Synthesis and structural study of new substituted chiral sulfamoyl oxazolidin-2-ones

Article abstract of DOI:10.1016/j.tet.2012.08.001

The synthesis of new series of oxazolidinones having sulfonamide moieties is described. These compounds are synthesized in good yield starting prochiral 1,3-dichloro-2-propanol and chlorosulfonyl isocyanate. This strategy involves the formation of carboxy

Full text of DOI:10.1016/j.tet.2012.08.001

Tetrahedron 68 (2012) 9125e9130
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis and structural study of new substituted chiral sulfamoyl
oxazolidin-2-ones
Carole Barbey a, Radia Bouasla b, Malika Berredjem b, Nathalie Dupont a, Pascal Retailleau c,
,
Nour-Eddine Aouf b, Marc Lecouveya
*
a
ꢀ
ꢀ
ꢀ ꢀ
ꢀ
ꢀ
Universite Paris 13, Sorbonne Paris Cite, Laboratoire de Chimie, Structures, Proprietes de Biomateriaux et d’Agents Therapeutiques, (CSPBAT), CNRS UMR 7244,
F-93017, Bobigny, France
b
ꢀ
ꢀ
Laboratoire de Chimie Organique Appliquee, Groupe de Chimie Bioorganique, Universite Badji-Mokhtar, Annaba, BP 12, Algeria
ˇ
c
ꢀ
Service de Cristallochimie, ICSN-CNRS, Bat. 27, 1 avenue de la Terrasse, F-91 198 Gif-sur-Yvette Cedex, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 8 June 2012
Received in revised form 26 July 2012
Accepted 1 August 2012
Available online 7 August 2012
The synthesis of new series of oxazolidinones having sulfonamide moieties is described. These com-
pounds are synthesized in good yield starting prochiral 1,3-dichloro-2-propanol and chlorosulfonyl
isocyanate. This strategy involves the formation of carboxylsulfamide by carbamoylationesulfamoylation
reaction followed by intermolecular cyclization. In order to determine the enantioselectivity during the
cyclization step, X-ray studies of products are performed.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Sulfamoyl oxazolidinone
Sulfonamide
X-ray study
1. Introduction
In this paper, we report the synthesis and the structural analysis of
compound (2a), a racemic mixture of (5R) and (5S)chloromethyl-2-
The emergence of bacterial resistance to the antibiotics poses
a serious concern for medical professionals during the last decades.
In particular, multi-drug-resistant Gram-positive bacteria are of
major concern. Oxazolidinones, exemplified by Linezolid,1,2 are
a novel class of totally synthetic antibacterial agents that have been
successfully implemented in the clinic. The literature reveals that
extensive chemical programmes exist.3,4 Previously, we reported
the synthesis of the N,N0-sulfonyl bis-oxazolidin-2-ones.5 In this
work, we describe the synthesis and structural study of oxazolidi-
nones having sulfonamide moieties. The sulfonamide group is
considered as a pharmacophore, which is present in number of bi-
ologicallyactive molecules, particularlyantimicrobial agents.6 It was
shown that sulfonamide moieties can enhance largely the activity of
antibacterial agents especially against both Gram-positive and
Gram-negative bacteria.7 In addition, the sulfonamide derivatives
constitute an important class of drugs, with several types of phar-
macological agents possessing antibacterial,8 antitumor,9 anti-
carbonic anhydrase,10 anticonvulsant11 or protease inhibitory
activity12 among others. Based on this fact, a positive effect to sul-
fonamide moieties on the activity of oxazolidinone was anticiped.
oxo-oxazolidine-3-sulfonic acid (3) fluorophenyl-amide and struc-
tural analysis of compound (2b), also a racemic mixture of (5R)and(5S)
chloromethyl-3-(3,4 dihydro-1H-isoquinoline-2-sulfonyl)-oxazolidin-
2-one. Packings of the two crystal structures presented herein are the
results of individually weak but synergistic non covalent interactions
like typical NeH/O]C hydrogen bonds or p/p stacking effects.
A search in the Cambridge Structural Database13 for sulfonyl N-
oxazolidinone fingerprint revealed 45 hits but a restriction on
sulfonamide derivatives focused only on position 5 substitution
revealed two hits, namely 2-oxo-3-oxazolidinesulfonamide (CSD
ref code FUWMOZ14) and the symmetric sulfonyl-bis(N-oxazolidi-
none) (CSD ref code PEQDAQ15). Scheme 1 resumes the structures
of the CSD hits and the two compounds detailed in this paper.
2. Results and discussion
2.1. Preparation of substituted sulfamoyl-oxazolidinones
The synthesis of sulfamides is usually performed by reacting an
amine with a substituted sulfonyl chloride or anhydride often in the
presence of a buffering base in an aprotic solvent. The yields are
variable, but can be improved after optimization. A number of
synthesis procedures have been reported for the preparation of
sulfonamides from acids using coupling reagents, such as EDC, DCC,
* Corresponding author. E-mail address: marc.lecouvey@smbh.univ-paris13.fr
(M. Lecouvey).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.08.001

9126
C. Barbey et al. / Tetrahedron 68 (2012) 9125e9130
reacted smoothly with chlorosulfonyl isocyanate in the presence of
dichloromethane to easily give carbamate. In the second step,
condensation of the carbamate with commercially available cor-
responding amines (3-fluoroaniline, 1-phenyl piperazine and
1,2,3,4-tetrahydroisoquinoline) in the presence of triethylamine at
0
ꢀC afford substituted sulfamides (1aec) in good yields. These
products were purified by chromatography on silica gel (eluted
with DCM/MeOH: 9.1). In the next stage of the synthesis, com-
pounds 1aec were subjected to the intramolecular cyclization in
diluted basic medium under solvent reflux. The cyclization were
attempt with potassium carbonate in acetone or acetonitrile at
room temperature yielding 5-chloromethyl-2-oxazolidinone de-
rivatives with a chiral center at the 5-position. A probable mecha-
nism of the cyclization-reaction course is shown in Scheme 3.
Identification of all isolated products (1aec) and (2aec) was
accomplished by 1H and 13C NMR and mass spectrometry. The
compounds 2a and 2b were submitted to X-ray crystallographic
analysis, which gave the structures shown in Fig. 1.
Scheme 1. Chemical formulas for the two compound (2a) and (2b) analyzed in this paper
and the two analogous CSD hits (ref code FUWMOZ and PEQDAQ) discussed herein.
CDI or Mukaiyama’s reagent.16 However, those approaches can be
limited by drastic reaction conditions, the formation of secondary
products, long times, and low yields.
Chlorosulfonyl isocyanate (CSI) has been found to be a versatile
reagent in organic synthesis with great interest in heterocyclic
chemistry.17 In our previous works, we have established that CSI is
a suitable reagent allowing the introduction a sulfonamide moiety
in biomolecules.18 CSI is also the reagent of choice for the prepa-
ration of sulfamoyl oxazolidin-2-ones. In this case CSI contains the
required sulfonyl group and the nitrogen, which is necessary for the
formation of oxazolidin-2-ones.
2.2. X-ray structural analyses
The compounds 2a and 2b are racemic mixture, both crystallize
in the centrosymmetric P21/c space group (nꢀ14) (Table 1). The
asymmetric units are only composed of one molecule; an ORTEP
view with numbering scheme of the asymmetric entities for the
two crystal structures is given on Fig. 1. For the two crystal struc-
tures, the sum of angles at N(1) [S(1)eN(1)eC(1)þS(1)eN(1)e
C(2)þC(1)eN(1)eC(2)] are both 360ꢀ consistent with trigonal pla-
nar geometry at nitrogen N(1) (Table 2).
The synthetic pathway followed for the preparation of the title
compounds was accomplished by a three-steps sequence as shown
in Scheme 2. Firstly, the prochiral alcohol, 1,3-dichloro-2-propanol,
Scheme 2.

C. Barbey et al. / Tetrahedron 68 (2012) 9125e9130
9127
Scheme 3.
Table 1
Crystallographic data for compound (2a) and (2b) and refinement data
Compound reference
Compound 2a
Compound 2b
Chemical formula
Formula mass
C10H10ClFN2O4S
308.8 g molꢁ1
Monoclinic
9.1300 (3)
8.9369 (2)
16.3629 (5)
90
97.4100(18)
90
1323.96 (7)
293 (2)
C13H15ClN2O4S
330.8 g molꢁ1
Monoclinic
14.5010 (12)
9.3963 (12)
10.6178 (12)
90
93.340 (7)
90
1444.3 (3)
293 (2)
Crystal system
ꢁ
a (A)
ꢁ
b (A)
ꢁ
c (A)
a
b
g
(ꢀ)
(ꢀ)
(ꢀ)
3
ꢁ
Unit cell volume (A )
Temperature (K)
Space group
Z
P21/c
4
P21/c
4
ꢁ
ꢁ
Radiation:
Mo K
a
(
l
¼0.71073 A)
Mo K
a
(
l
¼0.71073 A)
q
range for data collection:
Reflections collected/
unique/with [I>2 (I)]:
1.0e26.4ꢀ
0.41e24.13ꢀ
19,795/3240/2310
14,474/2440/1728
s
Data/restraints/parameters:
3036/0/172
1.036
2275/0/190
1.116
Goodness of fit on F2:
Final R indices [I>2
s
(I)]:
R1¼0.0435,
wR2¼0.1102
R1¼0.0623,
wR2¼0.1211
R1¼0.0448,
wR2¼0.1044
R1¼0.0640,
wR2¼0.1164
R indices (all data):
ꢁꢁ3
ꢁꢁ3
(
(
Dr
Dr
)
)
:
:
0.32 e A
0.17 e A
max
ꢁꢁ3
ꢁꢁ3
ꢁ0.38 e A
ꢁ0.28 e A
min
CCDC deposition number
885193
885192
101.24 and 105.66ꢀ. These led to torsion angle around C(2)eC(3)
bond extremely small (Table 2). So, molecules are characterized by
the planarity of the pentagonal ring in which N(1) behave a sp2
hybridization character favorable to a conjugation of O(1) C(1) O(2)
N(1) system. This latter enable a diminution of the bond lengths
around the C(1) in regards of standard values.19 Another conse-
quence is the significant difference between the S(1)eN(1) and
Fig. 1. ORTEP diagram of the asymmetric unit content of 2a (top) and 2b (bottom).
Displacement ellipsoïds are drawn at the 30% probability level, and H atoms are shown
as small spheres of arbitrary radii.
ꢁ
S(1)eN(2) bond distances (
D
l¼0.062 and 0.0676 A).
At a molecular scale, comparison shows a close similarity in the
ring conformation and angles in the molecules with the two similar
structures already present in the CSD (Fig. 2).
The oxazolidinone rings are arranged in a flat conformation, the
angles at O(1) are 111.15ꢀ and 111.23ꢀ, respectively, for the two
compounds and are typical trigonal planar geometry at oxygen,
while angles around tetrahedral C(2) and C(3) range between
Local environment around a central molecule gives rise to di-
mers in the crystal packing, the two (þ) (ꢁ) enantiomers facing
each other. Details of the local organization around a dimer in the
crystal structure of (2a) and (2b) are given on Fig. 3. Both crystal

9128
C. Barbey et al. / Tetrahedron 68 (2012) 9125e9130
Table 2
ꢀ
ꢀ
ꢁ
Selected bond distances (A), bond angles ( ) and torsion angles ( )
Compound reference
Compound 2a
Compound 2b
N(2)eS(1)
S(1)eN(1)
C(1)eO(2)
C(1)eO(1)
S(1)eN(1)eC(1)
S(1)eN(1)eC(2)
C(1)eN(1)eC(2)
C(1)eO(1)eC(3)
O(1)eC(3)eC(2)
N(1)eC(2)eC(3)
C(1)eO(1)eC(3)eC(2)
O(1)eC(3)eC(2)eN(1)
C(2)eN(1)eC(1)eO(1)
1.5993 (18)
1.6613 (16)
1.1993 (27)
1.3317 (24)
123.79 (0.14)
123.47 (0.13)
112.74 (0.17)
111.15 (0.16)
105.66 (0.19)
101.24 (0.16)
0.99 (0.23)
1.6076 (23)
1.6752 (23)
1.1983 (36)
1.3379 (36)
ꢁ124.06 (0.19)
ꢁ123.59 (0.19)
112.35 (0.21)
111.23 (0.21)
105.27 (0.22)
101.76 (0.23)
4.53 (0.29)
ꢁ1.49 (0.21)
ꢁ2.98 (0.27)
ꢁ1.11 (0.24)
2.10 (0.31)
Fig. 2. Superposition of the two compound 2a and 2b analyzed in this paper (in gray)
and the two analogous CSD hits (ref code FUWMOZ in green and PEQDAQ in blue). The
common sulfonyl N-oxazolidinone structure is highlighted by atom-type colors.
structures are described in the centrosymmetric space group P21/c,
thus these structures are composed of a racemic mixture of R and S
configuration at carbon C(3), with respect numbering scheme of
the cif file, which indicates the absence of enantioselectivity during
the cyclization process. Two symmetric entities of (2a) form a di-
mer via two mutual short intermolecular NH/O]C hydrogen bond
that link N(2) of the first molecule to O(2) of the second and vice
versa (Table 3). On the other hand, arrangement of aromatic rings is
Fig. 3. Molecular packing of compounds 2a (top) and 2b (bottom) projected along the
crystallographic b-axis (PLUTO diagram from PLATON).22 For the compound 2a, H
bonds showing the formation of dimers are represented as dashed lines. Aromatics
rings stack antiparallel and form slices parallels to c axis. For compound 2b, layers of
hydrophobic regions that enclose the benzopiremidic ring and layers of polar regions
are stacked parallel to the c-axis (H atoms are omitted for clarity).
Table 3
Intermolecular NHeO hydrogen bond parameters (distances in A and angles in ꢀ) for
ꢁ
compound 2a
a parallel-displaced alignment with an interplanar distance of
ꢁ
3.138 A. But
p/p intermolecular parallel stacking interactions be-
DeH
d (DeH) d (H/A) DHA
d (D/A)
A
tween fluoro-benzene cannot be really taken into account because
N(2)eH(2N) 0.860
2.101
157.08 2.912
O(2)/[ꢁxþ1; ꢁy, ꢁzþ2]
ꢁ
of the too large offset distance between centroids, almost 4 A in
ꢁ
comparison with a typical offset distance of 1.6e1.8 A for this kind
3. Conclusion
of interaction, observed in benzene dimer, and despite an expected
stacking distance.20 This crystal structure can be described as
a sandwich structure with slices pile up along the a direction. Hy-
drophobic slices are made of aromatic rings with van der Waals
interactions, and more thin hydrophilic slices are made of oxazo-
lidinone rings linked by hydrogen bond.
X-ray structure comparison shows a close similarity at the
molecular scale in the ring conformation and angles in the mole-
cules with the two similar structures already present in the CSD.
The mutual presence of the two enantiomers in the crystal struc-
tures gives rise to local organization in dimers connected either by
In the crystal structure of 2b a dimer organization is also ob-
H-bond, either by parallel p/p interactions. The study of the crystal
served with weak favorable face-to-face p/p interactions between
aromatic rings with distance of 3.815 A between the centroids of
aromatic rings. Typical distances between centroids range from 3.3
ꢁ
structures emphasizes weak intermolecular interaction network,
crucial for the crystal cohesion. This structural study shows that the
synthesis process is efficient but non-enantioselective.
ꢁ
to 3.8 A for
p/p face-to-face or parallel staking interactions in the
21
crystal structure benzene taken as reference. This dimer is con-
nected tri-dimensionally to other dimers via T-shaped in-
teractions. Distance of 5.307 A between the centroids is typical
distance observed for the most favorable interactions T-shaped
observed in the crystal structure of benzene.21 In 2b, the tri-
p/p
4. Experimental section
4.1. General
ꢁ
dimensional organization is made of ‘zig-zag’
nected themselves via effects.
p
/p
ribbons con-
Melting points were determined in open capillary tubes on an
Electro thermal apparatus and uncorrected. IR spectra were recorded
p/p

C. Barbey et al. / Tetrahedron 68 (2012) 9125e9130
9129
on a PerkineElmer FT-600 spectrometer. Proton nuclear magnetic
resonance was determined with a 360 WB or AC 250-MHz Bruker
spectrometer using DMSO-d6 and CDCl3 as a solvent and TMS as an
a one fraction. The reaction mixture was stirred at room tempera-
ture under inert atmosphere. Progress of the reaction is monitored
by TLC, which indicates complete disappearance of carbox-
ylsulfamide within 1.5 h. Then the reaction mixture was filtered and
concentrated under vacuum to give the crude product. Crystals
were grown from dichloromethane/diethylether solution of the
compounds at ambient temperature.
internal standard. Chemical shifts are reported in
d units (parts per
million). All coupling constants J are reported in hertz. Multiplicity is
indicated as s (singlet), d (doublet), t (triplet), q (quadruplet), m
(multiplet) andcombinationof thesesignals. Electronionization mass
spectra(30eV)were recordedinpositive ornegativemodeona Water
MicroMass ZQ. HRMS were recorded on a JEOL JMS DX-300 using NBA
as matrix in FABþ ionization 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. Visualiza-
tion was made with ultraviolet light. Column chromatographies were
performed on Merck silica gel 60H (Art. 9385).
4.3.1. 5-Chloromethyl-N-(3-fluorophenyl)-2-oxo-1,3-oxazolidinone-
3-sulfonamide (2a). Yield: 96%, white solid. Colorless crystals from
dichloromethane/diethylether, mp: 191e192 ꢀC, Rf¼0.75 (CH2Cl2/
MeOH, 9:1). 1H NMR (DMSO-d6,
d ppm): 4.0 (s, 1H, CHePh),
6.9e7e7.2 (m, 4H, HeAr), 3.9 (m, 2H, CH2-cyc), 4.9 (m, 1H, *CH),
3.6e3.8 (part of ABX, JAB¼5.69 Hz, JBx¼9.00 Hz, 2H, CH2Cl). 13C NMR
(DMSO-d6,
d ppm): 151.9, 149.6, 129.6, 121.9, 114.3, 81.4, 50.3, 43.7.
4.2. General procedure for the synthesis of
carboxylsulfamides
IR (KBr, cmꢁ1): 1752 (C]O), 1362 and 1391 (SO2). MS ESIþ 30 eV m/
z: 309.2 [MþH]þ. HRMS m/z (MHþ) 309.0118 (calcd for
C10H10ClFN2O4S: 309.0112).
To a stirred solution of chlorosulfonyl isocyanate (CSI) (1.62 g,
11.44 mmol) in (10 mL) of anhydrous dichloromethane at 0 ꢀC was
added (1.47 g, 11.39 mmol) of 1,3-dichloropropanol-2 in the same
solvent. After a period of 30 min, the resulting solution and (1.75 mL,
1.1 equiv) of triethylamine was slowly added into a solution contain-
ing 1 equiv of primary or secondary amine in (10 mL) of dichloro-
methane. The reaction did not rise above 5 ꢀC. The resulting reaction
solution was allowed to warm up to room temperature for over 2 h.
The reaction mixture diluted with 30 mL of dichloromethane, washed
with HCl 0.1 N and water. The organic layer was dried over Na2SO4,
filtered, and concentrated in vacuum to give the crude product. The
residue was purified by column chromatography on silica gel (CH2Cl2/
MeOH: 9.9/0.1) to give a carboxylsulfamides in good yields.
ꢀ
4.3.2. 1,2,3,4-Tetrahydroisoquinolyn, 5-(chloromethyl), oxazolidin-2-
one-3-sulfonamide (2b). Yield: 95%, white solid. Colorless crystals
from dichloromethane/diethylether, mp: 92e93 ꢀC, Rf¼0.67
(CH2Cl2). 1H NMR (DMSO-d6,
d
ppm): 3.0 (t, J¼2H, CH2ePh), 3.6 (t,
2H, CH2eN-cyc), 4.6 (s, 2H, CH2eN-cyc), 7.3 (m, 4H, HeAr), 4.8 (m,
1H, *CH), 4.1e4.2 (part of ABX, JAB¼5.26 Hz, JBx¼9.13 Hz, 2H, CH2Cl).
13C NMR (DMSO-d6,
d ppm): 167.7,151.9,131.1,115,110.5,104.8, 81.4,
43.3, 32.6. IR (KBr): 1750 (C]O),1360 and 1389 (SO2) cmꢁ1. MS ESIþ
30 eV m/z: 331.2 [MþH]þ. HRMS m/z (MHþ) 331.0525 (calcd for
C13H15ClN2O4S: 331.0519).
4.3.3. Phenylpeperazin, 5-(chloromethyl), oxazolidin-2-one-3-sul-
fonamide (2c). Yield: 91%, white solid. mp: 126e127 ꢀC, Rf¼0.72
4.2.1. 3-Fluoroanilyn, 1,3-dichloropropan-2-yl sulfonamide carba-
(CH2Cl2/MeOH, 9:1). 1H NMR (DMSO-d6,
d ppm): 3.1 (t, 4H,
mate (1a). Yield: 83%, white solid, mp: 139e140 ꢀC, Rf¼0.71
NeCH2-ph), 3.2 (t, 4H, NeCH2eCH2), 3.9 (m, 2H, CH2-cyc), 7.3
(m, 5H, HeAr), 4.9 (m, 1H, *CH), 3.6e3.8 (part of ABX,
JAB¼3.78 Hz, JBx¼4.16 Hz, 2H, CH2Cl). 13C NMR (DMSO-d6,
(CH2Cl2/MeOH, 9:1). 1H NMR (CDCl3,
d ppm): 8.2 (s, 1H, NH), 4.0 (s,
1H, NH-ph), 6.9e7e7.2 (m, 4H, HeAr), 3.8 (d, J¼5.25 Hz, 4H, 2CH2),
5.2 (m, 1H, CHe(CH2)2eCl2). 13C NMR (CDCl3,
d
ppm): 159.9, 159,
d ppm): 151.9, 149.9, 129.6, 121.9, 114.3, 81.4, 50.3, 43.7, 43.3,
130.2, 124.6, 112.5, 78.8, 45. IR (KBr, cmꢁ1): 3219 and 3284 (NH),
1716 (C]O), 1139 and 1351 (SO2). MS ESIþ 30 eV m/z: 367 [MþNa]þ.
HRMS m/z (MNaþ) 366.9705 (calcd for C10H11Cl2FN2O4S: 366.9698).
32.9. IR (KBr, cmꢁ1): 1739 (C]O), 1143 and 1310 (SO2). MS ESIþ
30 eV m/z: 360.1 [MþH]þ. HRMS m/z (MHþ) 360.0793 (calcd for
C14H18ClN3O4S 360.0784).
ꢀ
4.2.2. 1,2,3,4-Tetrahydroisoquinolyn, 1,3-dichloropropan-2-yl sulfon-
4.4. X-ray structure determination
amide carbamate (1b). Yield: 83%, oil, Rf¼0.63 (CH2Cl2). 1H NMR
(CDCl3,
d
ppm): 7.8 (s, 1H, NH), 7.2e7.0 (m, 4H, HeAr), 5.1 (m, 1H,
Suitable crystals were mounted for measurements. Data col-
CHeCH2), 4.6 (s, 2H, CH2eN), 3.6e3.8 (m, 6H, CH2eN-
lection was performed at 293 on a Nonius KappaCCD diffractometer
cycþ2CH2eCl2), 2.9 (t, J¼5.8 Hz, 2H, CH2-ph). 13C NMR (CDCl3,
using Mo K
a
(
l
¼0.71073 A) radiation and processed with the HKL
ꢁ
d
ppm): 159, 136.1, 134.1, 127.5, 126.9, 126.3, 125.7, 78.8, 47.4, 45,
package of programs.23 The crystal structure was solved with direct
methods using SHELXS-97 and final refinement, based on F2, was
carried out by full matrix least squares with SHELXL-97 soft-
ware.24,25 Refinement was performed anisotropically for all non-
hydrogen atoms. In general, in the final stages of least-squares re-
finement, hydrogen atoms were assigned to idealized positions and
were allowed to ride with thermal parameters fixed at 1.2 U eq of
the parent atom. The residual electron densities were of no
chemical significance.
44.3, 28.1. IR (CCl4, cmꢁ1): 3262 (NH), 1751(C]O), 1374 and 1159
(SO2). MS ESIþ 30 eV m/z: 367.1 [MþH]þ. HRMS m/z (MHþ)
367.0295 (calcd for C13H16Cl2N2O4S: 367.0286).
4.2.3. Phenylpiperazin, 1,3-dichloropropan-2-yl sulfonamide carba-
mate (1c). Yield: 86%, white solid, mp: 136e137 ꢀC, Rf¼0.68
(CH2Cl2/MeOH, 9:1). 1H NMR (CDCl3,
d ppm): 8.0 (s, 1H, NH),
7.0e6.9 (m, 5H, HeAr), 5.2 (m, 1H, CHeCH2), 3.9 (d, J¼5.2 Hz, 4H,
2CH2eCl), 3.5 (t, J¼5.2 Hz, 4H, 2CH2eN), 3.2 (t, J¼5.4 Hz, 4H,
2CH2eN). 13C NMR (CDCl3,
d
ppm): 159, 149.6, 129.6, 121.9, 114.3,
4.4.1. X-ray crystal data for 2a. C10H10ClFN2O4S, monoclinic space
ꢁ
78.8, 51.5, 45.8, 45. IR (KBr): 3028 (NH), 1739 (C]O), 1372 and 1167
(SO2) cmꢁ1. MS ESIþ 30 eV m/z: 396 [MþH]þ. HRMS m/z (MHþ)
396.0559 (calcd for C14H19Cl2N3O4S: 396.0551).
group P21/c: a¼9.1300(3), b¼8.9369(2), c¼16.3629(5) A,
3
ꢁ
b
¼97.4100(18)ꢀ; V¼1323.96(7) A , Z¼4, Dcalcd¼1.549 g/cm3;
m
¼0.469 mmꢁ1; F(000)¼632.0. A total of 19,795 reflections were
integrated in the
q
-range of 1.00e26.4ꢀ of which 3240 were
4.3. General procedure for the synthesis of sulfamoyl-
oxazolidinones
unique, leaving an overall R-merge of 0.043 and an overall re-
dundancy of 6.1. For solution and refinement, 3036 were con-
sidered as unique after merging for Fourier. The final agreement
A solution of carboxylsulfamides (0.47 g, 1.28 mmol) in dry
CH3CN (20 mL) or acetone was added a K2CO3 (0.17 g, 1.23 mmol)
factors were R1¼0.0435 for 2310 reflections with F>4
s(F);
R1¼0.0623 and wR2¼0.1211 for all the 2310 data; GOF¼1.036.

9130
C. Barbey et al. / Tetrahedron 68 (2012) 9125e9130
The residual electron density in the final difference Fourier does
ꢁꢁ3
References and notes
not show any feature above 0.32
ꢁꢁ3
e
A
and below ꢁ0.38
1. Brickner, S. J.; Hutchinson, D. K.; Barbachyn, M. R.; Manninen, P. R.; Ulanowicz,
D. A.; Garmon, S. A.; Grega, K. C.; Hendges, S. K.; Toops, D. S.; Ford, C. W.;
Zurenko, G. E. J. Med. Chem. 1996, 39, 673.
e A
.
4.4.2. X-ray crystal data for 2b. C13H15ClN2O4S, monoclinic space
2. Bain, K. T.; Wittbrodt, E. T. Ann Pharmacother. 2001, 35, 566.
3. Reck, F.; Zhou, F.; Girardot, M.; Kern, G.; Eyermann, C. J.; Hales, N. J.; Ramsay, R.
R.; Gravestock, M. B. J. Med. Chem. 2005, 48, 499.
4. Kim, S.-Y.; Park, H. B.; Cho, J. H.; Yoo, K. H.; Oh, C. H. Bioorg. Med. Chem. Lett.
2009, 19, 2558.
5. Berredjem, M.; Regainia, Z.; Dewynter, G.; Montero, J.-L.; Aouf, N. Heteroat.
Chem. 2006, 17, 61.
6. Joshi, S.; Khosla, N. Bioorg. Med. Chem. Lett. 2003, 13, 3747.
7. Jeon, H.; Jo, N. H.; Yoo, K. H.; Choi, J.-H.; Cho, H.; Cho, J. H.; Oh, C. H. Eur. J. Med.
Chem. 2007, 42, 358.
8. Kamal, A.; Reddy, K. S.; Ahmed, S. K.; Khan, N. A.; Sinha, R. K.; Yadav, J. S.; Arora,
S. K. Bioorg. Med. Chem. 2006, 14, 650.
9. Mader, M. M.; Shih, C.; Considine, E.; De Dios, A.; Grossman, C. S.; Hipskind, P.
A.; Lin, H.-S.; Lobb, K. L.; Lopez, B.; Lopez, J. E.; Martin Cabrejas, L. M.; Richett,
M. ;E.; White, W. T.; Cheung, Y. Y.; Huang, Z.; Reilly, J. E.; Dinn, S. R. Bioorg. Med.
Chem. Lett. 2006, 15, 617.
10. Supuran, C. T.; Maresca, A.; Gregan, F.; Remko, M. Posted online on February 3
J. Enzyme Inhib. Med. Chem. 2012, http://dx.doi.org/10.3109/14756366.2011.649269.
11. Wasowski, C.; Gavernet, L.; Barrios, I. A.; Villalba, M. L.; Pastore, V.; Samaja, G.;
Enrique, A.; Bruno-Blanch, L. E.; Marder, M. Biochem. Pharmacol. 2012, 83, 253.
12. Supuran, C. T.; Casini, A.; Scozzafava, A. Med. Res. Rev. 2003, 23, 535.
13. CSD, Version 5.33 of 2012 Allen, F. H. Acta Crystallogr. 2002, B58, 380.
14. Bonnaud, B.; Viani, R.; Agoh, B.; Delaunay, B.; Dewinter, G.; Montero, J.-L.;
Aycard, J.-P. Acta Crystallogr. 1987, C43, 2466.
15. Dewinter, G.; Abdaoui, M.; Toupet, L.; Montero, J. L. Tetrahedron Lett.1997, 38, 8691.
16. Wang, Y.; Sarris, K.; Sauer, D. R.; Djuric, S. W. Tetrahedron Lett. 2007, 48, 5181.
17. McDonald, R. I.; Stahl, S. S. Angew. Chem., Int. Ed. 2010, 49, 5529.
18. Abdaoui, M.; Dewynter, G.; Montero, J. L. Tetrahedron Lett. 1996, 37, 5695.
19. Orpen, A. G.; Brammer, L.; Allen, F. H.; Kennard, O.; Watson, D. G.; Taylor, R. Int.
Tables Crystallogr. 1992, C.
ꢁ
group P21/c: a¼14.5010(12), b¼9.3963(12), c¼10.6178 (12) A,
3
ꢀ
ꢁ
b
m
¼93.340 (7) ; V¼1444.3 (3) A , Z¼4, Dcalcd¼1.521 g/cm3;
¼0.426 mmꢁ1; F(000)¼688.0. A total of 14,474 reflections
were integrated in the range of 0.41ꢀ< <24.13ꢀ of which 2440
q
were unique, leaving an overall R-merge of 0.052 and an overall
redundancy of 5.9. For solution and refinement, 2275 were
considered as unique after merging for Fourier. The final
agreement factors were R1¼0.0448 for 1728 reflections with
F>4
s
(F); R1¼0.0640 and wR2¼0.1164 for all the 2275 data;
GOF¼1.116. The residual electron density in the final difference
ꢁꢁ3
Fourier does not show any feature above 0.17 e A and below
ꢁꢁ3
-0.28 e A
.
Acknowledgements
This work was generously supported by the (Direction Generale
ꢀ
de la Recherche Scientifique et du Developpement Technologique,
DG-RSDT) at MESRS (Ministry of Scientific Research, Algeria), and
Tassili Project CMEP 08 MDU 729.
Supplementary data
20. Meyer, E. A.; Castellano, R. K.; Diederich, F. Angew. Chem., Int. Ed. 2003, 42, 1210.
21. Klebe, G.; Diederich, F. Philos. Trans. R. Soc. London, Ser. A 1993, 345, 37.
22. PLATON/PLUTON: (a) Spek, A. L. Acta Crystallogr. 1990, A46, C34; (b) Spek, A. L.
PLATON, A Multipurpose Crystallographic Tool; Utrecht University: Utrecht, The
Netherlands, 1998; (c) Spek, A. L. J. Appl. Crystallogr. 2003, 36, 7.
23. Otwinowski, Z.; Minor, W. In Processing of X-ray Diffraction Data Collected in
Oscillation Mode, Methods in Enzymology; Carter, C. W., Jr., Sweet, R. M., Eds.;
Macromolecular Crystallography, Part A; Academic: 1997; Vol. 276, pp 307e326.
24. Sheldrick, G. M. SHELXL-97. A Program for Refining Crystal Structures; University
The crystal structures corresponding to 2a and 2b have been
deposited at the Cambridge Crystallographica Data Centre and re-
spectively allocated the deposition number CCDC 885193 and
885192. These detailed X-ray crystallographic data can obtained
free of charge on application to the Cambridge Crystallographic
Data Center, 12 Union Road Cambridge CB2 1EZ, UK. Email:
deposit@ccdc.cam.ac.uk.
€
of Gottingen: Germany, 1997.
25. Sheldrick, G. M. Acta Crystallogr. 2008, A64, 112.