Iodine-catalyzed N-sulfonylation of benzotriazoles with sodium sulfinates under mild conditions

Article abstract of DOI:10.1016/j.cclet.2016.03.024

A new and convenient procedure is developed for the preparation of N-sulfonylbenzotriazoles from sodium sulfinates and benzotriazoles using molecular iodine as catalyst via the S[sbnd]N bond formation reaction. This catalytic radical sulfonylation proceed

Full text of DOI:10.1016/j.cclet.2016.03.024

Accepted Manuscript
Title: Iodine-catalyzed N-sulfonylation of benzotriazoles with
sodium sulfinates under mild conditions
Author: Si-Xue Wu Yi-Kun Zhang Hong-Wei Shi Jie Yan
PII:
S1001-8417(16)30054-7
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.cclet.2016.03.024
CCLET 3644
To appear in:
Chinese Chemical Letters
Received date:
Revised date:
Accepted date:
27-1-2016
2-3-2016
7-3-2016
Please cite this article as: S.-X. Wu, Y.-K. Zhang, H.-W. Shi, J. Yan, Iodine-catalyzed N-
sulfonylation of benzotriazoles with sodium sulfinates under mild conditions, Chinese
Chemical Letters (2016), http://dx.doi.org/10.1016/j.cclet.2016.03.024
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Graphical Abstract
Iodine-catalyzed N-sulfonylation of benzotriazoles with sodium sulfinates under mild conditions
Si-Xue Wu, Yi-Kun Zhang, Hong-Wei Shi, Jie Yan*
College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310015, China
N
N
R1
R1
I2 (0.2 equiv)
N
N
R2SO2Na
EtOAc:H2O (10:1)
r.t. 3h
N
N
H
SO2R2
3
1
2
Using molecular iodine as catalyst, a new and convenient procedure is developed for the preparation of N-sulfonylbenzotriazoles
from sodium sulfinates and benzotriazoles via the S-N bond formation reaction.
Page 1 of 5

Original article
Iodine-catalyzed N-sulfonylation of benzotriazoles with sodium sulfinates under mild
conditions
Si-Xue Wu, Yi-Kun Zhang, Hong-Wei Shi, Jie Yan
College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310015, China
ARTICLE INFO
ABSTRACT
A
new and convenient procedure is developed for the preparation of N-
Article history:
sulfonylbenzotriazoles from sodium sulfinates and benzotriazoles using molecular iodine as
catalyst via the S-N bond formation reaction. This catalytic radical sulfonylation proceeds
efficiently in air at room temperature under neutral conditions, and in short reaction time, to
afford the corresponding N-sulfonylbenzotriazoles in good yields, thus extending the catalytic
application of molecular iodine in organic synthesis.
Received 27 January 2016
Received in revised form 2 March 2016
Accepted 7 March 2015
Available online
Keywords:
Sulfonylation
Benzotriazole
Sodium sulfinate
Molecular iodine
Catalysis
1. Introduction
The catalytic utilization of molecular iodine (I2) and its salts in organic synthesis is increasing in importance, with growing interest
in the development of environmentally benign synthetic transformations [1]. Due to the ease of handling, low toxicity, commercial
availability and mild reactivity, especially the metal-like behavior of iodine, a number of recent studies have demonstrated the utility of
iodine catalysis as an efficient and powerful tool for the formation of carbon-carbon and carbon-heteroatom bonds [2-11]. Lei and co-
workers have reported an I2-catalyzed radical alkenylation of sulfonyl hydrazides, and various alkenyl sulfones have been synthesized
[12]. Similarly, other methods for construction of carbon-sulfur bond using I2 as catalyst have also been developed from alkenes and
sodium sulfinates [13-19]. More recently, the I2-mediated or I2-catalyzed synthesis of sulfonamides from sodium sulfinates and amines
has been investigated [20-23], it is very interesting because this nitrogen-sulfur bond formation method is general, efficient and
environmentally friendly. In addition, the given protocol provides good to excellent yields of sulfonamides under mild reaction
conditions.
Previous work
BtH, bases
BtTMS
1) SO2
RSO2Cl
2) BtCl,base
BtSO2R
RLi
RSO Cl
2
This work
I2 (20% mol)
BtSO2R
RSO
2
Na
+
BtH
EtOAc/H2O (10/1)
air, r.t. 3h
Scheme 1. Methods for the synthesis of N-sulfonylbenzotriazoles.
N-Sulfonylbenzotriazoles are important intermediates in organic synthesis. As the advantageous sulfonylation reagents, they can
react smoothly with amines and phenols to afford the corresponding sulfonamides and sulfonates, respectively [24]. They are also
easily to convert carboxylic acids into N-acylbenzotriazoles which are especially useful when the corresponding acid chlorides are
difficult to obtain [25,26]. They have a wide applicability in C-sulfonylation, and a series of ɑ-cyanoalkyl sulfones,
sulfonylheteroaromatics, ɑ-(sulfonylalkyl)heterocycles, ɑ-sulfonylalkyl sulfones, and esters of ɑ-sulfonyl acids have been prepared in
excellent yields, respectively [27]. They are also useful as herbicides, mutagens, insecticides, fungicides and antibacterials [28-31]. The
universal methods for the preparation of N-sulfonylbenzotriazole include the reaction of sulfonyl chloride with benzotriazole (BtH) in
the presence of bases [25, 32] or with 1-(trimethylsilyl)benzotriazole (BtTMS) [31] for alkyl- and arylsulfonylbenzotriazoles, and the
reaction of organolithium reagents with sulfur dioxide at low temperature to obtain sulfinic acid salts, followed by the addition of N-
Corresponding author.
E-mail address: jieyan87@zjut.edu.cn
Page 2 of 5

chlorobenzotriazole (BtCl) for heteroarylsulfonylbenzotriazoles [32] (Scheme 1). However, these methods have some limitations such
as hazardous starting materials, harsh reaction conditions, long reaction time and so on. Therefore, development of a general, practical
and efficient method for the construction of N-sulfonylbenzotriazoles under mild conditions is still a challenge, and such a method is
highly desirable. Herein, we report a convenient I2-catalyzed reaction of sodium sulfinates with benzotriazoles for the synthesis of N-
sulfonylbenzotriazoles at room temperature (Scheme 1), which resulting in the target products in good yields under mild conditions.
2. Experimental
A typical procedure for the catalytic N-sulfonylation of benzotriazoles using I2 as catalyst includes: in EtOAc-H2O (10:1) mixture
solvent (2 mL), benzotriazole 1a (0.3 mmol), sodium benzenesulfinate 2a (0.9 mmol), I2 (0.06 mmol) were added successively. The
suspension mixture was vigorously stirred at room temperature for 3 h. Upon completion, the reaction was quenched by addition of sat.
aq. Na2S2O3 (2 mL), basified with sat. aq. Na2CO3 (8 mL) and H2O (5 mL). The mixture was extracted with CH2Cl2 (3×5 mL) and the
combined organic phase was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was then
purified by TLC technique (petroleum ether/ethyl acetate = 3:1, v/v) to furnish 1-phenylsulfonylbenzotriazole 3a [28] in 97% yield.
1
Compound 3a: Pale yellow solid; mp 122-123 °C; H NMR (500MHz, CDCl3): δ 8.15
-
8.11 (m, 3H), 8.09 (d, 1H, J = 8.4 Hz), 7.70
-
7.64 (m, 2H), 7.57
-7.53 (m, 2H), 7.52
-7.47 (m, 1H)
;
13C NMR (125 MHz, CDCl3): δ 145.4, 137.0, 135.2, 131.6, 130.3, 129.6, 127.8, 125.9,
ν 3094, 3069, 1586, 1480, 1386, 1194, 955, 726, 589; MS (EI, m/z, %): 260 (M+1, 100).
120.5, 111.9; IR (film, cm-1):
3. Results and discussion
Initially, we utilized benzotriazole (1a) and sodium benzenesulfinate (2a) as model substrates to investigate the reaction for the
direct preparation of 1-phenylsulfonylbenzotriazole (3a) using I2 as catalyst. It was found that simple stirring of a mixture of 0.1 equiv.
of I2 with 1.0 equiv. of 1a and 2.0 equiv. of 2a in ethyl acetate (EtOAc) for 12 h at room temperature in air, the expected product 3a
was obtained in 64% yield (Table 1, entry 1). Next, the procedure for the preparation of 3a catalyzed by I2 was optimized at room
temperature. The reaction was first evaluated in several solvents, providing the desired product in yields ranging from 13%-64%, in
which EtOAc had the best effect (entries 1-7); while using DMF or Et2NH as solvent, 3a was not detected (entries 8 and 9). Due to the
bad solubility of 2a in EtOAc, water was added in EtOAc to improve the reaction. When the volume ratio of EtOAc to H2O was 10:1,
the reaction yield increased to 74%; while more H2O was added, the yields decreased (entries 10-13). Therefore, the mixed solvent
EtOAc-H2O (10:1) was selected as the suitable solvent for the reaction. In the mixture solvent, the amount of catalyst I2 was evaluated
and 0.2 equiv proving the best choice; however, in the absence of it, no product was detected (entries 10, 14-16). Similar to I2, other
iodine-containing catalysts such as KI, NaI and NH4I can promote the reaction, giving moderate or low yields (entries 17-19). Finally,
the quantity of sodium benzenesulfinate was optimized, and 3.0 equiv of it was the most suitable (entries 14, 20-22). Using the
optimized conditions, the reaction processed smoothly and completed in 3 h (entries 22-25).
Table 1
Optimization of the N-sulfonylation of benzotriazoles using I2 as catalyst.
N
N
I2
Solvent, r.t.
N
N
PhSO2Na
N
N
H
SO2Ph
3a
1a
2a
Entry
2a
(equiv.)
I2 (equiv.)
Solvent
Time
(h)
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
6
Yield
(%)a
64
30
13
43
60
45
28
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
1
2.5
3
3
3
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.2
0.3
-
EtOAc
CH2Cl2
H2O
CH3CN
THF
CH2ClCH2Cl
EtOH
DMF
Et2NH
0
EtOAc-H2O (10:1)
EtOAc-H2O (10:3)
EtOAc-H2O (10:5)
EtOAc-H2O (10:7)
EtOAc-H2O (10:1)
EtOAc-H2O (10:1)
EtOAc-H2O (10:1)
EtOAc-H2O (10:1)
EtOAc-H2O (10:1)
EtOAc-H2O (10:1)
EtOAc-H2O (10:1)
EtOAc-H2O (10:1)
EtOAc-H2O (10:1)
EtOAc-H2O (10:1)
EtOAc-H2O (10:1)
74
65
32
24
82
87
0
48
37
62
49
87
98
97
97
KI (0.2)
NaI (0.2)
NH4I (0.2)
0.2
0.2
0.2
0.2
0.2
3
Page 3 of 5

25
3
0.2
EtOAc-H2O (10:1)
2
71
a Isolated yield.
Based on the extensive screening process, we arrived at the optimal reaction conditions. Next, the catalytic reaction of 1.0 equiv. of
benzotriazoles (1) with 3.0 equiv. of sodium sulfinates (2) and 0.2 equiv. of I2 in EtOAc-H2O (10:1) at room temperature for 3 h was
investigated, as a consequence a series of corresponding N-sulfonylbenzotriazoles (3) were obtained. The results are summarized in
Table 2.
Table 2
Preparation of N-sulfonylbenzotriazoles 3.
R1
R1
N
N
N
I2 (0.2 equiv.)
+
R2SO2Na
N
N
EtOAc:H2O (10:1)
r.t., 3 h
N
H
SO2R2
Yield
(%)a
97
78
61
99
86
68
82
70
58
87
72
Entry R1
R2
Ph
Product (3)
1
2
H
H
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
4'-MeC6H4
Me
Ph
4'-MeC6H4
Me
Ph
4'-MeC6H4
Me
3
H
4
5
6
7
8
9
Me
Me
Me
Cl
Cl
Cl
10
11
12
4,5-diCH3
4,5-diCH3
4,5-diCH3
Ph
4'-MeC6H4
Me
3k
3l
60
N
N
N
N
SO2Ph
13
Ph
48
N
N
3m
H
1e
a Isolated yields.
As shown in Table 2, the I2-catalyzed reaction was compatible with the studied benzotriazoles 1, affording the corresponding
sulfonylbenzotriazoles 3 in moderate to excellent yields (Table 2, entries 1–12). It is obvious that sodium benzenesulfinate 2a had the
best effect in the reaction compared with other two sodium sulfinates, and sodium methylsulfinate 2c usually resulted in moderate
yields. When 5-methylbenzotriazole 1b and 5-chlorobenzotriazole 1c were used in the reaction, these monosubstituted benzotriazoles
1
typically gave 5-substituted and 6-substituted mixture products which were difficult to be isolated, and by H NMR analysis the
ratios of 5-substituted products to 6-substituted products are ranging from 1:1 to 2:3 (entries 4–9). Under the same reaction
conditions, 1,2,4-triazole 1e was also treated with 2a, but the product 3m was obtained with a somewhat low yield 48% (entry 13).
To explore the efficiency and generally of our methodology, as the representative of one nitrogen atom heterocycles, indole resulted
in the 2-sulfonylated product, not the desired N-sulfonylated product [17]. Under the same reaction conditions, heterocycles with two
nitrogen atoms and four nitrogen atoms were also checked; however, the desired N-sulfonylated products were not obtained.
Therefore, the new and convenient N-sulfonylation is suitable for triazoles.
A proposed catalytic mechanism for the N-sulfonylation of benzotriazoles is shown in Scheme 2. Initially, sodium sulfinate reacts
with I2 to form the active sulfonyl iodide, which is easily subjected to homolysis, giving sulfonyl and iodine radicals due to its
instability [17, 33-34]. Then, the iodine radical or sulfonyl radical attacks the hydrogen of benzotriazole to produce the benzotriazole
radical, which finally reacts with sulfonyl radical to afford the N-sulfonylbenzotriazole. Meanwhile, the molecular iodine can be re-
generated via the oxidation of NaI or HI by oxygen in air.
RSO2
I
N
RSO2Na
N
N
N
H
air[O2]
I2
NaI
N
N
N
N
N
N
RSO2
N
N
air[O2]
HI
SO2R
Scheme 2 Proposed catalytic mechanism for the N-sulfonylation of benzotriazoles.
To identify the mechanism, several control experiments have been made. It was found that the I2-catalyzed reaction was faster in air
than in N2 atmosphere and gave higher yield, meaning oxygen in air can improve the reaction. When I2 was replaced by iodides, such
as KI, NaI and NH4I, the reaction also processed (Table 1, entries 17-19); if without oxygen, the reaction was difficult to carry out,
which supports above finding. That 5-methylbenzotriazole 1b and 5-chlorobenzotriazole 1c resulted in the mixture products, indicating
the benzotriazole radical was formed during the reaction. As a radical scavenger, 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) was
added in the reaction and no any sulfonylbenzotriazole was detected, demonstrating that a radical mechanism is involved. We also
found that simple stirring a mixture of I2 with sodium sulfinate, the product sulfonyl iodide was easily formed, after adding
Page 4 of 5

benzotriazole, 3a was produced quickly; however, only stirring a mixture of I2 and benzotriazole for a long time, no reaction proceeded,
which indicates that sulfonyl iodide is the key intermediate in the reaction
.
4. Conclusion
In summary, we have developed a new and convenient catalytic procedure for the preparation of sulfonylbenzotriazoles from
benzotriazoles and sodium sulfinates in the presence of catalytic amount of I2 at room temperature in air. This sulfonylation of
benzotriazoles has some advantages such as mild reaction conditions, simple procedure and giving good yields. Furthermore, the
catalytic reaction will extend the application scope of molecular iodine in organic synthesis.
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