Synthesis of N-sulfonylazetidin-2-imines via the copper(I) oxide catalyzed multicomponent reaction of alkynes, sulfonyl azides and diimines under solvent-free conditions

Article abstract of DOI:10.1055/s-0031-1289740

N-Sulfonylazetidin-2-imines are synthesized efficiently via three-component reactions of sulfonyl azides, terminal alkynes, and carbodiimides using copper(I) oxide as an inexpensive and eco-friendly catalyst under solvent-free conditions, without the need

Full text of DOI:10.1055/s-0031-1289740

PAPER
▌1323
paper
Synthesis of N-Sulfonylazetidin-2-imines via the Copper(I) Oxide Catalyzed
Multicomponent Reaction of Alkynes, Sulfonyl Azides and Diimines under
Solvent-Free Conditions
N-Sulfonylazetidin-2-imines
Xiaohu Yi,a Badru-Deen Barry,a Peiqiu Liao,*a Xihe Bi*a,b
a
Department of Chemistry, Northeast Normal University, 5268 Renmin Street, 130024 Changchun, P. R. of China
Fax +86(431)85099759; E-mail: bixh507@nenu.edu.cn; E-mail: liaopq774@nenu.edu.cn
b
State Key Laboratory of Fine Chemicals, School of Chemical Engineering, University of Technology, Dalian 116012, P. R. of China
Received: 30.01.2012; Accepted after revision: 01.03.2012
organic solvents or in the presence of ligands or bases.
Abstract: N-Sulfonylazetidin-2-imines are synthesized efficiently
Hence, the development of environmentally friendly, sim-
via three-component reactions of sulfonyl azides, terminal alkynes,
ple, general, and synthetically useful methods for the syn-
thesis of azetidin-2-imines is highly desirable.
and carbodiimides using copper(I) oxide as an inexpensive and eco-
friendly catalyst under solvent-free conditions, without the need for
an additional base or ligand. The same method is applied to the
preparation of an azetidin-2-ylidene derivative using a 1,2-diimine
as the nucleophile.
A large number of copper systems have been utilized suc-
cessfully for the catalysis of azide–alkyne cycloaddi-
tions.1 Of these copper(0–II) catalytic species, copper(I)
oxide (Cu2O) is the most readily available, and above all,
is inexpensive. As part of our interest in the development
of non-precious metal catalyzed organic reactions, in par-
ticular the synthesis of heterocycles,9 we previously de-
veloped a copper(I) oxide catalyzed azide–alkyne
cycloaddition for the synthesis of triazoles.9a In continua-
tion of this work, we found that N-sulfonylazetidin-2-im-
ines could be prepared via the copper(I) oxide catalyzed
three-component reaction of sulfonyl azides, phenylacet-
ylene and carbodiimides under solvent-free conditions.
Our results showed that this one-pot transformation pro-
ceeded well under neat conditions to afford the desired
azetidine derivatives in very short reaction times and in
good to high yields. In addition, no undesired side reac-
tions occurred.
Key words: N-sulfonylazetidin-2-imines, multicomponent reac-
tion, copper(I) oxide, solvent-free, sulfonyl azides
The copper-catalyzed azide–alkyne cycloaddition (Cu-
AAC) reaction has been the focus of significant interest in
organic synthesis, materials science, biosciences, and me-
dicinal chemistry.1 Previous reports showed that the key
intermediates generated in situ during the copper-cata-
lyzed reaction of terminal alkynes with sulfonyl azides
were ketenimines.2 On in situ reaction of the ketenimine
species with nucleophiles such as amines, alcohols, water,
or heteroaromatics, the ensuing copper-catalyzed multi-
component reaction affords the corresponding amidines,
imidates, amides, or functionalized heteroaromatics, re-
spectively.3 As a result of the intrinsic benefits of multi-
component reactions in modern organic synthesis, as well
as in the fields of combinatorial chemistry and drug dis-
covery,4 the copper-catalyzed azide–alkyne cycloaddition
multicomponent process has been utilized as a very im-
portant synthetic tool leading to satisfactory results.5 An
important example of this procedure is the synthesis of
azetidine-2-imine derivatives via the formal [2+2] cyclo-
addition of in situ generated ketenimine intermediates
with a range of imines.2b,6 The resulting azetidines contain
a β-lactam group which is a key structure in a variety of
antibiotics including the cephalosporins and penicillins.7
The interesting biological and antibacterial activities of
azetidin-2-imines have rendered them suitable as sub-
strates in the design and development of functionalized
antibacterial agents.8 The groups of Xu6a and Fokin6b have
reported several copper(I) iodide catalyzed multicompo-
nent reactions of sulfonyl azides, alkynes and imines to
construct such azetidine-2-imine ring systems. Disadvan-
tageously, however, these reactions either proceeded in
An initial investigation of the catalytic species was per-
formed using tosyl azide (1a), phenylacetylene (2a) and
N,N′-dicyclohexylcarbodiimide (DCC) (3a) as model
substrates (Table 1). Several copper(I) and copper(II) salts
(10 mol%) were examined as candidates. Copper(I) oxide
proved to be the best furnishing the desired N-sulfonyl-
azetidin-2-imine 4a in 80% yield after four hours (Table
1, entry 1). Surprisingly, copper(II) bromide (CuBr2) and
copper(II) acetate [Cu(OAc)2], both being copper(II)
salts, also promoted the reaction to provide the expected
imine in yields of 56% and 77% (Table 1, entries 3 and 4).
In contrast, the other screened copper salts showed very
little catalytic activity (Table 1, entries 2 and 5). In a con-
trol experiment, no transformation was observed when the
reaction was conducted in the absence of a catalyst, even
after an extended reaction time of five hours (Table 1, en-
try 6). These results corroborated our previous work on
triazoles in which copper(I) oxide was used as the catalyst
in water.9a
Having established an efficient catalytic system [cop-
per(I) oxide (10 mol%), solvent-free conditions, room
temperature], the scope of this three-component reaction
was explored using various sulfonyl azides, terminal al-
SYNTHESIS 2012, 44, 1323–1328
Advanced online publication: 05.04.2012
DOI: 10.1055/s-0031-1289740; Art ID: SS-2012-F0090-OP
© Georg Thieme Verlag Stuttgart · New York
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X

1324
X. Yi et al.
PAPER
Table 1 Optimization of the Copper Catalyst
O
S
O
O
N
S
[Cu] (10 mol%)
solvent-free, r.t.
N3
O
N
C
N
N
N
1a
2a
3a
4a
Yield (%)a
Entry
Catalyst
Cu2O
Time (h)
1
2
3
4
5
6
4
80
17
56
77
11
0
CuI
4.5
3
CuBr2
Cu(OAc)2
Cu(OTf)2
none
4
3
5
a Yield of isolated product.
Table 2 Copper(I) Oxide Catalyzed Multicomponent Reaction of Sulfonyl Azides, Alkynes and Carbodiimides for the Synthesis of N-Sulfo-
nylazetidin-2-imines 4a
NSO2R1
R2
O
O
Cu2O (10 mol%)
r.t.
R2
R3
N
C
N
R3
S
+
+
R1
N3
N
R3N
R3
1
2
3
4
R1
R2
R3
Yield (%)b
Entry
Time (h)
Product
1
2
4-MeC6H4 (1a)
Ph (2a)
c-Hex (3a)
4
2
4a
4b
4c
4d
4e
4f
80
72
76
85
81
89
94
59
93
74
78
88
90
0
1a
4-MeC6H4 (2b)
2-F3CC6H4 (2c)
BocNHCH2 (2d)
4-t-BuC6H4 (2e)
EtO2C (2f)
3-FC6H4 (2g)
c-Pr (2h)
3a
3
1a
3a
2.5
3
4
1a
3a
5
1a
3a
4
6
1a
3a
1
7
1a
3a
1.5
9
4g
4h
4i
8
1a
3a
9
Me (1b)
1a
2a
3a
2
10
11
12
13
14
2b
i-Pr (3b)
3b
5
4j
1a
2a
5
4k
4l
1a
4-FC6H4 (2i)
4-BrC6H4 (2j)
3-H2NC6H4 (2k)
3a
2
1a
3a
2
4m
4n
1a
3a
24
a Reaction conditions: sulfonyl azide (1.0 mmol), alkyne (1.2 mmol), carbodiimide (1.2 mmol), Cu2O (10 mol%), r.t., solvent-free.
b Yield of isolated product.
Synthesis 2012, 44, 1323–1328
© Georg Thieme Verlag Stuttgart · New York

PAPER
N-Sulfonylazetidin-2-imines
1325
kynes, and carbodiimides, and the results are summarized
in Table 2. Good to excellent yields of the azetidin-2-im-
ines 4a–g were obtained in short reaction times when the
aromatic sulfonyl azide 1a, possessing an electron-donat-
ing group (Table 2, entries 1–7), was treated with non-
substituted aromatic terminal alkyne 2a (Table 2, entry 1),
or with a range of substituted terminal alkynes bearing ei-
ther electron-donating (Table 2, entries 2, 4 and 5) or elec-
tron-withdrawing (Table 2, entries 3, 6 and 7)
substituents. It is noteworthy that although the best yield
of 94% was obtained using 1-ethynyl-3-fluorobenzene
(2g) (Table 2, entry 7), the conversion required a slightly
longer reaction time (1.5 hours) compared to the 89%
yield afforded by ethynyl propionate (2f) in one hour
(Table 2, entry 6). As expected, the reaction of tosyl azide
(1a) with non-aromatic ethynylcyclopropane (2h) and
N,N′-dicyclohexylcarbodiimide (3a) resulted in a low
yield of product (59%) after an extended reaction time of
nine hours (Table 2, entry 8). To further investigate the
scope of this procedure, we examined the reactions of to-
syl azide (1a) and various terminal alkynes with either 3a
or N,N′-diisopropylcarbodiimide (DIC) (3b). With the ex-
ception of alkyne 2k, the aromatic sulfonyl azide took part
in the reaction to give the corresponding N-sulfonylazeti-
din-2-imines in good to excellent yields (Table 2, entries
10–13). Interestingly, carbodiimide 3b reacted with phen-
ylacetylene (2a) and azide 1a to give the corresponding N-
sulfonylazetidin-2-imine 4k in a comparable yield to that
obtained from the analogous reaction using alkyne 2b
(Table 2, entries 10 and 11). With substrates 2i and 2j, im-
proved results were obtained when tosyl azide (1a) was
reacted with carbodiimide 3a (Table 2, entries 12 and 13).
Surprisingly, a very good 93% yield (Table 2, entry 9) was
obtained when aliphatic methylsulfonyl azide (1b) was
treated with phenylacetylene (2a) and carbodiimide 3a.
The employed reaction system is thus in agreement with
Xu’s work in which addition of a base as the promoter was
not required;6a the carbodiimide is believed to function as
both a reactant and weak base. On the other hand, treat-
ment of 1a with 2k did not result in any transformation
(Table 2, entry 14). From the observed effects of the R1
and R2 substituents (Table 2), it was apparent that our re-
action was adaptable, and this inspired us to investigate
possible diversification of the approach using a diimine as
the nucleophile.
Ph
TsN3
+
+
N
N
1a
2a
3a'
Cu2O (10 mol%)
neat, r.t.
N
N
N
Ph
4a' 80%
Ts
Scheme 1 Copper(I) oxide catalyzed synthesis of azetidin-2-ylidene
4a′ under neat conditions
Figure 1 X-ray crystal structure of compound 4a′
In conclusion, an efficient copper(I) oxide catalyzed, sol-
vent-free, multicomponent reaction of sulfonyl azides,
terminal alkynes, and carbodiimides has successfully
been established for the synthesis of N-sulfonylazetidin-
2-imines. In addition, a novel route for the selective syn-
thesis of azetidine-2-ylidene 4a′ using a 1,2-diimine as the
nucleophile has been described. This latter approach
turned out to be quite specific, with the coupling only pro-
ceeding with tosyl azide, phenylacetylene and 1,2-diimine
3a′ as the substrates. Further synthetic modifications ap-
Various sulfonyl azides and terminal alkynes were inves- plicable to reactions of a variety of substrates with a 1,2-
tigated in reactions with the 1,2-diimine nucleophile, 3a′ diimine nucleophile are currently under investigation.
under the optimized conditions (Scheme 1). To our sur-
prise, only the reaction of tosyl azide (1a), phenylacety-
All reagents were purchased from commercial sources and were
lene (2a) and 1,2-diimine 3a′ gave the expected azetidine
4a′ (80% yield). The structure of 4a′ was established from
1H NMR, 13C NMR and HRMS spectral data. Unambigu-
ous confirmation of the structure was obtained by X-ray
diffraction analysis10 (Figure 1). Our observations rein-
force the work of Chang11 in which an alcohol is used as
a carbon nucleophile instead, and by extension, supports
the fact that the cycloaddition involved participation of a
1,2-diimine nucleophile.
used without further treatment unless otherwise indicated. TLC was
performed on Quindao Haiyang plastic silica gel plates. The prod-
ucts were purified by column chromatography over ZCX-II 300–
400 mesh silica gel. Petroleum ether (PE) refers to the fraction boil-
ing in the 30–60 °C range. Melting points were obtained using a
1
Yuhua X-4 apparatus and are uncorrected. H (500 MHz) and 13C
(125 MHz) NMR spectra were recorded at 25 °C using a Varian
Unity 500 spectrometer. TMS was used as the internal standard.
Mass spectra were recorded on an AutoflexIII Smartbeam spec-
trometer. High-resolution mass spectra (ESI) were recorded on a
Bruck MicroTof instrument.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 1323–1328

1326
X. Yi et al.
PAPER
Compounds 4a, 4b, 4f, 4i, and 4k are known compounds.6a
13C NMR (125 MHz, CDCl3): δ = 166.6, 155.4, 148.2, 143.2, 138.5,
129.4, 126.6, 79.4, 58.5, 57.3, 52.7, 37.3, 35.0, 33.9, 33.8, 29.6,
29.4, 29.2, 28.2, 25.5, 25.1, 24.9, 24.8, 24.5, 24.4, 21.5.
HRMS (ESI): m/z [M + H]+ calcd for C28H43N4O4S: 531.3005;
found: 531.3018.
(Z)-N-[(E)-1-Cyclohexyl-4-(cyclohexylimino)-3-phenylazetidin-
2-ylidene]-4-methylbenzenesulfonamide (4a); Typical Proce-
dure
Tosyl azide (1a) (197 mg, 1.0 mmol), phenylacetylene (2a) (122
mg, 1.2 mmol), DCC (3a) (247 mg, 1.2 mmol) and Cu2O (14 mg,
0.1 mmol) were added to a flask containing a stir bar, and the result-
ing mixture was stirred at r.t. (25 °C) without exclusion of air. After
the reaction was complete (monitored by TLC), the mixture was di-
luted with CH2Cl2 (10 mL) and aq NH4Cl soln (10 mL). The mixture
was stirred for an additional 30 min and the two layers were sepa-
rated. The aq layer was extracted with CH2Cl2 (3 × 5 mL). The com-
bined organic layer was dried over MgSO4, filtered and the solvent
evaporated. The residue was purified by silica gel column chroma-
tography (PE–EtOAc, 15:1) to afford the title product 4a.
(Z)-N-[(E)-3-(4-tert-Butylphenyl)-1-cyclohexyl-4-(cyclohexyl-
imino)azetidin-2-ylidene]-4-methylbenzenesulfonamide (4e)
Yield: 0.43 g (81%); white solid; mp 230–231 °C.
IR (KBr): 2932, 2856, 1623, 1315, 1163, 936, 673 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.27 (d, J = 8.5 Hz, 2 H), 7.11–
7.08 (m, 4 H), 6.82 (d, J = 8.5 Hz, 2 H), 5.25 (s, 1 H), 3.83–3.80 (m,
1 H), 2.96–2.92 (m, 1 H), 2.30 (s, 3 H), 1.33 (s, 9 H), 2.09–0.79 (m,
20 H).
13C NMR (125 MHz, CDCl3): δ = 167.3, 151.5, 151.2, 142.4, 138.5,
128.9, 128.8, 127.8, 126.6, 125.6, 60.2, 58.7, 52.9, 34.6, 34.4, 33.4,
31.4, 29.7, 29.6, 25.3, 25.1, 24.8, 24.4, 24.2, 21.5.
Yield: 0.38 g (80%); white solid; mp 168–169 °C.
1H NMR (500 MHz, CDCl3): δ = 7.31–7.27 (m, 3 H), 7.19 (d,
J = 7.0 Hz, 2 H), 7.09 (d, J = 8.0 Hz, 2 H), 6.98 (d, J = 8.0 Hz, 2
H), 5.26 (s, 1 H), 3.83–3.79 (m, 1 H), 2.97–2.93 (m, 1 H), 2.32 (s, 3
H), 2.09–0.79 (m, 20 H).
HRMS (ESI): m/z [M + H]+ calcd for C32H44N3O2S: 534.3154;
found: 534.3125.
13C NMR (125 MHz, CDCl3): δ = 166.7, 151.1, 142.5, 138.1, 132.0,
128.8, 128.7, 128.0, 126.5, 60.4, 58.6, 52.9, 34.3, 33.3, 29.6, 29.5,
25.2, 25.0, 24.7, 24.3, 24.2, 21.3.
HRMS (ESI): m/z [M + Na]+ calcd for C28H35N3O2SNa: 500.2348;
found: 500.2349.
Ethyl (2E,4Z)-1-Cyclohexyl-2-(cyclohexylimino)-4-(tosylimi-
no)azetidine-3-carboxylate (4f)
Yield: 0.42 g (89%); white solid; mp 143–145 °C.
1H NMR (500 MHz, CDCl3): δ = 7.78 (d, J = 8.5 Hz, 2 H), 7.29 (d,
J = 8.5 Hz, 2 H), 4.84 (s, 1 H), 4.29–4.20 (m, 2 H), 3.74–3.68 (m, 1
H), 3.27–3.22 (m, 1 H), 2.42 (s, 3 H), 1.97–1.13 (m, 23 H).
13C NMR (125 MHz, CDCl3): δ = 164.8, 161.0, 144.4, 143.2, 138.0,
129.2, 126.7, 62.1, 59.7, 59.3, 53.3, 34.3, 34.2, 29.2, 25.2, 24.9,
24.6, 24.3, 24.2, 21.4, 13.8.
HRMS (ESI): m/z [M + Na]+ calcd for C25H35N3O4SNa: 496.2246;
found: 496.2233.
(Z)-N-[(E)-1-Cyclohexyl-4-(cyclohexylimino)-3-(p-tolyl)azeti-
din-2-ylidene]-4-methylbenzenesulfonamide (4b)
Yield: 0.35 g (72%); white solid; mp 171–172 °C.
1H NMR (500 MHz, CDCl3): δ = 7.11 (d, J = 8.0 Hz, 2 H), 7.06 (s,
4 H), 6.97 (d, J = 8.0 Hz, 2 H), 5.21 (s, 1 H), 3.83–3.78 (m, 1 H),
2.98–2.94 (m, 1 H), 2.37 (s, 3 H), 2.33 (s, 3 H), 2.08–0.82 (m, 20 H).
13C NMR (125 MHz, CDCl3): δ = 167.2, 151.3, 142.3, 138.2, 137.8,
129.3, 128.8, 128.7, 127.8, 126.4, 60.3, 58.5, 52.8, 34.4, 33.3, 29.5,
29.4, 25.2, 25.0, 24.6, 24.3, 24.2, 21.3, 21.1.
HRMS (ESI): m/z [M + Na]+ calcd for C29H37N3O2SNa: 514.2504;
found: 514.2495.
(Z)-N-[(E)-1-Cyclohexyl-4-(cyclohexylimino)-3-(3-fluorophe-
nyl)azetidin-2-ylidene]-4-methylbenzenesulfonamide (4g)
Yield: 0.46 g (94%); white solid; mp 158–159 °C.
IR (KBr): 2932, 2857, 1760, 1612, 1315, 1160, 854 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.29–7.25 (m, 1 H), 7.19 (d,
J = 8.0 Hz, 2 H), 7.05–6.99 (m, 4 H), 6.83 (d, J = 9.0 Hz, 1 H), 5.26
(s, 1 H), 3.83–3.78 (m, 1 H), 2.96–2.92 (m, 1 H), 2.34 (s, 3 H), 2.10–
0.83 (m, 20 H).
13C NMR (125 MHz, CDCl3): δ = 166.0, 163.7, 161.8, 150.3, 142.9,
138.1, 134.6, 134.5, 130.5, 130.4, 129.0, 126.4, 124.0, 115.2, 115.0,
114.9, 114.8, 60.1, 58.9, 53.1, 34.4, 33.5, 29.65, 29.58, 25.3, 25.1,
24.8, 24.4, 24.2, 21.4.
(Z)-N-{(E)-1-Cyclohexyl-4-(cyclohexylimino)-3-[2-(trifluoro-
methyl)phenyl]azetidin-2-ylidene}-4-methylbenzenesulfon-
amide (4c)
Yield: 0.42 g (76%); white solid; mp 166–167 °C.
IR (KBr): 2931, 2854, 1765, 1613, 1307, 1611, 811 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.76 (d, J = 8.0 Hz, 1 H), 7.43–
7.40 (m, 1 H), 7.32–7.30 (m, 3 H), 7.08–7.04 (m, 3 H), 5.64 (s, 1 H),
3.88–3.82 (m, 1 H), 3.05–2.99 (m, 1 H), 2.34 (s, 3 H), 2.12–0.74 (m,
20 H).
HRMS (ESI): m/z [M + H]+ calcd for C28H35FN3O2S: 496.2434;
found: 496.2459.
13C NMR (125 MHz, CDCl3): δ = 165.2, 149.3, 142.7, 138.3, 132.0,
131.1, 128.9, 128.7, 128.5, 128.3, 128.1, 127.3, 127.1, 127.0, 126.4,
125.0, 122.8, 57.5, 57.1, 53.0, 34.4, 33.5, 29.5, 25.2, 25.1, 24.7,
24.1, 21.4.
(Z)-N-[(E)-1-Cyclohexyl-4-(cyclohexylimino)-3-cyclopropyl-
azetidin-2-ylidene]-4-methylbenzenesulfonamide (4h)
Yield: 0.26 g (59%); white solid; mp 116–117 °C.
IR (KBr): 2932, 2851, 1652, 1585, 1537, 1271, 1136, 1092, 703 cm–1.
HRMS (ESI): m/z [M + H]+ calcd for C29H35F3N3O2S: 546.2402;
found: 546.2427.
1H NMR (500 MHz, CDCl3): δ = 7.83 (d, J = 8.0 Hz, 2 H), 7.29 (d,
J = 8.0 Hz, 2 H), 3.92 (d, J = 9.0 Hz, 1 H), 3.67–3.62 (m, 1 H),
3.28–3.24 (m, 1 H), 2.42 (s, 3 H), 1.98–1.12 (m, 21 H), 0.89–0.84
(m, 1 H), 0.75–0.70 (m, 1 H), 0.65–0.61 (m, 1 H), 0.35–0.30 (m, 1
H).
13C NMR (125 MHz, CDCl3): δ = 168.4, 150.5, 142.7, 139.5, 129.2,
126.4, 59.5, 52.5, 34.8, 34.6, 29.4, 29.3, 25.5, 25.1, 24.8, 24.7, 24.5,
21.5, 9.8, 6.2, 4.5.
tert-Butyl {[(2E,4Z)-1-Cyclohexyl-2-(cyclohexylimino)-4-(tosyl-
imino)azetidin-3-yl]methyl}carbamate (4d)
Yield: 0.45 g (85%); white solid; mp 158–159 °C.
IR (KBr): 2932, 2856, 1615, 1315, 1161, 1019, 890 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.83 (d, J = 7.0 Hz, 2 H), 7.31 (d,
J = 8.0 Hz, 2 H), 4.92 (br s, 1 H), 4.21 (s, 1 H), 3.96–3.86 (m, 2 H),
3.65–3.63 (m, 1 H), 3.38–3.36 (s, 1 H), 2.42 (s, 3 H), 1.39 (s, 9 H),
1.92–1.14 (m, 20 H).
HRMS (ESI): m/z [M + H]+ calcd for C25H36N3O2S: 442.2528;
found: 442.2550.
(Z)-N-[(E)-1-Cyclohexyl-4-(cyclohexylimino)-3-phenylazetidin-
2-ylidene]methanesulfonamide (4i)
Yield: 0.37 g (93%); white solid; mp 127–129 °C.
Synthesis 2012, 44, 1323–1328
© Georg Thieme Verlag Stuttgart · New York

PAPER
N-Sulfonylazetidin-2-imines
1327
1H NMR (500 MHz, CDCl3): δ = 7.38–7.35 (m, 2 H), 7.32–7.31 (m,
3 H), 5.21 (s, 1 H), 3.88–3.81 (m, 1 H), 2.98–2.92 (m, 1 H), 2.47 (s,
3 H), 2.14–0.81 (m, 20 H).
13C NMR (125 MHz, CDCl3): δ = 168.5, 150.7, 132.0, 129.0, 128.5,
127.9, 60.3, 58.8, 53.0, 41.7, 34.4, 33.4, 29.7, 29.6, 25.3, 25.1, 24.8,
24.4, 24.2.
(E)-N-{1-(2,6-Diisopropylphenyl)-4-[(E)-(2,6-diisopropylphe-
nylimino)methyl]-3-phenylazetidin-2-ylidene}-4-methylben-
zenesulfonamide (4a′)
Yield: 0.52 g (80%); white solid; mp 126–127 °C.
IR (KBr): 1594, 1388, 1197, 1170, 989, 765, 691, 676, 585, 539 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.70 (d, J = 6.5 Hz, 1 H), 7.39–
7.38 (m, 3 H), 7.36–7.33 (m, 5 H), 7.20 (d, J = 7.5 Hz, 1 H), 7.16
(d, J = 7.5 Hz, 1 H), 7.04–7.03 (m, 5 H), 5.09 (s, 1 H), 5.04 (d,
J = 6.5 Hz, 1 H), 3.30–3.27 (m, 1 H), 3.01–2.99 (m, 1 H), 2.40–2.37
(m, 2 H), 2.35 (s, 3 H), 1.32–1.29 (m, 6 H), 1.14 (d, J = 6.5 Hz, 3
H), 0.99–0.98 (m, 9 H), 0.89–0.87 (m, 6 H).
13C NMR (125 MHz, CDCl3): δ = 168.0, 160.8, 147.4, 146.9, 145.9,
142.2, 139.1, 136.1, 134.3, 130.0, 129.5, 129.2, 128.8, 128.2, 127.8,
126.6, 124.8, 124.7, 123.8, 122.8, 75.0, 55.8, 29.5, 29.4, 27.7, 24.6,
24.4, 23.8, 23.7, 23.3, 22.3, 21.4.
HRMS (ESI): m/z [M + Na]+ calcd for C22H31N3O2SNa: 424.2035;
found: 424.2023.
(Z)-N-[(E)-1-Isopropyl-4-(isopropylimino)-3-(p-tolyl)azetidin-
2-ylidene]-4-methylbenzenesulfonamide (4j)
Yield: 0.30 g (74%); white solid; mp 148–149 °C.
IR (KBr): 2968, 2931, 1610, 1316, 1166, 716, 665 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.12 (d, J = 8.0 Hz, 2 H), 7.09–
7.07 (m, 4 H), 6.98 (d, J = 8.5 Hz, 2 H), 5.22 (s, 1 H), 4.21–4.16 (m,
1 H), 3.35–3.30 (m, 1 H), 2.37 (s, 3 H), 2.32 (s, 3 H), 1.47–1.45 (m,
6 H), 1.06 (d, J = 6.5 Hz, 3 H), 0.70 (d, J = 6.5 Hz, 3 H).
HRMS (ESI): m/z [M + H]+ calcd for C41H50N3O2S: 648.3624;
found: 648.3609.
13C NMR (125 MHz, CDCl3): δ = 167.1, 151.0, 142.5, 138.3, 138.0,
129.5, 128.8, 128.7, 128.0, 126.5, 60.3, 50.7, 45.6, 24.4, 23.4, 21.4,
21.2, 19.9, 19.8.
Acknowledgment
HRMS (ESI): m/z [M + H]+ calcd for C23H30N3O2S: 412.2059;
found: 412.2085.
This work was supported financially by NSFC (20902010,
21172029), FRFCU (10JCXK005), and the Research Fund for the
Doctoral Program of Higher Education of China (RFDP
20100043120008).
(Z)-N-[(E)-1-Isopropyl-4-(isopropylimino)-3-phenylazetidin-2-
ylidene]-4-methylbenzenesulfonamide (4k)
Yield: 0.31 g (78%); white solid; mp 141–143 °C.
1H NMR (500 MHz, CDCl3): δ = 7.34–7.29 (m, 3 H), 7.22 (d,
J = 7.0 Hz, 2 H), 7.09 (d, J = 8.0 Hz, 2 H), 6.99 (d, J = 8.0 Hz, 2 H),
5.26 (s, 1 H), 4.21–4.18 (m, 1 H), 3.33–3.30 (m, 1 H), 2.31 (s, 3 H),
1.48–1.45 (m, 6 H), 1.07 (d, J = 6.0 Hz, 3 H), 0.67 (d, J = 6.0 Hz,
3 H).
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.omnorinIftangonmSorniuifIatoprtngiSutpor
References
13C NMR (125 MHz, CDCl3): δ = 166.5, 150.7, 142.6, 138.0, 131.8,
128.8, 128.2, 128.1, 126.5, 60.5, 50.8, 45.6, 24.4, 23.2, 21.3, 19.87,
19.82.
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HRMS (ESI): m/z [M + Na]+ calcd for C22H27N3O2SNa: 420.1722;
found: 420.1703.
(Z)-N-[(E)-1-Cyclohexyl-4-(cyclohexylimino)-3-(4-fluorophe-
nyl)azetidin-2-ylidene]-4-methylbenzenesulfonamide (4l)
Yield: 0.44 g (88%); white solid; mp 192–193 °C.
IR (KBr): 2934, 2857, 1761, 1612, 1316, 1160, 854, 693 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.18–7.15 (m, 4 H), 7.04 (d,
J = 8.0 Hz, 2 H), 6.96 (t, J = 8.5 Hz, 2 H), 5.25 (s, 1 H), 3.83–3.79
(m, 1 H), 2.94–2.90 (m, 1 H), 2.34 (s, 3 H), 2.08–0.82 (m, 20 H).
13C NMR (125 MHz, CDCl3): δ = 166.7, 163.4, 161.4, 150.9, 142.8,
138.2, 129.8, 129.7, 128.9, 127.9, 126.4, 115.9, 115.7, 59.7, 58.8,
53.0, 34.4, 33.4, 29.7, 29.6, 25.3, 25.1, 24.7, 24.4, 24.3, 21.4.
HRMS (ESI): m/z [M + H]+ calcd for C28H35FN3O2S: 496.2434;
found: 496.2412.
(Z)-N-[(E)-3-(4-Bromophenyl)-1-cyclohexyl-4-(cyclohexylimi-
no)azetidin-2-ylidene]-4-methylbenzenesulfonamide (4m)
Yield: 0.50 g (90%); white solid; mp 198–199 °C.
IR (KBr): 2929, 2855, 1764, 1741, 1610, 1317, 1160, 935, 689 cm–1.
1H NMR (500 MHz, CDCl3): δ = 7.36 (d, J = 8.5 Hz, 2 H), 7.16–
7.13 (m, 2 H), 7.05–7.03 (m, 4 H), 5.22 (s, 1 H), 3.81–3.79 (m, 1 H),
2.93–2.89 (m, 1 H), 2.34 (s, 3 H), 2.08–0.84 (m, 20 H).
13C NMR (125 MHz, CDCl3): δ = 166.4, 150.3, 142.8, 138.2, 131.9,
131.1, 129.7, 129.0, 126.3, 122.1, 59.8, 58.8, 53.1, 34.4, 33.5, 29.7,
29.6, 25.3, 25.1, 24.8, 24.3, 24.2, 21.5.
HRMS (ESI): m/z [M + H]+ calcd for C28H35BrN3O2S: 556.1633;
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© Georg Thieme Verlag Stuttgart · New York