One-pot synthesis of arylsulfonamides and azetidine-2,4-diones via multicomponent reaction of an amine, an acetylenic compound, and an arylsulfonyl isocyanate

Article abstract of DOI:10.1055/s-2008-1067026

An effective route to novel arylsulfonamides is described. It involves the reaction of an enamine derived from the addition of primary or secondary amines to acetylenecarboxylates (dialkyl acetylenedicarboxylates or alkyl propiolates) with an arylsulfonyl isocyanate. These arylsulfonamides show dynamic NMR behavior in solution. A different reactivity pattern was observed with the methyl 3-(diethylamino)acrylate. The latter, generated in situ from Et ₂NH and methyl propiolate, on reaction with an arylsulfonyl isocyanate afforded exclusively the azetidine-2,4-dione (malonimide) derivatives in good yield. These malonimides also show dynamic NMR behavior in solution because of restricted rotation around the C-N bond resulting from conjugation of the side-chain N-atom with the adjacent α,β-unsaturated carbonyl group.

Full text of DOI:10.1055/s-2008-1067026

PAPER
1747
One-Pot Synthesis of Arylsulfonamides and Azetidine-2,4-diones via
Multicomponent Reaction of an Amine, an Acetylenic Compound, and an
Arylsulfonyl Isocyanate
O
ne-Pot Synthesis
b
of
A
rylsulfo
d
namide
s
and
o
A
zetidine-2,
l
4-dion
a
es li Alizadeh,* Atieh Rezvanian
Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran 18716, Iran
Fax +98(21)88006544; E-mail: abdol_alizad@yahoo.com; E-mail: aalizadeh@modares.ac.ir
Received 5 February 2008; revised 27 February 2008
invention makes the process particularly suited to proce-
dures for preparing molded polyamides. Azetidine-2,4-di-
ones, that is, imides of malonic acid, are a rather little
known class of heterocycles and following their first syn-
Abstract: An effective route to novel arylsulfonamides is de-
scribed. It involves the reaction of an enamine derived from the ad-
dition of primary or secondary amines to acetylenecarboxylates
(dialkyl acetylenedicarboxylates or alkyl propiolates) with an aryl-
sulfonyl isocyanate. These arylsulfonamides show dynamic NMR thesis by Staudinger,13 they have been formed in a variety
of ways.14–19
behavior in solution. A different reactivity pattern was observed
with the methyl 3-(diethylamino)acrylate. The latter, generated in
situ from Et2NH and methyl propiolate, on reaction with an arylsul-
In the context of our ongoing studies on heterocyclic syn-
thesis mediated by enamine intermediates, the possibility
of trapping the 1:1 intermediate 5, formed between an
acetylenecarboxylate 2 and a primary or secondary amine
1, with an arysulfonyl isocyanate 3 appeared attractive
from the viewpoint of devising a novel multicomponent
reaction (MCR). Although the trapping of the 1:1 interme-
diate formed between dibenzoylacetylene or dialkyl acet-
ylenedicarboxylate and amines with arylsulfonyl
isocyanate has been studied in detail by our research
group,20–22 trapping of the initially formed 1:1 intermedi-
ate between primary amines and alkyl propiolates has not
been reported.
fonyl isocyanate afforded exclusively the azetidine-2,4-dione
(malonimide) derivatives in good yield. These malonimides also
show dynamic NMR behavior in solution because of restricted ro-
tation around the C–N bond resulting from conjugation of the side-
chain N-atom with the adjacent a,b-unsaturated carbonyl group.
Key words: amine, alkyl propiolate, enamine, isocyanate, malon-
imide, arylsulfonamide, multicomponent reaction
The importance of the sulfonamide group is well estab-
lished in pharmaceutical chemistry. A considerable num-
ber of sulfonamides are well known as antibacterial,1
carbonic anhydrase inhibitor,2 anticancer,3 and anti-
inflammatory agents.4
Herein, we report a simple one-pot reaction between
enamines, derived from the addition of primary or second-
ary amines to an acetylenic compound (dialkyl acetylene-
dicarboxylate or alkyl propiolate) and an arylsulfonyl
isocyanate leading to the corresponding arylsulfonamides
4 (Table 1). As far as we are aware, the present synthesis
represents a new method. We explored the use of Et2NH
and methyl propiolate in this reaction, which led to forma-
tion of the corresponding 1-(arylsulfonyl)-3-[(diethylami-
no)methylene]-2,4-azetidinedione derivatives 7.
Enaminones are widely used building blocks for the syn-
thesis of various organic compounds,5 especially for nat-
ural bioactive substances and their analogues.6 The
enamine is one of the most important intermediates for C–
C bond formation in both organic chemistry and the bio-
logical world. In organic synthesis, pyrrolidine deriva-
tives are used to efficiently form enamines with carbonyl
compounds in many reactions.
Azetidine-2,4-diones, which are highly strained mole-
cules, have been shown to possess anti-inflammatory and
sedative properties.7 Bachi and co-workers have reported8
that these compounds along with their 4-thioxo analogues
can serve as useful intermediates for a variety of b-lactam
antibiotics.9 The structurally related monothio- and
dithiophthalimides have also received attention due to
their synthetic potential in photochemical studies.10–12
Azetidinediones are employed as promoters in polymer-
izations and their use not only permits low polymerization
temperatures, but gives rise to faster polymerization reac-
tions than other procedures allow. The rapid polymeriza-
tion of caprolactam in accordance with the present
The reaction of amines 1, acetylenecarboxylates 2, and ar-
ylsulfonyl isocyanates 3 proceeded via a smooth 1:1:1 ad-
dition in anhydrous toluene at ambient temperature, to
produce arylsulfonamide derivatives 4 in 80–90% yields
(Table 1).
Compounds 4 apparently result from the initial addition of
an amine to the acetylenic system and subsequent attack
of the resulting reactive enamine 5 on the arylsulfonyl
isocyanate20–24 to yield a betaine 6, which under hydrogen
shift produce 4 (Scheme 1).
The structures of compounds 4a–g were deduced from el-
emental analyses, IR, 1H, and 13C NMR spectra. No prod-
ucts other than 4 could be detected. The mass spectrum of
4a displayed the molecular ion peak at m/z 324, which is
consistent with the structure of methyl (E)-3-(1-azetanyl)-
2-{[(phenylsulfonyl)amino]carbonyl]prop-2-enoate. The
SYNTHESIS 2008, No. 11, pp 1747–1752
x
x.
x
x
.
2
0
0
8
Advanced online publication: 16.04.2008
DOI: 10.1055/s-2008-1067026; Art ID: Z03808SS
© Georg Thieme Verlag Stuttgart · New York

1748
A. Alizadeh, A. Rezvanian
PAPER
Table 1 Arylsulfonamides 4 Prepared by MCR
R4
R2
O
O
R3
R1
N
O
N
toluene
r.t.
R1R2NH
+
+
Ar SO2NCO
H
R3
CO2R4
SO2Ar
1
2
3
4
Amine 1
Propargylic ester 2 ArSO2NCO 3 Product
Yield (%)a
R3
R4
Ar
MeO
N
O
O
H
N
H
Me
Ph
4a
4b
85
80
N
H
S
O
O
H
MeO
O
H
N
H
H
H
Me
Et
Ph
N
H
N
H
S
O
O
O
O
EtO
O
O
H
N
Ph
4c
90
85
N
N
H
S
S
O
O
O
H
O
O
O
MeO
N
Me
O
H
N
Me
4-MeC6H4
4d
N
H
O
H
O
Me
H
O
N
O
Me
Me
H
Me
Me
Me
Ph
4e
4f
90
90
90
H
NH2
MeO2C
N
O
O
S
O
O
Me
H
N
O
N
Ph
H
S
NH2
MeO2C
O
H
O
O
OMe
Me
MeO
O
N
O
OMe
4-MeC6H4
4g
H
S
NH2
MeO
H
N
O
Me
O
O
a Yields of isolated products.
IR spectrum of 4a exhibited the absorption bands for the (d = 3.70), a vinylic CH (d = 7.63), and an NH (d = 11.6)
carbonyl groups of ester and amide at 1672 and 1644 proton. The Ph moiety gave rise to characteristic signals
cm–1, respectively, for the conjugated C=C bond at 1583 in the aromatic region of the spectrum. The 1H-decoupled
cm–1, and for the sulfonyl moiety at about 1336 and 1166 13C NMR spectrum of 4a showed 12 distinct resonances
1
cm–1. The H NMR spectrum of 4a exhibited six signals in agreement with the proposed structure. Partial assign-
readily recognized as arising from three CH2 groups [d = ment of these resonances is given in the experimental sec-
2.29 (m), 4.25 (t, 3JH,H = 7.8 Hz), and 4.41 (m)], a CH3O tion. The 1H and 13C NMR spectra of compounds 4b–g are
Synthesis 2008, No. 11, 1747–1752 © Thieme Stuttgart · New York

PAPER
One-Pot Synthesis of Arylsulfonamides and Azetidine-2,4-diones
1749
R2
ently results from the initial addition of Et2NH to the acet-
ylenic system and subsequent attack of the resulting
reactive enamine 8 to the arylsufonyl isocyanate20–24 to
yield betaine 9, which apparently cyclizes, under the reac-
tion condition employed with loss of methanol to produce
the malonimide 7.
R2
R1
N
CO2R4
R1
N
CO2R4
3
H
N
1 + 2
4
R3
R3
O
SO2Ar
5
6
Scheme 1
We have unraveled some interesting reactivity profiles of
the intermediates 12, 13, 14, and 15.20–22 Intermediate 12
undergoes a proton transfer but intermediate 13 undergoes
cyclization leading to the corresponding products. This is
because, Ha in intermediate 12 is more acidic than Hb in
intermediate 13. Also in intermediate 15 carbonyl group
of COPh is more electrophilic than the carbonyl group of
CO2R in intermediate 14 (Scheme 3).
Table 2 Compounds 7 Prepared
O
H
Et2N
toluene
r.t.
+
+
Ar SO2NCO
N
SO2Ar
Et2NH
H
CO2Me
O
2
3
7
In summary, the reaction between Et2NH, methyl propi-
olate (2a) and an arylsulfonyl isocyanate 3 provides a sim-
ple one-pot synthesis of 3-[(diethylamino)methylene]-1-
(arylsulfonyl)-2,4-azetidinedione derivatives 7 of poten-
tial synthetic and pharmaceutical interest. With other
amines, the reaction leads to the formation of the corre-
sponding arylsulfonamides. The present method has the
advantage that it can be performed under neutral condi-
tions and requires no activation or modification of the
starting materials. The simplicity of the present procedure
makes it an interesting alternative to complex multistep
approaches.19
7
a
b
Ar
Ph
Yield (%)
90
90
4-MeC6H4
similar to those of 4a, except for the amine moiety, which
exhibits characteristic signals with the appropriate chem-
ical shifts (see experimental section).
In view of the success of the above reaction (Table 1), we
explored the use of Et2NH, which has shown a different
reactivity in this reaction. Treatment of Et2NH with meth-
yl propiolate (2a) in the presence of 3 in anhydrous tolu-
ene at room temperature gave 1-(arylsulfonyl)-3-
[(diethylamino)methylene]-2,4-azetidinedione
tives 7 in 90% yield (Table 2).
Methyl and ethyl acetylenecarboxylates, benzenesulfonyl isocyan-
ate, and tosyl isocyanate, were obtained from Merck (Germany) and
Fluka (Switzerland) and were used without further purification.
Melting points were measured on an Electrothermal 9100 appara-
tus. Elemental analyses for C, H, and N were performed using a
Heraeus CHN-O-Rapid analyzer. Mass spectra were recorded on a
Finnigan-Matt 8430 mass spectrometer operating at an ionization
potential of 70 eV. 1H, and 13C NMR, spectra were measured
(CDCl3 solution) with a Bruker DRX-500 Avance spectrometer at
deriva-
Although we have not established the mechanism of the
reaction of the enamine derived from the addition of
Et2NH to 2a and 3 in an experimental manner, a possible 500.1 and 125.7 MHz, respectively. IR spectra were recorded on a
Shimadzu IR-460 spectrometer.
explanation is proposed in Scheme 2. Compound 7 appar-
H
N
H
H
+
Et2NH
CO2Me
CO2Me
8
3
O
O
O
N
CO2Me
O
N
H
OMe
N
H
a)
b)
N
SO2Ar
b
a
N
O
H
ArO2S
N
11
9
10
SO2Ar
OMe
7
Scheme 2
Synthesis 2008, No. 11, 1747–1752 © Thieme Stuttgart · New York

1750
A. Alizadeh, A. Rezvanian
PAPER
O
N
R1
O
O
H
O
O
N
H O
R1
O
N
OR2
O
R
O
N
Ph
O
OR
O
R1
N
OR2
Ha
H
H
H
H Hb
NSO2Ar
N
Ph N
R2
SO2Ar
SO2Ar
SO2Ar
13
12
14
15
R1
RO
O
H
O
O
H O
R1
O
N
OR2
R1
N
H
N
H
O
H
N
R
N
Ph
N
SO2Ar
Ph
HO
O
O
SO2Ar
N
O HN
R2
O
SO2Ar
SO2Ar
Scheme 3
Methyl (E)-3-(1-Azetanyl)-2-{[(phenylsulfonyl)amino]carbon-
yl}prop-2-enoate (4a); Typical Procedure
MS: m/z (%) = 197 (4), 183 (13), 181 (3), 165 (13), 140 (31), 124
(24), 106 (7), 96 (13), 77 (100), 68 (10), 51 (46), 41 (28).
A solution of methyl propiolate (2a; 0.084 g, 1 mmol) and azetan
(1a; 0.057 g, 1 mmol) in anhyd toluene (5 mL) was magnetically
stirred for 5 h. To this solution was added dropwise a solution of
phenylsulfonyl isocyanate (0.18 g, 1 mmol) in anhyd toluene (3
mL) at 25 °C and the mixture was stirred for 12 h. The solvent was
removed under reduced pressure, and the residue was separated by
silica gel (Merck 230–240 mesh) column chromatography using
hexane–EtOAc (5:1) as eluent; yield: 0.27 g (85%); yellow liquid.
Anal. Calcd for C15H18N2O5S (338.37): C, 53.24; H, 5.36; N, 8.28.
Found: C, 53.63; H, 5.45; N, 8.14.
Ethyl (E)-3-Morpholino-2-{[(phenylsulfonyl)amino]carbon-
yl}prop-2-enoate (4c)
Yield: 0.33 g (90%); white powder; mp 172–174 °C.
IR (KBr): 3195 (NH), 1682 (CO2Me), 1640 (NCO), 1573 (NC=C),
1500 and 1455 (Ar), 1324 and 1156 (SO2), 1112 and 1082 cm–1 (C–
O).
IR (KBr): 3400 (NH), 1672 (CO2Me), 1644 (NCO), 1583 (NC=C),
1500 and 1433 (Ar), 1336 and 1166 (SO2), 1120 and 1078 cm–1 (C–
O).
1H NMR (500.1 MHz, MeOH-d4): d = 1.24 (3 H, t, 3JH,H = 7.2 Hz,
3
OCH2CH3), 3.37 (4 H, t, JH,H = 4.7 Hz CH2NCH2), 3.59 (4 H, t,
1H NMR (300.1 MHz, CDCl3): d = 2.29 (2 H, m, CH2), 3.70 (3 H,
s, OCH3), 4.25 (2 H, t, 3JH,H = 7.8 Hz, CH2N), 4.41 (2 H, m, CH2N),
7.47 (2 H, t, 3JH,H = 7.7 Hz, 2 CHmeta of Ph), 7.52 (1 H, t, 3JH,H = 7.2
3JH,H = 4.7 Hz, CH2OCH2), 4.07 (1 H, t, 3JH,H = 7.07 Hz, CH2CH3),
4.17 (1 H, t, 3JH,H = 7.0 Hz, CH2CH3), 7.54 (2 H, t, 3JH,H = 7.4 Hz, 2
CH of Ph), 7.63 (2 H, t, 3JH,H = 7.5 Hz, CH of Ph), 7.85 (1 H, s, NH),
7.98 (NCH=C), 7.99 (1 H, d, 3JH,H = 7.2 Hz, 2 CH of Ph).
3
Hz, CHpara of Ph), 7.63 (1 H, s, NCH=C), 8.04 (2 H, t, JH,H = 7.4
Hz, 2 CHortho of Ph), 11.60 (1 H, s, NH).
13C NMR (125.7 MHz, MeOH-d4): d = 14.84 (CH3CH2), 43.69
(CH2N), 44.23 (CH2N), 63.84 (CH2O), 66.57 (2 CH2O), 110.00
(NCH=C), 126.51 (2 CHmeta of Ph), 128.57 (2 CHortho of Ph), 128.86
(CHpara of Ph), 139.63 (Cipso of Ph), 142.10 (NCH=C), 153.07
(CON), 156.00 (CO2Me).
13C NMR (75.47 MHz, CDCl3): d = 22.93 (CH2), 57.62 (CH2N),
58.71 (CH2N), 68.09 (OCH3), 88.60 (NCH=C), 125.72 (2 CHmeta of
Ph), 126.28 (CHpara of Ph), 128.75 (2 CHortho of Ph), 130.88 (Cipso of
Ph), 156.58 (NCH=C), 167.50 (CON), 169.50 (CO2Me).
MS: m/z (%) = 324 (M+, 1), 287 (2), 257 (1), 229 (5), 183 (9), 167
(8), 141 (31), 110 (12), 94 (10), 77 (100), 56 (20), 51 (40), 41 (18).
MS: m/z (%) = 183 (17), 156 (16), 141 (33), 138 (7), 112 (10), 98
(4), 94 (5), 77 (100), 57 (12), 51 (39), 41 (10).
Anal. Calcd for C14H16N2O5S (324.35): C, 51.84; H, 4.97; N, 8.64.
Found: C, 51.66; H, 4.87; N, 8.76.
Anal. Calcd for C16H20N2O6S (368.40): C, 52.16; H, 5.47; N, 7.60.
Found: C, 52.31; H, 5.43; N, 7.54.
Methyl (E)-2-{[(Phenylsulfonyl)amino]carbonyl}-3-(1-pyrro-
lidinyl)prop-2-enoate (4b)
Yield: 0.27 g (80%); white powder; mp 145–147 °C.
Methyl (E)-2-({[(4-Methylphenyl)sulfonyl]amino}carbonyl)-3-
morpholinoprop-2-enoate (4d)
Yield: 0.31 g (85%); white powder; mp 90–92 °C.
IR (KBr): 3400 (NH), 1670 (CO2Me), 1635 (NCO), 1580 (NC=C),
IR (KBr): 3430 (NH), 1668 (CO2Me), 1644 (NCO), 1576 (NC=C),
1507 and 1418 (Ar), 1335 and 1177 (SO2), 1106 and 1040 cm–1 (C–
O).
1507 and 1422 (Ar), 1332 and 1161 (SO2), 1116 and 1071 cm–1 (C–
O).
1H NMR (300.1 MHz, CDCl3): d = 1.88 (4 H, s, 2 CH2 of pyrroli-
dine), 3.27 (2 H, s, CH2N of pyrrolidine), 3.62 (2 H, s, CH2N of pyr-
rolidine), 3.69 (3 H, s, OCH3), 7.44 (2 H, t, 3JH,H = 7.5 Hz, 2 CH of
Ph), 7.52 (1 H, t, 3JH,H = 6.9 Hz, CH of Ph), 8.02 (2 H, t, 3JH,H = 7.3
Hz, 2 CH of Ph), 8.03 (NCH=C), 11.45 (1 H, s, NH).
13C NMR (75.47 MHz, CDCl3): d = 24.05 (CH2 of pyrrolidine),
25.61 (CH2 of pyrrolidine), 51.42 (CH2N), 52.93 (CH2N), 56.25
(OCH3), 89.23 (NCH=C), 127.94 (2 CHmeta of Ph), 128.67 (2
CHortho of Ph), 133.06 (CHpara of Ph), 139.94 (Cipso of Ph), 156.63
(NCH=C), 162.55 (NCO), 168.80 (CO2Me).
1H NMR (500.1 MHz, CDCl3): d = 2.41 (3 H, s, CH3), 3.51 (4 H, br,
2 CH2N), 3.75 (4 H, s, 2 CH2O), 3.80 (3 H, s, OCH3), 7.29 (2 H, d,
3JH,H = 8.1 Hz, 2 CH of Ar), 7.92 (1 H, s, NCH=C), 7.96 (2 H, d,
3JH,H = 8.2 Hz, 2 CH of Ar), 11.41 (1 H, s, NH).
13C NMR (125.7 MHz, CDCl3): d = 21.49 (ArCH3), 51.61 (OCH3),
52.27 (NCH2), 55.98 (NCH2), 66.62 (2 CH2O), 88.68 (NCH=C),
128.19 (2 CH of Ar), 129.31 (2 CH of Ar), 137.18 (Cipso-SO2 of Ar),
143.97 (Cipso-CH3 of Ar), 159.16 (NCH=C), 162.82 (NCO), 168.71
(CO2Me).
Synthesis 2008, No. 11, 1747–1752 © Thieme Stuttgart · New York

PAPER
One-Pot Synthesis of Arylsulfonamides and Azetidine-2,4-diones
1751
MS: m/z (%) = 369 (M+ + 1, 0.3), 268 (1), 262 (0.3), 213 (1), 197
(34), 171 (24), 155 (58), 140 (30), 112 (29), 91 (100), 82 (24), 65
(30), 42 (17), 41 (17).
7.91 (CH=C), 7.96 (2 H, d, 3JH,H = 8.2 Hz, 2 CH of Ar), 9.91 (1 H,
t, 3JH,H = 5.9 Hz, NHCH2), 11.62 (1 H, s, NHCO).
13C NMR (75.47 MHz, CDCl3): d = 21.65 (ArCH3), 51.64 (NCH2),
51.82 (OCH3), 55.00 (2 OCH3), 89.18 (CH=C), 102.72 (CH),
128.12 (2 CH of Ar), 129.38 (2 CH of Ar), 137.05 (Cipso-SO2 of Ar),
144.14 (Cipso-CH3 of Ar), 160.99 (HC=C), 166.35 (CONH), 168.44
(CO2Me).
MS: m/z (%) = 386 (M+, 1), 355 (0.3), 326 (1), 279 (0.3), 231 (0.5).
215 (0.5), 199 (0.5), 186 (3), 171 (2), 155 (1), 139 (1), 123 (1), 108
(1), 91 (11), 75 (100), 65 (4), 47 (7), 41 (1).
Anal. Calcd for C16H20N2O6S (368.40): C, 52.16; H, 5.47; N, 7.60.
Found: C, 52.23; H, 5.53; N, 7.42.
Dimethyl (E)-2-(Isobutylamino)-3-{[(phenylsulfonyl)ami-
no]carbonyl}but-2-enedioate (4e)
Yield: 0.36 g (90%); white powder; mp 95–97 °C.
IR (KBr): 3335 (NH), 3140 (NH), 1742 (CO2Me), 1659 (NCO),
1634 (NC=C) 1575 and 1427 (Ar), 1331 and 1174 (SO2), 1231 and
1134 cm–1 (C–O).
Anal. Calcd for C16H22N2O7S (386.42): C, 49.73; H, 5.74; N, 7.25.
Found: C, 49.87; H, 5.69; N, 7.13.
1H NMR (500.1 MHz, CDCl3): d = 0.92 (6 H, d, 3JH,H = 6.7 Hz, 2
CH3), 1.85 (1 H, m, CH), 2.98 (2 H, t, 3JH,H = 6.6 Hz, CH2), 3.72 (3
H, s, OCH3), 3.89 (3 H, s, OCH3), 7.53 (2 H, t, 3JH,H = 7.9 Hz, 2 CH
3-[(Diethylamino)methylene]-1-(phenylsulfonyl)-2,4-aze-
tidinedione (7a)
Yield: 0.27 g (90%); colorless crystals; mp 62–64 °C.
3
of Ph), 7.62 (1 H, t, JH,H = 7.4Hz, CH of Ph), 8.08 (2 H, d,
3JH,H = 8.7 Hz, 2 CH of Ph), 11.36 (1 H, s, NHCH2), 11.78 (1 H, s,
IR (KBr): 1723 (CONCO), 1606 (NC=C), 1443 (Ar), 1349 and
1076 cm–1 (SO2).
CONH).
13C NMR (125.7 MHz, CDCl3): d = 19.85 (2 CH3), 28.86 (CH),
52.19 (OCH3), 52.87 (OCH3), 53.82 (CH2), 86.29 (NC=C), 128.21
(2 CHmeta of Ph), 128.75 (2 CHortho of Ph), 133.35 (CHpara of Ph),
139.74 (Cipso of Ph), 162.61 (NC=C), 162.68 (CON), 167.27
(CO2Me), 167.35 (CO2Me).
MS: m/z (%) = 398 (M+, 7), 367 (4), 323 (12), 302 (4), 291 (7), 270
(3) 257 (2), 242 (8), 225 (20), 215 (7), 208 (6), 193 (39), 172 (8),
160 (8), 141 (32), 140 (20), 126 (20), 100 (4), 94 (15), 77 (100), 57
(26), 51 (23), 41 (26).
3
1H NMR (300.1 MHz, CDCl3): d = 1.13 (3 H, t, JH,H = 7.2 Hz,
3
CH2CH3), 1.24 (3 H, t, JH,H = 7.2 Hz, CH2CH3), 3.37 (2 H, q,
3
3JH,H = 7.2 Hz, CH2CH3), 3.46 (2 H, q, JH,H = 7.2 Hz, CH2CH3),
7.41–7.55 (3 H, m, Ph), 7.87 (2 H, dd, 3JH,H = 8.0 Hz, 4JH,H = 1.8 Hz,
2 CHortho of Ph), 8.14 (1 H, s, CH).
13C NMR (75.47 MHz, CDCl3): d = 12.04 (CH2CH3), 14.45
(CH2CH3), 40.94 (CH2CH3), 47.08 (CH2CH3), 126.27 (C-3 of aze-
tidine ring), 126.30 (2 CH of Ph), 128.64 (2 CH of Ph), 131.69 (CH
of Ph), 142.55 (Cipso of Ph), 158.14 (2 C=O of azetidine ring and
CH).
Anal. Calcd for C17H22N2O7S (398.42): C, 51.25; H, 5.57; N, 7.03.
Found: C, 51.75; H, 5.36; N, 7.16.
MS: m/z (%) = 221 (3), 167 (14), 149 (35), 113 (5), 99 (38), 94 (9),
77 (58), 57 (42), 41 (40).
Dimethyl (E)-2-(sec-Butylamino)-3-{[(phenylsulfonyl)ami-
no]carbonyl}but-2-enedioate (4f)
Yield: 0.36 g (90%); white powder; mp 115–117 °C.
Anal. Calcd for C14H16N2O4S (308.35): C, 54.53; H, 5.23; N, 9.08.
Found: C, 55.00; H, 5.52; N, 9.00.
IR (KBr): 3415 (NH), 3125 (NH), 1743 (CO2Me), 1670 (NCO),
1610 (NC=C), 1571 and 1427 (Ar), 1343 and 1132 (SO2), 1105 and
1080 cm–1 (C–O).
3-[(Diethylamino)methylene]-1-[(4-methylphenyl)sulfonyl]-2,4-
azetidinedione (7b)
Yield: 0.28 g (90%); colorless crystals; mp 52–54 °C.
3
1H NMR (300.1 MHz, CDCl3): d = 0.87 (3 H, t, JH,H = 7.4 Hz,
IR (KBr): 1733 (CONCO), 1603 (NC=C), 1500 and 1442 (Ar),
1345 and 1141 cm–1 (SO2).
3
CH2CH3), 1.21 (3 H, d, JH,H = 6.4 Hz, CHCH3), 1.55 (2 H, m,
CH2CH3), 3.17 (1 H, m, NCH), 3.72 (3 H, s, OCH3), 3.89 (3 H, s,
3
1H NMR (500.1 MHz, CDCl3): d = 1.12 (3 H, t, JH,H = 7.2 Hz,
3
OCH3), 7.54 (2 H, t, JH,H = 7.7 Hz, 2 CH of Ph), 7.62 (1 H, t,
CH2CH3), 1.23 (3 H, t, 3JH,H = 7.2 Hz, CH2CH3), 2.37 (3 H, s, CH3),
3.36 (2 H, q, 3JH,H = 7.2 Hz, CH2CH3), 3.45 (2 H, q, 3JH,H = 7.2 Hz,
CH2CH3), 7.24 (2 H, d, 3JH,H = 8.1 Hz, 2 CH of Ar), 7.74 (2 H, d,
3JH,H = 8.1 Hz, 2 CH of Ar), 8.13 (1 H, s, CH).
3JH,H = 7.2 Hz, CHpara of Ph), 8.08 (2 H, t, 3JH,H = 7.4 Hz, 2 CH of
Ph), 11.22 (1 H, d, 3JH,H = 4.0 Hz, NHCH), 11.82 (1 H, s, NH).
13C NMR (75.47 MHz, CDCl3): d = 10.03 (CHCH3), 21.45
(CH2CH3), 30.11 (CH2CH3), 52.19 (OCH3), 52.86 (OCH3), 55.52
(CHNH), 85.67 (NC=C), 128.12 (2 CH of Ph), 128.77 (2 CH of Ph),
133.31 (CH of Ph), 139.73 (Cipso of Ph), 161.62 (NC=C), 162.70
(CONH), 167.29 (CO2Me), 167.33 (CO2Me).
13C NMR (125.7 MHz, CDCl3): d = 12.08 (CH2CH3), 14.49
(CH2CH3), 21.45 (ArCH3), 40.94 (NCH2CH3), 47.08 (NCH2CH3),
126.30 (C-3 of azetidine ring), 126.35 (2 CH of Ar), 129.30 (2 CH
of Ar), 139.85 (Cipso-SO2 of Ar), 142.29 (Cipso-CH3 of Ar), 158.14
(2 C=O of azetidine ring and CH).
MS: m/z (%) = 398 (7), 366 (3), 333 (9), 337 (18), 305 (10), 240
(11) 225 (16), 193 (40), 180 (11), 141 (40), 126 (30), 94 (13), 77
(100), 59 (20), 51 (24), 41 (48).
MS: m/z (%) = 254 (6), 226 (4), 213 (5), 207 (10), 194 (3), 175 (9),
155 (41), 153 (7), 126 (7), 123 (9), 108 (53), 91 (100), 72 (25), 65
(43), 44 (56).
Anal. Calcd for C17H22N2O7S (398.42): C, 51.25; H, 5.57; N, 7.03.
Found: C, 51.17; H, 5.36; N, 7.24.
Anal. Calcd for C15H18N2O4S (322.38): C, 55.80; H, 5.63; N, 8.69.
Found: C, 56.00; H, 5.70; N, 8.70.
Methyl (E)-[(2,2-Dimethoxyethyl)amino]-2-({[(4-methylphe-
nyl)sulfonyl]amino}carbonyl)prop-2-enoate (4g)
Yield: 0.35 g (90%); white powder; mp 80–82 °C.
References
IR (KBr): 3275 (NH), 1669 (C=O), 1596 and 1432 (Ar), 1321 and
1160 (SO2), 1111 and 1073 cm–1 (C–O).
1H NMR (300.1 MHz, CDCl3): d = 2.42 (3 H, s, CH3), 3.34–3.37 (2
H, m, CH2), 3.39 (6 H, s, 2 OCH3), 3.74 (3 H, s, OCH3), 4.35 (1 H,
t, 3JH,H = 5.08 Hz, CH), 7.31 (2 H, d, 3JH,H = 8.1 Hz, 2 CH of Ar),
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