Solvent-free synthesis of N-sulfonyl imines using WCl6 as a novel, highly efficient and reusable catalyst

Article abstract of DOI:10.1039/c3ra40681d

WCl₆ was used as a novel, efficient and reusable catalyst for the preparation of N-sulfonyl imines via the condensation of sulfonamides with aldehydes as well as isatin under solvent-free conditions. The turn-over frequency (TOF) value of the c

Full text of DOI:10.1039/c3ra40681d

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Solvent-free synthesis of N-sulfonyl imines using WCl6
as a novel, highly efficient and reusable catalyst
Cite this: DOI: 10.1039/c3ra40681d
Mohammad Ali Zolfigol,*a Mahsa Tavasoli,a Ahmad Reza Moosavi-Zare,*b
Parastoo Arghavani-Hadi,a Abdolkarim Zarec and Vahid Khakyzadeha
Received 7th February 2013,
Accepted 26th March 2013
DOI: 10.1039/c3ra40681d
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WCl6 was used as a novel, efficient and reusable catalyst for the
preparation of N-sulfonyl imines via the condensation of sulfo-
namides with aldehydes as well as isatin under solvent-free
conditions. The turn-over frequency (TOF) value of the catalyst is
several times higher than the previously reported catalysts. Clean
reaction, simple purification, short reaction time and high yield
are some other advantages of this work.
Scheme 1 Synthesis of sulfonyl imines using WCl6.
Imines bearing electron-withdrawing N-substituents are useful
intermediates in organic synthesis.1 Among them, N-sulfonyl
imines are the center of attention for organic chemists because the
sulfonyl moiety has proven to be a powerful activating group of the
CLN bond in these compounds. As a consequence, N-sulfonyl
imines have been widely used in organic transformations.2
Furthermore, they are excellent substrates in nucleophilic addi-
tions,3 reductions,4 aza Diels–Alder reactions,5 alternative aziridine
synthesis involving nucleophilic addition across N-sulfonyl aldi-
mines,6 asymmetric synthesis of b-amino acid derivatives,7 and
oxaziridine synthesis,8 as well as ene reactions.9 Several kinds of
synthetic routes toward N-sulfonyl imines have been developed
namely via the Lewis and protic acid catalyzed reactions of
sulfonamides with aldehyde precursors,10–22 rearrangement of
oxime O-sulfinates,23 tellurium mediated reaction of aldehydes
Scheme 2 Condensation of benzenesulfonamide with isatin using WCl6.
efficient, one-step and environmentally friendly procedure for the
preparation of N-sulfonyl imines is desirable.
Solvent-free reactions have been demonstrated to be an
efficient technique for various organic transformations instead
of using harmful organic solvents. Solvent-free conditions often
lead to a remarkable decrease in reaction times, increased yields,
easier workup, matches with green chemistry protocols, and may
enhance the regioselectivity and stereoselectivity of reactions.29–36
with chloramine
T by utilization of in situ generated
N,N9-ditosyltellurodiimide,24 application of N-sulfinyl sulfona-
mides instead of sulfonamides to generate sulfonyl imines in situ
via a [2 + 2] cycloaddition and extrusion of sulfur dioxide,25
generation of sulfonamidosulfones and basic elimination,26,27 and
catalyzed isomerization or rearrangement of N-sulfonyl aziri-
dines.28 However, some of the reported methods suffer from
drawbacks such as long reaction times, unsatisfactory yields,
harsh conditions, the use of expensive reagents, the use of
multiple steps and cumbersome procedures, and no agreement
with green chemistry protocols. Therefore, the development of an
Table 1 Effect of different amounts of the catalyst and temperature on the
reaction of 4-methylbenzenesulfonamide (1 mmol) with 4-chlorobenzaldehyde
(1 mmol)
Catalyst Mol% of Catalyst Temp. (uC) Time (min) Yielda (%)
WCl6
WCl6
WCl6
WCl6
WCl6
WCl6
1
2
3
1
1
1
100
100
100
60
80
110
45
45
45
90
60
45
87
87
87
71
80
87
aFaculty of Chemistry, Bu-Ali Sina University, Hamedan, 6517838683, Iran.
E-mail: mzolfigol@yahoo.com; Fax: +988118257407
bDepartment of Chemistry, University of Sayyed Jamaleddin Asadabadi, Asadabad,
6541835583, Iran. E-mail: moosavizare@yahoo.com
cDepartment of Chemistry, Payame Noor University, Iran
a
Isolated yield.
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Table 2 Preparation of N-sulfonyl imines in the presence of WCl6 at 100 uC
Entry
1
Product
Time (min)/Yielda (%)
45/88
M.p. (Lit.)Ref.
107–110 (108–109)16
2
3
4
5
6
7
40/86
40/85
40/90
45/86
45/83
75/79
75–77 (76–78)16
163–165 (164–166)17
159–162 (161–163)16
110–113 (112–114)16
114–116 (113–115)17
123–125 (124–126)16
8
9
45/87
35/91
169–172 (171–173)16
132–135 (131–133)17
10
11
12b
13
55/84
60/85
60/71
40/85
127–129 (128–129)16
129–131 (129–130)38
95–98 (98–100)18,19
164–167 (166–168)19
14
15
45/84
60/55
125–128 (127–129)16
135–136 (136–137)21
16
17
60/58
50/80
85–87 (84–86)21
142–144 (144–145)22
a
b
Isolated pure product. In this reaction, bis-N-sulfonyl imine was obtained in very low yield.
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Table 4 The comparative condensation of 4-methylbenzenesulfonamide with
4-chlorobenzaldehyde using previously reported catalysts versus WCl6
Catalyst amount
(mol%)
Catalyst
WCl6
Time (min) Yielda (%) TOFb
Ref.
c
1
45
20
87
95
70
91
80
86
77
1.93
0.023
0.29
—
[Msim]Cl 200
22
11
FeCl3
InCl3
DMTrCl
AlCl3
4
10
12.5
50
25
60
1440
50
100
15
0.0063 12
0.128
0.017
0.2
18
15
20
MgO
a
b
c
Isolated pure product. Turn-over frequency. Our work.
Scheme 3 Plausible mechanism for the synthesis of sulfonyl imines using WCl6.
Considering the above facts, in continuation of our investiga-
tions on the application of WCl6 in organic transformations,37 we
report here a highly efficient and simple method for the synthesis
of N-sulfonyl imines via the reaction of sulfonamides with
aromatic aldehydes, as well as isatin using WCl6 as a catalyst
under solvent-free conditions (Schemes 1 and 2).
To optimize the reaction conditions, as a model reaction, the
solvent-free condensation of 4-methylbenzenesulfonamide with
4-chlorobenzaldehyde was examined in the presence of different
amounts of WCl6 in the range 60–110 uC. Higher yield and shorter
reaction time were obtained when the reaction was carried out
using 1 mol% of WCl6 at 100 uC (Table 1).
Afterward, 4-methylbenzenesulfonamide and benzenesulfona-
mide were condensed with various aldehydes as well as with
isatin, in order to assess the applicability and scope of the catalyst;
the respective results are displayed in Table 2. As Table 2 indicates,
all reactions proceeded efficiently in the presence of WCl6 at 100
uC and the N-sulfonyl imines were produced in high to excellent
and in relatively short reaction times.
In this investigation, the influence of electron-withdrawing
substituents, electron-releasing substituents and halogens on the
aromatic ring of aldehydes upon the results of the reaction was
studied. The results displayed that electron-withdrawing substi-
tuents and halogens increased the reaction yields (Table 2, entries
3 and 4 as well as 8–11); however, electron-releasing substituents
slightly decreased the yields (Table 2, entries 5, 6 and 7). Moreover,
the condensation of sulfonamides with dicarbonyl compounds as
well as isatin can be powerfully carried out using WCl6 as the
catalyst (Scheme 2 and Table 2, entries 12 and 15).
In a plausible mechanism, which was supported by the
literature,11,37 WCl6 could catalyze the synthesis of N-sulfonyl
imines as a Lewis acid. Then the tungsten(VI) chloride was
coordinated with the carbonyl group, which increased the
electrophilicity of the aldehyde against the sulfonamide as a
nucleophile. From the reaction of sulfonamide with activated
aldehyde, one molecule of H2O was removed and the sulfonyl
imine was prepared (Scheme 3).
In another study, to compare the efficiency as well as the
capacity of the solvent-free conditions with respect to solution
conditions, the model reaction was examined in the presence of
WCl6 in several solvents (5 mL) under reflux conditions; the
corresponding results are displayed in Table 3. As Table 3
indicates, the solvent-free condition is more efficient.
To compare the applicability and efficiency of WCl6 with
reported catalysts in the synthesis of N-sulfonyl imines, we have
tabulated the turn-over frequency (TOF) of these catalysts in the
condensation reaction of 4-methylbenzenesulfonamide with
4-chlorobenzaldehyde (Table 4). As shown in Table 4, WCl6,
relative to the previously reported catalysts, is superior in terms of
TOF.
In another investigation, the reusability of the catalyst was
examined upon the reaction of 4-methylbenzenesulfonamide (1
mmol) with 4-chlorobenzaldehyde (1 mmol). The reaction mixture
was extracted with dichloromethane and separated from the
catalyst. Afterward, the reused catalyst was employed for another
reaction. We observed that the catalytic activity of the catalyst was
restored within the limits of the experimental errors for four
successive runs (Table 5).
Table 3 The condensation of 4-methylbenzenesulfonamide with 4-chloroben-
zaldehyde using WCl6 (1 mol%) in different solvents (5 mL) under reflux
conditions
Table 5 The reaction of 4-methylbenzenesulfonamide with 4-chlorobenzalde-
hyde in the presence of reused WCl6 under solvent-free conditions at 90 uC
Entry
Solvent
Time (min)
Yielda (%)
1
2
3
4
5
6
EtOH
45
50
45
50
45
45
79
78
75
72
81
87
Entry
Cycle
Time (min)
Yielda (%)
CH3OH
CH3CN
CH2Cl2
CH3COOC2H5
—
1
2
3
4
1st run
2nd run
3rd run
4th run
45
47
50
60
87
84
81
79
a
a
Isolated yield.
Isolated yield.
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22 M. A. Zolfigol, A. Khazaei, A. R. Moosavi-Zare and A. Zare, J.
Iran. Chem. Soc., 2010, 7, 646.
Conclusions
In summary, we have introduced tungsten(VI) chloride (WCl6), as a
novel, efficient and reusable catalyst for the efficient synthesis of
N-sulfonyl imines via the condensation of sulfonamides with
aldehydes, as well as isatin, under solvent-free conditions.39
23 D. L. Boger and W. L. Corbett, J. Org. Chem., 1992, 57, 4777.
24 B. M. Trost and C. Marrs, J. Org. Chem., 1991, 56, 6468.
25 A. K. McFarlane, G. Thomas and A. Whiting, Tetrahedron Lett.,
1993, 34, 2379.
26 A. M. Kanazawa, J.-N. Denis and A. E. Greene, J. Org. Chem.,
1994, 59, 1238.
27 F. Chemla, V. Hebbe and J.-F. Normant, Synthesis, 2000, 75.
28 J. P. Wolfe and J. E. Ney, Org. Lett., 2003, 5, 4607.
29 K. Tanaka, Solvent-Free Organic Synthesis, Wiley-VCH, GmbH
and KGaA, Weinheim, 2004.
30 A. Khazaei, M. A. Zolfigol, A. R. Moosavi-Zare, A. Zare,
M. Khojasteh, Z. Asgari, V. Khakyzadeh and A. Khalafi-
Nezhad, Catal. Commun., 2012, 20, 54.
31 M. A. Zolfigol, A. Khazaei, A. R. Moosavi-Zare, A. Zare and
V. Khakyzadeh, Appl. Catal A, 2011, 400, 70.
32 G. H. Imanzadeh, A. Khalafi-Nezhad, A. Zare, A. Hasaninejad, A.
R. Moosavi-Zare and A. Parhami, J. Iran. Chem. Soc., 2007, 4,
229.
33 G. H. Imanzadeh, A. Zare, A. Khalafi-Nezhad, A. Hasaninejad, A.
R. Moosavi-Zare and A. Parhami, J. Iran. Chem. Soc., 2007, 4,
467.
34 A. Zare, T. Yousofi and A. R. Moosavi-Zare, RSC Adv., 2012, 2,
7988.
Acknowledgements
The authors gratefully acknowledge partial support of this
work by the Research Affairs Office of Bu-Ali Sina University
(Grant number 32-1716 entitled development of chemical
methods, reagents and molecules), and Center of Excellence in
Development of Chemical Method (CEDCM), Hamedan, I. R.
Iran.
References
1 S. Kobayashi and H. Ishitani, Chem. Rev., 1999, 99, 1069.
2 A. Vass, J. Dudas and R. S. Varma, Tetrahedron Lett., 1999, 40,
4951.
3 M. Yi and H. N. C. Wong, J. Org. Chem., 2004, 69, 2892.
4 H. Nishikori, R. Yoshihara and A. Hosomi, Synlett, 2003, 561.
5 D. L. Boger, W. L. Corbett, T. T. Curran and A. M. Kasper, J. Am.
Chem. Soc., 1991, 113, 1713.
35 A. Khazaei, M. A. Zolfigol, A. R. Moosavi-Zare, Z. Asgari,
M. Shekouhy, A. Zare and A. Hasaninejad, RSC Adv., 2012, 2,
8010.
36 A. Khazaei, A. R. Moosavi-Zare, Z. Mohammadi, A. Zare,
V. Khakyzadeh and G. Darvishi, RSC Adv., 2013, 3, 1323.
37 M. A. Zolfigol, A. R. Moosavi-Zare, P. Arghavani-Hadi, A. Zare,
V. Khakyzadeh and G. Darvishi, RSC Adv., 2012, 2, 3618.
38 K. Y. Lee, C. G. Lee and J. N. Kim, Tetrahedron Lett., 2003, 44,
1231.
¨
6 N. Giubellina, S. Mangelinckx, K. W. Tornroos and N.
D. Kimpe, J. Org. Chem., 2006, 71, 5881.
7 F. Colpaert, S. Mangelinckx and N. D. Kimpe, Org. Lett., 2010,
12, 1904.
8 X.-T. Zhou, Y.-R. Lin, L.-X. Dai, J. Sun, L.-J. Xia and M.-H. Tang,
J. Org. Chem., 1999, 64, 1331.
9 M. J. Melnick, S. M. Weinreb and A. Freyer, Tetrahedron Lett.,
1988, 29, 3891.
10 A. Hasaninejad and H. Sharghi, Phosphorus, Sulfur Silicon Relat.
Elem., 2007, 182, 873.
11 X. F. Wu, C. V. L. Bray, L. Bechki and C. Darcel, Tetrahedron,
2009, 65, 7380.
12 G. S. Deng, J. Y. Zou and T. F. Sun, Chin. Chem. Lett., 2011, 22,
511.
13 F. A. Davis, J. M. Kaminski, E. W. Kluger and H. S. Freilich, J.
Am. Chem. Soc., 1975, 97, 7085.
14 F. A. Davis, U. Nadir, E. W. Kluger, T. C. Sedergran, T.
W. Panunto, R. Billmers, R. Jenkins, I. J. Turchi, W. H. Watson,
J. S. Chen and M. Kimura, J. Am. Chem. Soc., 1980, 102, 2000.
15 H. Sharghi, M. Hosseini-Sarvari and S. Ebrahimpourmoghaddam,
ARKIVOC, 2007, xv, 255.
16 A. Hasaninejad and A. Zare, J. Sulfur Chem., 2007, 28, 357.
17 A. Hasaninejad, A. Zare, H. Sharghi and M. Shekouhy,
ARKIVOC, 2008, xi, 64.
18 A. Khalafi-Nezhad, A. Parhami, A. Zare, A. Nasrolahi Shirazi, A.
R. Moosavi-Zare and A. Hasaninejad, Can. J. Chem., 2008, 86,
456.
19 A. Zare, A. Hasaninejad, M. Shekouhy and A. R. Moosavi-Zare,
Org. Prep. Proced. Int., 2008, 40, 457.
20 A. Hasaninejad, A. Zare, A. R. Moosavi-Zare, A. Parhami,
H. Sharghi and A. Khalafi-Nezhad, Phosphorus, Sulfur Silicon
Relat. Elem., 2008, 183, 2769.
21 A. Zare, A. R. Moosavi-Zare, A. Hasaninejad, A. Parhami,
A. Khalafi-Nezhad and M. H. Beyzavi, Synth. Commun., 2009, 39,
3156.
39 General procedure for the synthesis of N-sulfonyl imines and
recycling of WCl6: to a mixture of compounds consisting of
sulfonamide (1 mmol) and carbonyl compound (1 mmol) in a
25 mL round-bottomed flask was added WCl6 (3.9 mg, 0.01
mmol, 1 mol%) as a catalyst. The resulting mixture was stirred
at 100 uC for the appropriate time (Table 2). After completion of
the reaction, as monitored by TLC, the reaction mixture was
extracted with dichloromethane (2 6 10 mL) and filtered to
separate the catalyst. The solvent was evaporated and the crude
product was dissolved in warm ethyl acetate (4 mL), treated
with n-hexane (12–15 mL), and was allowed to stand at room
temperature for 5–6 h. During this time, crystals of product
formed which were collected by filtration, washed with
n-hexane and dried. Afterward, the remaining WCl6 was dried
and used for the next run under identical reaction conditions.
(E)-N-Benzylidenebenzenesulfonamide (Table 2, entry 2). White
solid; m.p. 75–77 uC (Lit. [16] m.p. 76–78 uC); 1H NMR (CDCl3):
d 7.61 (m, 6H), 8.02 (m, 4H), 9.05 (s, 1H); 13C NMR (CDCl3): d
127.1, 128.3, 129.5, 130.3, 131.7, 132.8, 134.0, 136.1.0, 171.2. (E)-
N-(4-Methylbenzylidene)-4-methylbenzenesulfonamide (Table 2,
entry 5). White powder; m.p. 110–113 uC (Lit. [16] m.p. 112–114
uC); 1H-NMR (CDCl3): d 2.42 (s, 6H), 7.26 (d, J = 7.5 Hz, 2H), 7.34
(d, J = 7.8 Hz, 2H), 7.82 (d, J = 7.5 Hz, 2H), 7.90 (d, J = 7.5 Hz,
2H), 8.96 (s, 1H). 13C NMR(CDCl3): d 22.0, 126.8, 128.4, 129.9,
130.2, 130.3, 131.8, 135.7, 144.9, 170.4. (E)-N-(4-
Chlorobenzylidene)-4-methylbenzenesulfonamide (Table 2,
entry 8). White needles; m.p. 169–172 uC (Lit. [16] m.p. 171–
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173 uC); 1H NMR (CDCl3): d 2.46 (s, 3H), 7.15 (d, J = 9.1 Hz, 2H),
[22] m.p. 144–145 uC); 1H NMR (DMSO-d6): d 6.89 (m, 1H), 7.05
(m, 1H), 7.34 (m, 2H), 7.48 (m, 1H), 7.56 (m, 2H), 7.84 (m, 2H),
11.00 (s, 1H); 13C NMR (DMSO-d6): d 112.2, 117.8, 122.7, 124.6,
125.5, 128.8, 131.7, 138.3, 144.1, 150.7, 159.3, 184.3.
7.38 (d, J = 9.0 Hz, 2H), 7.86 (d, J = 8.9 Hz, 4H), 9.01 (s, 1H). 13
C
NMR (CDCl3): d 22.0, 128.5, 129.9, 130.2, 131.2, 132.7, 135.3,
141.8, 145.2, 169.0. (E)-N-(2-Oxoindolin-3-ylidene)benzenesulfo-
namide (Table 2, entry 15). Orange solid; m.p. 142–144 uC (Lit.
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