Ring opening of N-sulfonyl aziridines by amines in silica-water

Article abstract of DOI:10.1002/cjoc.201400300

Ring opening reactions of N-sulfonyl aziridines by primary and secondary amines in silica gel (SG)-water system were achieved, which provided a mild, practical and environmentally benign method to synthesize mono- and bis-sulfonyl substituted amines. When

Full text of DOI:10.1002/cjoc.201400300

FULL PAPER
DOI: 10.1002/cjoc.201400300
Ring Opening of N-Sulfonyl Aziridines by Amines
in Silica-Water
Tiantian Li,a Xiaosi Ma,a Junmei Qi,a Feifei Sun,a,b and Ning Ma*,a,b
a Department of Chemistry, School of Science, Tianjin University, Tianjin 300072, China
b Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, China
Ring opening reactions of N-sulfonyl aziridines by primary and secondary amines in silica gel (SG)-water sys-
tem were achieved, which provided a mild, practical and environmentally benign method to synthesize mono- and
bis-sulfonyl substituted amines. When primary and secondary amines were used in excess, they reacted with
N-sulfonyl aziridines smoothly at room temperature, mainly affording 1∶1 ring opening products. Reactions of
primary amines with 2 equiv. of aziridines produced 2∶1 ring opening products. Some 1∶1 products can be cy-
clized with CS2 to synthesize N-sulfonyl cyclothioureas also in water.
Keywords aziridines, ring opening, amines, silica gel, reactions in water
Introduction
aziridines are generally performed by Lewis acids or
Brönsted acids catalysis in organic media.[38-40] In recent
years, new approaches for the ring opening of aziridines,
including microwave acceleration[41] as well as catalysis
by trialkylphosphine,[42,43] N-heterocyclic carbene[44]
and tetrabutylammonium bromide,[45] have been dem-
onstrated. In most of the aforementioned literatures, the
substrates are aziridines or N-sulfonyl aziridines with at
least one group at carbon atoms of the ring. Moasser
and co-workers reported the reactions of the para-sub-
stituted anilines with N-tosylaziridine in water, afford-
ing useful N-aryl-N′-tosylethylenediamines ligands.[46]
However, most of the reactions were carried out at 50
℃ to ensure the complete conversion of the anilines.
Herein, we wish to report ring opening reactions of
N-sulfonylaziridines by primary and secondary amines
in SG-H2O system at room temperature (Scheme 1).
According to the criteria of green chemistry, water is
an ideal media for chemical reactions due to its low cost,
safety and environmental compatibility. Although or-
ganic reactions in/on water have boosted in the past
decades, water has not been commonly used as a solvent
for organic reactions because of the poor solubility of
most organic molecules in pure water.[1-7] To solve this
problem, organic co-solvents and phase transfer cata-
lysts (PTC) were introduced into aqueous reactions.[8-12]
Recently, Minakata and co-workers have developed
the ring formation and opening reactions of aziridines in
silica gel (SG)-water system.[13-16] SG accelerated the
reactions like the function of PTC. Because SG is cheap,
nontoxic, recyclable and environmentally benign,
SG-water system provides a practical method to aque-
ous reactions. Moreover, other SG-promoted reactions
have been reported in recent years.[17-27] SG was com-
monly thought to promote these reactions due to the
moderate acidity and adsorptive nature of its surface.
Inspired by these prominent works, we have proposed
synthetic methods toward N-sulfonyl cyclothioureas
from N-sulfonyl diamines and CS2 in water, which
could be promoted by SG.[28,29]
Scheme 1 The 1∶1 reaction of aziridines and amines
O2
S
R2
sillica gel, water
R3R4NH
2a - 2f
R1
+
N
r.t.
1a - 1c
1a, R1 = p-tolyl, R2 = H;
1b, R1 = Ph, R2 = H;
1c, R1 = p-tolyl, R2 = Et
R3,R4 = H,
alkyl, aryl
In organic synthesis, aziridine and its derivatives are
important intermediates to prepare a variety of com-
pounds, such as functionalized amines and nitrogen het-
erocyles.[30-33] Due to the ring strains, three-membered
rings, such as aziridines, epoxides and cyclopropanes,
are easily opened.[34-37] The ring opening reactions of
R3
N
R2
O2
S
R1
N
R4
H
3a - 3m
*
E-mail: mntju@tju.edu.cn; Tel.: 0086-022-27403475; Fax: 0086-022-27403475
Received May 9, 2014; accepted August 16, 2014; published online October 8, 2014.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201400300 or from the author.
Chin. J. Chem. 2014, 32, 1135—1142 © 2014 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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Li et al.
FULL PAPER
Experimental
General
N-(2-(Cyclohexylamino)ethyl)-4-methylbenzene-
sulfonamide (3a) Yield 66%; pale yellow solid; m.p.
60－61 ℃; H NMR (400 MHz, CDCl3) δ: 0.96－1.78
1
All reagents were purchased from commercial
sources and used without any further purification.
N-Sulfonyl aziridines were prepared according to the
method reported in the literature.[47] The melting points
were obtained on a Laboratory Devices X-4 melting
(m, 10H, cyclohexane-H), 2.24 (m, 1H, cyclohexane-H),
2.45 (s, 3H, CH3), 2.72 (t, J＝5.4 Hz, 2H, cyclohex-
ane-NHCH2), 2.97 (t, J＝5.7 Hz, 2H, SO2NHCH2), 7.33
(d, J＝8.0 Hz, 2H, ArH), 7.77 (d, J＝8.2 Hz, 2H, ArH);
13C NMR (100 MHz, CDCl3) δ: 21.49, 24.93, 26.0, 33.7,
43.0, 44.8, 56.0, 127.2, 129.6, 137.0, 143.3; IR (KBr)
vmax: 3281, 1334, 1160 cm−1; HRMS (ESI) m/z: (M＋
H ＋ ) calcd for C15H24N2O2SH ＋ 297.1637; found
297.1635.
1
apparatus and are uncorrected. H NMR and 13C NMR
spectra were recorded in CDCl3 using TMS as an inter-
nal standard on a Bruker AVANCE III 400 (or 600)
spectrometer at 400 (or 600) MHz and 100 (or 150)
MHz respectively. HRMS data were obtained on a
Bruker microOTOF-Q II (or Agilent Accurate-Mass-Q-
TOF MS 6520) instrument.
N-(2-(Cyclohexylamino)ethyl)benzenesulfon-
amide (3b) Yield 58%; pale yellow solid; m.p. 77－
1
78 ℃; H NMR (400 MHz, CDCl3) δ: 0.95－1.78 (m,
10H, cyclohexane-H), 2.23 (m, 1H, cyclohexane-H),
2.72 (t, J＝5.7 Hz, 2H, cyclohexane-NHCH2), 2.99 (t,
J＝5.6 Hz, 2H, SO2NHCH2), 7.54 (t, J＝7.4 Hz, 2H,
ArH), 7.60 (t, J＝7.3 Hz, 1H, ArH), 7.90 (d, J＝7.3 Hz,
1H, ArH); 13C NMR (100 MHz, CDCl3) δ: 24.9, 26.0,
33.7, 43.0, 44.8, 56.0, 127.1, 129.0, 132.5, 139.9; IR
(KBr) vmax: 3280, 1328, 1157 cm−1. HRMS (ESI) m/z:
(M＋H＋) calcd for C14H22N2O2SH＋ 283.1480; found
283.1477.
General procedure for synthesis of compounds 3a－
3m
SG (0.1 g, 40－60 mesh) was stirred to a dispersion
of N-sulfonyl aziridines (1 mmol) and amines (2 mmol
2a－2e or 1.5 mmol 2f) in water (1 mL). The reaction
mixture was stirred at room temperature for 12－14 h.
After completion of the reaction (screened by TLC),
ethyl acetate (10 mL) was added. The mixture was
stirred for 10 min and centrifuged. The upper layer was
separated and the lower layer was extracted with ethyl
acetate (10 mL×2) repeatedly. The combined ethyl
acetate layer was dried over anhydrous magnesium sul-
fate. Then the solvent was removed under reduced
pressure and the residue was purified by flash column
chromatography on SG using a mixture of ethyl acetate,
petroleum ether and triethylamine as eluents to give the
desired products.
N-(2-(tert-Butylamino)ethyl)-4-methylbenzene-
sulfonamide (3c) Yield 53%; white solid; m.p. 62－
1
64 ℃; H NMR (400 MHz, CDCl3) δ: 1.02 (s, 9H,
C(CH3)3), 2.44 (s, 3H, PhCH3), 2.63 (t, J＝5.5 Hz, 2H,
C(CH3)NHCH2), 2.96 (t, J＝5.5 Hz, 2H, SO2NHCH2),
7.31 (d, J＝7.8 Hz, 2H, ArH), 7.77 (d, J＝8.0 Hz, 2H,
ArH); 13C NMR (100 MHz, CDCl3) δ: 21.5, 29.0, 41.0,
43.6, 50.3, 127.2, 129.6, 137.0, 143.2; IR (KBr) vmax
:
3427, 1336, 1161 cm−1; HRMS (ESI) m/z: (M＋H＋)
calcd for C13H22N2O2SH＋ 271.1475; found 271.1481.
N-(2-(tert-Butylamino)ethyl)benzenesulfon-
amide (3d) Yield 48%; white solid; m.p. 86－88 ℃;
1H NMR (400 MHz, CDCl3) δ: 1.02 (s, 9H, C(CH3)3),
2.63 (t, J＝5.6 Hz, 2H, C(CH3)NHCH2), 3.00 (t, J＝5.6
Hz, 2H, SO2NHCH2), 7.53 (t, J＝7.4 Hz, 2H, ArH),
7.59 (t, J＝7.1 Hz, 1H, ArH), 7.90 (d, J＝7.6 Hz, 2H,
ArH); 13C NMR (100 MHz, CDCl3) δ: 29.0, 41.0, 43.6,
50.3, 127.1, 129.1, 132.5, 140.0; IR (KBr) vmax: 3449,
1321, 1163 cm−1; HRMS (ESI) m/z: (M＋H＋) calcd for
C12H20N2O2SH＋ 257.1324; found 257.1321.
General procedures for synthesis of compounds 4a－
4f
SG (0.2 g, 40－60 mesh) was stirred to a dispersion
of N-sulfonyl aziridines (2 mmol) and amines (1 mmol)
in water (2 mL). The reaction mixture was stirred at
room temperature or 40 ℃ for 9－14 h. After comple-
tion of the reaction (screened by TLC), compounds
4a－4f were obtained by procedure similar to the
preparation of 3a－3k.
General procedure for synthesis of compounds 5a
and 5b
4-Methyl-N-(2-(octylamino)ethyl)benzenesulfon-
1
amide (3e) Yield 50%; Yellow viscous liquid; H
To a stirred suspension of 3a or 3b (1.5 mmol) in
water (10 mL) was added potassium hydroxide (3.0
mmol) and carbon disulfide (2.0 mmol) at 45 ℃. After
the solid was dissolved, potassium chloroacetate (2.0
mmol) was added and the reaction mixture was stirred
for 5 h at 45 ℃. Then the reaction mixture was ex-
tracted with ethyl acetate (10 mL×3). The combined
organic layer was dried over anhydrous magnesium
sulfate overnight. The solvent was removed under re-
duced pressure and the residue was purified by flash
column chromatography on SG using a mixture of ethyl
acetate, petroleum ether and triethylamine as eluents to
give the desired products.
NMR (400 MHz, CDCl3) δ: 0.88 (t, J＝6.4 Hz, 3H,
octane-H), 1.25 (s, 12H, octane-H), 1.32 (t, J＝6.5 Hz,
2H, octane-H), 2.42 (s, 3H, PhCH3), 2.44 (m, 2H,
octane-H), 2.69 (t, J＝6.0 Hz, 2H, octane-NHCH2),
2.99 (t, J＝6.0 Hz, 2H, SO2NHCH2), 7.30 (d, J＝7.9 Hz,
2H, ArH), 7.75 (d, J＝8.1 Hz, 2H, ArH); 13C NMR (100
MHz, CDCl3) δ: 14.0, 21.5, 22.6, 27.2, 29.2, 29.4, 29.8,
31.8, 42.2, 47.9, 49.1, 127.12, 129.6, 137.0, 143.2; IR
(KBr) vmax: 3281, 1328, 1160 cm−1; HRMS (ESI) m/z:
(M＋H＋) calcd for C17H30N2O2SH＋ 327.2106; found
327.2107.
4-Methyl-N-(2-(phenylamino)ethyl)benzenesul-
1136
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© 2014 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2014, 32, 1135—1142

Ring Opening of N-Sulfonyl Aziridines by Amines in Silica-Water
fonamide (3f)[42] Yield 80%; white solid; m.p. 89－90
℃; H NMR (400 MHz, CDCl3) δ: 2.43 (s, 3H, CH3),
N-(2-(Diethylamino)ethyl)benzenesulfonamide
(3k) Yield 60%; yellow liquid; H NMR (400 MHz,
1
1
3.17 (s, 2H, PhNHCH2), 3.26 (s, 2H, SO2NHCH2), 3.94
(s, 1H, PhNH), 5.20 (s, 1H, SO2NH), 6.54 (d, J＝7.2 Hz,
2H, ArH), 6.75 (d, J＝6.5 Hz, 1H, ArH), 7.15 (t, J＝6.7
Hz, 2H, ArH), 7.29 (d, J＝6.9 Hz, 2H, ArH), 7.76 (d,
J＝7.3 Hz, 2H, ArH); 13C NMR (100 MHz, CDCl3) δ:
21.5, 42.3, 43.4, 113.0, 118.0, 127.1, 129.3, 129.8,
136.7, 143.6, 147.4; IR (KBr) vmax: 3056, 3310, 1319,
1154 cm−1; HRMS (ESI) m/z: (M＋H＋ ) calcd for
C15H18N2O2SNa＋ 313.0987; found 313.0986.
CDCl3) δ: 0.90 (t, J＝7.1 Hz, 6H, CH2CH3), 2.39 (q,
J＝7.0 Hz, 4H, CH2CH3), 2.48 (t, J＝5.8 Hz, 2H,
NCH2), 2.97 (t, J＝5.8 Hz, 2H, SO2NHCH2), 7.54 (t,
J＝7.4 Hz, 2H, ArH), 7.60 (t, J＝7.3 Hz, 1H, ArH),
7.90 (d, J＝7.3 Hz, 2H, ArH); 13C NMR (100 MHz,
CDCl3) δ: 11.6, 40.2, 46.2, 50.9, 127.1, 129.0, 132.5,
139.7; IR (KBr) vmax: 3295, 1330, 1163 cm−1; HRMS
(ESI) m/z: (M ＋ H ＋ ) calcd for C12H20N2O2SH ＋
257.1318; found 257.1320.
N-(2-(Phenylamino)ethyl)benzenesulfonamide (3g)
Yield 74%; white solid; m.p. 72－73 ℃; 1H NMR (400
MHz, CDCl3) δ: 3.22 (t, J＝5.7 Hz, 2H, PhNHCH2),
3.30 (t, J＝5.6 Hz, 2H, SO2NHCH2), 3.86 (s, 1H,
PhNH), 4.92 (s, 1H, SO2NH), 6.57 (d, J＝8.0 Hz, 2H,
ArH), 6.76 (t, J＝7.3 Hz, 1H, ArH), 7.17 (t, J＝7.7 Hz,
2H, ArH), 7.53 (t, J＝7.6 Hz, 2H, ArH), 7.61 (t, J＝7.3
Hz, 1H, ArH), 7.87 (d, J＝7.8 Hz, 2H, ArH); 13C NMR
(100 MHz, CDCl3) δ: 42.4, 43.5, 113.1, 118.2, 127.0,
129.2, 129.4, 132.8, 139.8, 147.3; IR (KBr) vmax: 3028,
3390, 1317, 1162 cm−1; HRMS (ESI) m/z: (M＋H＋)
calcd for C14H16N2O2SH＋ 277.1011; found 277.1010.
N-(2-((4-Methoxyphenyl)amino)ethyl)-4-methyl-
benzenesulfonamide (3h)[42] Yield 78%; white solid;
N-(1-((4-Methoxyphenyl)amino)butan-2-yl)-4-
methylbenzenesulfonamide (3l) Yield 65%; white
solid; m.p. 109－110 ℃; H NMR (600 MHz, CDCl3)
1
δ: 0.79 (t, J＝7.4 Hz, 3H, CH2CH3), 1.42－1.47 (m, 1H,
CH2CH3), 1.52－1.58 (m, 1H, CH2CH3), 2.42 (s, 3H,
PhCH3), 2.98 (dd, J＝12.8, 7.2 Hz, 1H, PhNHCH2),
3.09 (dd, J＝12.7, 4.6 Hz, 1H, PhNHCH2), 3.29－3.34
(m, 1H, SO2NHCH), 3.52 (s, 1H, PhNH), 3.74 (s, 3H,
OCH3), 4.69 (s, 1H, SO2NH), 6.42 (d, J＝8.8 Hz, 2H,
ArH), 6.72 (d, J＝8.8 Hz, 2H, ArH), 7.26 (d, J＝8.6 Hz,
2H, ArH), 7.75 (d, J＝8.1 Hz, 2H, ArH); 13C NMR (150
MHz, CDCl3) δ: 9.8, 21.5, 26.4, 48.5, 54.8, 55.8, 114.3,
114.8, 127.1, 129.6, 137.7, 141.8, 143.4, 152.4; IR (KBr)
vmax: 3260, 1316, 1159 cm−1; HRMS (ESI) m/z: (M＋
H ＋ ) calcd for C18H24N2O3SH ＋ 349.1580; found
349.1576.
1
m.p. 99－100 ℃; H NMR (400 MHz, CDCl3) δ: 2.42
(s, 3H, PhCH3), 3.15 (t, J＝5.7 Hz, 2H, PhNHCH2),
3.22 (t, J＝4.8 Hz, 2H, SO2NHCH2), 3.51 (s, 1H,
PhNH), 3.74 (s, 3H, OCH3), 4.79 (s, 1H, SO2NH), 6.51
(d, J＝8.9 Hz, 2H, ArH), 6.75 (d, J＝8.8 Hz, 2H, ArH),
7.29 (d, J＝8.0 Hz, 2H, ArH), 7.73 (d, J＝8.2 Hz, 2H,
ArH); 13C NMR (100 MHz, CDCl3) δ: 21.5, 42.4, 44.4,
55.8, 114.6, 114.9, 127.1, 129.8, 136.7, 141.5, 143.6,
152.6; IR (KBr) vmax: 3285, 1516, 1158 cm−1.
N-(1-(Cyclohexylamino)butan-2-yl)-4-methylben-
zenesulfonamide (3m) Yield 67%; Yellow viscous
1
liquid; H NMR (600 MHz, CDCl3) δ: 0.81 (t, J＝7.4
Hz, 3H, CH2CH3), 0.86－0.92 (m, 2H, cyclohexane-H),
1.11－1.19 (m, 3H, cyclohexane-H), 1.46－1.53 (m, 2H,
CH2CH3), 1.56－1.76 (m, 5H, cyclohexane-H), 2.10－
2.15 (m, 1H, cyclohexane-H), 2.42 (s, 3H, PhCH3),
2.46－2.54 (m, 2H, cyclohexane-NHCH2), 3.03－3.07
(m, 1H, SO2NHCH), 7.28 (d, J＝8.1 Hz, 2H, ArH),
7.75 (d, J＝8.1 Hz, 2H, ArH); 13C NMR (150 MHz,
CDCl3) δ: 9.8, 21.5, 24.9 (2C), 26.0, 26.3, 33.4 (2C),
48.6, 54.8, 56.0. 127.1, 129.3, 137.9, 143.0; IR (KBr)
vmax: 3283, 2929, 1327, 1159 cm−1; HRMS (ESI) m/z:
(M＋H＋) calcd for C17H28N2O2SH＋ 325.1944; found
325.1943.
N-(2-((4-Methoxyphenyl)amino)ethyl)benzene-
sulfonamide (3i) Yield 68%; white solid; m.p. 79－
1
80 ℃; H NMR (400 MHz, CDCl3) δ: 3.18 (t, J＝5.6
Hz, 2H, PhNHCH2); 3.23 (t, J＝5.2 Hz, 2H, SO2NH-
CH2), 3.50 (s, 1H, PhNH), 3.74 (s, 3H, －OCH3), 4.81
(s, 1H, SO2NH), 6.52 (d, J＝8.8 Hz, 2H, ArH), 6.75 (d,
J＝8.8 Hz, 2H, ArH), 7.51 (t, J＝7.5 Hz, 2H, ArH),
7.59 (t, J＝7.3 Hz, 1H, ArH), 7.86 (d, J＝7.3 Hz, 2H,
ArH); 13C NMR (100 MHz, CDCl3) δ: 42.4, 44.4, 55.8,
114.6, 114.9, 127.0, 129.2, 132.75, 139.7, 141.5, 152.6;
IR (KBr) vmax: 3057, 3254, 1313, 1158 cm−1; HRMS
(ESI) m/z: (M ＋ H ＋ ) calcd for C15H18N2O3SH ＋
307.1116; found 307.1115.
N,N'-((Cyclohexylazanediyl)bis(ethane-2,1-diyl))-
bis(4-methylbenzenesulfonamide) (4a) Yield 55%;
1
white solid; m.p. 95－96 ℃; H NMR (400 MHz,
CDCl3) δ: 1.05－1.71 (m, 10H, cyclohexane-H), 2.11 (s,
1H, cyclohexane-H), 2.45 (s, 6H, CH3), 2.51 (t, J＝5.8
Hz, 4H, NCH2), 2.86 (t, J＝5.1 Hz, 4H, SO2NHCH2),
5.00 (s, 2H, NH), 7.35 (d, J＝8.0 Hz, 4H, ArH), 7.80 (d,
J＝8.0 Hz, 4H, ArH); 13C NMR (100 MHz, CDCl3) δ:
21.5, 25.9, 26.0, 28.7, 41.5, 49.6, 59.2, 127.2, 129.8,
N-(2-(Diethylamino)ethyl)-4-methylbenzenesul-
1
fonamide (3j) Yield 56%; light yellow liquid; H
NMR (400 MHz, CDCl3) δ: 0.91 (t, J＝7.1 Hz, 6H,
CH2CH3), 2.38 (q, J＝7.2 Hz, 4H, CH2CH3); 2.45 (s,
PhCH3, 3H), 2.49 (t, J＝5.8 Hz, 2H, NCH2), 2.95 (t,
J＝5.8 Hz, 2H, SO2NHCH2), 7.33 (d, J＝8.0 Hz, 2H,
ArH), 7.78 (d, J＝8.2 Hz, 2H, ArH); 13C NMR (100
MHz, CDCl3) δ: 11.6, 21.5, 40.2, 46.2, 51.0, 127.1,
129.6, 136.8, 143.2; IR (KBr) vmax: 3289, 1331, 1162
cm−1; HRMS (ESI) m/z: (M＋H＋) calcd for C13H22N2-
O2SH＋ 271.1475; found 271.1478.
137.0, 143.4; IR (KBr) vmax: 3266, 2935, 1335, 1165
＋
cm−1; HRMS (ESI) m/z: (M ＋ H ) calcd for
C24H35N3O4S2H＋ 494.2147; found 494.2161.
N,N'-((tert-Butylazanediyl)bis(ethane-2,1-diyl))-
dibenzenesulfonamide (4b) Yield 53%; white sticky
1
solid; H NMR (400 MHz, CDCl3) δ: 0.98 (s, 9H,
C(CH3)3), 2.57 (t, J＝6.2 Hz, 4H, NCH2), 2.86 (t, J＝
Chin. J. Chem. 2014, 32, 1135—1142
© 2014 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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1137

Li et al.
FULL PAPER
6.0 Hz, 4H, SO2NHCH2), 4.97 (s, 2H, NH), 7.54 (t, J＝
7.2 Hz, 4H, ArH), 7.59 (t, J＝7.3 Hz, 4H, ArH), 7.89 (d,
J＝8.1 Hz, 2H, ArH); 13C NMR (100 MHz, CDCl3) δ:
27.0, 43.3, 50.5, 55.2, 127.0, 129.1, 132.6, 140.1; IR
(KBr) vmax: 3444, 1321, 1160 cm−1; HRMS (ESI) m/z:
(M＋H＋) calcd for C20H29N3O4S2H＋ 440.1678; found
440.1675.
N,N'-((Benzylazanediyl)bis(ethane-2,1-diyl))bis(4-
methylbenzenesulfonamide) (4c) Yield 63%; white
sticky solid; 1H NMR (400 MHz, CDCl3) δ: 2.43 (s, 6H,
PhCH3), 2.53 (t, J＝5.6 Hz, 4H, NCH2CH2), 2.94 (d,
J＝5.4 Hz, 4H, SO2NHCH2), 3.44 (s, 2H, PhCH2), 5.08
(s, 2H, NH), 7.15 (d, J＝6.2 Hz, 2H, ArH), 7.30 (t, J＝
7.3 Hz, 7H, ArH), 7.74 (d, J＝8.0 Hz, 4H, ArH); 13C
NMR (100 MHz, CDCl3) δ: 21.5, 40.7, 53.2, 58.5, 127.2,
127.4, 128.6, 128.9, 129.8, 136.7, 137.8, 143.4; IR (KBr)
vmax: 3446, 1325, 1159 cm−1; HRMS (ESI) m/z: (M＋
H ＋ ) calcd for C25H31N3O4S2H ＋ 502.1829; found
502.1832.
N,N'-((Benzylazanediyl)bis(ethane-2,1-diyl))di-
benzenesulfonamide (4d) Yield 70%; white sticky
solid; 1H NMR (400 MHz, CDCl3) δ: 2.53 (t, J＝5.7 Hz,
4H, NCH2CH2), 2.95 (q, J＝5.4 Hz, 4H, SO2NHCH2),
3.45 (s, 2H, PhCH2), 5.18 (s, 2H, NH), 7.16 (d, J＝7.2
Hz, 2H, ArH), 7.28 (d, J＝7.2 Hz, 3H, ArH), 7.51 (t,
J＝7.6 Hz, 4H, ArH), 7.58 (t, J＝7.2 Hz, 2H, ArH),
7.87 (d, J＝7.8 Hz, 4H, ArH); 13C NMR (100 MHz,
CDCl3) δ: 40.7, 53.3, 58.5, 127.1, 127.5, 128.6, 128.9,
129.2, 132.6, 137.7, 139.7; IR (KBr) vmax: 3445, 1316,
1160 cm−1; HRMS (ESI) m/z: (M＋H＋ ) calcd for
C23H27N3O4S2H＋ 474.1516; found 474.1522.
N,N'-(((2-Hydroxyethyl)azanediyl)bis(ethane-2,1-
diyl))bis(4-methylbenzenesulfonamide) (4e) Yield
47%; white solid; m.p. 78－79 ℃; 1H NMR (400 MHz,
CDCl3) δ: 2.44 (s, 6H, CH3), 2.55 (m, 6H, NCH2), 2.97
(t, J＝4.8 Hz, 4H, SO2NHCH2), 3.70 (t, J＝4.7 Hz, 2H,
CH2OH), 6.24 (s, 2H, NH), 7.36 (d, J＝8.0 Hz, 4H,
ArH), 7.82 (d, J＝8.2 Hz, 4H, ArH); 13C NMR (100
MHz, CDCl3) δ: 21.5, 40.9, 54.0, 55.6, 59.6, 127.1,
129.8, 136.9, 143.3; IR (KBr) vmax: 3431, 3284, 1325,
1159 cm−1; HRMS (ESI) m/z: (M＋H＋ ) calcd for
C20H29N3O5S2H＋ 456.1621; found 456.1626.
8.0 Hz, 2H, ArH), 7.79 (d, J＝8.2 Hz, 2H, ArH); 13C
NMR (100 MHz, CDCl3) δ: 21.7, 25.2, 25.3, 29.2, 42.1,
46.0, 55.3, 129.0, 129.2, 135.0, 144.8, 176.6; IR (KBr)
vmax: 3441, 2935, 1361, 1171 cm−1; HRMS (ESI) m/z:
(M＋H＋) calcd for C16H22N2O2S2Na＋ 361.1020; found
361.1035.
1-Cyclohexyl-3-(phenylsulfonyl)imidazolidine-2-
thione (5b) Yield 71%; white solid; m.p. 190－191
℃; 1H NMR (400 MHz, CDCl3) δ: 1.05－1.56 (m, 10H,
cyclohexane-H), 3.57 (t, J＝8.6 Hz, 2H, cyclohexane-
NCH2), 4.14 (t, J＝8.6 Hz, 2H, SO2NCH2), 4.35 (m, 1H,
cyclohexane-H), 7.52 (t, J＝7.7 Hz, 2H, ArH), 7.62 (d,
J＝7.4 Hz, 1H, ArH), 8.11 (d, J＝7.6 Hz, 2H, ArH); 13C
NMR (100 MHz, CDCl3) δ: 25.2, 25.3, 29.2, 42.1, 45.9,
55.4, 128.9, 129.0, 133.8, 138.0, 176.6; IR (KBr) vmax
:
3663, 2938, 1354, 1170 cm−1; HRMS (ESI) m/z: (M＋
H ＋ ) calcd for C15H20N2O2S2Na ＋ 347.0864; found
347.0854.
Crystal structure determinations
X-ray crystallographic analysis of 4a was performed
at 113 K by using a Brucker Smart 1000 CCD-X dif-
fractometer with Mo Kα radiation (λ＝0.71073 Å) and a
graphite monochromator. Crystal system: triclinic, P1.
Crystal dimensions: 0.26 mm×0.20 mm×0.18 mm.
Crystal data: Z＝4, a＝12.060 (2) Å, b＝15.661 (3) Å,
c＝16.751 (3) Å, α＝102.60 (3)°, β＝108.34 (3)°, γ＝
92.74(3)°, V＝2907.5(10) Å3. ρcalcd＝1.033 g/cm3, μ＝
0.219 mm–1, 26600 total reflections (2θmax＝50.0°),
10187 unique reflections (Rint＝0.044), R1＝0.0633
[I＞2(I)], wR2 (all data)＝0.2312, GOF＝1.081 (744
parameters) (CCDC-991013).
Results and Discussion
Initially we chose ring opening of N-tosylaziridine
(1a) by cyclohexylamine (2a) as model reaction. When
the solvent was selected from ethyl ether, THF, acetoni-
trile and ethanol, TLC analysis showed a variety of by-
products emerged at ambient temperature although 1a
was poorly converted. Notably, 1a was so easy to po-
lymerize in an organic solvent at raised temperature that
the reaction generated complicated products under re-
flux in the abovementioned solvents. Then water was
employed as the reaction media. However, 1a was dis-
solved in water so poorly that it reacted with the amine
slowly; sometimes the reaction mixture became viscous
and caused stirring trouble. Then SG was incorporated
into the reaction mixture and the ring opening in
SG-H2O system was achieved satisfactorily. We found
that the reaction was affected by the amount of SG. A
total of 1 g SG for 1 mmol 1a was too much to cause the
increase of 2∶1 ring opening product and other by-
products. Further experiments indicated that the type of
SG, either 40－60 mesh or 200－300 mesh for column
chromatography is not critical, which is somewhat dif-
ferent from the literature.[23] SG (40－60 mesh) was
preferred in this reaction because it facilitated the fol-
N,N'-(((2-Hydroxyethyl)azanediyl)bis(ethane-2,1-
diyl))dibenzenesulfonamide (4f) Yield 60%; white
sticky solid; 1H NMR (400 MHz, CDCl3) δ: 2.54 (t, J＝
4.9 Hz, 6H, NCH2), 2.99 (t, J＝4.8 Hz, 4H, SO2NH-
CH2), 3.70 (d, J＝4.1 Hz, 2H, CH2OH), 7.57 (m, 6H,
ArH), 7.94 (d, J＝7.0 Hz, 4H, ArH); 13C NMR (100
MHz, CDCl3) δ: 40.9, 53.9, 55.6, 59.6, 127.1, 129.2,
132.6, 139.9; IR (KBr) vmax: 3436, 1331, 1160 cm−1;
HRMS (ESI) m/z: (M＋H＋) calcd for C18H25N3O5S2Na＋
450.1133; found 450.1132.
1-Cyclohexyl-3-tosylimidazolidine-2-thione (5a)
1
Yield 51%; white solid; m.p. 193－194 ℃; H NMR
(400 MHz, CDCl3): δ 1.09－1.77 (m, 10H, cyclo-
hexane-H), 2.42 (s, 3H, CH3), 3.56 (t, J＝8.6 Hz, 2H,
cyclohexane-NCH2), 4.12 (t, J＝8.6 Hz, 1H, SO2NCH2),
4.36 (m, J＝11.8 Hz, 1H, cyclohexane-H), 7.31 (d, J＝
1138
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© 2014 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2014, 32, 1135—1142

Ring Opening of N-Sulfonyl Aziridines by Amines in Silica-Water
lowing filtration. Without water, the stirring was diffi-
cult and the reaction was not complete in 24 h. Grinding
the mixture in a mortar could accelerate the reaction and
1a was entirely consumed in 1 h. However, even with
large excess of cyclohexylamine the selectivity of the
reaction was not good and complicated products were
observed by TLC. Finally the optimum reaction condi-
tions were found as follows: 0.1 g SG (40－60 mesh)
for 1 mmol aziridine, 1∶2 ratio of N-sulfonyl aziridines
to amine, and room temperature.
Next, the reactions of different amines were investi-
gated. As summarized in Table 1, aliphatic and alicyclic
primary amines (2a－2c) reacted with N-tosylaziridine
and N-phenylsulfonylaziridine steadily to give ring
opening products 3a－3e in moderate yields (Entries 1
－5). However, aniline and p-methoxyaniline under-
went similar reactions to afford the corresponding
products in good yields (Entries 6－9). Secondary
amine such as diethylamine afforded the corresponding
products 3j and 3k in moderate yields (Entries 10, 11).
Interestingly, the regioselectivities of the ring opening
reactions of 2-ethyl-N-tosylaziridine with p-methoxy-
aniline and cyclohexylamine were satisfactory, and the
yields of the corresponding products 3l and 3m were
65% and 67%, respectively (Entries 12, 13). Moreover,
2∶1 ring opening reactions in SG-H2O was investi-
gated by treatment of amines with 2 equiv. of aziridines
(Scheme 2). As shown in Table 2, cyclohexylamine,
t-butylamine, benzylamine and aminoethanol reacted
with N-sulfonyl aziridines at different temperatures to
give desired disulfonyl triamines in moderate yields. It
is worthy to note that the reaction of aminoethanol with
N-sulfonyl aziridines generated complicated products
without SG and the target products were hard to isolate.
Unlike 1∶1 ring opening products, most of the 2∶1
products were isolated as white viscous oils and became
solids gradually in a refrigerator. However, 4a was ob-
tained as a white solid. Its structure was revealed by
single-crystal X-ray diffraction study (Figure 1) in addi-
tion to IR, 1H NMR, 13C NMR and HRMS analysis.
Figure 1 Crystal structure of 4a (H atoms were omitted for
clarity).
Scheme 3 Possible function of silica gel-water system
O2
S
H2O
R2R3NH
H2O
R1
H2O
N
H2O
R2
NH R3
H2O
O2
S
H2O H2O
N
R1
H2O
H2O
H2O
H2O
Surface of silica gel
H2O
H2O
R3
H2O
H2O
H2O
O2
S
N
R1
NH
R2
H2O
H2O
mulate them on the surface of SG. The sulfonylaziridine
is insoluble in water, and most of its molecules are ab-
sorbed on the SG surface due to the hydrophobic effect.
Therefore, on the surface of SG an interface will gener-
ate, in which the concentrations of both sulfonylazi-
ridine and amine are high enough to let the reaction
between them take place readily. When amine was in
excess, the firstly formed monosulfonyl diamine was
pushed out of SG surface by amine molecules, so it
scarcely contacted with sulfonylaziridine and the forma-
tion of 2∶1 product was inhibited. On the contrary, the
2∶1 product was yielded dominantly when sulfon-
ylaziridine was in excess.
For developing the application of the reaction, we
used 3a and 3b as the substrates for cyclizations with
CS2 in water.[29,48] Nucleophilic additions of 3a and 3b
with CS2 generated dithiocarbamates, which were sub-
sequently treated with chloroacetic acid to yield substi-
tuted N-sulfonylcyclothioureas 5a and 5b, respectively
(Scheme 4). As such, aqueous one-pot synthetic method
to N-sulfonylcyclothioureas can be achieved via ring
opening of sulfonylaziridines with primary amines and
the following cyclizations with CS2 in the presence of
Scheme 2 The 2∶1 reaction of aziridines and primary amines
sillica gel, water
r.t. or 40 oC
O2
S
R2 NH2
+
2R1
N
2a - 2b
2g - 2h
1a - 1b
R2
O2
O2
S
N
H
N
S
R1
R1
N
H
4a - 4f
Enlightened by the role of silica gel and water estab-
lished by Minakata and co-workers,[16] we proposed a
plausible pathway for this reaction (Scheme 3). Most of
the amines employed are soluble in water. Silica gel can
absorb them from water via hydrogen bonds and accu-
Chin. J. Chem. 2014, 32, 1135—1142
© 2014 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
1139

Li et al.
FULL PAPER
Table 1 The 1∶1 reaction products of aziridines and aminesa
Entry Aziridine
Amine
Product
t/h
Yieldb/%
66
O2
S
H
N
NH2
N
H
N
Ts
1
2
3
4
5
6
7
8
9
14
1a
2a
2a
3a
O2
S
O2
S
H
N
NH2
N
N
H
12
14
12
12
14
12
12
12
58
53
48
50
80
74
78
68
1b
3b
O2
S
H
N
N
H
H2N
2b
1a
1b
1a
1a
1b
1a
1b
3c
O2
H
N
S
H2N
2b
N
H
3d
O2
H
N
S
CH3
( )7
H3C
NH2
( )7
N
H
2c
3e
O2
S
H
N
NH2
NH2
N
H
2d
3f
O2
S
H
N
N
H
2d
3g
O2
H
S
N
O
NH2
N
H
2e
O
3h
O2
S
H
N
O
NH2
N
H
2e
O
3i
O2
S
N
HN
N
10
11
14
12
56
60
1a
1b
H
2f
2f
3j
O2
S
N
HN
O
N
H
3k
H
N
O2
S
O
S
NH2
NH
OCH3
N
12
13
12
12
65
67
O
1c
2e
H
O
S
N
NH2
N
1c
H
O
2a
a Reaction conditions: N-sulfonyl aziridine (1 mmol), amine (2 mmol 2a－2e, 1.5 mmol 2f), SG (0.1 g, 40－60 mesh), 1 mL H2O, room
temperature. b Isolated yield.
1140
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© 2014 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2014, 32, 1135—1142

Ring Opening of N-Sulfonyl Aziridines by Amines in Silica-Water
Table 2 The 2∶1 reaction products of aziridines and aminesa
Entry
Aziridine
Amine
Product
t/h
T/℃
Yieldb/%
55
N
Ts
NH2
O2
S
O2
S
1
9
40
N
1a
N
H
N
H
2a
4a
O2
S
O2
S
O2
S
H2N
N
N
2
3
9
9
40
40
53
63
N
H
N
H
2b
1b
4b
O2
S
O2
S
1a
N
NH2
N
H
N
H
2g
2g
4c
O2
S
O2
S
4
5
6
9
40
r.t.
r.t.
70
47
60
1b
1a
1b
NH2
OH
N
N
H
N
H
4d
OH
O2
S
O2
S
H2N
N
14
14
N
H
N
H
2h
2h
4e
OH
O2
S
O2
S
OH
H2N
N
N
H
N
H
4f
a Reaction conditions: N-sulfonyl aziridine (2 mmol), amine (1 mmol), SG (0.2 g, 40－60 mesh), 2 mL H2O, room temperature or 40 ℃.
b Isolated yield.
ClCH2CO2K.
products in moderate to good yields. Furthermore, reac-
tions of primary amines with 2 equiv. of aziridines af-
forded 2∶1 ring opening products in moderate yields.
The 1∶1 products of primary amines and aziridines can
be further transformed to N-sulfonylcyclothioureas by
CS2 and chloroacetic acid in water. In summary, we
described a mild, practical method to produce mono-
and bis-sulfonyl substituted amines in an environmen-
tally benign SG-H2O system.
Scheme 4 The synthesis of N-sulfonylcyclothioureas
O2
S
H
N
KOH, then ClCH2CO2K
H2O, 45 oC
R1
N
CS2
+
H
3a, 3b
S
O2
S
R1
N
N
Acknowledgement
5a, R1 = p-tolyl
5b, R1 = Ph
We appreciate the financial support from the Na-
tional Natural Science Foundation of China (No.
20802049).
Conclusions
References
The ring opening of N-tosylaziridine and N-phenyl-
sufonylaziridine by primary and secondary amines took
place smoothly in silica gel-H2O system at room tem-
perature to give the corresponding 1∶1 ring opening
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Chin. J. Chem. 2014, 32, 1135—1142