Zirconium tetrachloride mediated regioselective transformation of N-tosylaziridines into β-chlorosulfonamides

Article abstract of DOI:10.3184/030823407X198285

Regioselective ring opening of N-tosylaziridines has efficiently been carried out with ZrCl₄ at room temperature to afford the corresponding β-chlorosulfonamides in high yields within a short reaction time.

Full text of DOI:10.3184/030823407X198285

82 RESEARCH PAPER
FEbRuARy, 82–83
JOURNAL OF CHEMICAL RESEARCH 2007
Zirconium tetrachloride mediated regioselective transformation of
N-tosylaziridines into b-chlorosulfonamides1
Biswanath Das*, Maddeboina Krishnaiah and Keetha Laxminarayana
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad-500 007, India
Regioselective ring opening of N-tosylaziridines has efficiently been carried out with ZrCl4 at room temperature to
afford the corresponding b-chlorosulfonamides in high yields within a short reaction time.
Keywords: N-tosylaziridine, ZrCl4, β-chlorosulfonamide
Aziridines are important intermediates in organic synthesis.2
They behave as carbon electrophiles capable of reacting with
different nucleophiles.3 On treatment with suitable metal
halides they can be converted into β-chloroamines which
are useful precursors for the synthesis of various bioactive
compounds.4 However, the methods involving the ring opening
of aziridines with metal halides are limited.5 Moreover,
the metal chlorides, such as CeCl3.7H2O and ZnCl2 work
under reflux conditions5a,c and InCl3 requires longer reaction
times.5b Thus, an efficient, mild and useful method for the
conversion of aziridines into β-chloroamines is required.
Recently, ZrCl4 has been used in various chemical
transformations as it possesses an interesting reactivity,
is less costly and is less toxic than other reagents.6
In continuation of our work7 on the applications of ZrCl4 in
synthesis we have recently observed that it can be used for
the cleavage of N-tosylaziridines to form the corresponding
β-chlorosulfonamides. Several N-tosylaziridines were
treated with ZrCl4 at room temperature to form a series of
β-chlorosulfonamides in high yields (Scheme 1, Table 1).
The conversion was complete within 30–70 min. N-Tosyl
aziridines possessing aromatic or aliphatic substituents
underwent the conversion smoothly. The presence of an
electron-donating or electron withdrawing group on the
aromatic ring did not effect the reaction.
NHTs
Cl
NTs
ZrCl4
MeCN
Cl
NHTs
+
R
R
R
r. t.
30–70 min
84–96%
Scheme 1
Table 1 ZrCl4 mediated ring-opening of N-tosylaziridinesa
Entry Aziridine
Product
Time/
min
Isolated
yield/%b
1
2
Cl
NTs
NHTs
a
30
40
40
88
85
84
Cl
NTs
NHTs
NHTs
NHTs
b
Cl
NTs
c
Br
Cl
Br
Cl
Cl
NTs
d
e
40
40
89
85
Cl
NTs
NHTs
MeO
O2N
MeO
O2N
The ring opening of N-tosylaziridines with ZrCl4 was
found to be highly regioselective. N-Tosyl-2-aryl aziridines
furnished the products by nucleophile attack of the chloride
ion at the benzylic position and N-tosyl-2-alkyl aziridines
formed the products by the attack at the terminal position.
The cleavage of bicyclic N-tosyl aziridines afforded the
corresponding N-tosyl-β-chloroamines which possessed
a trans-configuration. The structures and stereochemistry
of the products were established from their analytical and
Cl
NTs
NHTs
f
40
50
86
86
Cl
NTs
NHTs
g
O
O
NTs
NHTs
h
i
35
40
92
Cl
NHTs
NTs
86(6)
Cl
1
spectroscopic (1H, 13C NMR and MS) data. In the H NMR
NHTs
NTs
NTs
spectra of the β-chlorosulfonamides 2a–2h the proton of the
–NH– group appeared as a triplet while in the spectra of 2i–
2m it appeared as a doublet. Thus the regiochemistry of the
productswasclearlysettled. Inthecyclicβ-chlorosulfonamides
2n–2p the coupling constants of the ring proton attached to
–Cl suggested the trans- stereochemistry of the molecules.
In conclusion, we have developed a simple, mild and
suitable method for the preparation of β-chlorosulfonamides
by ZrCl4 mediated ring opening of N-tosylaziridines at room
temperature. The application of a less costly reagent, short
reaction times, high yields and good regioselectivity are the
notable advantages of the method.
j
70
70
60
60
85(7)
83(8)
82(7)
83(6)
Cl
NHTs
Cl
k
l
NHTs
NTs
Cl
( )
( )
7
7
NHTs
NTs
m
Cl
( )
( )
10
10
NHTs
NTs
n
o
p
50
50
60
95
96
94
Cl
NHTs
NTs
NTs
Experimental
Cl
General experimental procedure for conversion of N-tosylaziridines
into β-chlorosulfonamides
To a solution of an N-tosylaziridine (1 mmol) in MeCN (5 ml), ZrCl4
(0.5 mmol) was added. The mixture was stirred at room temperature
NHTs
Cl
aAll the products were characterised by spectroscopic
(1H, 13C NMR and MS) and analytical data.
bYield reported in parentheses is for other regioisomer.
* Correspondent. E-mail: biswanathdas@yahoo.com
PAPER: 06/4360

JOURNAL OF CHEMICAL RESEARCH 2007 83
and the reaction was monitored by TLC. After completion,
the mixture was diluted with EtOAc (10 ml) and subsequently washed
with brine (20 ml) and water (2 ¥ 10 ml). The organic layer was
separated, dried over Na2SO4 and concentrated. The crude product
was purified by column chromatography (silica gel, hexane–EtOAc)
to afford pure β-chlorosulfonamide.
1H), 3.46–3.32 (m, 2 H), 3.17 (m, 1H), 2.40 (s, 3H), 1.52–1.33
(m, 2H), 1.29–1.02 (m, 4 H), 0.82 (t, J = 7.0 Hz, 3 H); 13C NMR
(CDCl3, 50 MHz): 144.2, 137.0, 129.8, 126.7, 51.2, 44.3, 31.7, 27.8,
21.9, 21.4, 13.4; FABMS: m/z 290, 292 [M + H]+., Anal. Calc. for
C13H20ClNO2S: C, 53.89; H, 6.91; N, 4.84%. Found: C, 53.78; H,
6.96; N, 4.95%.
2k: White solid; m.p. 98–99°C; 1H NMR (CDCl3, 200 MHz):
δ 7.30 (d, J = 8.2 Hz, 2H), 7.81 (d, J = 8.2 Hz, 2H), 4.61 (d, J = 6.0 Hz,
1H), 3.46–3.30 (m, 2H), 3.12 (m, 1H), 2.41 (s, 3H), 1.39–1.12 (m,
10H), 0.81 (t, J = 7.2 Hz, 3H); FABMS: m/z 318, 320 [M + H]+.,
Anal. Calc. for C15H24ClNO2S: C, 56.69; H, 7.56; N, 4.41%. Found:
C, 56.68; H, 7.52; N, 4.46%.
The spectroscopic and analytical data of the products are given
below.
2a: Colourless solid; m.p. 95–96°C; 1H NMR (CDCl3, 200 MHz):
δ 7.73 (d, J = 8.4 Hz, 2H), 7.43–7.11 (m, 7H), 4.88 (t, J = 6.5 Hz,
1H), 4.87 (dd, J = 5.9, 7.1 Hz, 1H), 3.36–3.53 (m, 2H), 2.44 (s, 3H);
13C NMR (CDCl3, 50 MHz): 143.3, 137.6, 136.4, 129.4, 128.5,
128.4, 126.9, 126.6, 61.4, 50.0, 21.3; FABMS: m/z 310, 312 [M +
H]+., Anal. Calcd. for C15H16ClNO2S: C, 58.15; H, 5.12; N, 4.52%.
Found: C, 58.16; H, 4.98; N, 4.43%.
2l: Colourless liquid; 1H NMR (CDCl3, 200 MHz): δ 7.30 (d,
J = 8.2 Hz, 2H), 7.80 (d, J = 8.2 Hz, 2H), 4.65 (d, J = 6.0 Hz, 1H),
3.45–3.28 (m, 2H), 3.10 (m, 1H), 2.40 (s, 3H), 1.38–1.10 (m, 16H),
0.83 (t, J = 7.2 Hz, 3H); 13C NMR (CDCl3, 50 MHz): 143.2, 136.8,
128.3, 127.4, 56.4, 47.2, 33.1, 31.2, 30.2, 30.0, 28.2, 27.9. 28.1,
23.2, 21.3, 13.6; FABMS: m/z 360, 362 [M + H]+., Anal. Calc. for
C18H30ClNO2S: C, 60.08; H, 8.34; N, 3.89%. Found: C, 60.10; H,
8.29; N, 3.85%.
2b: Colourless solid; m.p. 119–120°C; 1H NMR (CDCl3, 200 MHz):
δ 7.72 (d, J = 8.0 Hz, 2 H), 7.30 (d, J = 8.0 Hz, 2 H), 7.16 (d,
J = 8.0 Hz 2H), 7.08 (d, J = 8.0 Hz, 2H), 4.85 (t, J = 7.1 Hz, 1H),
4.81 (t, J = 7.1 Hz, 1H), 3.38 (t, J = 7.1 Hz, 2H), 2.42 (s, 3H), 2.31
(s, 3H); 13C NMR (CDCl3, 50 MHz): 143.8, 137.7, 137.1, 135.4,
129.1, 128.8, 127.2, 126.6, 61.2, 52.5, 21.5, 21.4; FABMS: m/z 324,
326 [[M + H]+., Anal. Calcd. for C16H18ClNO2S: C, 59.35; H, 5.56;
N, 4.33%. Found: C, 59.36; H, 5.49; N, 4.32%.
2m: Colourless liquid; 1H NMR (CDCl3, 200 MHz): δ 7.29 (d,
J = 8.0 Hz, 2H), 7.80 (d, J = 8.0 Hz, 2H), 4.71 (d, J = 7.0 Hz, 1H),
3.48–3.30 (m, 2H), 3.15 (m, 1H), 2.40 (s, 3H), 1.35–1.10 (m, 22H),
0.82 (t, J = 7.2 Hz, 3H); FABMS: m/z 402, 404 [M + H]+., Anal. Calc.
For C21H36ClNO2S: C, 62.76; H, 8.97; N, 3.49%. Found: C, 62.79;
H, 8.91; N, 3.52%.
2c: Colourless solid; m.p. 98–100°C; 1H NMR (CDCl3, 200 MHz):
δ 7.70 (d, J = 8.2 Hz, 2H), 7.32–7.16 (m, 6H), 4.86 (dd,
J = 6.2, 7.8 Hz, 1H), 4.80 (t, J = 6.8 Hz,1H), 3.50–3.28 (m, 2H),
2.43 (s, 3H); FABMS: m/z 388, 390, 392 [[M + H]+., Anal. Calcd. for
C15H15ClbrNO2S: C, 46.33; H, 3.86, N, 3.60%. Found: C, 46.41; H,
3.91, N, 3.63%.
2n: White solid; m.p. 86–87°C; 1H NMR (CDCl3, 200 MHz):
δ 7.81 (d, J = 8.3 Hz, 2H), 7.32 (d, J = 8.3 Hz, 2H), 5.92 (d,
J = 6.0 Hz, 1H), 4.08 (ddd, J = 9.8, 9.1, 3.7 Hz, 1H), 3.54 (m, 1H)
2.45 (s, 3H), 2.21–2.02 (m, 2H), 1.88–1.69 (m, 3H), 1.43 (m, 1H);
13C NMR (CDCl3, 50 MHz): 144.1, 137.5, 130.0, 127.2, 63.5, 54.4,
34.7, 30.8, 21.9, 21.3; FABMS: m/z 274, 276 [M + H]+., Anal. Calc.
for C12H16ClNO2S: C, 52.65; H, 5.85; N, 5.12%. Found: C, 52.78; H,
5.81; N, 5.23%.
2d: Colourlss solid; m.p. 100–102°C; 1H NMR (CDCl3, 200
MHz): δ 7.71 (d, J = 8.4 Hz, 2H), 7.35–7.20 (m, 6H), 4.87 (dd,
J = 6.2, 7.8 Hz, 1H), 4.81 (t, J = 6.8 Hz,1H), 3.50–3.33 (m, 2H),
2.44 (s, 3H); 13C NMR (CDCl3, 50 MHz): 143.5, 137.3, 136.2, 134.4,
129.6, 128.7, 128.5, 126.7, 60.5, 50.0, 21.5; FABMS: m/z 344, 346,
348 [M + H]+., Anal. Calcd. for C15H15Cl2NO2S: C, 52.33; H, 4.36;
N, 4.07%. Found: C, 52.31, H, 4.32; N, 4.05%.
1
2o: White solid; m.p. 100–102°C; H NMR (CDCl3, 200 MHz):
2e: Colourless solid; m.p. 118–120°C; 1H NMR (CDCl3, 200 MHz):
δ 7.62 (d, J = 8.1 Hz, 2H), 7.21 (d, J = 8.1 Hz, 2H), 7.03 (d,
J = 8.6 Hz, 2H), 6.76 (d, J = 8.6 Hz, 2H), 4.89 (dd, J = 5.9, 7.2 Hz,
1H), 4.82 (t, J = 6.6 Hz,1H), 3.80 (s, 3H), 3.61–3.36 (m. 2H), 2.40
(s, 3H); 13C NMR (CDCl3, 50 MHz): 159.1, 143.2, 136.7, 129.3,
129.1, 127.9, 126.9, 113.7, 60.9, 55.0, 55.2, 21.5; FABMS: m/z 340,
342 [M + H]+., Anal. Calcd. for C16H18ClNO3S: C, 56.55; H, 5.30; N,
4.12%. Found: C, 56.52, H, 5.36, N, 4.10%.
δ 7.80 (d, J = 8.04 Hz, 2H), 7.30 (d, J = 8.04 Hz, 2H), 4.85 (d, J = 6.5 Hz,
1H), 3.71 (ddd, J = 9.5, 9.1, 3.8 Hz, 1H), 3.20 (m, 1H), 2.40 (s, 3H),
2.10–2.30 (m, 2H), 1.75–1.55 (m, 3H), 1.40–1.20 (m, 3H); 13C NMR
(CDCl3, 50 MHz): 143.3, 137.0, 129.4, 127.1, 62.1, 58.6, 34.9, 32.4,
24.3, 23.4, 21.6: FABMS: m/z 288, 290 [M + H]+., Anal. Calc. for
C13H18ClNO2S: C, 54.26; H, 6.26; N, 4.87%. Found: C, 54.29; H,
6.28; N, 4.71%.
2p: Whilte solid; m.p. 92–93°C; 1H NMR (CDCl3, 200 MHz):
δ 7.79 (d, J = 8.0 Hz 2H), 7.30 (d, J = 8.0 Hz, 2H), 5.75 (d, J = 7. 0 Hz,
1H), 5.61–5.38 (m, 2H), 4.10 (ddd, J = 9.5, 9.1, 3.9 Hz, 1H), 3.39
(m, 1H), 2.42 (s, 3H), 2.30–1.95 (m, 4H); FABMS: m/z 286, 288
[M + H]+., Anal. Calc. For C13H16ClNO2S: C, 54.64; H, 5.60; N,
4.90%. Found: C, 54.68; H, 5.62; N, 4.87%.
1
2f: Yellow solid; m.p. 112–113°C; H NMR (CDCl3, 200 MHz):
δ 8.15 (d, J = 8.6 Hz 2H), 7.68 (d, J = 8.1 Hz, 2H), 7.49 (d, J = 8.6 Hz,
2H), 7.29 (d, J = 8.1 Hz, 2H), 5.20 (t, J = 6.5 Hz, 1H), 5.00
(t, J = 6.7 Hz, 1H), 3.54–3.38 (m, 2H), 2.43 (s, 3H); 13C NMR
(CDCl3, 50 MHz): 147.5, 144.6, 143.8, 136.2, 129.6, 128.3, 126.6,
123.7, 59.6, 49.8, 21.4; FABMS: m/z 355, 357 [M + H]+., Anal.
Calcd. for C15H15ClN2O4S: C, 50.78; H, 4.23; N, 7.90%. Found: C,
50.75, H, 4.28, N, 7.76%.
The authors thank CSIR, New Delhi for financial assistance.
This is IICT Communication 070207.
2g: Colourless solid; m.p. 120–121°C; 1H NMR (CDCl3, 200 MHz):
δ 7.90 (d, J = 8.2 Hz, 2H), 7.79 (d, J = 8.0 Hz, 2H), 7.52 (d,
J = 8.2 Hz, 2H), 7.30 (d, J = 8.0 Hz 2H), 5.01 (t, J = 6.5 Hz, 1H), 4.92
(dd, J = 6.2, 7.4 Hz, 1H), 3.55–3.30 (m, 2H), 2.41 (s, 3H) 2.32 (s, 3H);
FABMS: m/z 352, 354 [M + H]+., Anal. Calcd. for C17H18ClNO3S: C,
58.04, H, 5.12, N, 3.98%. Found: C, 58.01, H, 5.15, N, 4.01%.
2h: White solid; m.p. 97–98°C; 1H NMR (CDCl3, 200 MHz):
δ 7.75 (d, J = 8.2 Hz, 2H), 7.30 (d, J = 8.2 Hz, 2H), 4.95 (t,
J = 6.8 Hz, 1H), 3.55 (t, J = 5.8, 5.7 Hz, 2H), 3.31–3.28 (m, 2H),
2.40 (s, 3H); 13C NMR (CDCl3, 50 MHz): 144.3, 136.5, 127.4, 128.5,
45.7, 45.3, 21.4; FABMS: m/z 234, 236 [M + H]+., Anal. Calcd.
for C9H12ClNO2S: C, 46.25; H, 5.14; N, 6.00%. Found: C, 46.32;
H, 5.19; N, 5.89%.
Received 15 December 2006; accepted 23 January 2007
Paper 06/4360
doi:10.3184/030823407X198285
References
1
2
Part 96 in the series, Studies on novel synthetic methodologies.
(a) D. Tanner, Angew. Chem. Int. Ed., 1994, 33, 599; (b) W. McCoull
and F.A. Davis, Synthesis, 2000, 1347.
3
J.E.G. Kemp, in Comprehensive Organic Synthesis, b.M. Trost and
I. Fleming, (eds) Pergamon Press: Oxford, 1991, Vol. 7, p. 469.
(a) C. Bonini, G. Righi and R. D’Achille, Tetrahedron Lett., 1996, 37,
6893; (b) G. Righi, T. Franchini and C. Bonini, Tetrahedron Lett., 1998,
39, 2385.
4
2i: White solid; m.p. 101–102°C; 1H NMR (CDCl3, 200 MHz):
δ 7.78 (d, J = 8.2 Hz, 2H), 7.30 (d, J = 8.2 Hz, 2H), 5.30 (d, J = 6.2 Hz,
1H), 3.45–3.30 (m, 2H), 3.15 (m, 1H), 2.40 (s, 3H), 1.49–1.35 (m,
2H), 0.90 (t, J = 7.2 Hz, 3H); 13C NMR (CDCl3, 50 MHz): 143.2,
136.8, 128.4, 127.4, 54.5, 46.7, 30.5, 21.3, 14.2; FABMS: m/z 262,
264 [M + H]+., Anal. Calcd. for C11H16ClNO2S: C, 50.48; H, 6.12;
N, 5.35%. Found: C, 50.51; H, 6.15; N, 5.32%.
5
(a) G. Sabitha, R.S. Babu, M. Raikumar, Ch. S. Reddy and J.S. Yadav,
Tetrahedron Lett., 2001, 42, 3955; (b) J.S. Yadav, B.V.S. Reddy and
G.M. Kumar, Synlett, 2001 1417; (c) M.K. Ghorai, K. Das, A. Kumar and
K. Ghosh, Terahedron Lett., 2005, 46, 4103; (d) M.K. Pandy, A. Bisai and
V.K. Singh, Tetrahedron Lett., 2004, 45,9661.
6
7
J.E. Huheey, Inorganic Chemistry, 3rd edn. Roger and Harper Row,
Singapore, Ch. 18 1990.
(a) B. Das and V. S. Reddy, Chem. Lett., 2004, 33, 1428; (b) B. Das,
M.R. Reddy, V.S. Reddy, and R. Ramu, Chem. Lett. 2004, 33, 1526.
1
2j: White solid; m.p. 103–104°C; H NMR (CDCl3, 200 MHz):
δ 7.75 (d, J = 8.0 Hz, 2 H), 7.24 (d, J = 8.0 Hz, 2 H), 5.32 (d, J = 6.0 Hz,
PAPER: 06/4360