A new sulfa-heterocyclic compounds containing aziridine moiety, 3-benzyl-2-thia-1,3-diazabicyclo[3.1.0]hexane 2,2-dioxide and its reaction with nucleophiles

Article abstract of DOI:10.3987/COM-08-11389

New sulfa-heterocyclic containing aziridine moiety derivatives such as 3-benzyl-2-thia-1,3-diazabicyclo[3.1.0]hexane 2,2-dioxide has been obtained starting from 2-benzyl-4-chloromethyl-1,2,5-thiadiazolidine 1,1-dioxide in alkaline conditions. The aziridine moiety was opened by various nucleophiles to give vicinal diamines which used as an intermediate in the preparation of other bicyclic compounds with orthogonal protections such as 2,5-dibenzyl-1,2,5- thiadiazolo[2,3-a]pyrazine 1,1-dioxide in good yield. The Japan Institute of Heterocyclic Chemistry.

Full text of DOI:10.3987/COM-08-11389

HETEROCYCLES, Vol. 75, No. 9, 2008
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HETEROCYCLES, Vol. 75, No.9, 2008, pp. 2243 - 2250. © The Japan Institute of Heterocyclic Chemistry
Received, 8th March, 2008, Accepted, 2nd May, 2008, Published online, 8th May, 2008. COM-08-11389
A NEW SULFA-HETEROCYCLIC COMPOUNDS CONTAINING
AZIRIDINE MOIETY, 3-BENZYL-2-THIA-1,3-DIAZABICYCLO[3.1.0]-
HEXANE 2,2-DIOXIDE AND ITS REACTION WITH NUCLEOPHILES
Nawel Khettache, Malika Berredjem, Zine Régaïnia, and Nour-Eddine Aouf*
LCOA. Bioorganic Chemistry Group. Sciences Faculty, Chemistry Department.
Badji Mokhtar, Annaba University. Box.12 Annaba-Algeria
*To whom correspondence should be addressed: noureddineaouf@yahoo.fr
Phone/Fax: 00 213 38 87 27 89
Dedicated to the memory of Pr. Chabbi Yacine (1955-2008)
Abstract – New sulfa-heterocyclic containing aziridine moiety derivatives such
as 3-benzyl-2-thia-1,3-diazabicyclo[3.1.0]hexane 2,2-dioxide has been obtained
starting from 2-benzyl-4-chloromethyl-1,2,5-thiadiazolidine 1,1-dioxide in
alkaline conditions. The aziridine moiety was opened by various nucleophiles to
give vicinal diamines which used as an intermediate in the preparation of other
bicyclic
compounds
with
orthogonal
protections
such
as
2,5-dibenzyl-1,2,5-thiadiazolo[2,3-a]pyrazine 1,1-dioxide in good yield.
INTRODUCTION
Heterocyclic compounds containing aziridine moiety constitute an important class of compounds, which
have found use in organic and medicinal chemistry. The presence of aziridine motif into heterocyclic
structure can leads to interesting new chemical and/or pharmacological potentialities. Some of these
compounds showed immunomodulatory proprieties. For example, Imexon I1 is active against various
transplanted syngeneic tumors in rodents2 and transplanted human tumors.3
Dauban et al4 described a bicyclic fused aziridines II starting from olefinic sulfamates undergo
copper-catalyzed aziridination in the presence of iodosylbenzene. The latter were opened by various
nucleophiles to give the corresponding substituted cyclic sulfamates.
The versatility of aziridines as precursors to amine derivatives drives the development of preparative
methods for this unique class of heterocycles.5 They are useful and versatile synthetic intermediates, as
relief ring-strain provides a driving force for efficient ring opening or ring expansion reactions.6 The
importance of aziridines7 is also well recognized in asymmetric synthesis, where the need for chiral

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HETEROCYCLES, Vol. 75, No. 9, 2008
auxiliaries and ligands continuously increasing. In our previous work,8 we have reported the synthesis and
the reactivity of cyclosulfamides. In this report, we extended our studies in the reactivity of this
heterocycles by intramolecular aziridination. We present a new and easy method to access at the new
aziridine fused with cyclosulfamide with benzyl protection. Aziridines fused with cyclosulfamide such as
3-benzyl-2-thia-1,3-diazabicyclo[3.1.0]hexane 2,2-dioxide III constitutes an original intermediate in
synthesis of heterocycles. It can be considered as a sulfonyl equivalent of aziridine fused with cyclourea I
and an analogue of cyclosulfamate II Figure 1.
R 2
H N
R 1
N
O
H N
N
O
B n
N
N
S
II
S
O
O
O
I
O
III
Figure 1
We describe also the efficient and high yielding ring opening of III with nucleophiles such as ethoxide
and amines. With nitrogen nucleophiles such as primary amine, aziridines yield vicinal secondary
diamines which react with 1,2-dibromoalkane to give 2,5-dibenzylhexahydro-2H-[1,2,5]thiadiazolo
[2,3-a]pyrazine 1,1-dioxide 7. The structure of cyclosulfamide 7 correspond to an analogue of
2,7-dialkylhexahydroimidazo[1,5-a]pyrazin-3-one IV known for anti-inflammatory, coronary dilator and
C.N.S depressant activities9 and an 2,7-dibenzylhexahydropyrazino[1.2-c]pyrimidin-6-one V tested for
antifilarial activity.10
R'
N
N
N
R
N
N
N
N
N
N
S
O
O
O
O
v
IV
7
Figure 2
RESULTS AND DISCUSSION
The starting racemic N2-Boc-N5-benzyl-3-chloromethyl-1,2,5-thiadiazolidine 1 has been previously
described by our group.8a-b As outlined in Scheme 1, the heterocycles 2, 3, 4 and 5 were synthesized after
differents steps. Starting from 1, regioselective cleavage of the tertio-butyloxycarbonyl (Boc) protection
under trifluoroacetic acid gives compound 2. The deprotected heterocycle 2 was obtained in 95% yield
and found to be able to be stored for several weeks at room temperature without notable decomposition.
Compound 2 was then engaged in a direct intramolecular aziridination in alkaline medium (triethylamine,
K2CO3, Cs2CO3) and afforded bicyclic aziridine 5 in quantitative yield. No other products could be

HETEROCYCLES, Vol. 75, No. 9, 2008
2245
detected by TLC analysis of the crude reaction mixture. In perspective to access fused-bicyclic
cyclosulfamide and cyclourea via intermediate 3, the addition reaction of 2 with chlorosulfonyl
isocyanate (CSI) was carried out to give compound 4. The intermediate, chlorosulfonyl derivative 3,
could not be isolated because of its instability in standard conditions. Treatment of 4 with triethylamine
(TEA) in dichloromethane or K2CO3 in acetonitrile afforded aziridine 5, comparatively with treatment of
2 in the same conditions (Scheme 1). The one-pot procedure appeared to be efficient than two-step
procedure involving isolation of the intermediate 4. 1H NMR spectral properties were in accordance with
that of aziridine structure. The two protons of the aziridine ring methylene group were non equivalent.
The small couplings (~2.8 Hz) have been observed for geminal protons and the smaller coupling to the
methylene group.
Cl
Cl
i
ii
N
N
Bn
N
Boc
Bn
NH
Bn
N
N
S
1
S
2
S
5
O
O
O
O
O
O
iii
iv
Bn
iv
Cl
Cl
NH2
N
S
N
NH
N
NHSO2Cl
Bn
N
N
N
Bn
O
S
S
O
O
O
O
O
O
O
O
3
4
Scheme 1. Reagents and conditions: (i) TFA, CH2Cl2, 0 °C and rt, (95%); (ii) Et3N, CH2Cl2, or K2CO3,
MeCN, rt, (95%) (iii) CSI, CH2Cl2, 0 °C and rt, (75%); (iv) Et3N, CH2Cl2, rt, (85%).
We next focalised our attention to the study of the electrophilic reactivity of these new types of
heterocyclic structures particularly with respect to any possible regioselectivity of ring opening.
Nucleophilic attack on 5 would be expected to occur at the methylene group of the aziridine ring to give
5-membered ring 6. Reaction of 5 with sodium ethoxide in absolute ethanol gave only the contracted
product 6a (Scheme 2) which was proven to have five-membred system by NMR proton analysis. If the
reaction is effected with amines in aprotic medium, the nucleophilic opening of the aziridine ring leading
to the formation of vicinal diamines 6b-6d derivatives in good yield.
The choice of benzylamine as the amine nucleophile has special significance because the products are
vicinal diamines which have varied applications in organic synthesis and generated the same benzyl
protection. A nucleophilic attack on the methylene carbon of aziridine led to the formation of
5-membered; the nucleophilic attack of the aziridine carbon adjacent to the cyclosulfamide moiety would
have resulted in the formation of 6-membered ring which was not detected in crude mixtures by TLC and
1HNMR analysis.

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HETEROCYCLES, Vol. 75, No. 9, 2008
Yield %
Entry
Nu
Regents and Conditions
6a
6b
Nu
EtO
90
85
EtOH/EtONa, reflux
NuH
BnNH2, Et3N, THF, reflux
BnNH
NH
O
Bn N
N
O
N
O
Bn
NH , MeCN, reflux
S
O
55
N
O
S
6c
6d
O
NH
N
, Et3N, THF, reflux 58
6
5
Scheme 2
The regioselective aziridine ring-opening reaction then afforded the opportunity to introduce a second
nucleophile which can be reacted with different nucleophiles by condensation and substitution reactions.
Also, in these compounds, the sulfonyl group SO2 increases the acidity of the adjacent NH and allows an
expedient intermolecular cyclization.10
On the other hand, the derivative 6b was reacted with a 1,2-dibromoethane in alkaline conditions and in
aprotic medium occur an orthogonally protected benzylpiperazine 7 fused with cyclic sulfamide as solid
in 69% yield (Scheme 3).
H
N
Bn
Bn
N
BrCH2CH2Br
Bn
N
Bn
N
N
O
H
N
O
S
S
NaH, THF, 100 °C
O
O
6b
7
Scheme 3
EXPERIMENTAL
All commercial chemicals and solvents were used without further purification. All reactions were carried
out under inert argon atmosphere. Melting points were determined in open capillary tubes on a Büchi
apparatus and are uncorrected. Microanalysis were performed in analyse center of Vernaison (Lyon
1
France). H-and 13C NMR spectra were recorded in a 250 MHz Brücker spectrometer. 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), q (quartet), m (multiplet) and combination of theses signals. Electron
ionisation mass spectra (30 eV) were recorded in positive or negative mode on a Water MicroMass ZQ.
High-resolution mass spectra were measured on a Jeol SX102 mass spectrometer and recorded in FAB
positive mode. All reactions were monitored by TLC on silica Merck 60 F254 precoated aluminium plates
and were developed by spraying with ninhydrin solution. Columns chromatographies were performed on
Merck silica gel (230-400 mesh).

HETEROCYCLES, Vol. 75, No. 9, 2008
2247
The synthesis of the racemic 2-Boc-5-Bn-3-chloromethyl-1,2,5-thiadiazolidine 1,1-dioxyde 1 has been
previously reported.8a
2-Benzyl-4-(chloromethyl)-1,2,5-thiadiazolidine 1,1-dioxide 2. To a stirred solution of racemic 1
(1.09 g, 3 mmol) in dry CH2Cl2 (3.6 mL) was added dropwise to l 3.6 mL of TFA/CH2Cl2 (50:50)
solution in ice bath. The mixture was stirred until TLC analysis indicated the disappearance of the starting
material. The solvent was removed in vacuum and then by coevaporation four times with Et2O. The crude
residue was purified on silica gel (CH2Cl2). Compound 2 was obtained as a white powder in 95% yield
after recrystallization from hexanes/AcOEt (9:1)
1
Rf = 0.30 (CH2Cl2), (mp 64 °C), IR (KBr, ν cm-1): 3263 (NH), 1319 and 1172 (SO2); H NMR (CDCl3):
2
δ 3.18 (m, 1H, CH), 3.40-3.70 (m, 3H, CH2 + CH), 3.90 (m, 1H, HCasy), 4.18 and 4.30 (AB, 2H, J =
13
13.70 Hz, CH2Ph), 4.90 (br s, 1H, NH), 7.35 (m, 5H, H-Ar); C NMR (CDCl3) δ 44.70, 50.62, 56.32,
59.90, 125.32, 127.54, 128.45, 140.15; MS ESI+ 30eV m/z: 283 ([M+Na]+, 100%), 285 ([M+Na]++2
40%). M = 260/262.
Anal. Calcd for C10H13N2O2SCl: C, 46.06; H, 5.03; N, 10.74. Found: C, 46.12; H, 5.01; N, 10.71.
5-Benzyl-3-(chloromethyl)-1,2,5-thiadiazolidine-2-carboxamide 1,1-dioxide 4.
To a stirred solution of chlorosulfonyl isoyanate (0.84 mL, 0.9 mmol) in dry CH2Cl2 at 0 °C under argon,
was added (0.25 g, 0.9 mmol) a solution of 2 in the same solvent. The mixture was stirred at rt for 2 h.
The reaction mixture was diluted with 50 mL of CH2Cl2, washed with 0.1 N HCl and brine. The organic
layer was dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified on silica gel
(CH2Cl2) to afford 4 as a white solid in 75% yield; Rf = 0.25 (CH2Cl2), (mp 106-107 °C), IR (KBr, ν
1
cm-1): 3363.6 (NH2), 1681 (CO), 1319 and 1164 (SO2); H NMR (CDCl3): δ 3.30 (dd, 1H, J = 4.10 and
6.50 Hz, CH), 3.45 (dd, 1H, J = 3.10 and 7.40 Hz, CH), 3.60 (m, 1H, CH), 3.90 (dd, 1H, J = 3.50 and
7.20 Hz, CH), 4.15 and 4.30 (AB, 2H, 2J = 13.80 Hz, CH2Ph), 4.45 (m, 1H, HCasy), 5.6 (br s, 2H, NH2),
13
7.40 (m, 5H, Harom); C NMR (CDCl3) δ 44.80, 50.70, 56.20, 59.90, 125. 45, 127.50, 128.72, 140.15,
157.85; MS ESI+ 30eV m/z: 326.09 ([M+Na]+, 100%), 328 ([M+Na]++2, 40%), 285 (([M+Na]+
+2)–NHCO, 10%), 283 ([M+Na]+–NHCO, 23%). M = 303/305.
Anal. Calcd for C11H14N3O3SCl: C, 43.49; H, 4.65; N, 13.83. Found: C, 43.17; H, 4.70; N, 13.87.
3-Benzyl-2-thia-1,3-diazabicyclo[3.1.0]hexane 2,2-dioxide 5. A solution of 2 (0.54 g, 2 mmol) and
K2CO3 (0.55 g, 4 mmol) in MeCN (20 mL) was stirred at rt for 2 h. The reaction was monitored with
TLC (UV and ninhydrine). The mixture was filtered and concentrated in vacuo. Aziridine 5 was obtained
in 98% yield as white solid without purification; Rf = 0.66 (CH2Cl2), (mp 98 °C), IR (KBr, ν cm-1): 1326

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HETEROCYCLES, Vol. 75, No. 9, 2008
and 1168 (SO2); 1H NMR (CDCl3): δ 2.40 (dd, 1H, J = 1.40 and 3.60 Hz, CH), 2.65 (dd, 1H, J = 1.30 and
2.70 Hz, CH), 3.12 (m, 1H, HCasy), 3.31 (dd, 1H, J = 3.90 and 6.10 Hz, CH), 3.44 (dd, 1H, J = 10 and
3.90 Hz, CH), 3.90 and 4.48 (AB, 2H, 2J = 13.80 Hz, CH2Ph), 7.40 (m, 5H, Harom); 13C NMR (CDCl3) δ
40.60, 47.40, 51.30, 62.80, 125.45, 126.80, 128.70, 141.56, 157.8; MS ESI+ 30eV m/z: 247 [M+Na]+,
100%). M = 224.
Anal. Calcd for C10H12N2O2S: C, 53.55; H, 5.39; N, 12.49. Found: C, 53.62; H, 5.34; N, 12.47.
Nucleophylic opening of aziridine
2-Benzyl-4-(ethoxymethyl)-1,2,5-thiadiazolidine 1,1-dioxide 6a.
Sodium (0.06 g, 2 mmol) was put into 10 mL of absolute EtOH and the solution was stirred for 30 min to
build in situ the sodium ethoxide. After this step, (0.1 g, 0.4 mmol) of 5 was added into solution as a
powder and the reaction mixture being refluxed for 3 h. The solvent was removed and the residue diluted
with 100 mL of CH2Cl2, acidified with 0.1 N HCl and washed with water. The organic layer was dried
(Na2SO4) and concentrated in vacuo. The crude residue was purified on silica gel column (CHCl3) to
afford the product 6a as oil.
Yield = 90%; Rf = 0.34 (CH2Cl2); oil; 1H NMR (CDCl3): δ 1.23 (t, 3H, J = 6.90 Hz, CH3), 3.30 (m, 5H ,
2CH2+HCasy), 3.50 (m, 1H, CH), 3.73 (m, 1H, CH), 4.10 and 4.62 (AB, 2H, 2J = 13.90Hz; CH2Ph), 7.25
13
(m, 5H, Harom) ; C NMR (CDCl3) δ 18.30, 51.12, 52.10, 58.20, 64.20, 65.10, 125.20, 127.30, 128.50,
141.60; MS ESI+ 30eV m/z: 538.92 ([2M-H]- , 10%), 563.05 ([2M+Na], 25%), 293,15 ([M+Na]+, 100%),
271 ([M+H]+, 60%), 268,96 ([M-H]-, 10%). M = 270.
Anal. Calcd for C12H18N2O3S: C, 53.31; H, 6.71; N, 10.36. Found: C, 53.29; H, 6.74; N, 10.38.
N-Benzyl-N-[(5-benzyl-1,1-dioxido-1,2,5-thiadiazolidin-3-yl)methyl]amine 6b.
To a solution of 5 (0.1 g, 0.40 mmol) and benzylamine in anhydrous THF (10 mL) was added dropwise
triethylamine (0.06 mL, 0.44 mmol) in the same solvent and the mixture was refluxed for 3 h. The
reaction was monitored by TLC (ninhydrine and UV). The solvent was removed and the residue was
diluted with 100 mL of CH2Cl2 acidified with 1N HCl and washed with water. The organic layer was
dried (Na2SO4) and evaporated under reduced pressure on a rotary evaporator. The residue was purified
by chromatography on silica gel (CH2Cl2) to give 6b as white solid in 85% yield; Rf = 0.43,
(CH2Cl2/MeOH, 98:2), (mp 128-129 °C); 1H NMR (CDCl3): δ 2.8 (br s, 1H, NH), 3.10 (dm, 1H, J = 8.40
2
Hz, CH), 3.40 (m, 3H, 2CH+C*H), 3.62 (m, 3H, CH+CH2Ph); 3.80 and 4.87 (AB, 2H, J = 13.7 Hz,
13
CH2Ph), 4.80 (br s, 1H, NH), 7.45 (m, 10H, Harom); C NMR (CDCl3) δ 48.42, 49.51, 50.25, 53.11,
61.88, 125.42, 126.12, 126.43, 128.23, 128.68, 128.85, 139.74, 142.49. MS ESI+ 30eV m/z: 354.04
([M+Na]+, 30%), 331.96 ([M+H]+, 100%), 330.34 ([M-H]-, 10%). M = 331.

HETEROCYCLES, Vol. 75, No. 9, 2008
2249
Anal. Calcd for C17H21N3O2S :C, 61.61; H, 6.39; N, 12.68. Found: C, 61.67; H, 6.37; N, 12.63.
4-[(5-Benzyl-1,1-dioxido-1,2,5-thiadiazolidin-3-yl)methyl]morpholine 6c.
To a solution of 5 (0.03 g, 0.10 mmol) MeCN (10 mL) and morpholine (8.70 g, 100 mmol) was added
dropwise in the same solvent and the mixture was refluxed for 3 h. The reaction was monitored by TLC.
The solvent was removed and the residue was diluted with 100 mL of CH2Cl2 acidified with 1N HCl and
washed with water. The organic layer was dried (Na2SO4) and evaporated under reduced pressure on a
rotary evaporator. The residue was purified by chromatography on silica gel (CHCl3) to give 6c as an oil
1
in 55% yield; Rf = 0.37 (CH2Cl2/MeOH, 98:2); H NMR (CDCl3): δ 2.30 (m, 2H, CH2), 2.62 (m, 4H,
2CH2), 3.20 (m, 2H, CH2), 3.70 (m, 6H, 2CH2O+HCasy+CHPh), 4.55 (AB, 1H, 2J=13.20Hz, CHPh), 7.37
13
(m, 5H, Harom); C NMR (CDCl3) δ 51.28, 59.00, 59.30, 59.70, 60.00, 62.40, 125.20, 127.30, 128.50,
141.45. MS ESI+ 30 eV m/z: 334.10 ([M+Na], 40%), 311.90 ([M+H]+, 100%). M = 311.
Anal. Calcd for C14H21N3O3S :C, 54.00; H, 6.80; N, 13.50. Found: C, 54.06; H, 6.77; N, 13.53.
4-[(5-Benzyl-1,1-dioxido-1,2,5-thiadiazolidine-3-yl]piperidine 6d.
To a solution of 5 (0.11 g, 0.49 mmol) and piperidine (0.045 g, 0.52 mmol) in anhydrous THF (10 mL)
was added drop wise triethylamine (0.07 mL, 0.53 mmol) in the same solvent and the mixture was
refluxed for 3 h. The reaction was monitored by TLC (ninydrine and UV). The solvent was removed and
the residue was diluted with 100 mL of CH2Cl2 acidified with 1N HCl and washed with water. The
organic layer was dried (Na2SO4) and evaporated under reduced pressure on a rotary evaporator. The
residue was purified by chromatography on silica gel (CHCl3) to give 6d as pal white solid in 70% yield,
Rf = 0.30 (CH2Cl2/MeOH:98/2), (mp 71-72 °C) ; 1H NMR (CDCl3): δ 1.50 (m, 6H. 3 CH2 ), 2.40 (m, 3H,
CH2+CH), 2.55 (m, 3H, CH2+CH), 2.90 and 3.25 (ABX, 2H, J = 2.60, 3.10 and 6.90 Hz, CH2), 3.76
(m,1H, HCasy), 3.90 and 4.30 (AB, 2H, 2J =13.40, CH2Ph), 7.40 (m, 5H, Harom); MS ESI+ 30eV m/z :
310 ([M+H]+, 100%. M = 309.
Anal. Calcd for C15H23N3O2S: C, 58.22; H, 7.49; N, 13.58. Found: C, 58.18; H, 7.41; N, 13.53.
2,5-Dibenzylhexahydro-2H-[1,2,5]thiadiazolo[2,3-a]pyrazine 1,1-dioxide 7.
6b (0.04 g, 0.12 mmol) and 1,2-dibromoethane (0.24 mmol, 0.045 g) of in dry THF (5 mL) were added
slowly to a stirred solution of NaH (0.0086 g, 0.36 mmol) in the same solvent (5 mL) at 0 °C. After
complete addition, the reaction mixture was heated at 80 °C for 2 h. The reaction was monitored by TLC
(ninhydrine and UV). Upon cooling to rt, the reaction mixture was filtered and concentrated under
reduced pressure. The residue was purified by chromatography on silica gel (CHCl3) to give 7 as white
solid in 69 % yield; Rf = 0.38 (CH2Cl2); (mp 146-147 °C); 1H NMR (CDCl3): δ 2.50 (m, 1H, CH), 2.60

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HETEROCYCLES, Vol. 75, No. 9, 2008
(t, 1H, J = 2.20 Hz, CH), 2.92 (dd, 1H, J = 2.20 and 10.30 Hz, CH), 3.30 (s, 2H, CH2Ph), 3.31-3.57 (m,
4H, 2CH+CH2), 3.60 (AB, 1H, 2J = 13.30 Hz, CHPh), 3.90 (dm, 1H, J = 11.90 Hz, CH), 4.15 (dt, 1H, J =
2
2.10 and 9.60 Hz, CH), 4.88 (AB, 1H, J = 13.30 Hz, CHPh), 7-7.30 (m, 10H, Harom); 13C NMR
(CDCl3): δ 41.98, 42.82, 50.02, 53.01, 56.38, 66.78, 125.42, 127.39, 128.85, 128.94, 128.56, 139.60,
142.23. MS ESI+ 30eV m/z: 380.04 ([M+Na]+; 10%); 358.15 ([M+H]+,100%). M = 357.
Anal. Calcd for C19H23N3O2S: C, 63.86; H, 6.44; N, 11.76. Found: C, 63.88; H, 6.41; N, 11.80.
ACKNOWLEDGEMENTS
This work is partially supported by Algerian Ministry of Scientific Research, National Project cnepru N°
E 01120060035, Applied Organic Laboratory (FNR 2000), National Fund of Research and CMEP 08
MDU 729. Fruitful discussions with Pr. Marc Lecouvey (Univ. Paris 13) are greatly appreciated.
REFERENCES
1. U. Bicker,W. Kampe, and W. Steingross, U. S. Patent 4,083, 987, Apr 11, 1978.
2. U. Bicker and G. Hebold, Med. Sci. Cancer. Hematol. Immunol. Allergy. Pharmacol., 1977, 5, 428.
3. E. M. Herch, R. T. Dorr, and R. A. Curtis, Proc. Am. Asssoc. Cancer. Res., 1995, 36, 294.
4. F. Duron, L. Leman, A. Ghini, G. Burton, P. Dubon, and R. H. Dodd, Org. Lett., 2002, 4, 2481.
5. X. E. Hu, Tetrahedron, 2004, 60, 2701. (b) H. Lebel, O. Leogane, K. Huard, and S. Lectard, Pure Appl.
Chem., 2006, 78, 363.
6. (a) W. McCoull and F. A. Davis, Synthesis, 2000, 1347. (b) K. M. L. Rai and A. Hassner, Adv. Stain.
Interst. Org. Mol., 2000, 8, 187.
7. (a) T. Kametani and T. Honda, 'Advances in Heterocyclic Chemistry: Application of Aziridines to the
Synthesis of Natural Products,' Vol. 39, ed. by A. R. Katritzky, Academic Press, Inc., London, 1986,
181.
(b) J. B. Sweeney, Chem. Soc. Rev., 2002. 31, 247.
8. (a) Z. Régaïnia, M. Abdaoui, N-E. Aouf, G. Dewynter, and J. L. Montero, Tetrahedron, 2000, 56, 381.
(b) A. Bendjeddou, R. Djeribi, Z. Régaïnia, and N. E. Aouf, Molecules, 2005, 10, 1387.
9. A. Omodei-Salé and E. Toja, II Farmaco, Ed. Pr., 1975, 30, 650.
10. S. Sharma, R. Bindra, R. N. Iyer, and N. Anand, J. Med. Chem., 1975, 18, 913.
11. A. Bendjeddou, H. Djebbar, M. Berredjem, Z. Hattab, Z. Regainia, and N. E. Aouf, Phosphorus
Sulfur and Silicon, 2006, 181, 1351.