. Found: C, 62.51; H, 7.81. N, 9.09.;
4-Methyl-N-(2-piperidin-1-yl-cyclopentyl)benzenesulfonamide (3bD): mp 105.1–106.3 8C. 1H NMR (600 MHz, CDCl3): d 7.76 (d, 2H,
J = 8.4 Hz), 7.31 (br d, 2H, J = 8.4 Hz), 5.11 (br s, 1H), 3.10 (q, 1H, J = 7.8, NCH), 2.55 (q, 1H, J = 9.0), 2.43 (s, 3H), 2.19–2.30 (m, 4H), 1.82–
1.97 (m, 1H), 1.25–1.62 (m, 9H), 0.93–0.95 (m, 2H); IR (KBr) n: 3232, 1598, 1435, 1323, 1155, 1093 cmꢀ1. EI-MS: m/z (%) 322 (M+, 0.4), 155,
124 (100), 91, 78, 44; Anal. calcd. for C17H26N2O2S: C, 63.32; H, 8.13; N, 8.69. Found: C, 63.21; H, 8.01; N, 8.64.