Br?nsted acid-assisted N-alkylation of sulfonamides using ethers as the alkylation reagents

Article abstract of DOI:10.1016/j.tet.2013.11.036

N-Alkylation of sulfonamides using cyclic ethers as alkylation reagents and Br?nsted acid as a catalyst produced pyrrolidine and piperidine derivatives in good yields. When using symmetrical and unsymmetrical ethers as alkylation reagents, mono-N-alkylation of sulfonamides took place to afford the corresponding products.

Full text of DOI:10.1016/j.tet.2013.11.036

Tetrahedron 70 (2014) 434e438
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Brønsted acid-assisted N-alkylation of sulfonamides using ethers
as the alkylation reagents
,
b,
Wei Shi a, Chun-Mei Bai a, Kai Zhu a, Dong-Mei Cui a , Chen Zhang
*
*
a College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, PR China
b School of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 9 July 2013
Received in revised form 8 November 2013
Accepted 14 November 2013
Available online 20 November 2013
N-Alkylation of sulfonamides using cyclic ethers as alkylation reagents and Brønsted acid as a catalyst
produced pyrrolidine and piperidine derivatives in good yields. When using symmetrical and un-
symmetrical ethers as alkylation reagents, mono-N-alkylation of sulfonamides took place to afford the
corresponding products.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
N-Alkylation
Sulfonamide
Brønsted acid
Ether
Pyrrolidine
1. Introduction
exploration of new, direct methods for N-alkylation of sulfon-
amides using various alkylating agents under mild conditions is still
Alkyl amines are important functional groups in organic
chemistry, and the development of preparation methods for these
compounds is a challenging area of organic synthesis.1 In this
context, N-alkylation reactions of sulfonamides have attracted
significant attention, because the sulfonamide moiety is found in
a large number of agrochemicals and pharmaceuticals.2 In addition,
sulfonamides have also been used as protecting groups, which can
be readily removed.3 Thus, N-alkylated sulfonamides can be easily
converted to yield primary or secondary alkyl amines. The most
common reported method for synthesizing alkylated sulfonamides
involves the condensation of amines with sulfonyl chlorides.4
Syntheses of N-alkylated sulfonamides have also been reported
using other approaches, including the N-alkylation of sulfonamides
using alkyl halides,5 olefins,5 esters,6 or alcohols7 as alkyl sources;
reductive amination of sulfonamides and nucleophilic substitutions
with alkyl halides;8 and reacting sulfinates with amines following
oxidation.9 However, there are several drawbacks associated with
such reactions, including the use of heavy metals and sensitive
substrates for storage and handling, and the generation of un-
wanted inorganic salts or toxic byproducts in multistep processes.
Considering the widespread application of N-alkylated sulfonamide
for the synthesis of pharmaceuticals and agrochemicals, the
needed. The use of ether as an alkylating agent has the advantage of
high atom efficiency and the formation of water as the only
byproduct. Zeng and co-workers reported the N-alkylation of sul-
fonamides using acyclic ethers by TiCl4 or BF3$Et2O.10 Herein, we
report the N-alkylation of sulfonamides using cyclic and acyclic
ethers as alkyl sources under mild reaction conditions.
2. Results and discussion
First, we examined the reaction of p-toluenesulfonamide (1a)
with tetrahydrofuran (THF) (2a) as a cyclic ether under various
conditions. The results are summarized in Table 1. Reacting 1a with
2a in the presence of TfOH (20 mol %) at 170 ꢀC in toluene for 18 h
afforded the corresponding alkylation product pyrrolidine de-
rivative 3a at 98% yield (Table 1, entry 1). We observed that the
formation of 3a was related with the amount of TfOH and the
temperature: decreasing the amount of TfOH to 10 mol % or low-
ering the reaction temperature to 120 ꢀC resulted in a slightly lower
yield (Table 1, entries 2 and 4). A good yield of 3a (96%) was also
obtained with 40 mol % of TfOH at 120 ꢀC (Table 1, entry 5). Other
proton acid catalysts, such as the inorganic acid H2SO4, were uti-
lized to afford 2 at a lower yield and the reaction did not proceed in
the presence of either CF3CO2H or TsOH (Table 1, entries 7e9).
Different solvents were screened, and toluene was found to be the
best one (Table 1, entries 1, 12e17).
* Corresponding authors. E-mail address: cuidongmei@zjut.edu.cn (D.-M. Cui).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.11.036

W. Shi et al. / Tetrahedron 70 (2014) 434e438
435
Table 1
Optimization of the reaction conditionsa
O
O
SO2NH2
S
cat.
N
+
O
1a
2a
3a
Entry
Cat. (mol %)
Solvent
Temp (ꢀC)
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
TfOH (20)
TfOH (10)
TfOH (10)
TfOH (20)
TfOH (40)
TfOH (40)
CF3CO2H (20)
TsOH (20)
H2SO4 (20)
TfOH (20)
TfOH (20)
TfOH (20)
TfOH (20)
TfOH (20)
TfOH (20)
TfOH (20)
TfOH (20)
TfOH (20)
TfOH (20)
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Xylene
170
170
140
120
120
100
170
170
170
170
170
170
170
170
170
170
170
170
170
18
18
18
21
31
18
18
18
18
18
18
18
18
18
18
18
18
18
18
98
77
28
69
96
52
0
0
9
14
74
99
60
43
96
0
0
0
0
97
10c
11d
12
13
14
15
16
17
18
19e
Dioxane
Cyclohexane
DMSO
DMF
CH3CN
H2O
d
a
The reactions were performed with 1a (0.5 mmol), 2a (2.0 mmol), and catalyst (10e40 mol %) in solvent (1 mL).
b
c
Isolated yields.
2a (1.0 mmol).
2a (3.0 mmol).
2a (1.0 mL).
d
e
With the optimized reaction conditions determined, the sub-
A possible reaction pathway for 3 and 4 is depicted in
Scheme 1.7,10 Cyclic esters, such as THF were activated by initial
coordination between oxygen and TfOH, and ethereoxygen bonds
were attacked sulfonamide nitrogen, generating the N-acylation
intermediate; the corresponding sulfonamide nitrogen continued
to attack the carboneoxygen bond activated by TfOH via intra-
molecular displacement or a carbocation mechanism, leading to
the formation of product 3. On the other hand, the rearranged
isomers 3m, 4f2, and 4g2 were also produced. We propose that the
N-alkylation reaction of esters occurs through a carbocation
mechanism.
strate scope was further examined. As shown in Table 2, we first
examined the reactions of sulfonamides bearing various functional
groups on the aromatic ring. The reactions of electron-deficient
sulfonamides gave good to excellent yields in the presence of
TfOH (40 mol %), while longer reaction times were necessary in the
cases of 3b and 3f. Methanesulfonamide was also a good substrate.
We also investigated the N-alkylation of 1a with several cyclic
ethers, conducted under the optimized reaction conditions. Re-
actions with THF bearing methyl, benzyl, and chloromethyl groups
at the aliphatic ring produced the corresponding pyrrolidine
products at good to excellent yields. Chloro substituent was toler-
ant in this catalytic system. In addition, tetrahydropyran was also
an efficient substrate; the ring transformation of oxygen-
containing heterocycles into nitrogen-containing heterocycles
proceeded smoothly to give the corresponding piperidine de-
rivative 3k at 50% yield. Furthermore, when reacting of hexam-
ethylene oxide with 1a afforded a 20:80 mixture of azapane
derivative 3l and pyrrolidine derivative 3m in 45% combined yield.
We next examined the N-alkylation of sulfonamides using
symmetrical and unsymmetrical ethers as alkyl sources, applying
the optimized reaction conditions. As shown in Table 3, the reaction
of 1a with di-iso-propyl ether (2a) in the presence of 40 mol % of
TfOH in toluene at 120 ꢀC proceeded efficiently to form N-alkyl
sulfonamide 3a at 85% yield without detectable formation of N,N-
dialkylated sulfonamide byproduct (Table 3, entry 1). Sulfonamides
with not only steric hindrance but also electron-withdrawing
groups on the benzene ring gave excellent yields (entries 2 and
4). Various symmetrical ethers were then examined, and obtained
the products shown in Table 3 (entries 5e7). For dibutyl ether and
diisopentyl ether, two mono-N-alkyl sulfonamides, 4f1 and 4f2 and
4g1 and 4g2, respectively, were obtained (Table 2, entries 8 and 9).
Moreover, when 1a was treated with unsymmetrical ethers, the
alkylation reaction took place smoothly to afford two mono-N-alkyl
sulfonamides (Table 3, entries 8 and 9).
3. Conclusion
In conclusion, we have developed an efficient, generally appli-
cable method for N-alkylation of sulfonamides using cyclic and
acyclic ethers as alkyl sources under metal-free conditions. This
reaction may be of interest for ring transformation of tetrahydro-
furan and tetrahydropyran derivatives into pyrrolidine and piper-
idine derivatives that are commonly found in natural products and
biologically active molecules.2e,f
4. Experimental section
4.1. General procedure
Under otherwise noted, materials were obtained from com-
mercial suppliers and used without further purification. Thin layer
chromatography (TLC) was performed using silica gel 60 F254 and
visualized using UV light. Column chromatography was performed
with silica gel (mesh 300e400). 1H NMR and 13C NMR spectra were
recorded on a Bruker Avance 500 MHz spectrometer in CDCl3 with
Me4Si as an internal standard. Data were reported as follows:
chemical shift in parts per million (
d
), multiplicity (s¼singlet,

436
W. Shi et al. / Tetrahedron 70 (2014) 434e438
Table 2
Scope of the synthesis of 3a
O
R1
O
O
S
R2
( )n
R3
TfOH (40 mol%)
N
R1SO2NH2
+
( )n
toluene, 120 oC
R3
R2
1
2
3
O
O
O
O
O
O
O
O
O
O
S
S
S
S
S
N
N
N
N
N
Cl
Br
3a, 98% (18 h)
3b, 57% (35 h)
3c, 82% (18 h)
3d, 80% (18 h)
3e, 84% (18 h)
O
O
O
O
O
O
O
O
S
O
O
S
S
N
S
N
N
S
N
H3C
N
Bn
I
Cl
3f, 70% (42 h)
3g, 78% (18 h)
3h, 86% (42 h)
3i, 60% (40 h)
3j, 62% (35 h)
O
S
O
O
O
O
O
S
N
S
N
N
and
3k, 50% (42 h)
3l and 3m, 45% (3l: 3m = 20:80, 40 h)
Isolated yields.
aReaction conditions: 1 (0.5 mmol), 2 (2.0 mmol), TfOH (40 mol %), toluene (1 mL), 120
Table 3
N-Alkylation of sulfonamides by TfOHa
TfOH (40 mol%)
toluene, 120 oC
O
RSO2NHR3
R2
R3
RSO2NH2
+
RSO2NHR2
+
1
2
4
5
Entry
R
R2
R3
Time (h)
Yield of 4b
Yield of 5b
1
2
3
4-CH3C6H4
2-CH3C6H4
C6H5
4-BrC6H4
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
i-Pr
i-Pr
i-Pr
i-Pr
Bn
n-Bu
i-Pentyl
t-Bu
i-Pr
i-Pr
i-Pr
i-Pr
14
35
35
45
25
34
31
22
25
4a: 85%
4b: 85%
4c: 69%
4d: 70%
4e: 50%
4f: 60%c
4g: 53%c
4h: 40%
4i: 38%
4
5d
6
Bn
n-Bu
i-Pentyl
Me
7d
8
5a: 23%
5a: 19%
9d
PhCH2CH2
Me
a
Reaction conditions: 1 (0.5 mmol), 2 (2.0 mmol), TfOH (40 mol %), toluene (1 mL), 120 ꢀC.
Isolated yields; ratio was determined by 1H NMR spectroscopy.
Ratio of 4f (4f1 and 4f2) was 75:25; ratio of 4g (4g1 and 4g2) was 83:17.
TfOH (20 mol %), 170 ꢀC.
b
c
d
O
O
O
S
O
O
O
O
O
S
S
S
N
N
N
N
H
H
H
H
4g1
4g2
4f1
4f2

W. Shi et al. / Tetrahedron 70 (2014) 434e438
437
[H+]
[H+]
[H+]
cyclic ether
R
O
R
OH2
R
O
R
N
R1SO2NH2
RSO2NH
-H2O
SO2R1
R1SO2NH2
2
3
acyclic ether
NHSO2R1
R
4
Scheme 1. Plausible reaction mechanism for N-alkylation of sulfonamides.
d¼doublet, t¼triplet, q¼quartet, br¼broad, and m¼multiplet),
1H), 3.46e3.41 (m, 1H), 3.17e3.12 (m, 1H), 2.43 (s, 3H), 1.85e1.80
(m, 1H), 1.71e1.67 (m, 1H), 1.56e1.31 (m, 2H), 1.31 (d, J¼6.5 Hz, 3H).
coupling constant in Hertz (Hz) and integration.
4.2.9. 2-(Chloromethyl)-1-tosylpyrrolidine (3i).16 Yellow solid; mp
4.2. In a typical procedure
45e47 ꢀC; 1H NMR (500 MHz, CDCl3)
(d, J¼8.0 Hz, 2H), 3.89e3.86 (m, 1H), 3.82e3.78 (m, 1H), 3.51e3.44
(m, 2H), 3.16e3.11 (m,1H), 2.44 (s, 3H),1.97e1.92 (m,1H),1.88e1.82
(m, 1H), 1.75e1.55 (m, 2H).
d
7.73 (d, J¼8.2 Hz, 2H), 7.33
To a mixture of tolsulfonamide (0.5 mmol) and THF (2 mmol) in
toluene (1 mL), was added TfOH (40 mol %). The resulting mixture
was than sealed and stirred for 18 h at 120 ꢀC. After quenching with
satd aq NaHCO3, the reaction mixture was extracted three times
with EtOAc, dried over Na2SO4, and concentrated in vacuo. The
residue was purified by flash chromatography with PE and EtOAc
(3:1) as the eluent to give the pure product.
4.2.10. 3-Benzyl-1-tosylpyrrolidine (3j).17 Light yellow oil; 1H NMR
(500 MHz, CDCl3)
d
7.72 (d, J¼8.2 Hz, 2H), 7.34e7.32 (m, 2H),
7.29e7.26 (m, 2H), 7.22e7.18 (m, 1H), 7.06 (d, J¼8.2 Hz, 2H),
3.42e3.33 (m, 2H), 3.23e3.18 (m, 1H), 2.95e2.92 (m, 1H), 2.55 (d,
J¼7.8 Hz, 2H), 2.44 (s, 3H), 2.35e2.32 (m, 1H), 1.90e1.86 (m, 1H),
1.54e1.46 (m, 1H).
4.2.1. 1-[(4-Methylphenyl)sulfonyl]-pyrrolidine (3a). Colorless solid;
mp 132e133 ꢀC (lit.11 123 ꢀC); 1H NMR (500 MHz, CDCl3)
d 7.71 (d,
J¼8.5 Hz, 2H), 7.32 (d, J¼8.5 Hz, 2H), 3.22 (t, J¼7.8 Hz, 4H), 2.43 (s,
4.2.11. 1-[(4-Methylphenyl)sulfonyl]-piperidine (3k). Brown solid;
3H), 1.74 (t, J¼7.8 Hz, 4H).
mp 95e97 ꢀC (lit.18 93 ꢀC); 1H NMR (500 MHz, CDCl3)
d 7.64 (d,
J¼8 Hz, 2H), 7.32 (d, J¼8 Hz, 2H), 2.98e2.96 (m, 4H), 2.44 (s, 3H),
4.2.2. 1-[(2-Methylphenyl)sulfonyl]-pyrrolidine (3b). Colorless oil;
1.67e1.62 (m, 4H), 1.44e1.40 (m, 2H).
1H NMR (500 MHz, CDCl3)
d
7.89e7.91 (m, 1H), 7.42e7.45 (m, 1H),
7.29e7.32 (m, 2H), 3.29e3.31 (m, 4H), 2.64 (s, 3H), 1.88e1.91 (m,
4H); 13C NMR (125 MHz, CDCl3)
137.9, 137.2, 132.6, 132.5, 129.5,
4.2.12. 4-Methyl-N-(1-methylethyl)-benzenesulfonamide (4a). Pale
yellow solid; mp 57e59 ꢀC (lit.19 48 ꢀC); 1H NMR (500 MHz, CDCl3)
d
126.0, 47.3, 25.5, 20.6; Registry number: 1071420-35-3.
d
7.78 (d, J¼8.0 Hz, 2H), 7.29 (d, J¼8.0 Hz, 2H), 4.96 (d, J¼7.5 Hz, 1H),
3.39e3.45 (m, 1H), 2.42 (s, 3H), 1.06 (d, J¼6.5 Hz, 6H).
4.2.3. 1-(Phenylsulfonyl)-pyrrolidine (3c). Colorless solid; mp
161e162 ꢀC (lit.9 154e155 ꢀC); 1H NMR (500 MHz, CDCl3)
4.2.13. N-Isopropyl-2-methyl-benzenesulfonamide (4b).20 Light yel-
d
7.84e7.82 (m, 2H), 7.59e7.57 (m, 1H), 7.54e7.51 (m, 2H),
low oil; 1H NMR (500 MHz, CDCl3)
d 8.01e8.03 (m, 1H), 7.44e7.45
3.26e3.22 (m, 4H), 1.76e1.73 (m, 4H).
(m, 1H), 7.31e7.34 (m, 2H), 4.48 (d, J¼7.2 Hz, 1H), 3.41e3.51 (m, 1H),
2.66 (s, 3H), 1.09 (d, J¼6.5 Hz, 6H).
4.2.4. 1-[(4-Chlorophenyl)sulfonyl]-pyrrolidine (3d).9 Colorless oil;
1H NMR (500 MHz, CDCl3)
2H), 3.24e3.21 (m, 4H), 1.78e1.75 (m, 4H).
d
7.76 (d, J¼8.5 Hz, 2H), 7.49 (d, J¼8.5 Hz,
4.2.14. N-Isopropyl-benzensulfonamide (4c).21 Light yellow oil; 1H
NMR (500 MHz, CDCl3) d 7.91e7.89 (m, 2H), 7.59e7.56 (m, 1H),
7.53e7.50 (m, 2H), 4.77 (d, J¼6.4 Hz, 1H), 3.50e3.44 (m, 1H), 1.08 (d,
4.2.5. 1-[(4-Bromophenyl)sulfonyl]-pyrrolidine (3e).12 Pale yellow
J¼6.5 Hz, 6H).
solid; mp 95e96 ꢀC; 1H NMR (500 MHz, CDCl3)
d
7.70 (d, J¼8.7 Hz,
2H), 7.67 (d, J¼8.7 Hz, 2H), 3.25e3.22 (m, 4H), 1.79e1.76 (m, 4H).
4.2.15. 4-Bromo-N-isopropyl-benzenesulfonamide (4d).22 Light yel-
low solid; mp 94e97 ꢀC; 1H NMR (500 MHz, CDCl3)
d 7.76 (d,
4.2.6. 1-[(4-Iodophenyl)sulfonyl]-pyrrolidine (3f).13 White solid;
J¼8.6 Hz, 2H), 7.66 (d, J¼8.6 Hz, 2H), 4.60 (d, J¼7.3 Hz, 1H),
mp 143 ꢀC; 1H NMR (500 MHz, CDCl3)
(d, J¼8.5 Hz, 2H), 3.25e3.21 (m, 4H), 1.79e1.76 (m, 4H).
d
7.88 (d, J¼8.5 Hz, 2H), 7.54
3.45e3.51 (m, 1H), 1.10 (d J¼6.5 Hz, 6H).
4.2.16. 4-Methyl-N-(phenylmethyl)-benzenesulfonamide
4.2.7. 1-(Methylsulfonyl)-pyrrolidine (3g). Pale yellow solid; mp
(4e). White solid; mp 112e114 ꢀC (lit.23 119 ꢀC); 1H NMR
74e75 ꢀC (lit.14 68e69 ꢀC); 1H NMR (500 MHz, CDCl3)
(m, 4H), 2.80 (s, 3H), 1.94e1.91 (m, 4H).
d
3.32e3.28
(500 MHz, CDCl3)
d
7.76 (d, J¼8.0 Hz, 2H), 7.31 (d, J¼8.0 Hz, 2H),
7.20e7.28 (m, 5H), 4.95 (t, J¼¼6.2 Hz, 1H), 4.12 (d, J¼6.2 Hz, 2H),
2.45 (s, 3H).
4.2.8. 2-Methyl-1-[(4-methylphenyl)sulfonyl]-pyrrolidine (3h). Pale
yellow solid; mp 102e104 ꢀC (lit.15 94e95 ꢀC); 1H NMR (500 MHz,
4.2.17. N-Tosylbutylamine (4f1).19 Colorless oil; 1H NMR (500 MHz,
CDCl3)
d
7.72 (d, J¼8.0 Hz, 2H), 7.31 (d, J¼8.0 Hz, 2H), 3.73e3.69 (m,
CDCl3)
d
7.78 (d, J¼8.0 Hz, 2H), 7.30 (d, J¼8.0 Hz, 2H), 4.82 (br, 1H),

438
W. Shi et al. / Tetrahedron 70 (2014) 434e438
(d) Banerjee, M.; Poddar, A.; Mitra, G.; Surolia, A.; Owa, T.; Bhattacharyya, B. J.
Med. Chem. 2005, 48, 547; (e) Heinrich, D. M.; Flanagan, J. U.; Jamieson, S. M. F.;
Silva, S.; Rigoreau, L. J. M.; Trivier, E.; Raynham, T.; Turnbull, A. P.; Denny, W. A.
Eur. J. Med. Chem. 2013, 62, 4367; (f) Cheng, G.; Muench, S. P.; Zhou, Y.; Afa-
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C. W.; Hickman, M. R.; Lee, P. L.; Leed, S. E.; Auschwitz, J. M.; Rice, D. W.;
Mcleod, R. Bioorg. Med. Chem. Lett. 2013, 23, 2035.
2.94e2.90 (m, 2H), 2.43 (s, 3H), 1.45e1.42 (m, 2H), 1.31e1.26 (m,
2H), 0.84 (t, J¼7.4 Hz, 3H).
4.2.18. N-Isopentyl-4-methylbenzenesulfonamide (4g1).24 Colorless
oil; 1H NMR (400 MHz, CDCl3)
d
7.73 (d, J¼8.0 Hz, 2H), 7.30 (d,
J¼8.0 Hz, 2H), 4.57 (br, 1H), 2.95e2.90 (m, 2H), 2.41 (s, 3H),
3. Quaal, K. S.; Ji, S.; Kim, Y. M.; Closson, W. D.; Zubieta, J. A. J. Org. Chem. 1978, 43,
1311.
1.76e1.48 (m, 1H), 1.36e1.30 (m, 2H), 0.82 (d, J¼6.4 Hz, 6H).
4. (a) Fieser, L. F.; Fieser, M. Reagents for Organic Synthesis; Wiley: New York, NY,
1967, Vol. 1, p 1179; (b) Caddick, S.; Wilden, J. D.; Wadman, S. J.; Bush, H. D.;
Judd, D. B. Org. Lett. 2002, 4, 2549.
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6043; (b) Burton, G.; Cao, P.; Li, G.; Rivero, R. Org. Lett. 2003, 5, 4373; (c)
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4.2.19. N-(1,1-Dimethylethyl)-4-methyl-benzenesulfonamide
(4h). Pale yellow solid; mp 117e118 ꢀC (lit.25 111e114 ꢀC); 1H NMR
(500 MHz, CDCl3)
4.77 (s, 1H), 2.42 (s, 3H), 1.22 (s, 9H).
d
7.78 (d, J¼8.5 Hz, 2H), 7.28 (d, J¼8.5 Hz, 2H),
6. Nishikata, T.; Nagashima, H. Angew. Chem., Int. Ed. 2012, 51, 5363.
7. For selected examples, see: (a) Shi, F.; Tse, M. K.; Cui, X.; Gordes, D.; Michalik,
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4.2.20. 4-Methyl-N-(2-phenylethyl)-benzenesulfonamide
(4i).26 Brown oil; 1H NMR (500 MHz, CDCl3)
d
7.70 (d, J¼8.2 Hz, 2H),
7.10 (d, J¼8.2 Hz, 2H), 7.23e7.31 (m, 5H), 4.46 (t, J¼5.9 Hz, 1H),
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Shi, F.; Tse, M. K.; Gordes, D.; Thurow, K.; Beller, M.; Deng, Y. Adv. Synth. Catal.
3.20e3.25 (m, 2H), 2.77 (t, J¼7.0 Hz, 2H), 2.44 (s, 3H).
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4.2.21. N-4-Dimethylbenzenesulfonamide (5a). White solid; mp
77e80 (lit.27 79e80 ꢀC); 1H NMR (500 MHz, CDCl3)
d 7.76 (d,
J¼8.0 Hz, 2H), 7.32 (d, J¼8.0 Hz, 2H), 4.71 (br, 1H), 2.64 (d, J¼5.4 Hz,
2H), 2.43 (s, 3H).
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d 7.67 (d,
J¼8.0 Hz, 2H), 7.27 (d, J¼8.0 Hz, 2H), 3.25 (t, J¼5.9 Hz, 4H), 2.41 (s,
3H), 1.73e1.66 (m, 4H), 1.62e1.54 (m, 4H).
4.2.23. 2-Ethyl-1-tosylpyrrolidine (3m).29 1H NMR (500 MHz,
CDCl3)
d
7.71 (d, J¼8.3 Hz, 2H), 7.30 (d, J¼8.3 Hz, 2H), 3.56e3.50 (m,
1H), 3.40e3.35 (m, 1H), 3.21e3.16 (m, 1H), 2.41 (s, 3H), 1.88e1.83
(m, 1H), 1.79e1.73 (m, 1H), 1.61e1.42 (m, 4H), 0.91 (t, J¼7.5 Hz, 3H).
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Supplementary data
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Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2013.11.036.
References and notes
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