Synthesis of mono- and bis-chlorosulfonylarylpyrones and related sulfonates and sulfonamides

Article abstract of DOI:10.1080/10426507.2010.484904

New 2,6-bis[(3-chlorosulfonyl-4-methyl)phenyl]-4H-pyran-4-one and 2-[(3-chlorosulfonyl-4-methyl)phenyl]-6-methyl-4H-pyran-4-one were synthesized by means of a reaction of chlorosulfonic acid with corresponding pyrones at 050C and were treated with various

Full text of DOI:10.1080/10426507.2010.484904

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Phosphorus, Sulfur, and Silicon and the
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Synthesis of Mono- and Bis-
chlorosulfonylarylpyrones and Related
Sulfonates and Sulfonamides
Aziz Shahrisa a , Maryam Zirak a , Neda Torfeh a & Mahnaz Saraei b
a Department of Organic Chemistry, Faculty of Chemistry ,
University of Tabriz , Tabriz, Iran
b Payame Noor University , Tabriz, Iran
Published online: 13 Jan 2011.
To cite this article: Aziz Shahrisa , Maryam Zirak , Neda Torfeh & Mahnaz Saraei (2010) Synthesis of
Mono- and Bis-chlorosulfonylarylpyrones and Related Sulfonates and Sulfonamides, Phosphorus, Sulfur,
and Silicon and the Related Elements, 186:1, 105-114, DOI: 10.1080/10426507.2010.484904
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Phosphorus, Sulfur, and Silicon, 186:105–114, 2011
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2010.484904
SYNTHESIS OF MONO- AND
BIS-CHLOROSULFONYLARYLPYRONES AND RELATED
SULFONATES AND SULFONAMIDES
Aziz Shahrisa,1 Maryam Zirak,1 Neda Torfeh,1
and Mahnaz Saraei2
1Department of Organic Chemistry, Faculty of Chemistry, University of Tabriz,
Tabriz, Iran
2Payame Noor University, Tabriz, Iran
GRAPHICAL ABSTRACT
O
O
1. ClSO3H, 0
2. RXH
50 °C
RXO2S
SO2XR
O
O
RXH = Amine, Alcohol
20-82%
Abstract New 2,6-bis[(3-chlorosulfonyl-4-methyl)phenyl]-4H-pyran-4-one and 2-[(3-
chlorosulfonyl-4-methyl)phenyl]-6-methyl-4H-pyran-4-one were synthesized by means of a
reaction of chlorosulfonic acid with corresponding pyrones at 0→50◦C and were treated with
various alcohols and primary and secondary alkyl and aryl amines to give the corresponding
sulfonates 4a–e in 20–49% and sulfonamides 3a–l in 55–82% yields.
Keywords Chlorosulfonyl derivatives; 4-pyrone derivatives; sulfonamide; sulfonate
INTRODUCTION
The importance of the sulfonamide unit in medicinal chemistry can not be over-
stated.1 This functional group constitutes the largest class of antimicrobial agents and has
been shown to be a transition state mimetic of peptide hydrolysis, and in particular, the
critical motif for potent irreversible inhibitors of cysteine proteases.2 Starting in the 1950s,
potent carbonic anhydrase inhibitors (CAIs) belonging to the heterocyclic sulfonamide
class were developed that led to the benzothiadiazine and high ceiling diuretics, as well
as to the systematic antiglaucoma drugs.3 The discovery of these drugs highly benefited
the chemistry of sulfonamides, as thousands of derivatives belonging to the heterocyclic,
aromatic, and bis-sulfonamide classes have been synthesized and investigated for their bi-
ological activity.3b To date, the generation of sulfonamides has almost exclusively relied on
Received 22 February 2010; accepted 19 March 2010.
We thank the Research Council of University of Tabriz for financial support.
Address correspondence to Aziz Shahrisa, Department of Organic Chemistry, Faculty of Chemistry,
University of Tabriz, P.O. Box 51664, Tabriz, Iran. E-mail: ashahrisa@yahoo.com
105

106
A. SHAHRISA ET AL.
the synthesis of sulfonyl chlorides which then undergo reactions with amines.4 In addition,
various sulfonates inhibit interesting pharmacological properties.5 The reaction of sulfonyl
chlorides with alcohols in the presence of a base provides a well-established access for alkyl
sulfonates.4d,6 Other methods include the reaction of sulfonic acids with orthoformates7 and
other electrophiles such as epoxides8 or aziridines.9
4-Pyrone and the corresponding derivatives have been the subject of much research
due to their importance in various applications and their widespread biological signifi-
cance.10 In addition, 4-pyrone derivatives constitute a useful class of heterocyclic com-
pounds that are widely distributed in nature.11 Several synthetic routes to 4-pyrone deriva-
tives have been reported in the literature.12
As part of our research on the synthesis and reactions of 4-pyrone derivatives,13 in this
article we report the synthesis of mono- and bis-chlorosulfonyl, sulfonamide, and sulfonate
derivatives of 4H-pyran-4-ones 1 and 6.
RESULTS AND DISCUSSION
2,6-Bis(4-methylphenyl)-4H-pyran-4-one 1 was synthesized through cyclization of
the related 1,3,5-triketone under acidic conditions, which represents an important method
for the synthesis of a variety of 4-pyrone structures.14 The reaction of pyrone 1 with
chlorosulfonic acid resulted in the formation of sulfonyl chloride 2 (Scheme 1).
O
ClSO3H
50°C, 6h
O
0
Me
Me
1
O
O O
S
O O
S
Cl
O
Cl
Me
Me
2
Scheme 1 Synthesis of bis-chlorosulfonyl derivative 2.
In dry media, 2,6-bis[(3-chlorosulfonyl-4-methyl)phenyl]-4H-pyran-4-one 2 was un-
stable, so its spectroscopic investigation was impossible. Therefore in wet form it was
treated with various nucleophiles such as amines and alcohols to give the corresponding
sulfonamide and sulfonate derivatives, respectively.
As shown in Scheme 2, the bis-sulfonamides 3a–l were synthesized by the reaction
of bis-sulfonylchloride 2 with excess amounts of various primary and secondary aliphatic
and aromatic amines under solvent-free conditions at room temperature in 55–82% yields.
The results are summarized in Table 1.
The reaction of bis-sulfonylchloride 2 with alcohols was investigated using excess
amounts of alcohols under reflux conditions to give the corresponding sulfonates 4a–e in
20–49% yields (Scheme 3).

SULFONAMIDE AND SULFONATE DERIVATIVES OF 4-PYRONE
107
O
O O
S
O O
Amine, rt
< 1min
R'
S
R'
2
N
O
N
R
R
3a-l
Me
Me
Scheme 2 Synthesis of bis-sulfonamides 3a–l.
As shown in Scheme 4, the reaction of bis-chlorosulfonyl 2 with sodium azide was
carried out in THF at room temperature, and 2,6-bis[3-(azidosulfonyl)-4-methylphenyl]-
4H-pyran-4-one 5 was obtained in 80% yield.
In continuation of our investigation, the mono-sulfonamides 8a,b were synthesized
via the reaction of mono-sulfonyl chloride 7 with excess amounts of diethyl amine and
morpholine under solvent-free conditions at room temperature in 76% and 61% yields,
respectively. Treatment of 7 with an excess amount of ethanol under reflux conditions
Table 1 Yields of bis-sulfonamides 3a–l
Entry
Amine
Product
Yield(%)a
1
2
3
3a
3b
3c
60
65
59
4
5
6
3d
3e
3f
73
75
60
7
3g
59
8
9
3h
3i
68
82
10
11
12
3j
3k
3l
71
72
55
aIsolated yields.

108
A. SHAHRISA ET AL.
O
O O
S
O O
S
R
R
ROH
O
O
O
2
reflux
4
Me
Me
a: R = Me, 40%
b: R = Et, 45%
c
: R = n-Pr, 49%
d: R = n-Bu, 49%
e
: R = iso-Bu, 20%
Scheme 3 Synthesis of bis-sulfonates 4a–e.
O
O O
S
O O
S
NaN3
N3
O
N3
2
1 min, rt
THF, 80%
5
Me
Me
Scheme 4 Synthesis of bis-sulfonyl azide 5.
O
O
O
O O
S
ClSO3H
Me
0
50°C, 6h
Me
O
Cl
6
7
Me
O
Me
O O
S
R
Me
O
N
R
R2NH, rt
8a,b
Me
< 1 min
NH
8a: R2NH =
76%, 8b: R2NH =
61%
NH
O
7
EtOH
O
reflux
O O
S
Et
Me
O
O
9
42%
Me
Scheme 5 Synthesis of mono-sulfonamides 8a,b and sulfonate 9.

SULFONAMIDE AND SULFONATE DERIVATIVES OF 4-PYRONE
109
produced the mono-sulfonate 9 in 42% yield (Scheme 5). Mono-sulfonyl chloride 7 was
synthesized by the reaction of 6 with chlorosulfonic acid under the same conditions as
described for compound 2 (Scheme 5).
CONCLUSION
We have synthesized new N-alkyl and -arylsulfonamide and alkyl sulfonate deriva-
tives of 2,6-bis-(4-methylphenyl)-4H-pyran-4-one 1 and 2-methyl-6-(4-methylphenyl)-4H-
pyran-4-one 6 by chlorosulfonylation using chlorosulfonic acid followed by reaction with
amines and alcohols under solvent-free conditions. The reaction of chlorosulfonyl deriva-
tives with amines was carried out at ambient temperature, but the reactions with alcohols
needed to be heated. Because of the higher nucleophilicity of amines compared with alco-
hols, the yield of sulfonamides was higher than that of the sulfonates.
EXPERIMENTAL
All chemicals were purchased and used without any further purification. Melting
points were determined on an Electrothermal MEL-TEMP apparatus (model 1202D) and
are uncorrected. FT-IR spectra were obtained with a Bruker Tensor 27 spectrometer. NMR
spectra were recorded at 400 or 500 MHz for protons and at 100 or 125 MHz for carbon
nuclei in CDCl3 and DMSO-d6. Elemental analyses were done by a Vario EL III, Elementar.
General Procedure for the Synthesis of Chlorosulfonylpyrones 2 and 7
To 0.2 g (0.72 mmol) of 2,6-bis-(4-methylphenyl)-4H-pyran-4-one (1) or 0.2 g
(1 mmol) of 2-methyl-6-(4-methylphenyl)-4H-pyran-4-one (6), distilled chlorosulfonic
acid (0.48 mL, 7.2 mmol, or 0.66 mL, 10 mmol) was added dropwise at 0◦C, respectively.
The mixture was stirred at 0◦C for 15 min. Then the reaction mixture was heated at 50◦C
for 6 h. After the completion of the reaction, the mixture was cooled to room temperature
and poured into crushed ice (15 g). The resulting white solids were separated by filtration
and washed with cold water (20 mL).
General Procedure for the Synthesis of Sulfonamides 3a–l and 8a,b
To the wet solid obtained from the reaction of 0.2 g (0.72 mmol) of 1 or 0.2 g (1 mmol)
of 6 with chlorosulfonic acid (0.48 mL, 7.2 mmol, or 0.66 mL, 10 mmol, respectively),
amine (3 mmol) was added at room temperature, and the reaction mixture rapidly solidified.
The excess amount of amine was removed under vacuum, and resulting solid was washed
with water (20 mL) and dried in air.
2,6-Bis[3-(N-ethylaminosulfonyl)-4-methylphenyl]-4H-pyran-4-one (3a).
Recrystallized from MeOH:CHCl3 (2:1), white crystals. Yield: 60%. Mp: 106–108◦C.
FT-IR (KBr): ν 3304 (NH), 3148, 2979, 2930, 2874, 1643 (C O), 1587, 1417, 1322
1
(SO2), 1154 (SO2) cm−1; H NMR (500 MHz, DMSO-d6): δ 8.31 (d, J = 1.2 Hz, 2H,
CHAr), 8.14 (dd, J = 1.2 Hz, J = 7.8 Hz, 2H, CHAr), 7.79 (s, br, 2H, NH), 7.62 (d, J =
8.1Hz, 2H, CHAr), 7.02 (s, 2H, CHPyrone), 2.87–2.92 (m, 4H, CH2Ethyl), 2.66 (s, 6H, CH3),
0.99 (t, J = 7.2 Hz, 6H, CH3Ethyl) ppm; 13C NMR (125 MHz, DMSO-d6(δ 179.4 (C O),
162.1, 141.0, 140.8, 134.4, 130.3, 129.9, 126.3, 112.3, 38.3, 20.7, 15.9 ppm. Anal. Calcd
for C23H26N2O6S2: C 56.31; H 5.34; N 5.71. Found: C 56.20; H 5.45; N 5.43.

110
A. SHAHRISA ET AL.
2,6-Bis[3-(N-butylaminosulfonyl)-4-methylphenyl]-4H-pyran-4-one (3b).
Purified by plc on silica gel using a mixture of acetone:hexane (3:7), colorless crystals.
Yield: 65%. Mp: 98–100◦C. FT-IR (KBr): ν 3288 (NH), 3176, 2866, 1648 (C O), 1319
(SO2), 1151 (SO2) cm−1; 1H NMR (400 MHz, CDCl3): δ 8.51 (d, J = 1.3 Hz, 2H, CHAr),
7.87 (dd, J = 1.3 Hz, J = 8.0 Hz, 2H, CHAr), 7.49 (d, J = 8.0 Hz, 2H, CHAr), 6.88 (s,
2H, CHPyrone), 5.07 (t, J = 5.9 Hz, 2H, NH), 3.01–3.07 (m, 4H, CH2), 2.74 (s, 6H, CH3),
1.47–1.54 (m, 4H, CH2), 1.28–1.34 (m, 4H, CH2), 0.85 (t, J = 7.3 Hz, 6H, CH3Butyl) ppm;
13C NMR (100 MHz, CDCl3): δ 178.8 (C O), 160.5, 140.0, 139.0, 132.6, 128.2, 128.1,
125.2, 110.5, 42.0, 30.9, 19.4, 18.6, 12.5 ppm. Anal. Calcd for C27H34N2O6S2: C 59.32; H
6.27; N 5.12; Found: C 59.21; H 6.35; N 4.98.
2,6-Bis[3-(N-2-ethanolaminosulfonyl)-4-methylphenyl]-4H-pyran-4-one
(3c). Recrystallized from EtOH:CHCl3 (2:1), white crystals. Yield: 59%. Mp: 204–206◦C.
FT-IR (KBr): ν 3379 (OH), 3254 (NH), 3165, 2942, 2866, 1651 (C O), 1594, 1410,
1320 (SO2), 1152 (SO2), 1076, 956 cm−1; 1H NMR (500 MHz, DMSO-d6): δ 8.35 (s, 2H,
CHAr), 8.15 (d, J = 8.0 Hz, 2H, CHAr), 7.86 (s, br, 2H, NH), 7.63 (d, J = 8.1 Hz, 2H,
CHAr), 7.04 (s, 2H, CHPyrone), 4.69 (t, J = 5.4 Hz, 2H, OH), 3.37–3.42 (m, 4H, CH2),
2.93–2.94 (m, 4H, CH2), 2.66 (s, 6H, CH3) ppm; 13C NMR (125 MHz, DMSO-d6(δ 179.5
(C O), 162.1, 141.1, 141.0, 134.4, 130.2, 129.9, 126.2, 112.3, 60.8, 45.8, 20.7 ppm. Anal.
Calcd for C23H26N2O8S2: C 52.86; H 5.01; N 5.36. Found: C 52.73; H 4.90; N 5.31.
2,6-Bis[3-(N-2-(S)-propanolaminosulfonyl)-4-methylphenyl]-4H-pyran-4-
one (3d). Recrystallized from MeOH:CHCl3 (2:1), white crystals. Yield: 73%. Mp:
155–157◦C. FT-IR (KBr): ν 3308 (NH), 3158 (OH), 2974, 2917, 1640 (C O), 1570, 1421,
1318 (SO2), 1151 (SO2), 1079, 945 cm−1; 1H NMR (500 MHz, DMSO-d6): δ 8.34 (d, J =
1.5 Hz, 2H, CHAr), 8.15 (dd, J = 1.5 Hz, J = 7.9 Hz, 2H, CHAr), 7.82 (s, br, 2H, NH), 7.62
(d, J = 8.0 Hz, 2H, CHAr), 7.04 (s, 2H, CHPyrone), 4.68 (d, J = 4.7 Hz, 2H, OH), 3.58–3.63
(m, 2H, CH), 2.79 (d, J = 5.6 Hz, 4H, CH2), 2.66 (s, 6H, CH3), 0.99 (d, J = 6.2 Hz, 6H,
CH3) ppm; 13C NMR (125 MHz, DMSO-d6(δ 179.5 (C O), 162.2, 141.1, 140.9, 134.3,
130.2, 129.9, 126.2, 112.3, 66.1, 50.8, 21.6, 20.7 ppm. Anal. Calcd for C25H30N2O8S2: C
54.53; H 5.49; N 5.09. Found: C 54.20; H 5.45; N 4.91.
2,6-Bis[3-(N,N-di-ethylaminosulfonyl)-4-methylphenyl]-4H-pyran-4-one
(3e). Purified by plc on silica gel using acetone:hexane (3:7), white crystals. Yield: 75%.
Mp: 138–140◦C. FT-IR (KBr): 3073, 2880, 1658 (C O), 1319 (SO2), 1148 (SO2) cm−1
;
1H NMR (400 MHz, CDCl3): δ 8.36 (s, 2H, CHAr), 7.87 (d, J = 7.7 Hz, 2H, CHAr), 7.47
(d, J = 7.7 Hz, 2H, CHAr), 6.83 (s, 2H, CHPyrone), 3.35 (q, J = 7.0 Hz, 8H, CH2), 2.67 (s,
6H, CH3), 1.15 (t, J = 7.0 Hz, 12H, CH3Ethyl) ppm; 13C NMR (100 MHz, CDCl3): δ 178.4
(C O), 160.9, 140.3, 139.0, 132.6, 128.3, 128.2, 125.7, 111.1, 39.9, 19.3, 12.7 ppm. Anal.
calcd for C27H34N2O6S2: C 59.32; H 6.27; N 5.12; Found: C 58.95; H 6.30; N 5.20.
2,6-Bis[3-(N,N-di-propylaminosulfonyl)-4-methylphenyl]-4H-pyran-4-
one (3f). Purified by plc on silica gel using a mixture of acetone:hexane (1:2), pale
yellow solid. Yield: 60%. Mp: 118–120◦C. FT-IR (KBr): ν 3069, 2967, 2934, 2876, 1652
(C O), 1613, 1461, 1402, 1372, 1325 (SO2), 1146 (SO2), 993 cm−1; 1H NMR (500 MHz,
CDCl3): δ 8.37 (s, 2H, CHAr), 7.91 (d, J = 7.8 Hz, 2H, CHAr), 7.50 (d, J = 7.9 Hz, 2H,
CHAr), 6.86 (s, 2H, CHPyrone), 3.26 (t, J = 7.4 Hz, 8H, CH2), 2.71 (s, 6H, CH3), 1.56–1.63
(m, 8H, CH2), 0.86 (t, J = 7.3 Hz, 12H, CH3Propyl) ppm; 13C NMR (125 MHz, CDCl3(:
δ 179.9 (C O), 162.4, 141.8, 140.5, 134.1, 129.7, 129.6, 127.0, 112.3, 49.1, 21.8, 20.9,
11.5 ppm. Anal. Calcd for C31H42N2O6S2: C 61.77; H 7.02; N 4.65. Found: C 61.63; H
7.15; N 4.53.
2,6-Bis[3-(N,N-di-2-ethanolaminosulfonyl)-4-methylphenyl]-4H-pyran-
4-one (3g). Recrystallized from MeOH:CHCl3 (2:1), white crystals. Yield: 59%. Mp:

SULFONAMIDE AND SULFONATE DERIVATIVES OF 4-PYRONE
111
200–202◦C. FT-IR (KBr): ν 3365 (OH), 3038, 2964, 2929, 2882, 1646 (C O), 1614,
1406, 1331 (SO2), 1156 (SO2), 993 cm−1; 1H NMR (400 MHz, DMSO-d6): δ 8.34 (d, J =
1.3 Hz, 2H, CHAr), 8.16 (dd, J = 1.3 Hz, J = 7.7 Hz, 2H, CHAr), 7.64 (d, J = 7.7 Hz, 2H,
CHAr), 7.07 (s, 2H, CHPyrone), 4.90 (s, 4H, OH), 3.52 (t, J = 6.0 Hz, 8H, CH2), 3.38 (t, J
= 5.7 Hz, 8H, CH2), 2.63 (s, 6H, CH3) ppm; 13C NMR (100 MHz, DMSO-d6): δ 178.7
(C O), 161.3, 140.5, 139.8, 133.7, 129.7, 129.2, 125.2, 111.6, 59.4, 49.9, 20.0 ppm. Anal.
calcd for C27H34N2O10S2: C 53.10; H 5.61; N 4.59. Found: C 52.88; H 5.50; N 4.54.
2,6-Bis[4-methyl-3-(pyrrolidin-1-ylsulfonyl)phenyl]-4H-pyran-4-one (3h).
Recrystallized from EtOH (96%), white crystals. Yield: 68%. Mp: 207–209◦C. FT-IR
1
(KBr): ν 3084, 2970, 1645 (C O), 1366 (SO2), 1154 (SO2) cm−1; H NMR (400 MHz,
CDCl3): δ 8.37 (d, J = 1.6 Hz, 2H, CHAr), 7.87 (dd, J = 1.6 Hz, J = 8.0Hz, 2H, CHAr),
7.49 (d, J = 8.0 Hz, 2H, CHAr), 6.82 (s, 2H, CHPyrone), 3.34 (t, J = 6.6 Hz, 8H, CH2),
2.71 (s, 6H, CH3), 1.92 (m, 8H, CH2) ppm; 13C NMR (100 MHz, CDCl3): δ 178.4 (C O),
160.9, 140.5, 137.7, 132.7, 128.4, 128.3, 125.8, 110.9, 46.4, 24.6, 19.7 ppm. Anal. calcd
for C27H30N2O6S2: C 59.76; H 5.57; N 5.16. Found: C 59.70; H 5.38; N 5.20.
2,6-Bis[4-methyl-3-(piperidin-1-ylsulfonyl)phenyl]-4H-pyran-4-one (3i).
Recrystallized from MeOH:CHCl3 (2:1), white crystals. Yield: 82%. Mp: 200–202◦C.
FT-IR (KBr): ν 2946, 2855, 2807, 2737, 1650 (C O), 1606, 1401,1372 (SO2), 1165 (SO2)
cm−1; 1H NMR (500 MHz, CDCl3): δ 8.39 (d, J = 1.0 Hz, 2H, CHAr), 7.91 (dd, J = 1.3
Hz, J = 7.9 Hz, 2H, CHAr), 7.52 (d, J = 8.0 Hz, 2H, CHAr), 6.86 (s, 2H, CHPyrone), 3.23
(t, J = 5.2Hz, 8H, CH2), 2.73 (s, 6H, CH3), 1.65–1.67 (m, 8H, CH2), 1.56–1.59 (m, 4H,
CH2) ppm; 13C NMR (125 MHz, CDCl3(: δ 179.5 (C O), 162.3, 142.0, 138.4, 134.2,
129.9, 129.8, 127.9, 112.4, 46.6, 25.8, 24.1, 21.2 ppm. Anal. Calcd for C29H34N2O6S2: C
61.03; H 6.00; N 4.91. Found: C 60.90; H 5.97; N 4.88.
2,6-Bis[4-methyl-3-(morpholin-4-ylsulfonyl)phenyl]-4H-pyran-4-one (3j).
Recrystallized from EtOH (96%), white crystals. Yield: 71%. Mp: 250–252◦C. FT-IR
1
(KBr): ν 3080, 2856, 1647 (C O), 1333 (SO2), 1158 (SO2) cm−1; H NMR (400 MHz,
CDCl3): δ 8.38 (d, J = 2.2Hz, 2H, CHAr), 7.89 (dd, J = 2.2Hz, J = 8.0Hz, 2H, CHAr),
7.52 (d, J = 8.0Hz, 2H, CHAr), 6.84 (s, 2H, CHPyrone), 3.75 (t, J = 4.0 Hz, 8H, CH2), 3.22
(t, J = 4.0 Hz, 8H, CH2), 2.72 (s, 6H, CH3) ppm; 13C NMR (100 MHz, CDCl3): δ 178.3
(C O), 160.5, 140.7, 135.6, 133.0, 128.7, 128.5, 126.6, 111.1, 65.3, 44.4, 20.0 ppm. Anal.
calcd for C27H30N2O8S2: C 56.43; H 5.26; N 4.87. Found: C 56.58; H 5.15; N 5.10.
2,6-Bis[4-methyl-3-(phenylaminosulfonyl)phenyl]-4H-pyran-4-one (3k).
White crystals. Yield: 72%. Decomp. 274◦C. FT-IR (KBr): ν 3283 (NH), 3114, 3072,
1
2883, 2846, 1648 (C O), 1596, 1340 (SO2), 1150 (SO2) cm−1; H NMR (400 MHz,
DMSO-d6): δ 10.57 (s, 2H, NH), 8.37 (s, 2H, CHAr), 8.05 (d, J = 7.9 Hz, 2H, CHAr),
7.58 (d, J = 8.1 Hz, 2H, CHAr), 7.14–7.22 (m, 8H, CHPh), 9.95–6.98 [m, 2H (CHPh), 2H
(CHPyrone)], 2.67 (s, 6H, CH3) ppm; 13C NMR (100 MHz, DMSO-d6): δ 178.5 (C O),
160.9, 140.4, 138.6, 137.3, 133.6, 130.1, 129.3, 129.0, 126.4, 123.8, 119.1, 111.6, 19.7
ppm. Anal. calcd for C31H26N2O6S2: C 63.46; H 4.47; N 4.77. Found: C 63.11; H 4.22; N
4.69.
2,6-Bis[4-methyl-3-(3-methyl-1H-pyrazol-1-ylsulfonyl)phenyl]-4H-pyran-
4-one (3l). Recrystallized from MeOH:CHCl3 (2:1), white crystals. Yield: 55%. Decomp.
192◦C. FT-IR (KBr): ν 3068, 2967, 1663 (C O), 1608, 1461, 1402, 1373 (SO2), 1134
1
(SO2), 771 cm−1; H NMR (500 MHz, CDCl3): δ 8.48 (d, J = 1.3 Hz, 2H, CHAr), 8.11
(d, J = 2.6 Hz, 2H, CHPyrazole), 7.90 (dd, J = 1.4 Hz, J = 8.0 Hz, 2H, CHAr), 7.45 (d, J
= 8.0 Hz, 2H, CHAr), 6.78 (s, 2H, CHPyrone), 6.21 (d, J = 2.6Hz, 2H, CHPyrazole), 2.64 (s,
6H, CH3), 2.19 (s, 6H, CH3Pyrazole) ppm; 13C NMR (125 MHz, CDCl3/DMSO-d6(: δ 179.5
(C O), 161.5, 155.9, 142.8, 137.5, 134.4, 133.0, 131.4, 130.3, 127.9, 112.6, 110.0, 20.9,

112
A. SHAHRISA ET AL.
14.3 ppm. Anal. calcd for C27H24N4O6S2: C 57.43.; H 4.28; N 9.92. Found: C 57.09; H
4.12; N 9.61.
General Procedure for the Synthesis of Sulfonates 4a–e, 9
To the wet solid obtained from the reaction of 0.2 g (0.72 mmol) of 1 or 0.2 g (1 mmol)
of 6 with chlorosulfonic acid (0.48 mL, 7.2 mmol or 0.66 mL, 10 mmol), respectively, and
as mentioned above alcohol (10 mL) was added, and refluxed until the mixture would be
clear, then the solution was kept in a freezer for 24 h. The resulting solid was separated by
filtration and washed with cold alcohol and dried in air.
2,6-Bis[3-(methoxysulfonyl)-4-methylphenyl]-4H-pyran-4-one (4a). Puri-
fied by plc on silica gel using ethyl acetate/petroleum ether 60–80◦C (3:7), white crystals.
Yield: 40%. Mp: 191–193◦C. FT-IR (KBr): ν 3053, 2857, 1653 (C O), 1355 (SO2), 1179
1
(SO2), 988, 785 cm−1; H NMR (400 MHz, CDCl3): δ 8.47 (d, J = 1.6 Hz, 2H, CHAr),
7.96 (dd, J = 1.6 Hz, J = 8.0 Hz, 2H, CHAr), 7.57 (d, J = 8.0 Hz, 2H, CHAr), 6.88 (s, 2H,
CHPyrone), 3.84 (s, 6H, OCH3), 2.74 (s, 6H, CH3) ppm; 13C NMR (100 MHz, CDCl3): δ
178.2 (C O), 160.4, 141.2, 134.3, 132.8, 129.5, 128.6, 126.5, 111.3, 55.5, 19.3 ppm. Anal.
calcd for C21H20O8S2: C 54.30; H 4.34. Found: C 54.13; H 4.31.
2,6-Bis[3-(ethoxysulfonyl)-4-methylphenyl]-4H-pyran-4-one (4b). Puri-
fied by plc on silica gel using acetone:ethyl acetate:petroleum ether 60–80◦C (3:3:7), white
crystals. Yield: 45%. Mp: 178–180◦C. FT-IR (KBr): ν 3052, 2933, 1652 (C O), 1354
1
(SO2), 1179 (SO2), 909 cm−1; H NMR (400 MHz, CDCl3): δ 8.46 (d, J = 1.6 Hz, 2H,
CHAr), 7.94 (dd, J = 1.6 Hz, J = 8.0 Hz, 2H, CHAr), 7.56 (d, J = 8.0 Hz, 2H, CHAr), 6.86
(s, 2H, CHPyrone), 4.20 (q, J = 8.0 Hz, 4H, CH2Ethyl), 2.75 (s, 6H, CH3), 1.36 (t, J = 8.0 Hz,
6H, CH3Ethyl) ppm; 13C NMR (100 MHz, CDCl3): δ 178.2 (C O), 160.4, 140.9, 135.2,
132.6, 129.3, 128.5, 126.2, 111.1, 66.4, 19.3, 13.7 ppm. Anal. calcd for C23H24O8S2: C
56.08; H 4.91. Found: C 55.97; H 5.11.
2,6-Bis[3-(propoxysulfonyl)-4-methylphenyl]-4H-pyran-4-one (4c). Puri-
fied by plc on silica gel using acetone:ethyl acetate:petroleum ether 60–80◦C (1:2:3), white
crystals. Yield: 49%. Mp: 170–172◦C. FT-IR (KBr): ν 3051, 2883, 1652 (C O), 1354
1
(SO2), 1179 (SO2), 961, 836 cm−1; H NMR (400 MHz, CDCl3): δ 8.46 (s, 2H, CHAr),
7.95 (d, J = 7.2 Hz, 2H, CHAr), 7.56 (d, J = 8.0 Hz, 2H, CHAr), 6.85 (s, 2H, CHPyrone),
4.07 (t, J = 6.5 Hz, 4H, CH2), 2.74 (s, 6H, CH3), 1.68–1.77 (m, 4H, CH2), 0.94 (t, J = 7.3
Hz, 6H, CH3) ppm; 13C NMR (100 MHz, CDCl3): δ 178.2 (C O), 160.4, 140.9, 135.1,
132.6, 129.3, 128.5, 126.2, 111.1, 71.8, 21.3, 19.3, 9.0 ppm. Anal. calcd for C25H28O8S2:
C 57.68; H 5.42. Found: C 57.44; H 5.40.
2,6-Bis[3-(butoxysulfonyl)-4-methylphenyl]-4H-pyran-4-one (4d). Puri-
fied by plc on silica gel using a mixture of acetone:ethyl acetate:petroleum ether 60–80◦C
(3:3:7), white crystals. Yield: 49%. Mp: 165–167◦C. FT-IR (KBr): ν 3053, 2872, 1652
(C O), 1354 (SO2), 1179 (SO2), 946, 807 cm−1; 1H NMR (400 MHz, CDCl3): δ 8.45 (d,
J = 2.0 Hz, 2H, CHAr), 7.95 (dd, J = 2.0 Hz, J = 8.0 Hz, 2H, CHAr), 7.56 (d, J = 8.0
Hz, 2H, CHAr), 6.86 (s, 2H, CHPyrone), 4.02 (t, J = 6.4 Hz, 4H, CH2), 2.74 (s, 6H, CH3),
1.65–1.70 (m, 4H, CH2), 1.35–1.41 (m, 4H, CH2), 0.88 (t, J = 7.3 Hz, 6H, CH3Butyl) ppm;
13C NMR (100 MHz, CDCl3): δ 178.2 (C O), 160.4, 140.9, 135.1, 132.6, 129.3, 128.5,
126.2, 111.1, 70.0, 29.8, 19.3, 17.6, 12.3 ppm. Anal. calcd for C27H32O8S2: C 59.10; H
5.88. Found: C 59.22; H 5.85.
2,6-Bis[3-(isobutoxysulfonyl)-4-methylphenyl]-4H-pyran-4-one (4e). Pu-
rified by plc on silica gel using a mixture of acetone:hexane (3:7), white crystals. Yield:

SULFONAMIDE AND SULFONATE DERIVATIVES OF 4-PYRONE
113
20%. Mp: 180–182◦C. FT-IR (KBr): ν 3054, 2965, 2878, 1653 (C O), 1609, 1406, 1355
1
(SO2), 1181 (SO2), 975 cm−1; H NMR (500 MHz, CDCl3): δ 8.50 (d, J = 1.2 Hz, 2H,
CHAr), 7.99 (dd, J = 1.2 Hz, J = 7.8 Hz, 2H, CHAr), 7.59 (d, J = 7.8 Hz, 2H, CHAr), 6.89
(s, 2H, CHPyrone), 3.91 (d, J = 6.4Hz, 4H, CH2), 2.78 (s, 6H, CH3), 2.01–2.06 (m, 2H, CH),
0.98 (d, J = 6.7 Hz, 12H, CH3) ppm; 13C NMR (125 MHz, CDCl3): δ 179.6 (C O), 161.8,
142.3, 136.5, 134.3, 130.7, 129.9, 127.7, 112.6, 77.2, 28.5, 20.8, 19.1 ppm. Anal. calcd for
C27H32O8S2: C 59.10; H 5.88 Found: C 59.02; H 5.77.
Procedure for the Synthesis of Sulfonazide 5
To the wet solid obtained from the reaction of 0.5 g (1.8 mmol) of 1 with chloro-
sulfonic acid (1.2 mL, 18 mmol) as mentioned above, NaN3 (0.2 g, 3.07 mmol) in THF
was added at room temperature, and the reaction mixture rapidly solidified. The solid was
separated by filtration, washed with cold water, and dried in air.
2,6-Bis[3-(azidosulfonyl)-4-methylphenyl]-4H-pyran-4-one
(5). White
crystals. Yield: 80%. Decomp. 160◦C. FT-IR (KBr): ν 3051, 2982, 2137 (N3), 1652
1
(C O), 1605, 1360 (SO2), 1170 (SO2) cm−1; H NMR (400 MHz, DMSO-d6): δ 8.50
(d, J = 1.7Hz, 2H, CHAr), 8.36 (dd, J = 1.8 Hz, J = 8.0 Hz, 2H, CHAr), 7.81 (d, J =
8.0 Hz, 2H, CHAr), 7.18 (s, 2H, CHPyrone), 2.69 (s, 6H, CH3) ppm; 13C NMR (100 MHz,
DMSO-d6): δ 179.0 (C O), 161.0, 142.0, 138.4, 134.2, 131.2, 130.0, 126.6, 112.5, 20.6
ppm. Anal. calcd for C19H14N6O6S2: C 46.91; H 2.90; N 17.28. Found: C 46.74; H 2.71;
N 16.99.
2-[3-(N,N-Di-ethylaminosulfonyl)-4-methylphenyl]-6-methyl-4H-pyran-
4-one (8a). White crystals. Yield: 76%. Mp: 134–136◦C. FT-IR (KBr): ν 3054, 2976,
2933, 1661 (C O), 1613, 1405, 1308 (SO2), 1143 (SO2), 925 cm−1; 1H NMR (400 MHz,
CDCl3): δ 8.25 (d, J = 1.4 Hz, 1H, CHAr), 7.76 (dd, J = 1.8 Hz, J = 8.0 Hz, 1H, CHAr),
7.39 (d, J = 8.0 Hz, 1H, CHAr), 6.68 (d, J = 2.0 Hz, 1H, CHPyrone), 6.16 (s, 1H, CHPyrone),
3.31 (q, J = 7.0 Hz, 4H, CH2), 2.62 (s, 3H, CH3), 2.36 (s, 3H, CH3), 1.12 (t, J = 7.0
Hz, 6H, CH3) ppm; 13C NMR (100 MHz, CDCl3): δ 178.7 (C O), 164.4, 160.8, 139.9,
138.7, 132.4, 128.3, 128.0, 125.4, 113.4, 110.0, 39.7, 19.2, 18.8, 12.5 ppm. Anal. Calcd
for C17H21NO4S: C 60.87; H 6.31; N 4.18. Found: C 60.66; H 6.30; N 4.37.
2-Methyl-6-[4-methyl-3-(morpholinosulfonyl)phenyl]-4H-pyran-4-one
(8b). Recrystallized from EtOH (96%), yellow crystals. Yield: 61%. Mp: 186–188◦C.
FT-IR (KBr): ν 3021, 2976, 2891, 2856, 1660 (C O), 1614, 1399, 1336 (SO2), 1163
1
(SO2), 932 cm−1; H NMR (400 MHz, CDCl3): δ 8.25 (d, J = 2.0 Hz, 1H, CHAr), 7.80
(dd, J = 1.6 Hz, J = 8.0Hz, 1H, CHAr), 7.44 (d, J = 8.0 Hz, 1H, CHAr), 6.69 (d, J = 2.0
Hz, 1H, CHPyrone), 6.17 (d, J = 1.2 Hz, 1H, CHPyrone), 3.70 (t, J = 4.0 Hz, 4H, CH2), 3.16
(t, J = 4.0 Hz, 4H, CH2), 2.67 (s, 3H, CH3), 2.37 (s, 3H, CH3) ppm; 13C NMR (100 MHz,
CDCl3): δ 178.6 (C O), 164.5, 160.5, 140.2, 135.3, 132.7, 128.6, 128.6, 126.3, 113.5,
110.2, 65.1, 44.2, 19.7, 18.8 ppm. Anal. Calcd for C17H19NO5S: C 58.44; H 5.48; N 4.01.
Found: C 58.18; H 5.55; N 4.11.
2-[3-(Ethoxysulfonyl)-4-methylphenyl]-6-methyl-4H-pyran-4-one (9). Pu-
rified by plc on silica gel using hexane:acetone (2:1), pink crystals. Yield: 42%. Mp:
129–131◦C. FT-IR (KBr): ν 3096, 2963, 2925, 2856, 1668 (C O), 1618, 1402, 1375
1
(SO2), 1176 (SO2), 916 cm−1; H NMR (400 MHz, CDCl3): δ 8.37 (d, J = 4.0 Hz, 1H,
CHAr), 7.85 (dd, J = 4.0Hz, J = 8.0 Hz, 1H, CHAr), 7.48 (d, J = 8.0 Hz, 1H, CHAr), 6.73
(d, J = 2.1 Hz, 1H, CHPyrone), 6.20 (d, J = 1.2Hz, 1H, CHPyrone), 4.15 (q, J = 8.0Hz, 2H,
CH2), 2.71 (s, 3H, CH3), 2.40 (s, 3H, CH3), 1.34 (t, J = 8.0Hz, 3H, CH3) ppm; 13C NMR

114
A. SHAHRISA ET AL.
(100 MHz, CDCl3): δ 178.7 (C O), 164.6, 160.4, 140.5, 134.9, 132.4, 129.2, 128.7, 125.9,
113.6, 110.3, 66.2, 19.3, 18.9, 13.7 ppm. Anal. calcd for C15H16O5S: C 58.43; H 5.23;
Found: C 58.39; H 5.33.
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