One-Pot synthesis of sulfonamides from primary and secondary amine derived sulfonate salts using cyanuric chloride

Article abstract of DOI:10.1055/s-0029-1217020

A convenient, mild and efficient one-pot synthesis of new sulfonamides is described. The reaction of primary or secondary amine derived sulfonate salts in the presence of cyanuric chloride, triethylamine as base, and anhydrous acetonitrile as solvent at room temperature gives the corresponding sulfonamides in good to excellent yields. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1217020

PAPER
3983
One-Pot Synthesis of Sulfonamides from Primary and Secondary Amine
Derived Sulfonate Salts Using Cyanuric Chloride
One-PotSynthesisof
So
ulfonamideshammad Navid Soltani Rad,*a Ali Khalafi-Nezhad,*b Zeinab Asrari,b Somayeh Behrouz,b Zohreh Amini,a
Marzieh Behrouzb
a
Department of Chemistry, Faculty of Basic Sciences, Shiraz University of Technology, Shiraz 71555-313, Iran
Fax +98(711)7354523; E-mail: soltani@sutech.ac.ir; E-mail: nsoltanirad@gmail.com
Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454, Iran
b
Received 9 July 2009; revised 17 July 2009
harsh reaction conditions, long reaction times, tedious
work-ups and low yields of products. Hence, there is still
demand for establishing novel straightforward methods
for accessing sulfonamides under mild reaction condi-
Abstract: A convenient, mild and efficient one-pot synthesis of
new sulfonamides is described. The reaction of primary or second-
ary amine derived sulfonate salts in the presence of cyanuric chlo-
ride, triethylamine as base, and anhydrous acetonitrile as solvent at
room temperature gives the corresponding sulfonamides in good to tions.
excellent yields.
Cyanuric chloride [2,4,6-trichloro-1,3,5-triazine (TCT)]
Key words: one-pot reaction, sulfonamides, amine–sulfonate salt,
is a stable, non-volatile, inexpensive and safe reagent
which has been used in various organic transformations
and in synthesis.13 For example, cyanuric chloride and its
derivatives have been employed for the dehydration of
amides to nitriles,14 deoxygenation of sulfoxides,15
Swern-type oxidation,16 lactonization of hydroxycarboxy-
lic acids,17 conversion of carboxylic acids into acyl chlo-
rides,18a acyl azides18b amides,18a,19 ketones,20 Weinreb
amides, hydroxamates,21 diazoketones22 and alcohols.23 It
has also been used for the conversion of sulfonic acids
into sulfonyl chlorides,24 formamides into isonitriles,25
ketoximes into amides (Beckmann rearrangement),26 and
for the preparation of b-chlorohydrins from epoxides (in
water),27 and the conversion of alcohols into alkyl
chlorides28a and formate esters.28b Cyanuric chloride has
also been used as an in situ source of hydrochloric acid in
aqueous conditions for catalyzing various conversions.29
cyanuric chloride, triethylamine
Sulfonamides (sulfa drugs) were the first drugs largely
employed and systematically used as preventive and che-
motherapeutic agents against various diseases.1 They are
utilized as antihypertensive,2a antiglaucoma,2b antibacteri-
al,2c antiviral,2d antiprotozoal,2e antifungal,2f antitumor,2g
antiinflammatory2h and anticonvulsant agents.2h They are
also effective for the treatment of urinary, intestine and
ophthalmic infections,2i scalds,2i ulcerative colitis,2i rheu-
matoid arthritis,2j male erectile dysfunction2k and obesi-
ty.2l The synthesis of sulfonamides also represents a
useful strategy for the protection of primary and second-
ary amines.3 Furthermore, sulfonamides are employed as
herbicides,4a plaguicides,4b pesticides4c and surfactants.4c,d
Traditionally, sulfonamides are prepared by reaction of
ammonia or an amine (primary or secondary) with a sul-
fonyl chloride in an organic or aqueous solvent.5 Another
method for the synthesis of sulfonamides involves reac-
tion of a sulfinic acid salt with an electrophilic source of
nitrogen such as hydroxylamine-O-sulfonic acid6 or
bis(2,2,2-trichloroethyl)azodicarboxylate.7 Additionally,
sulfonamides are synthesized by reaction of sulfonic acids
with isocyanides in the presence of water,8 via direct reac-
tion of amines with sulfur dioxide,9 by reaction of sulfonic
acids with amines using trichloroacetonitrile–triphe-
nylphosphine,10 and from a sulfonic acid and triphe-
nylphosphine ditriflate.11 Furthermore, arylsulfonamides
have been prepared by reduction of arylsulfonyl azides.12
However, several of these methods suffer from disadvan-
tages including the use of reagents that are toxic, corro-
sive, expensive and difficult to access, problems in
handling sulfonyl chlorides and amines, bis-sulfonylation,
Recently, De Luca and Giacomelli reported a two-step
microwave-assisted synthesis of sulfonamides from sul-
fonic acids or their sodium salts and various amines using
cyanuric chloride.30 Their procedure involved exposure of
a mixture of the sulfonic acid (1 equiv), cyanuric chloride
(1 equiv) and triethylamine (1 equiv) in acetone in a
sealed tube to microwave irradiation at 80 °C for 20 min-
utes. The resulting precipitate was removed by filtration
and the filtrate added to an aqueous solution of sodium hy-
droxide in tetrahydrofuran. Addition of the amine (1
equiv) followed by further microwave irradiation in a
sealed tube at 50 °C for ten minutes gave the desired prod-
uct. The drawbacks of this method are the harsh reaction
conditions and somewhat cumbersome procedure.
Herein, we report a one-pot, mild and highly efficient
method for the preparation of sulfonamides from various
primary and secondary derived amine sulfonate salts
(R1SO3NH2R2R3) using cyanuric chloride in the presence
of triethylamine as base and acetonitrile as solvent at
room temperature (Scheme 1).
SYNTHESIS 2009, No. 23, pp 3983–3988
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x.
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x
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0
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Advanced online publication: 23.09.2009
DOI: 10.1055/s-0029-1217020; Art ID: Z15009SS
© Georg Thieme Verlag Stuttgart · New York
Our studies on the one-pot synthesis of sulfonamides were
influenced by the method of Blotny24 who prepared sulfo-

3984
M. N. Soltani Rad et al.
PAPER
R2
R3
Table 1 Effect of Various Solvents and Bases on the Conversion of
the p-Toluenesulfonate Salt of Pyrrolidine into 1-[(4-Methylphe-
nyl)sulfonyl]pyrrolidine
O
S
O
TCT, Et3N
+
R1
N
R1
S
NH2R2R3
O
MeCN, r.t.,1–2 h
O
O
O
S
O
S
R1 = alkyl, aryl
TCT, base, solvent
r.t.
H2N
O
N
R2, R3 = H, alkyl, aryl, allyl, benzyl, heterocycle
O
O
Cl
Entry
1
Solvent
MeCNb
Base
Time (h) Yield (%)a
TCT:
N
N
Cl
N
Cl
Et3N
1.5
1
82
(Me)2COb
HMPA
CHCl3
Et3N
50
Scheme 1 Preparation of sulfonamides from amine–sulfonate salts
using cyanuric chloride
2
3
Et3N
1
32
nyl chlorides from sulfonic acids using cyanuric chloride.
In this context, we conducted the reaction of p-toluene-
sulfonic acid (3 equiv), pyrrolidine (3 equiv), triethyl-
amine (3 equiv) and cyanuric chloride (1 equiv) in
anhydrous acetone at both room temperature and at reflux.
However, none of the corresponding sulfonamide was ob-
tained. The p-toluenesulfonic acid remained unchanged,
and instead, pyrrolidine reacted with cyanuric chloride to
4
Et3N
6
10
5
CH2Cl2
DMFb
Et3N
6
10
6
Et3N
6
NRc
NRc
40
7
DMSO
MeCNb
MeCNb
MeCNb
MeCNb
MeCNb
MeCNb
Et3N
6
8
K2CO3
DBU
DBN
DABCO
MgO
1.5
6
9
60
afford
a
pyrrolidine–cyanuric chloride adduct
(Scheme 2). Using equimolar amounts of all the reagents,
and replacing p-toluenesulfonic acid with its cesium or
potassium salt, accompanied by addition of a catalytic
amount of 18-crown-6 or tetrabutylammonium bromide
(TBAB) had no significant effect on the outcome of the
reaction.
10
11
12
13
6
55
6
NRc
10
2
d
Al2O3
2
20
a Yield of isolated product.
b Anhydrous solvent used.
c No reaction.
Thus, we decided to use the p-toluenesulfonate salt of pyr-
rolidine instead of p-toluenesulfonic acid and pyrrolidine,
in order to enhance the nucleophilicity of the sulfonic acid
and to prevent the amine reacting with cyanuric chloride.
Initially, cyanuric chloride (1 equiv) was added to the p-
toluenesulfonate salt of pyrrolidine (3 equiv) in anhydrous
acetonitrile and the reaction was allowed to stir at room
temperature for 30 minutes. During this time, the con-
sumption of cyanuric chloride and formation of p-toluene-
sulfonyl chloride and a p-toluenesulfonic acid–cyanuric
chloride adduct were observed (as indicated by TLC mon-
itoring). Subsequently, a solution of anhydrous triethyl-
amine (3 equiv) in anhydrous acetonitrile was added to the
d Basic alumina.
reaction mixture which was then stirred at ambient tem-
perature for one hour. Gratifyingly, 1-[(4-methylphe-
nyl)sulfonyl]pyrrolidine was obtained (Scheme 3), the
structure of which was confirmed by IR, NMR and mass
spectroscopic analysis. Encouraged by this result, we next
investigated the influence of various aprotic solvents and
bases on this reaction (Table 1). Of the examined sol-
vents, anhydrous acetonitrile (Table 1, entry 1) afforded
O
S
N
O
O
TCT, Et3N, acetone
r.t. or reflux , 24 h
S
OH
+
N
O
N
N
H
N
N
N
N
90–95%
Scheme 2 An attempted one-pot synthesis of 1-[(4-methylphenyl)sulfonyl]pyrrolidine
R2
R3
O
O
S
O
S
TCT
Et3N
+
+
R1
S
N
R1
O
R1
NH2R2R3
NH2R2R3
+
Cl
MeCN, r.t.,1 h
– Et3NH+
MeCN, r.t.,1 h
O
O
O
Scheme 3 One-pot synthesis of 1-[(4-methylphenyl)sulfonyl]pyrrolidine
Synthesis 2009, No. 23, 3983–3988 © Thieme Stuttgart · New York

PAPER
One-Pot Synthesis of Sulfonamides
3985
Table 2 One-pot Conversion of Various Structurally Diverse
Amine–Sulfonate Salts into the Corresponding Sulfonamidesa
(continued)
the highest yield of product and was the solvent of choice
for all further reactions.
The effect of various organic and inorganic bases on the
reaction was also studied (Table 1). Triethylamine
(Table 1, entry 1) proved to be the most satisfactory base
in terms of yield. In general, heterogeneous inorganic
bases (Table 1, entries 8, 12 and 13) afforded lower yields
of 1-[(4-methylphenyl)sulfonyl]pyrrolidine while other
organic bases were not as efficient as triethylamine.
Entry Sulfonamideb
Time (h) Mp (°C) Yield (%)c
O
O
S
n-Bu
N
10
1
oil
86
n-Bu
O
O
Table 2 One-pot Conversion of Various Structurally Diverse
S
Amine–Sulfonate Salts into the Corresponding Sulfonamidesa
11
12
1.5
1.5
71
87
90
N
Me
Entry Sulfonamideb
111,30
Time (h) Mp (°C) Yield (%)c
O
O
S
O
O
121
96
N
S
N
H
2
204
48
82
85
80
O
O
S
231
O
135c
O
1.5
1
89
82
N
S
i-Pr
1.5
1
N
H
O
O
O
O
O
S
145c
176
S
S
N
n-Bu
N
H
3
oil
N
Ph
Bn
O
O
S
O
15
2
1
1
2
127
53
90
86
87
89
N
Bn
45c,8
1
2
2
2
113
oil
80
83
80
81
N
H
O
O
S
S
S
165c
O
O
O
Me
N
N
O
N
S
S
N
N
N
N
5
N
H
Ph
Bn
Bn
O
O
O
17
158
93
Me
O
Me
N
H
6
oil
O
18
Me
N
O
O
i-Pr
S
7
oil
N
H
N
a Reagents and conditions: TCT (0.33 equiv), Et3N (1 equiv), MeCN
i-Pr
(40 mL), r.t.
b All products were characterized by 1H and 13C NMR, IR, CHN and
O
O
MS analysis.
c Yield of isolated product.
S
S
i-Pr
8
9
1
1
76
79
88
85
N
i-Pr
We next investigated the versatility and scope of this
method (Table 2). Primary and secondary amines gave
excellent yields of the corresponding sulfonamides in
short reaction times. Allylamine (Table 2, entry 1), alkyl
amines (Table 2, entries 2, 3 and 8–11), benzylamine
(Table 2, entry 4), cyclic amines (Table 2, entries 12, 13,
15 and 18) and 1,2-diamines (Table 2, entries 7, 14, 16
and 17) were efficiently converted into their correspond-
O
O
Me
N
Me
Synthesis 2009, No. 23, 3983–3988 © Thieme Stuttgart · New York

3986
M. N. Soltani Rad et al.
PAPER
Next, Et3N (0.012 mol) was added and the soln stirred for a further
30–90 min (until TLC indicated completion of the reaction). The re-
action mixture was concd under vacuum and the residue was dis-
solved in CHCl3 (100 mL). The organic layer was washed with
water (2 × 100 mL), dried over anhyd Na2SO4 and evaporated in
vacuo. The residue was purified by short column chromatography
on silica gel eluting with a mixture of PE–EtOAc.
ing sulfonamides. This synthetic method also worked well
with hydrazine derivatives (Table 2, entries 5 and 6) and
is also applicable to aliphatic sulfonic acid salts such as
amino salts of methanesulfonic acid (Table 2, entries 16–
18).
Mechanistically, this reaction proceeds via an initial
SNAr-type reaction between the sulfonate anion and cy-
anuric chloride. Next, the released chloride ion attacks the
sulfur atom of the sulfonate–cyanuric chloride adduct to
afford the corresponding sulfonyl chloride. The primary
or secondary amine (liberated from its ammonium salt by
triethylamine) then reacts with the sulfonyl chloride to
give the sulfonamide product. However, in contrast to the
observation of Blotny,24 the sulfonyl chloride was not the
sole intermediate. High-performance liquid chromatogra-
phy indicated that the formation of the 2-mono-, 2,4-di-
and 2,4,6-trisulfonate–cyanuric chloride adducts could
also have occurred. Unfortunately, attempts to separate
the sulfonate–cyanuric chloride adducts by conventional
column chromatography failed due to their decomposi-
tion. The use of semi-empirical (AM1 and PM3) and ab
N-Butyl-4-methylbenzenesulfonamide (Table 2, Entry 3)
IR (film): 3292, 3010, 2970, 1573, 1296, 1157 cm–1.
1H NMR (250 MHz, CDCl3): d = 0.72 (t, 3 H, J = 7.0 Hz, CH2CH3),
1.15–1.29 (m, 2 H, CH2CH3), 1.32–1.41 (m, 2 H, NCH2CH2), 2.34
(s, 3 H, ArCH3), 2.79 (t, 2 H, J = 5.4 Hz, NCH2), 4.91 (br s, 1 H, NH,
exchangeable with D2O), 7.29 (d, 2 H, J = 7.0 Hz, ArH), 7.67 (d, 2
H, J = 7.0 Hz, ArH).
13C NMR (62.5 MHz, CDCl3): d = 13.5, 19.7, 21.5, 31.5, 42.7,
127.1, 129.6, 136.9, 143.2.
MS (EI): m/z (%) = 227.1 (16) [M+].
Anal. Calcd for C11H17NO2S: C, 58.12; H, 7.54; N, 6.16; S, 14.11.
Found: C, 58.19; H, 7.50; N, 6.12; S, 14.15.
4-Methyl-N-morpholin-4-ylbenzenesulfonamide (Table 2,
Entry 5)
initio (Hartree–Fock, 6-31G)32 quantum mechanical cal- IR (film): 3433, 2962, 1620, 1442, 1180 cm–1.
1H NMR (250 MHz, DMSO-d6): d = 2.25 (s, 3 H, CH3), 3.70–4.30
(m, 9 H, 2 NCH2CH2O, NH), 6.71 (d, 2 H, J = 7.4 Hz, ArH), 7.63
(d, 2 H, J = 7.4 Hz, ArH).
13C NMR (62.5 MHz, DMSO-d6): d = 24.3, 55.1, 63.9, 127.2,
129.4, 136.7, 141.6.
culations revealed that among the three possible sul-
fonate–cyanuric chloride adducts, formation of the 2,4,6-
trisulfonate–cyanuric chloride adduct requires much low-
er energy (DHf) and hence is the most likely to form.32
In summary, we have developed a mild, one-pot synthetic
method for the preparation of alkyl and aryl sulfonamides
from primary and secondary amine derived sulfonate salts
MS (EI): m/z (%) = 256.1 (17) [M+].
Anal. Calcd for C11H16N2O3S: C, 51.54; H, 6.29; N, 10.93; S, 12.51.
using readily available cyanuric chloride and triethyl- Found: C, 51.59; H, 6.27; N, 10.99; S, 12.46.
amine in anhydrous acetonitrile. This method proved to be
4-Methyl-N-(4-methylpiperazin-1-yl)benzenesulfonamide
useful for the conversion of structurally diverse amines
into sulfonamides in good to excellent yields. Further-
more, the use of amine–sulfonate salts as substrates over-
comes the problems usually associated with handling
toxic and corrosive amines and sulfonic acids or their ha-
lide derivatives.
(Table 2, Entry 6)
IR (film): 3440, 2980, 1615, 1447, 1180 cm–1.
1H NMR (250 MHz, DMSO-d6): d = 2.27 (s, 3 H, CH3), 2.51 (s, 3
H, NCH3), 2.69 [t, 4 H, J = 5.3 Hz, MeN(CH2)2], 2.84 [t, 4 H,
J = 5.3 Hz, NN(CH2)2], 3.67 (br s, 1 H, NH, exchangeable with
D2O), 7.17 (d, 2 H, J = 7.5 Hz, ArH), 7.42 (d, 2 H, J = 7.5 Hz, ArH).
13C NMR (62.5 MHz, CDCl3): d = 20.2, 21.4, 31.1, 42.7, 127.3,
All chemicals were purchased from commercial sources. The
amine–sulfonate salts were freshly prepared according to the de-
scribed procedure.33 Solvents were purified and dried using report-
ed methods34 and stored over 3 Å molecular sieves. The reaction
progress was monitored by TLC using SILG/UV 254 silica gel
plates. Column chromatography was carried out on silica gel 60,
(0.063–0.200 mm, 70–230 mesh, ASTM). IR spectra were run on a
Shimadzu FTIR-8300 spectrophotometer. 1H NMR (250 MHz) and
13C NMR (62.5 MHz) were recorded using a Bruker Avance DPX-
250, FT-NMR spectrometer with chemical shift (d) values reported
in ppm, and coupling constants (J) in Hz. Mass spectra were record-
ed on a Shimadzu GC MS-QP 1000 EX apparatus. Microanalyses
were performed on a Perkin–Elmer 240-B microanalyzer. Melting
points were recorded on a Büchi 510 apparatus in open capillary
tubes and are uncorrected. Full analytical data are provided for nov-
el products and references are given for known compounds (see
Table 2).
129.6, 137.0, 143.1.
MS (EI): m/z (%) = 269.1 (25) [M+].
Anal. Calcd for C12H19N3O2S: C, 53.51; H, 7.11; N, 15.60; S, 11.90.
Found: C, 53.55; H, 7.08; N, 15.64; S, 11.92.
N-(2-(Diisopropylamino)ethyl)-4-methylbenzenesulfonamide
(Table 2, Entry 7)
IR (film) : 3450, 2985, 1620, 1456, 1185 cm–1.
1H NMR (250 MHz, DMSO-d6): d = 0.97 (d, 12 H, J = 4.4 Hz, 4
CH3), 2.25 (s, 3 H, CH3), 2.34 (t, 2 H, J = 5.6 Hz, NCH2), 2.76–2.79
(m, 2 H, 2 NCH), 3.33 (t, 2 H, J = 5.6 Hz, SNCH2), 3.77 (s, 1 H, NH,
exchangeable with D2O), 7.17 (d, 2 H, J = 7.5 Hz, ArH), 7.51 (d, 2
H, J = 7.5 Hz, ArH).
13C NMR (62.5 MHz, DMSO-d6): d = 20.7, 20.9, 41.7, 45.6, 49.2,
125.5, 128.8, 138.1, 144.1.
MS (EI): m/z (%) = 298.2 (32) [M+].
Sulfonamide Preparation; General Procedure
Anal. Calcd for C15H26N2O2S: C, 60.37; H, 8.78; N, 9.39; S, 10.74.
Found: C, 60.42; H, 8.81; N, 9.37; S, 10.77.
To a soln of freshly prepared primary or secondary amine derived
sulfonate salt31(0.01 mol) in anhyd MeCN (40 mL) was added TCT
(0.0033 mol) and the reaction mixture was stirred at r.t. for 30 min.
Synthesis 2009, No. 23, 3983–3988 © Thieme Stuttgart · New York

PAPER
One-Pot Synthesis of Sulfonamides
3987
N,N-Diisopropyl-4-methylbenzenesulfonamide (Table 2, Entry
4-Benzyl-1-[(4-methylphenyl)sulfonyl]piperidine (Table 2,
Entry 15)
8)
IR (KBr): 2939, 2854, 1458, 1334, 1157 cm–1.
IR (KBr): 3031, 2908, 1566, 1311, 1234 cm–1.
1H NMR (250 MHz, CDCl3): d = 1.02 (d, 12 H, J = 4.5 Hz, 4 CH3),
2.30 (s, 3 H, CH3), 2.75–2.80 (m, 2 H, 2 CH), 7.17 (d, 2 H, J = 7.5
Hz, ArH), 7.66 (d, 2 H, J = 7.5 Hz, ArH).
13C NMR (62.5 MHz, CDCl3): d = 21.4, 25.3, 30.2, 126.9, 129.6,
137.4, 142.8.
1H NMR (250 MHz, CDCl3): d = 0.99–1.17 (m, 1 H, CH), 1.57–
1.73 (m, 4 H, CH2CHCH2), 2.45 (s, 3 H, CH3), 2.58 (t, 4 H, J = 5.6
Hz, 2 NCH2), 4.55 (d, 2 H, J = 12.5 Hz, PhCH2), 7.02–7.21 (m, 9 H,
ArH).
13C NMR (62.5 MHz, CDCl3): d = 31.8, 32.1, 38.3, 43.1, 43.8,
126.0, 128.3, 129.2, 136.5, 138.4, 140.1, 144.1, 149.6.
MS (EI): m/z (%) = 255.1 (30) [M+].
MS (EI): m/z (%) = 329.1 (38) [M+].
Anal. Calcd for C13H21NO2S: C, 61.14; H, 8.29; N, 5.48; S, 12.56.
Found: C, 61.10; H, 8.33; N, 5.44; S, 12.60.
Anal. Calcd for C19H23NO2S: C, 69.27; H, 7.04; N, 4.25; S, 9.73.
Found: C, 69.32; H, 7.09; N, 4.31; S, 9.77.
N,N,4-Trimethylbenzenesulfonamide (Table 2, Entry 9)
IR (KBr): 3100, 2862, 1458, 1157 cm–1.
4-Benzyl-1-(methylsulfonyl)piperazine (Table 2, Entry 17)
IR (KBr): 3029, 2915, 1566, 1312, 1237 cm–1.
1H NMR (250 MHz, CDCl3): d = 2.50 (s, 3 H, CH3), 2.58 (s, 6 H, 2
NCH3), 7.33 (d, 2 H, J = 7.5 Hz, ArH), 7.92 (d, 2 H, J = 7.5 Hz,
ArH).
1H NMR (250 MHz, CDCl3): d = 1.33–1.47 (m, 8 H, 4 NCH2), 2.79
(s, 3 H, CH3), 4.04 (s, 2 H, PhCH2), 6.97–7.91 (m, 5 H, ArH).
13C NMR (62.5 MHz, CDCl3): d = 21.5, 37.9, 127.8, 129.6, 132.4,
143.5.
13C NMR (62.5 MHz, CDCl3): d = 39.8, 43.0, 52.1, 61.8, 127.0,
128.1, 128.8, 137.7.
MS (EI): m/z (%) = 199.1 (26) [M+].
MS (EI): m/z (%) = 254.1 (29) [M+].
Anal. Calcd for C9H13NO2S: C, 54.25; H, 6.58; N, 7.03; S, 16.09.
Found: C, 54.23; H, 6.61; N, 6.99; S, 16.07.
Anal. Calcd for C12H18N2O2S: C, 56.67; H, 7.13; N, 11.01; S, 12.61.
Found: C, 56.62; H, 7.15; N, 11.07; S, 12.68.
N,N-Dibutyl-4-methylbenzenesulfonamide (Table 2, Entry 10)
4-Benzyl-1-(methylsulfonyl)piperidine (Table 2, Entry 18)
IR (film): 3025, 2939, 2854, 1458, 1334, 1157 cm–1.
IR (KBr): 3115, 2916, 1567, 1442, 1319, 1141 cm–1.
1H NMR (250 MHz, CDCl3): d = 0.69–0.80 (m, 6 H, 2 CH2CH3),
1.11–1.25 (m, 4 H, 2 CH2CH3), 1.33–1.45 (m, 4 H, 2 NCH2CH2),
2.27 (s, 3 H, ArCH3), 2.95–3.13 (t, 4 H, J = 5.3 Hz, 2 NCH2), 7.18
(d, 2 H, J = 7.6 Hz, ArH), 7.55 (d, 2 H, J = 7.6 Hz, ArH).
13C NMR (62.5 MHz, CDCl3): d = 13.5, 19.8, 21.2, 30.4, 48.0,
126.9, 129.4, 137.0, 142.87.
1H NMR (250 MHz, CDCl3): d = 1.20–1.35 (m, 4 H, CH2CHCH2),
1.50–1.63 (m, 3 H, PhCH2CH), 2.47–2.58 (t, 4 H, J = 5.4 Hz, 2
NCH2), 2.66 (s, 3 H, CH3), 7.04–7.24 (m, 5 H, ArH).
13C NMR (62.5 MHz, CDCl3): d = 31.5, 34.5, 37.5, 42.7, 46.2,
126.1, 128.3, 129.1, 139.7.
MS (EI): m/z (%) = 253.1 (24) [M+].
MS (EI): m/z (%) = 283.2 (20) [M+].
Anal. Calcd for C13H19NO2S: C, 61.63; H, 7.56; N, 5.53; S, 12.66.
Found: C, 61.68; H, 7.59; N, 5.51; S, 12.70.
Anal. Calcd for C15H25NO2S: C, 63.56; H, 8.89; N, 4.94; S, 11.31.
Found: C, 63.49; H, 8.92; N, 4.96; S, 11.29.
Acknowledgment
N-Cyclohexyl-N,4-dimethylbenzenesulfonamide (Table 2,
Entry 11)
We thank Shiraz University of Technology and Shiraz University
Research Councils for partial support of this work.
IR (KBr): 3015, 2931, 1566, 1450, 1334, 1296 cm–1.
1H NMR (250 MHz, CDCl3): d = 1.16–1.19 (m, 6 H, 3 CH2), 1.62–
1.65 (m, 4 H, 2 NCHCH2), 2.33 (s, 3 H, ArCH3), 2.64 (s, 3 H,
NCH3), 3.63–3.72 (m, 1 H, NCH), 7.18 (d, 2 H, J = 8.2 Hz, ArH),
7.59 (d, 2 H, J = 8.2 Hz, ArH).
13C NMR (62.5 MHz, CDCl3): d = 20.9, 24.8, 25.2, 28.1, 29.7, 56.2,
126.3, 129.1, 136.9, 142.3.
References
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MS (EI): m/z (%) = 267.1 (16) [M+].
(2) (a) Kanda, Y.; Kawanishi, Y.; Oda, K.; Sakata, T.; Mihara,
S.; Asakura, K.; Kanemasa, T.; Ninomiya, M.; Fujimoto,
M.; Kanoike, T. Bioorg. Med. Chem. 2001, 9, 897.
(b) Mincione, F.; Starnotti, M.; Menabuoni, L.; Scozzafava,
A.; Casini, A.; Supuran, C. T. Bioorg. Med. Chem. Lett.
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Found: C, 62.85; H, 7.90; N, 5.28; S, 11.97.
1-[(4-Methylphenyl)sulfonyl]pyrrolidine (Table 2, Entry 12)
IR (KBr): 3020, 2970, 1570, 1440, 1334, 1164 cm–1.
1H NMR (250 MHz, CDCl3): d = 1.63–1.68 (m, 4 H, 2 CH2), 2.34
(s, 3 H, ArCH3), 3.11–3.17 (t, 4 H, J = 5.6 Hz, 2 NCH2), 7.22 (d, 2
H, J = 8.0 Hz, ArH), 7.61 (d, 2 H, J = 8.0 Hz, ArH).
13C NMR (62.5 MHz, CDCl3): d = 21.5, 25.1, 47.9, 127.5, 129.6,
133.7, 143.3.
MS (EI): m/z (%) = 225.1 (26) [M+].
Zoumpoulakis, P.; Geronikaki, A.; Soković, M.;
Anal. Calcd for C11H15NO2S: C, 58.64; H, 6.71; N, 6.22; S, 14.23.
Found: C, 58.70; H, 6.65; N, 6.25; S, 14.26.
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S. H.; Khalil, E. A.; Leit, S.; Fournel, M.; Yan, P. T.; Trachy-
Synthesis 2009, No. 23, 3983–3988 © Thieme Stuttgart · New York

3988
M. N. Soltani Rad et al.
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was stirred at r.t. for 15 min and the reaction was judged to
be complete when pH paper indicated that the soln was
neutral. The soln was evaporated under vacuum and the
remaining solid was crystallized from hot MeOH. The
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Synthesis 2009, No. 23, 3983–3988 © Thieme Stuttgart · New York