An efficient method for the synthesis of novel n-acylsulfonamides using tin (IV) chloride as catalysts

Article abstract of DOI:10.1080/10426507.2013.843000

A series of novel N-acylsulfonamides derivatives were synthesized via direct condensation of parent sulfonamide with ethyl lactate as an acylating agent in the presence of tin (IV) chloride (SnCl₄) as a Lewis acid catalyst. The sulfonamides were prepared, starting from chlorosulfonyl isocyanate (CSI), in three steps (carbamoylation, sulfamoylation, and deprotection) with excellent yields. Copyright

Full text of DOI:10.1080/10426507.2013.843000

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Phosphorus, Sulfur, and Silicon and the
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An Efficient Method for the Synthesis of
Novel N-acylsulfonamides Using Tin (IV)
Chloride as Catalysts
Fouzia Bouchareba, Wahida Boufasa, Hadjer Cheloufia, Malika
Berredjema & Nour-Eddine Aoufa
a LCOA, Bioorganic Chemistry Group, Chemistry Department,
Sciences Faculty, Badji Mokhtar University-Annaba, BP 12, Annaba
23000, Algeria
Accepted author version posted online: 23 Sep 2013.Published
online: 14 May 2014.
To cite this article: Fouzia Bouchareb, Wahida Boufas, Hadjer Cheloufi, Malika Berredjem & Nour-
Eddine Aouf (2014) An Efficient Method for the Synthesis of Novel N-acylsulfonamides Using Tin (IV)
Chloride as Catalysts, Phosphorus, Sulfur, and Silicon and the Related Elements, 189:5, 587-595, DOI:
10.1080/10426507.2013.843000
To link to this article: http://dx.doi.org/10.1080/10426507.2013.843000
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Phosphorus, Sulfur, and Silicon, 189:587–595, 2014
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2013.843000
AN EFFICIENT METHOD FOR THE SYNTHESIS OF NOVEL
N-ACYLSULFONAMIDES USING TIN (IV) CHLORIDE AS
CATALYSTS
Fouzia Bouchareb, Wahida Boufas, Hadjer Cheloufi,
Malika Berredjem, and Nour-Eddine Aouf
LCOA, Bioorganic Chemistry Group, Chemistry Department, Sciences Faculty,
Badji Mokhtar University-Annaba, BP 12, Annaba 23000, Algeria
GRAPHICAL ABSTRACT
O
C
O
S
CH3
R
Cl
S
N
C
O
NH
NH
O
OH
O
O
F
H
R= CH3(CH2)2
,
,
CH3
,
,
Abstract A series of novel N-acylsulfonamides derivatives were synthesized via direct con-
densation of parent sulfonamide with ethyl lactate as an acylating agent in the presence of
tin (IV) chloride (SnCl4) as a Lewis acid catalyst. The sulfonamides were prepared, start-
ing from chlorosulfonyl isocyanate (CSI), in three steps (carbamoylation, sulfamoylation, and
deprotection) with excellent yields.
Keywords Chlorosulfonyl isocyanate; deprotection; α-hydroxyester; N-acylsulfonamide;
sulfonamide; Tin (IV) chloride
INTRODUCTION
The N-acylsulfonamide group, a functionality often found in various drugs and
therapeutic agents, is a well-known bioisostere of a carboxylic acid in medicinal chemistry.1
The replacement of carboxyl groups by acidic surrogates, such as N-acylsulfonamide, is
a useful modification in drug design2–7 (Fig. 1) because the pKa value of an acidic NH
proton in N-acylsulfonamides is similar to that of a carboxylic acid proton,8 while their
resistance to chemical and enzymatic hydrolysis renders them amenable for use as enzyme
inhibitors.9
Received 9 May 2013; accepted 16 August 2013.
This work was generously supported by the General Directorate for Scientific Research and Technological
Development (DG-RSDT), Algerian Ministry of Scientific Research, Applied Organic Laboratory (FNR 2000).
Address correspondence to Malika Berredjem, Laboratory of Applied Organic Chemistry, Badji-Mokhtar
University, BP 12 El-Hadjar, Annaba, 23000, Algeria. E-mail: mberredjem@yahoo.fr
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/gpss.
587

588
F. BOUCHAREB ET AL.
Figure 1 N-Acylsulfonamide analogs as a novel EP3 and IP receptor antagonist.
Moreover, a number of enzyme inhibitors,10 new therapeutic agents for Alzheimer’s
disease,11 antagonists for Angiotensin II,12 Leukotriene D4-receptors,13 and hepatitis C
virus NS protease inhibitors14 are derived from N-acylsulfonamides.
For example, a small molecule ABT-737 with an N-acylsulfonamide motif was shown
to be a potent inhibitor of interaction with BH3 domain-only proteins,15 and is currently
under clinical trials as a potential therapeutic agent for the treatment of cancer.
Most N-acylsulfonamides are prepared starting from parent sulfonamides with car-
boxylic acid chlorides or anhydrides in the presence of an activating reagent.16–18 It has
been found that Al(HSO4)3 and Zr(HSO4)4 efficiently catalyzed the N-acylation of differ-
ent primary and secondary sulfonamides under solvent-free and heterogeneous conditions.9
Moreover, the preparation of acylsulfonamide from aryl halide and sulfonamide catalyzed
by Pd (II) and Mo(CO)6 under microwave irradiation was also reported.19 Herein we re-
port an attractive reaction using (SnCl4) as catalyst for N-acylation of different primary
sulfonamide 2a–e (Scheme 1) in the presence of ethyl lactate as an acylating agent.
RESULTS AND DISCUSSION
An alternative preparation method for the synthesis of N-acylsulfonamides is to use
a carboxylic ester as an acylating agent in the presence of various kinds of Lewis acid
promoters such as AlCl3, FeCl3, TiCl4, ZrCl4, Fe2O3, MgO, FeCl2, ZrCl4, ZnCl2, CuCl,
Cu(OAc)2.H2O, FeCl2.4H2O, MnCl2.4H2O, CdCl2.2.5H2O, and NiCl2.6H2O. It was found
that TiCl4 was only a promoter for the N-acylation of sulfonamide with ethyl acetate, and
other Lewis acids did not provide sufficient yields (<5%) except FeCl3.20

NOVEL N-ACYLSULFONAMIDES
589
Scheme 1 Synthesis of N-acylsulfonamide.
Based on this study and the various articles in the literature which used Lewis acid as
a catalyst, we found interest in trying to prepare a new series of N-acylsulfonamides from
parent sulfonamides with ethyl lactate as an acylating agent in the presence of SnCl4 as
Lewis acid, when the reaction was realized in CH3CN or toluene.
We found satisfactory yields (45–60%) when we used sulfonamide derived of primary
amine (2a–e) in CH3CN, but the yield did not exceed 40% in toluene (yields 20–40%)
(Table 1). Notably, no product was observed when the reaction was realized in the absence
of SnCl4 catalyst even after 48 h in either of the two solvents.
Table 1 N-Acylation of primary sulfonamides using SnCl4
Yields (%)
Entry
1
Sulfonamidea
Acylating agent Time (h)
12
Productb
CH3CN Toluene
60
55
45
40
39
20
2
3
—
—
12
12
4
5
—
—
12
12
49
50
35
38
a, bAll products were characterized by 1H NMR, 13C NMR, MS, and IR spectroscopy.
Reaction was carried out at 82◦C in CH3CN, and at 110◦C in toluene.

590
F. BOUCHAREB ET AL.
Several sulfonamides (2a–e) illustrating the usefulness of this efficient procedure are
summarized in Scheme 1. The carboxylsulfonamides (1a–e) were prepared in excellent
yields (88–97%) following two steps (carbamoylation and sulfamoylation).
Carbamoylation: This step involves addition of tert-butanol and chlorosulfonyl isocyanate
in anhydrous methylene chloride at 0◦C for 30 min.
Sulfamoylation: The carbamate chlorosulfonyl formed in the first step is added to a solution
of primary amine (1 equiv.) in the same solvent in the presence of triethylamine (1.1 equiv.)
at 0◦C. The reaction is left under magnetic stirring at room temperature for 2 h. After
treatment, protected sulfonamides (1a–e) were obtained as a white powder with excellent
yields.21–23
Deprotection: The protected sulfonamides (1a–e) were refluxed in water for 15–30 min to
afford deprotected sulfonamides (2a–e) in good yields. The disappearance of C=O ester
1
band in IR and (CH3)3 signal in H NMR confirms the removal of the BOC (Protecting
group) fragment.24
N-acylation: Usually, N-acylsulfonamides can be obtained by acylation of sulfonamides;
acylation can be accomplished by the reaction of sulfonamides with acids, anhydrides, ester,
and acid chlorides. A number of synthetic procedures haves been reported for preparation
of sulfonamide from acids using coupling reagents such as EDC, DCC, and DCI.16–18 In
our case, N-acylsulfonamides were formed by using ethyl lactate as an acylating agent and
SnCl4 as catalyst refluxing in CH3CN or toluene for 12 h.
CONCLUSIONS
In summary, a new series of N-acylsoulfonamides derivatives were synthesized in
four steps (carbamoylation, sulfamoylation, deprotection, and N-acylation) starting from
chlorosulfonylisocyanate (CSI) and primary amine. We have demonstrated SnCl4-catalyzed
direct intermolecular N-acylation of sulfonamide with ethyl lactate as an acylating agent.
The structures of all compounds synthesized were unambiguously confirmed by usual
spectroscopic methods, i.e. 1H NMR, 13C NMR, mass spectrometry, and IR.
EXPERIMENTAL
Melting points were determined in open capillary tubes on an electrothermal appa-
ratus, and uncorrected IR spectra were recorded on a Perkin–Elmer FT-600 spectrometer.
Proton nuclear magnetic resonance was determined with a 360 WB or AC 250 MHz Bruker
spectrometer using CDCl3 and DMSO-d6 as a solvent and tetramethylsilane (TMS) as an
internal standard. Chemical shifts are reported in δ units (ppm). All coupling constants
(J) are reported in Hertz. Multiplicity is indicated as s (singlet), d (doublet), t (triplet),
m (multiplet), and combination of these signals. Electron ionization mass spectra (30 ev)
were recorded in positive mode on a Water Micro Mass ZQ. The highest resolution mass
was measured on a Joel SX 102 mass spectrometer and recorded in an FAB positive mode.
All reactions were monitored by TLC on silica Merck h60 F254 (Art. 5554) precoated
aluminum plates and were developed by spraying with ninhydrin solution.
General Procedure for the Preparation of Carboxylsulfonamide
To the stirred solution of chlorosulfonyl isocyanate (CSI) (1.62 g, 1 mL, 11.48 mmol)
in anhydrous methylene chloride (10 mL) at 0◦C was added tert-butanol (0.85 g, 1.09 mL,

NOVEL N-ACYLSULFONAMIDES
591
11.48 mmol) in the same solvent (10 mL). After a period of 30 min, the resulting solution
and triethylamine (1.75 mL, 1.1 equiv.) was slowly added to a solution containing primary
amine (1 equiv.) in anhydrous methylene chloride (10 mL) at 0◦C. The resulting reaction
solution was allowed to warm up to room temperature for over a period of 2 h. The reaction
mixture was diluted with methylene chloride (30 mL) and washed with HCl 0.1 N (20 mL)
and then with water (25 mL). The organic layer was dried over anhydrous sodium sulphate
and concentrated in vacuo to give carboxyl sulfonamides (1a–e) in excellent yields.
Tert-Butyl(1-Propyl)Amino Sulfonylcarbamate 1a
Yield: 97%. mp: 110–111 ◦C. Rf = 0.80 (CH2Cl2/MeOH: 9/1). 1H NMR (CDCl3, δ
ppm): 7.28 (s, 1H, NH-C=O); 5.22 (t, J = 6.04 Hz, 1H, NH-CH2); 3.05 (q, J = 7.11 Hz,
2H, CH2-NH); 1.59 (m, 2H, CH2-CH3); 1.50 (s, 9H, (CH3)3); 0.98 (t, 3H, J = 7.35 Hz,
CH3). 13C NMR (CDCl3, δ ppm): 151.1; 80.6; 42.1; 28.0; 22.2; 12.0. IR (KBr, v cm−1):
3441 and 3262 (2NH); 1715 (C=O); 1362 and 1142 (SO2). MS-ESI+ 30 ev m/z: 239
[M+H] + 100%. Anal. Calcd for C8H18N2O4S (238): C, 40.32; H, 7.61; N, 11.76. Found:
C, 40.35; H, 7.69; N, 11.73
Tert-Butyl(1-Cyclohexyl)Amino Sulfonylcarbamate 1b
◦
1
Yield: 90%. mp: 109–110 C. Rf = 0.90 (CH2Cl2/MeOH: 9/1). H NMR (CDCl3,
δ ppm): 7.32 (s, 1H, NH-C=O), 5.12 (d, J = 7.35 Hz, 1H, NHcyc), 3.30 (m, 1H, CH-
NH), 1.96 (m, 2H, CH2 cyc), 1.73 (m, 2H, CH2-cyc), 1.60 (m, 2H, CH2-cyc); 1.51 (s, 9H,
(CH3)3); 1.33 (m, 4H, 2CH2-cyc),.13C NMR (CDCl3, δ ppm): 150.0; 83.6; 53.4; 33.2; 28.0;
25.1; 24.5. IR (KBr, v cm−1): 3438 and 3258 (2NH); 1720 (C=O); 1357 and 1132 (SO2).
MS-ESI+ 30 ev m/z: 279 [M+H] + 100%. Anal. Calcd for C11H22N2O4S (278): C, 47.46;
H, 7.97; N, 10.06. Found: C, 47.50; H, 7.81; N, 10.15.
Tert-Butyl(1-Methylbenzyl)Amino Sulfonylcarbamate 1c
Yield: 94%. mp: 130–131 ◦C. Rf = 0.78 (CH2Cl2/MeOH:9/1). 1H NMR (CDCl3, δ
ppm): 7.30 (s, 5H, H-Ar); 7.07 (s, 1H, NH-C=O); 5.50 (d, J = 7.52 Hz, 1H, NH-CH∗); 4.55
(m, 1H, CH∗); 1.55 (d, J = 6.51 Hz 3H, CH3); 1.36 (s, 9H, (CH3)3). 13C NMR (CDCl3, δ
ppm): 149.5; 141.2; 128.5; 127.5, 125.8; 83.2; 54.2; 27.5; 22.7. IR (KBr, v cm−1): 3421 and
3251 (2NH); 1723 (C=O); 1643 (C=C); 1363 and 1135 (SO2). MS-ESI+30 ev m/z: 301
[M+H] + 100%. Anal. Calcd for C13H20N2O4S (300): C, 51.98; H, 6.71; N, 9.33. Found:
C, 51.91; H, 6.77; N, 9.35.
Tert-Butyl (3-Fluorophenyl)Amino Sulfonylcarbamate 1d
Yield: 88%. mp: 137–138 ◦C. Rf = 0.90 (CH2Cl2/MeOH: 9/1). 1H NMR (CDCl3, δ
ppm): 10.50 (s, 1H, NH-C=O); 7.50–6.75 (m, 4H, H-Ar); 1.35 (s, 9H, (CH3)3).13C NMR
(CDCl3, δ ppm): 162.2; 151.3; 138.0; 130.0; 112.1; 109.8; 103.7; 84.0; 27.2. IR (KBr, v
cm−1): 3442 and 3261 (2NH); 1716 (C=O); 1651 (C=C); 1361 and 1143 (SO2). MS-ESI+
30 ev m/z: 291 [M+H] +100%. Anal. Calcd for C11H15FN2O4S (290): C, 45.51; H, 5.21;
N, 9.65. Found: C, 45.55; H, 5.18; N, 9.67.

592
F. BOUCHAREB ET AL.
Tert-Butyl(1-Phenyl)Amino Sulfonyl Carbamate 1e
Yield: 95%. mp: 129–131 ◦C. Rf = 0.85 (CH2Cl2/MeOH: 9/1). 1H NMR (CDCl3, δ
ppm): 7.40–7.20 (m, 5H, H-Ar); 7.07 (s, 1H, NH-C=O); 1.45 (s, 9H, (CH3)3).13C NMR
(CDCl3, δ ppm): 149.8; 135.7; 129.4; 126.6; 122.8; 84.1; 27.2. IR (KBr, v cm−1): 3443 and
3268 (2NH); 1718 (C=O); 1655 (C=C); 1358 and 1151 (SO2). MS-ESI+ 30 ev m/z: 273
[M+H] +100%. Anal. Calcd for C11H16N2O4S (272): C, 48.52; H, 5.92; N, 10.29. Found:
C, 48.59; H, 5.84; N, 10.33.
General Procedure for the Preparation of Sulfonamide
The deprotection reaction of sulfonamide (1a–e) (1g) was carried out in distilled
water (30 mL); the reaction mixture was refluxed for 15–30 min, then it was extracted with
ethyl acetate (3 × 30 mL). The organic layer was dried over anhydrous sodium sulphate
and concentrated under reduced pressure to give sulfonamides (2a–e) in good yields.
N-(1-Propyl)Sulfamide 2a
Yield: 89% mp: 158–159 ◦C. Rf = 0.67 (CH2Cl2/MeOH: 9/1). 1H NMR (DMSO, δ
ppm): 4.49 (s, 3H, NH+NH2); 3.00 (t, J = 7.11 Hz, 2H, CH2-NH); 1.50 (m, 2H, CH2-
CH2); 0.90 (t, J = 7.35 Hz, 3H, CH3).13C NMR (CDCl3, δ ppm): 45.0; 22.0; 10.0. IR
(KBr, v cm−1): 3055 and 2985 (NH, NH2); 1338 and 1161 (SO2). MS-ESI+ 30 ev m/z: 139
[M+H]+ 100%. Anal. Calcd for C3H10N2O2S (138): C, 26.07; H, 7.29; N, 20.27. Found:
C, 26.12; H, 7.32; N, 20.24.
N-(1-Cyclohexyl)Sulfamide 2b
◦
1
Yield: 87%. mp: 178–179 C. Rf = 0.60 (CH2Cl2/MeOH: 9/1). H NMR (DMSO,
δ ppm): 4.90 (d, J = 6.2 Hz, 1H, NH-cyc); 3.60 (s, 2H, NH2); 3.25 (m, 1H, CH-NH),
1.85 (m, 2H, CH2 cyc), 1.55 (m, 2H, CH2-cyc), 1.35 (m, 2H, CH2-cyc); 1.20 (m, 4H, 2
CH2-cyc). 13C NMR (CDCl3, δ ppm): 42.9; 33.5; 26.1; 25.9. IR (KBr, v cm−1): 3005 and
2985 (NH, NH2); 1300 and 1161 (SO2). MS-ESI+ 30 ev m/z: 179 [M+H]+ 100%. Anal.
Calcd for C6H14N2O2S (178): C, 40.43; H, 7.92; N, 15.72. Found: C, 40.40; H, 7.90; N,
15.75.
N-(1-Methylbenzyl)Sulfamide 2c
Yield: 91%. mp: 175–176 ◦C. Rf = 0.70 (CH2Cl2/MeOH: 9/1). 1H NMR (DMSO, δ
ppm): 7.35–7.20 (m, 5H, H-Ar); 5.26 (s, 1H, NH-CH∗); 4.55 (m, 1H, CH∗); 1.45 (d, J =
6.93 Hz, 3H, CH3). 13C NMR (CDCl3, δ ppm): 141.9; 128.2; 127.1; 125.6; 53.4; 22.6. IR
(KBr, v cm−1): 3011 and 2988 (NH, NH2); 1642 (C=C); 1305 and 1163 (SO2). MS-ESI+
30 ev m/z: 201 [M+H]+ 100%. Anal. Calcd for C8H12N2O2S (200): C, 47.98; H, 6.04; N,
13.99. Found: C, 47.91; H, 6.18; N, 13.96.
N-(3-Fluorophenyl)Sulfamide 2d
◦
1
Yield: 78%. mp: 183–184 C. Rf = 0.80 (CH2Cl2/MeOH: 9/1). H NMR (DMSO,
δ ppm): 7.50–6.75 (m, 4H, H-Ar); 4.70 (s, 2H, NH2). 13C NMR (CDCl3, δ ppm): 161.8;

NOVEL N-ACYLSULFONAMIDES
593
138.0; 129.7; 111.9; 110.0; 103.3. IR (KBr, v cm−1): 3100 and 299 (NH, NH2); 1652
(C=C); 1361 and 1155 (SO2). MS-ESI+ 30 ev m/z: 191 [M+H]+ 100%. Anal. Calcd for
C6H7FN2O2S (190): C, 37.89; H, 3.71; N, 14.73. Found: C, 37.91; H, 3.74; N, 14.78.
N-(1-Phenyl)Sulfamide 2e
Yield: 90%. mp: 174–175 ◦C. Rf = 0.65 (CH2Cl2/MeOH: 9/1). 1H NMR (DMSO, δ
ppm): 7.60–7.20 (m, 5H, H-Ar); 6.63 (s, 1H, NH); 4.76 (s, 2H, NH2). 13C NMR (CDCl3,
δ ppm): 136.0; 129.5; 125.2; 120.8. IR (KBr, v cm−1): 3085 and 2900 (NH, NH2); 1658
(C=C); 1364 and 1159 (SO2). MS-ESI+ 30 ev m/z: 173 [M+H]+ 100%. Anal. Calcd for
C6H8N2O2S (172): C, 41.85; H, 4.68; N, 16.27. Found: C, 41.80; H, 4.61; N, 16.23.
General Procedure for the Preparation of N-Acylsulfonamide
The N-acylation reaction of sulfonamide (2a–e) (2 mmol) with ethyl lactate (0.47 g,
0.46 mL, 4 mmol) was carried out in acetonitrile or toluene (4.5 mL) in the presence of
SnCl4 (0.78 g, 0.35 mL, 1.5 equiv., 3 mmol) for 12 h. The reaction mixture was evaporated
and diluted with methylene chloride (30 mL) and then washed with water. The organic
layer was dried over anhydrous sodium sulphate and concentrated in vacuo. The residue
was purified by silica gel chromatography diluted with CH2Cl2 to give N-acysulfonamides
(3a–e).
2-Hydroxy-N-(N-Propylsulfamoyl) Propanamide 3a
Yield: 60%. Rf = 0.75 (CH2Cl2/MeOH: 9/1). 1H NMR (CDCl3, δ ppm): 5.20 (s, 1H,
∗
NH); 4.15 (m, 1H, CH); 2.95 (t, J = 7.11 Hz, 2H, CH2-NH); 1.50 (m, 3H, OH+CH2-
CH3); 1.20 (d, J = 6.3 Hz, 3H, CH3); 0.90 (t, J = 7.35 Hz, 3H, CH3-CH2). 13C NMR
(CDCl3, δ ppm): 176.6; 41.5; 20.0; 18.0; 12.0. IR (KBr, v cm−1): 3500 (OH); 2945 and
2860 (2 NH); 1727 (C=O); 1370 and 1181 (SO2). MS-ESI+ 30 ev m/z: 211 [M+H]+
100%. Anal. Calcd for C6H14N2O4S (210): C, 34.28; H, 6.71; N, 13.32. Found: C, 34.31;
H, 6.78; N, 13.29.
2-Hydroxy-N-(N-Cyclohexylsulfamoyl) Propanamide3b
1
Yield: 55%. Rf = 0.72 (CH2Cl2/MeOH: 9/1). H NMR (CDCl3, δ ppm): 4.95 (q,
∗
J = 7.00 Hz, 1H, CH); 4.60 (d, J = 7.35 Hz, 1H, NH); 3.40 (m, 1H, CHcyc); 2.10
(m, 2H, CH2cyc); 1.75 (m, 2H, CH2cyc); 1.65 (m, 3H, CH2cyc+OH); 1.30 (m, 7H,
CH3+2CH2cyc).13C NMR (CDCl3, δ ppm): 170.3, 61.9; 54.2; 34.1; 25.4; 25.3; 18.2; 15.3.
IR (KBr, v cm−1): 3448 (OH); 2931 and 2854 (2NH); 1735 (C=O),1303 and 1180 (SO2).
MS-ESI+ 30 ev m/z: 251 [M+H]+ 100%. Anal. Calcd for C9H18N2O4S (250): C, 43.18;
H, 7.25; N, 11.19. Found: C, 43.21; H, 7.29; N, 11.25.
2-Hydroxy-N-(N-(1-Methylbenzyl)sulfamoyl) Propanamide 3c
Yield: 45%. Rf = 0.75 (CH2Cl2/MeOH: 9/1). 1H NMR (CDCl3, δ ppm): 7.50–7.00
(m, 5H, H-Ar); 4.70 (m, 1H, CH∗-NH); 4.60 (q, J = 7.00 Hz, 1H, CH∗-C=O); 1.60 (d, J
= 6.88 Hz, 3H, CH3); 1.28 (d, J = 6.93 Hz, 3H, CH3).13C NMR (CDCl3, δ ppm): 174.0;

594
F. BOUCHAREB ET AL.
145.0; 127.0; 126.5; 126.1; 64.0; 47.0; 21.0; 20.0. IR (KBr, v cm−1): 3400 (OH); 2925 and
2853 (2NH); 1726 (C=O); 1640 (C=C); 1311 and 1182 (SO2). MS-ESI+ 30 ev m/z: 273
[M+H]+ 100%. Anal. Calcd for C11H16N2O4S (272): C, 48.52; H, 5.92; N, 10.29. Found:
C, 48.57; H, 5.98; N, 10.25.
2-Hydroxy-N-(N-(3-Fluorophenyl)sulfamoyl) Propanamide 3d
Yield: 49%. Rf = 0.85 (CH2Cl2/MeOH: 9/1). 1H NMR (CDCl3, δ ppm): 8.00 (s, 1H,
NH); 7.20–6.40 (m, 4H, H-Ar); 4.15 (s, 1H, NH); 4.00 (q, J = 7.00 Hz, 1H, CH∗); 1.14 (J
= 6.94 Hz, 3H, CH3). 13C NMR (CDCl3, δ ppm): 176.0; 162.0; 138.0; 132.0; 118.0; 110.0;
105.0; 67.0; 19.0. IR (KBr, v cm−1): 3500 (OH); 2982 and 2861 (2NH); 1736 (C=O);
1651 (C=C); 1361 and 1183 (SO2). MS-ESI+ 30 ev m/z: 263 [M+H]+ 100%. Anal. Calcd
for C9H11FN2O4S: (262) C, 41.22; H, 4.23; N, 10.68. Found: C, 41.19; H, 4.25; N, 10.74.
2-Hydroxy-N-(N-Phenylsulfamoyl) Propanamide 3e
Yield: 50%. Rf = 0. 82 (CH2Cl2/MeOH: 9/1). 1H NMR (CDCl3, δ ppm): 7.60–7.15
∗
(m, 5H, H-Ar); 6.95 (s, 1H, NH-C=O); 5.05 (q, J = 7.00 Hz, 1H, CH); 1.67 (m, 1H,
OH); 1.60 (d, J = 6.98 Hz, 3H, CH3).13C NMR (CDCl3, δ ppm): 170.3; 129.8; 126.1;
121.9; 62.6; 18.4. IR (KBr, v cm−1): 3440 (OH); 2956 and 2834 (2NH); 1730 (C=O);
1650 (C=C); 1304 and 1184 (SO2). MS-ESI+ 30 ev m/z: 245 [M+H]+ 100%. Anal. Calcd
for C9H12N2O4S (244): C, 44.25; H, 4.95; N, 11.47. Found: C, 44.20; H, 4.91; N, 11.42.
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