A highly efficient and general method for the ring-opening of aziridines with various nucleophiles in DMSO

Article abstract of DOI:10.1039/b611707d

Ring-opening of aziridines with various nucleophiles (such as amines, thiols, and silylated nucleophiles) in DMSO under mild conditions without any catalyst afforded the corresponding products in good to excellent yields. The Royal Society of Chemistry 20

Full text of DOI:10.1039/b611707d

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www.rsc.org/obc | Organic & Biomolecular Chemistry
A highly efficient and general method for the ring-opening of aziridines with
various nucleophiles in DMSO
Jie Wu,*a,b Xiaoyu Sun and Wei Sun
a
a
Received 14th August 2006, Accepted 21st September 2006
First published as an Advance Article on the web 13th October 2006
DOI: 10.1039/b611707d
Ring-opening of aziridines with various nucleophiles (such as amines, thiols, and silylated nucleophiles)
in DMSO under mild conditions without any catalyst afforded the corresponding products in good to
excellent yields.
Table 1 Reactin of aziridine 1a with thiophenol or aniline under different
solvents and temperatures
Introduction
Ring-opening reactions of aziridines with nucleophiles are a
useful protocol in organic synthesis, and many reagents have
recently been developed to effect the opening of the aziridine
1
ring. However, most of these methods are complicated by the
fact that a Lewis acid or strong base is necessary for the reaction
to take place. Moreover, different reaction conditions are needed
2
◦
a
Entry
NuH
Solvent
Temp./ C
Time/h
Yield (%)
for different aziridines and nucleophiles because of their varying
1
2
3
4
5
6
7
8
9
PhSH
PhSH
PhSH
PhSH
PhSH
PhSH
PhSH
PhNH2
DMSO
DMSO
THF
DMF
MeCN
40
25–30
40
40
40
40
40
50
50
1.5
1.5
18
1.5
1.5
10
18
10
10
10
90
24
17
79
85
NR
13
57
16
36
85
3–5
reactivity and the structural complexity of the aziridines. Re-
cently, small molecules have been utilized as organocatalysts in the
6,7
ring-opening reactions of aziridines with various nucleophiles.
For example, Hou has developed tributylphosphine-catalyzed
H
2
O
6
ring-opening reactions of aziridines with nucleophiles. However,
Toluene
DMSO
MeCN
DMF
the catalyst, Bu
3
P, is not stable and is easily oxidized in air.
PhNH
PhNH
PhNH
2
2
2
Furthermore, a high catalyst loading (at least 10%) was necessary
to achieve respectable yields; the yield and rate dramatically
decreased if catalyst loading was reduced. In addition, we have
developed tertiary amine catalyzed ring-opening reactions of
1
1
0
1
50
60
DMSO
6
a
Isolated yield based on aziridine.
7
aziridines with various nucleophiles, such as amines and thiols. In
these two examples, the organocatalysts initially form a complex
4
protons at the trans-positions. Further exploration showed that
6,7
with the aziridine, which acts as a ‘trigger’ for the reaction.
DMSO was the best solvent among those screened, and that the
reaction worked most efficiently at 40 C. No product was detected
when this reaction was performed in water, due to the insolubility
of aziridine 1a. When aniline was used as the nucleophile, the
reaction of 1a also proceeded well in DMSO at 60 C (85% yield,
Table 1, entry 11). Reactions performed in MeCN and DMF
showed inferior results (Table 1, entries 9 and 10).
A variety of aziridines and nucleophiles were examined for the
ring-opening reactions using the optimized reaction conditions,
and the results are summarized in Table 2. As shown in Table 2,
this reaction is general, and useful for ring-openings of a range of
aziridines 1 with both electron-withdrawing and electron-donating
groups attached to the nitrogen atom. In most cases, reactions
were very clean and the desired products were isolated in good
to excellent yield. It is noteworthy that, in contrast to previous
reports, activated aziridines (such as 1a and 1d), as well as
an unactivated aziridine (1c), were all suitable substrates for
nucleophilic attack. For example, when aziridine 1c reacted with
thiophenol and aniline, the products were obtained in 80% and
8
Oriyama recently reported that DMSO, when used as the
solvent, acted as a nucleophilic activator of several organic
transformations. Inspired by these results, we envisaged that
DMSO may also be effective in the ring-opening reactions of
aziridines with various nucleophiles. Herein, we disclose our
preliminary results for this kind of transformation, which was
performed in DMSO without any catalyst under mild conditions
with a variety of nucleophiles.
◦
◦
Results and discussion
Initial studies revealed that without any catalyst, the reaction of
aziridine 1a with thiophenol proceeded smoothly in DMSO at
◦
40
C to afford the corresponding product in high yield (90%,
Table 1, entry 1). The anti-stereochemistry of the product 2a was
confirmed by the coupling constants for the two cyclic methine
4–7
a
Department of Chemistry, Fudan University, 220 Handan Road, Shanghai,
2
00433, China. E-mail: jie_wu@fudan.edu.cn; Fax: +86 21 6510 2412;
6
8% yield, respectively (Table 2, entries 6 and 17). Although the
Tel: +86 21 5566 4619
reactions of aziridines with aromatic thiols or amines proceeded
well under these conditions, reactions that employed aliphatic
nucleophiles were sluggish (Table 2, entries 4 and 15). However,
b
State Key Laboratory of Organometallic Chemistry, Shanghai Institute
of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road,
Shanghai, 200032, China
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Table 2 Ring-opening reactions of aziridines with various nucleophiles in DMSO
◦
a
Entry
Aziridine
Nu
Temp./ C
Time/h
Product
Yield (%)
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
1a
1a
1a
1a
1b
1c
1d
1e
1e
1f
1g
1a
1a
1a
1a
1b
1c
1e
1f
C
6
H
5
SH
4-MeOC
4-ClC
40
40
40
40
40
40
40
40
40
40
40
60
60
60
60
60
60
60
60
60
40
40
40
40
40
1.5
2
2
24
5
14
5
3.5
2
3.5
3.5
6
7
7
24
12
24
10
6.5
10
12
9
2a
90
90
83
15
73
80
96
96
86
68
89
85
77
92
Trace
62
68
96
92
92
89
95
93
95
97
6
H
SH
SH
4
SH
2b
6
H
4
2c
C
C
C
C
C
6
6
6
6
6
H
H
H
H
H
5
5
5
5
5
CH
SH
SH
SH
SH
2
2d
2e
2f
2g
2h
4-ClC
6
H
4
SH
2i
b
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
C
C
C
6
6
6
H
H
H
5
5
5
SH
SH
NH
2j/3j (2.3 : 1)
b
2k/3k (1 : 1)
2
2l
4-MeOC
4-FC NH
CH NH
6
H
4
NH
2
2
2m
2n
2o
2p
2q
2r
6
H
4
C
C
C
C
C
C
6
6
6
6
6
6
H
H
H
H
H
H
5
5
5
5
5
5
2
2
NH
NH
NH
NH
NH
2
2
2
2
2
b
2s/3s (1 : 5)
2t/3t (1 : 6)
2u
2v
2w
2x
2y
b
1g
1a
1a
1b
1e
1e
TMSN
TMSCl
TMSN
TMSN
3
3
10
10
10
3
TMSCl
a
b
1
Isolated yield based on aziridine. Ratio was determined by H NMR.
8
–10
the conditions were suitable for the ring-opening reactions of
aziridines with silyl nucleophiles. For example, reaction of 1a
with trimethylsilyl azide or chloride afforded the corresponding
products in 89% and 95% yield, respectively (Table 2, entries 21
and 22). In the case of the unsymmetrically substituted aziridine
process, as previously reported. For the reactions of aziridines
with thiols or amines, we have previously reported that DABCO
7
can react with aziridine to trigger that reaction. Therefore, we
treated aziridine 1a with DMSO at 40 C for 10 h, but no change
was observed, which excludes the possibility that DMSO acts as
a trigger in this transformation. In the reactions of aziridines
with silyl nucleophiles, we believe that DMSO coordinates to the
◦
1e, complete regioselectivity, with the attack of nucleophile on the
less substituted aziridine carbon, was observed (Table 2, entries 8,
1
9,10
9
, 18, 24, and 25). For substrates 1f and 1g, as previously reported,
trimethylsilyl group to form hypervalent silicon compounds,
it is reasonable that regioselectivity is not as specific as others
due to an electronic effect (Table 2, entries 10, 11, 19, and 20).
Thus, mixtures of regioisomers were generated, since both a steric
effect and electron effect control the reaction process. For example,
when aziridine 1f or 1g reacted with aniline under the optimized
conditions (Table 2, entries 19 and 20), the major product was
that resulting from nucleophilic attack on the benzylic position.
We also carried out the reaction of aziridine 1a with trimethylsilyl
which are active towards further nucleophilic attack (Fig. 1).
Fig. 1 Proposed mechanism for the reaction of aziridines with silyl
nucleophiles.
◦
azide in the presence of 1.0 equiv. of DMSO at 40 C in THF,
giving 79% isolated yield of the desired product 2u after 72 h. The
reaction was retarded when 10% of DMSO was utilized under the
conditions above.
As regards the role of DMSO in the ring-opening of aziridines
with nucleophiles, although the mechanism is not clear since there
is no supporting evidence at present, we suggest that DMSO may
act as a Lewis base to activate the nucleophile during the reaction
Conclusions
In conclusion, we have developed an efficient and convenient
method for the ring-opening of aziridines with various nucle-
ophiles. This reaction has the following synthetic advantages: (1)
4
232 | Org. Biomol. Chem., 2006, 4, 4231–4235
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in contrast to the known ring-opening reactions of aziridines, the
present procedure needs neither a base nor a metal catalyst; (2)
both activated and unactivated aziridines are suitable substrates;
(s, 3H), 2.91 (m, 1H), 3.50–3.59 (m, 2H), 5.04 (s, 1H), 7.22–7.32
(m, 7H), 7.76 (d, J = 8.4 Hz, 2H).
7
4-Methyl-N-(2-(phenylthio)cyclopentyl)benzenesulfonamide (2e).
(
3) various nucleophiles, including thiols, amines, and trimethylsi-
1
H NMR (500 MHz, CDCl
3
): d 1.47–1.51 (m, 1H), 1.54–1.60 (m,
lyl azide or chloride, can be employed in this reaction; (4) the atom
economy is high, as almost all of the reagent is consumed; (5)
mild reaction conditions; and (6) ease of experimental operation.
Further investigations for the desymmetrization of meso-aziridines
with various nucleophiles are underway in our laboratory.
1H), 1.65–1.71 (m, 2H), 2.09–2.14 (m, 2H), 2.43 (s, 3H), 3.27–3.34
(
8
m, 2H), 4.80 (d, J = 4.2 Hz, 1H), 7.25–7.28 (m, 7H), 7.66 (d, J =
.1 Hz, 2H).
13
1
N-(2-(Phenylthio)cyclohexyl)benzenamine
(2f).
H NMR
(400 MHz, CDCl
3
): d 1.21–1.42 (m, 3H), 1.49–1.60 (m, 1H), 1.62–
1
.78 (m, 2H), 2.07–2.10 (m, 1H), 2.31–2.34 (m, 1H), 3.07–3.08
Experimental
(
m, 1H), 3.15–3.20 (m, 1H), 4.03 (s, 1H), 6.53 (d, J = 7.84 Hz,
All reactions were performed in test tubes under nitrogen atmo-
sphere. Flash column chromatography was performed using silica
2H), 6.68–6.70 (m, 1H), 7.10–7.19 (m, 2H), 7.25–7.27 (m, 3H),
7.36–7.42 (m, 2H).
˚
gel (60 A pore size, 32–63 lm, standard grade, Sorbent Tech-
6
a
1
N-(2-(Phenylthio)cyclohexyl)benzamide
400 MHz, CDCl ): d 1.21–1.33 (m, 4H), 1.68–1.72 (m, 2H),
.12–2.13 (m, 1H), 2.30–2.33 (m, 1H), 3.07–3.09 (m, 1H),
(2g).
H
NMR
nologies). Analytical thin-layer chromatography was performed
using glass plates pre-coated with 0.25 mm 230–400 mesh silica
gel impregnated with a fluorescent indicator (254 nm). Aziridines
were prepared according to literature methods. Solvents were re-
distilled prior to use in the reactions. Other commercial reagents
were used as received.
(
3
2
3
7
.91–3.93 (m, 1H), 6.39 (d, J = 7.8 Hz, 1H), 7.22–7.25 (m, 3H),
1
.36–7.44 (m, 5H), 7.68 (d, J = 7.32 Hz, 2H).
12
4-Methyl-N-(1-(phenylthio)hexan-2-yl)benzenesulfonamide (2h).
1
H NMR (400 MHz, CDCl
3
): d 0.83 (t, J = 7.32 Hz, 3H), 1.02–
General procedure
1.18 (m,4H), 1.31–1.41 (m, 1H), 1.58–1.69 (m, 1H), 2.39 (s, 3H),
.78–2.80 (m, 1H), 3.12–3.17 (m, 1H), 3.29–3.39 (m, 1H), 4.90 (d,
2
General procedure for the reactions of aziridines 1 with various
nucleophiles: the nucleophile (1.0 equiv.) was added to a solution
of substrate 1 (0.25 mmol) in DMSO (2.0 mL). The reaction
mixture was stirred at 40 C or 60 C for the period of time
indicated in Table 2. After the reaction was complete (as indicated
by TLC,) the mixture was washed with water and extracted with
J = 7.32 Hz, 1H), 7.22–7.26 (m, 7H), 7.65 (d, J = 7.84 Hz, 2H).
N-(1-(4-Chlorophenylthio)hexan-2-yl)-4-methylbenzenesulfona-
12
1
◦
◦
mide (2i). H NMR (400 MHz, CDCl
3
): d 0.83 (t, J = 7.32 Hz,
3
2
1
8
H), 0.98–1.24 (m, 4H), 1.31–1.41 (m, 1H), 1.58–1.61 (m, 1H),
.40 (s, 3H), 2.78–2.81 (m, 1H), 3.12–3.17 (m, 1H), 3.24–3.33 (m,
H), 4.98 (d, J = 7.84 Hz, 1H), 7.19–7.23 (m, 6H), 7.66 (d, J =
.28 Hz, 2H).
ethyl acetate. The organic extracts were dried (MgSO ), filtered,
4
and concentrated under reduced pressure. Purification by column
chromatography on silica gel afforded the corresponding product.
All the products are known compounds, and their data was
6a
4
-Methyl-N-(1-phenyl-2-(phenylthio)ethyl)benzenesulfonamide
2j). H NMR (400 MHz, CDCl ): d 2.36 (s, 3H), 3.16–3.21 (m,
1
(
2
3
4–7,11–14
identical to that in the literature.
H), 4.26–4.32 (m, 1H), 5.36 (d, J = 3.92 Hz, 1H), 7.05–7.12 (m,
6a
4H), 7.18–7.30 (m, 6H), 7.50 (d, J = 7.8 Hz, 2H), 7.62 (d, J =
4
-Methyl-N-(2-(phenylthio)cyclohexyl)benzenesulfonamide (2a).
H NMR (500 MHz, d -DMSO) d 1.20–1.50 (m, 4H), 1.50–1.75
1
6
7.8 Hz, 2H).
(
(
7
m, 2H), 2.00–2.10 (m, 1H), 2.20–2.30 (m, 1H), 2.45 (s, 3H), 3.00
6a
4
-Methyl-N-(2-phenyl-2-(phenylthio)ethyl)benzenesulfonamide
t, J = 11.4 Hz, 1H), 3.10 (t, J = 11.1 Hz, 1H), 7.10–7.30 (m, 7H),
1
(
3j). H NMR (400 MHz, CDCl ): d 2.43(s, 3H), 3.35–3.40 (m,
3
.63 (d, J = 8.2 Hz, 2H), 7.80 (d, J = 7.5 Hz, 1H); EIMS: 361
2
7
2
H), 4.13 (t, J = 7.32 Hz, 1H), 4.75 (s, 1H), 7.05–7.12 (m, 4H),
+
(
M ); Calc. for C19
H
23NO
2
2
S : C, 63.13; H, 6.41; N, 3.87. Found:
.18–7.30 (m, 6H), 7.50 (d, J = 7.8 Hz, 2H), 7.62 (d, J = 7.8 Hz,
C, 63.07; H, 6.48; N, 3.91%.
H).
N-(2-(4-Methoxyphenylthio)cyclohexyl)-4-methylbenzenesulfona-
N -(1-(4-Chlorophenyl)-2-(phenylthio)ethyl)-4-methylbenzene-
7
1
mide (2b). H NMR (500 MHz, CDCl
3
): d 1.26–1.31 (m, 3H),
12
1
sulfonamide (2k). H NMR (400 MHz, CDCl ): d 2.37 (s, 3H),
3
1
3
1
.57–1.61 (m, 3H), 1.96–1.99 (m, 1H), 2.31–2.33 (m, 1H), 2.45 (s,
H), 2.67–2.68 (m, 1H), 2.88–2.90 (m, 1H), 3.80 (s, 3H), 5.27 (s,
3
7
7
.12–3.14 (m, 2H), 4.21–4.28 (m, 1H), 5.55 (s, 1H), 7.00 (d, J =
.8 Hz, 2H), 7.10–7.12 (m, 2H), 7.16–7.26 (m, 7H), 7.49 (d, J =
H), 6.77 (d, J = 8.63 Hz, 2H), 7.19 (d, J = 8.66 Hz, 2H), 7.30
.8 Hz, 2H).
(
d, J = 8.08 Hz, 2H), 7.76 (d, J = 8.11 Hz, 2H).
N -(2-(4-Chlorophenyl)-2-(phenylthio)ethyl)-4-methylbenzene-
12
1
N-(2-(4-Chlorophenylthio)cyclohexyl)-4-methylbenzenesulfona-
sulfonamide (3k). H NMR (400 MHz, CDCl ): d 2.43 (s, 3H),
3
12
1
mide (2c). H NMR (500 MHz, CDCl
3
): d 1.26 (m, 3H),
3.30–3.35 (m, 2H), 4.14 (t, J = 7.84 Hz, 1H), 4.92 (s, 1H), 7.03 (d,
1
2
1
2
.39–1.40 (m, 1H), 1.56–1.63 (m, 2H), 1.98–2.01 (m, 1H),
J = 7.8 Hz, 2H), 7.10–7.12 (m, 2H), 7.16–7.26 (m, 7H), 7.63 (d,
.21–2.23 (m, 1H), 2.44 (s, 3H), 2.92–2.93 (m, 1H), 2.99–3.00 (m,
H), 5.27 (d, J = 4.7 Hz, 1H), 7.18–7.22 (m, 4H), 7.26–7.29 (m,
H), 7.73 (d, J = 8.20 Hz, 2H).
J = 7.8 Hz, 2H).
6a
4
-Methyl-N -(2-(phenylamino)cyclohexyl)benzenesulfonamide
1
(
2l). H NMR (400 MHz, CDCl ): d 1.0–1.07 (m, 1H), 1.20–1.31
3
7
N-(2-(Benzylthio)cyclohexyl)-4-methylbenzenesulfonamide (2d).
(m, 3H), 1.65 (d, J = 11.76 Hz, 2H), 2.0–2.04 (m, 1H), 2.15–2.18
(m, 1H), 2.44 (s, 3H), 2.90 (dt, J = 9.76, 2.92 Hz, 1H), 3.04 (dt, J =
9.76, 2.92 Hz, 1H), 3.43 (s, 1H), 5.04 (s, 1H), 6.47 (d, J = 7.84 Hz,
1
H NMR (500 MHz, CDCl
3
): d 1.18–1.25 (m, 3H), 1.38–1.45 (m,
1
H), 1.58–1.63 (m, 3H), 2.00–2.02 (m, 1H), 2.23–2.25 (m, 1H), 2.41
This journal is © The Royal Society of Chemistry 2006
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1
1b
2
2
H), 6.69 (t, J = 7.32 Hz, 1H), 7.11–7.13 (m, 2H), 7.27–7.29 (m,
H), 7.75 (d, J = 8.28 Hz, 2H).
N-(2-Azidocyclohexyl)-4-methylbenzenesulfonamide
(2u).
1
H NMR (500 MHz, CDCl
3
): d 1.18–1.31 (m, 4H), 1.63–1.68 (m,
H), 2.00–2.03 (m, 2H), 2.43 (s, 3H), 2.92–2.96 (m, 1H), 3.08–3.10
m, 1H), 5.18 (d, J = 6.25 Hz, 1H), 7.31 (d, J = 8.28, 2H), 7.81
2
(
(
N-(2-(4-Methoxyphenylamino)cyclohexyl)-4-methylbenzenesul-
7
1
fonamide (2m). H NMR (500 MHz, CDCl
3
): d 0.97–1.00 (m,
d, J = 8.28 Hz, 2H).
1
2
5
8
H), 1.21–1.31 (m, 3H), 1.65–1.67 (m, 2H), 2.05–2.12 (m, 2H),
11b
.46 (s, 3H), 2.80–2.83 (m, 1H), 2.90–2.92 (m, 2H), 3.75 (s, 3H),
.01 (d, J = 4.1 Hz, 1H), 6.46 (d, J = 8.8 Hz, 2H), 6.75 (d, J =
.9 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 7.76 (d, J = 8.2 Hz, 2H).
N-(2-Chlorocyclohexyl)-4-methylbenzenesulfonamide
H NMR (400 MHz, CDCl ): d 1.20–1.30 (m, 3H), 1.61–1.71 (m,
3H), 2.12–2.27 (m, 2H), 2.43 (s, 3H), 3.11–3.12 (m, 1H), 3.72–3.74
m, 1H), 5.20 (d, J = 4.88 Hz, 1H), 7.30 (d, J = 7.84 Hz, 2H),
(2v).
1
3
(
7
N-(2-(4-Fluorophenylamino)cyclohexyl)-4-methylbenzenesulfo-
.78 (d, J = 8.32 Hz, 2H).
7
1
namide (2n). H NMR (400 MHz, CDCl
3
): d 1.04–1.29 (m, 4H),
11b
1
3
6
.64–1.66 (m, 2H), 1.97–1.98 (m, 1H), 2.13–2.17 (m, 1H), 2.42 (s,
N-(2-Azidocyclopentyl)-4-methylbenzenesulfonamide
H NMR (500 MHz, CDCl ): d 1.36–1.41 (m, 1H), 1.59–1.69 (m,
3H), 1.95–2.00 (m, 2H), 2.44 (s, 3H), 3.37–3.42 (m, 1H), 3.70–3.73
(2w).
1
H), 2.83 (m, 1H), 2.94–2.98 (m, 2H), 5.08 (d, J = 5.0 Hz, 1H),
3
.44–6.46 (m, 2H), 6.85–6.87 (m, 2H), 7.26–7.30 (m, 2H), 7.75 (d,
J = 8.2 Hz, 2H).
(m, 1H), 4.72 (d, J = 6.25 Hz, 1H), 7.31 (d, J = 7.8 Hz, 2H), 7.79
7
(d, J = 8.2 Hz, 2H).
4
-Methyl-N -(2-(phenylamino)cyclopentyl)benzenesulfonamide
1
11b
(
2p). H NMR (500 MHz, CDCl
3
): d 1.26–1.46 (m, 2H), 1.68–
N-(1-Azidohexan-2-yl)-4-methylbenzenesulfonamide
(2x).
1
1.71 (m, 2H), 1.88–1.90 (m, 1H), 2.17–2.21 (m, 1H), 2.42 (s, 3H),
3.40–3.51 (m, 2H), 4.91 (d, J = 6.1 Hz, 1H), 6.53–6.58 (m, 2H),
6.70–6.73 (m, 1H), 7.11–7.15 (m, 2H), 7.26–7.27 (m, 2H), 7.76 (d,
H NMR (400 MHz, CDCl ): d 0.83 (t, J = 7.32 Hz, 3H),
3
1.06–1.26 (m, 4H), 1.34–1.48 (m, 2H), 2.43 (s, 3H), 3.30–3.40 (m,
3H), 5.01 (d, J = 7.36 Hz, 1H), 7.31 (d, J = 7.80 Hz, 2H), 7.78
(d, J = 7.84 Hz, 2H).
J = 8.2 Hz, 2H).
1
2
5d
1
11b
N ,N -Diphenylcyclohexane-1,2-diamine
400 MHz, CDCl ): d 1.22–1.28 (m, 2H), 1.38–1.42 (m, 2H),
.76–1.78 (m, 2H), 2.33–2.36 (m, 2H), 3.18–3.20 (m, 2H), 3.81 (s,
H), 6.60–6.62 (m, 4H), 6.68–6.72 (m, 2H), 7.15–7.17 (m, 4H).
(2q).
H
NMR
N-(1-Chlorohexan-2-yl)-4-methylbenzenesulfonamide
(2y).
1
(
1
2
3
H NMR (400 MHz, CDCl ): d 0.84 (t, J = 6.84 Hz, 3H),
3
1.10–1.26 (m, 4H), 1.40–1.60 (m, 2H), 2.40 (s, 3H), 3.44–3.51 (m,
3H), 5.00 (d, J = 8.32 Hz, 1H), 7.31 (d, J = 7.80 Hz, 2H), 7.77
(d, J = 7.80 Hz, 2H).
1
4
4
-Methyl-N-(1-(phenylamino)hexan-2-yl)benzenesulfonamide
1
(
2r). H NMR (400 MHz, CDCl
3
): d 0.83 (t, J = 6.84 Hz, 3H),
1
3
3
6
7
.02–1.20 (m, 4H), 1.31–1.39 (m, 1H), 1.45–1.50 (m, 1H), 2.41 (s,
Acknowledgements
H), 3.04–3.05 (m, 1H), 3.12–3.14 (m, 1H), 3.35–3.37 (m, 1H),
.92 (s, 1H), 4.79 (d, J = 7.32 Hz, 1H), 6.48 (d, J = 8.32 Hz, 2H),
.70 (t, J = 7.32 Hz, 1H), 7.10–7.15 (m, 2H), 7.20–7.26 (m, 2H),
.75 (d, J = 8.32 Hz, 2H).
We thank Professor Pengyuan Yang for his invaluable advice
during the course of this research. Financial support from the
National Natural Science Foundation of China (20502004), the
Ministry of Education of China, the Science and Technology
Commission of Shanghai Municipality (05ZR14013), and Fudan
University is gratefully acknowledged.
7
4
-Methyl-N-(1-phenyl-2-(phenylamino)ethyl)benzenesulfonamide
1
(
2s). H NMR (400 MHz, CDCl
3
): d 2.38 (s, 3H), 3.12–3.18
(
m, 1H), 3.29–3.38 (m, 1H), 4.35–4.40 (m, 1H), 5.10 (s, 1H),
5
2
8
.52 (d, J = 3.92 Hz, 1H), 7.08–7.12 (m, 2H), 7.41–7.48 (m,
H), 7.53–7.61 (m, 6H), 7.76 (d, J = 8.32 Hz, 2H), 7.83 (d, J =
.32 Hz, 2H).
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