Convenient sulfonylation of benzotriazoles with the in situ–generated sulfonyl bromides

Article abstract of DOI:10.1080/00397911.2016.1209684

A convenient procedure is developed for the preparation of N-sulfonylbenzotriazoles from sodium sulfinates, benzotriazoles, and sodium bromide in the present of m-chloroperbenzoic acid as oxidant. This radical sulfonylation proceeds efficiently at room te

Full text of DOI:10.1080/00397911.2016.1209684

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
Chemistry
ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
Convenient sulfonylation of benzotriazoles with
the in situ–generated sulfonyl bromides
Sixue Wu, Yikun Zhang & Jie Yan
To cite this article: Sixue Wu, Yikun Zhang & Jie Yan (2016) Convenient sulfonylation of
benzotriazoles with the in situ–generated sulfonyl bromides, Synthetic Communications, 46:17,
1432-1437, DOI: 10.1080/00397911.2016.1209684
To link to this article: http://dx.doi.org/10.1080/00397911.2016.1209684
View supplementary material
Accepted author version posted online: 18
Jul 2016.
Published online: 18 Jul 2016.
Submit your article to this journal
Article views: 8
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=lsyc20
Download by: [95.181.217.98]
Date: 10 September 2016, At: 03:37

SYNTHETIC COMMUNICATIONS®
016, VOL. 46, NO. 17, 1432–1437
2
http://dx.doi.org/10.1080/00397911.2016.1209684
Convenient sulfonylation of benzotriazoles with the
in situ–generated sulfonyl bromides
Sixue Wu, Yikun Zhang, and Jie Yan
College of Chemical Engineering, Zhejiang University of Technology, Hangzhou, China
ABSTRACT
ARTICLE HISTORY
Received 5 April 2016
A convenient procedure is developed for the preparation of
N-sulfonylbenzotriazoles from sodium sulfinates, benzotriazoles,
and sodium bromide in the present of m-chloroperbenzoic acid as
oxidant. This radical sulfonylation proceeds efficiently at room
temperature under neutral conditions, affording the corresponding
N-sulfonylbenzotriazoles in moderate to good yields in a short time.
KEYWORDS
Benzotriazole; radical
reaction; sodium bromide;
sodium sulfonate;
sulfonylation
GRAPHICAL ABSTRACT
Introduction
N-Sulfonylbenzotriazoles are important intermediates in organic synthesis. As
advantageous sulfonylation reagents, they can react smoothly with amines and phenols
to afford the corresponding sulfonamides and sulfonates, respectively.[1] They also easily
convert carboxylic acids into N-acylbenzotriazoles, which are especially useful when
[
2,3]
the corresponding acid chlorides are difficult to obtain.
They have wide applicability
in C-sulfonylation and a series of α-cyanoalkyl sulfones, sulfonylheteroaromatics,
α-(sulfonylalkyl)heterocycles, α-sulfonylalkyl sulfones, and esters of α-sulfonyl acids have
[
4]
been prepared in excellent yields. As stabilizers, N-sulfonylbenzotriazoles are often used
[
5–10]
in manufacturing the photosensitive materials.
mutagens, insecticides, fungicides, and antibacterials.
the preparation of N-sulfonylbenzotriazole include the reaction of sulfonyl chloride with
They are also useful as herbicides,
[
11–15]
The universal methods for
[
2,16]
[15]
benzotriazole in the presence of bases
or with 1-(trimethylsilyl)benzotriazole
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
[
16]
of N-chlorobenzotriazole for heteroarylsulfonylbenzotriazoles.
However, these methods
have some limitations such as the availability of sulfonyl chlorides, some of which are hard
to prepare and difficult to store or handle. Therefore, development of a general, practical,
and efficient method for the construction of N-sulfonylbenzotriazoles under mild
CONTACT Jie Yan
jieyan87@zjut.edu.cn
College of Chemical Engineering, Zhejiang University of Technology,
Hangzhou 310015, P.R. China.
Supplemental data (Full experimental detail) can be accessed on the publisher’s website.
2016 Taylor & Francis
©

SYNTHETIC COMMUNICATIONS®
1433
conditions is still desirable. Herein, we report a convenient sulfonylation of benzotriazoles
with sodium sulfinates and sodium bromide in the present of m-chloroperbenzoic acid.
This radical sulfonylation proceeds efficiently at room temperature under neutral
conditions, affording the corresponding N-sulfonylbenzotriazoles in moderate to good
yields in short time.
Results and discussion
Similar to the sulfonylation of sulfonyl chloride with benzotriazole, we initially investigated
the reaction of sulfonyl bromide with benzotriazole and obtained a good result. Because
sulfonyl bromides can be prepared by bromination of sulfinic acids or their salts,[17,18]
and to develop a simpler route for preparation of N-sulfonylbenzotriazoles, we then tried
the one-pot reaction of benzotriazole (1a), sodium benzenesulfinate (2a), sodium bromide,
and m-chloroperbenzoic acid (mCPBA). It was found that when the mixture of 1.0 equiv of
1
a, sodium bromide, and mCPBA with 2.0 equiv of 2a was stirred in ethyl acetate (EtOAc)
for 12 h at room temperature, the expected product 1-phenylsulfonylbenzotriazole (3a) was
obtained in 32% yield (Table 1, entry 1). In light of the successful formation of 3a, the reac-
tion conditions were optimized and the results are summarized in Table 1. The reaction
was first evaluated in many solvents, giving poor yields (Table 1, entries 1–6). To improve
the reaction, several mixed solvents were checked and EtOAc/MeOH (4:1) had the best
effect, in which the yield of 3a increased greatly to 78% (entries 7–13). Similar to NaBr,
other bromides such as KBr, NH Br, and (C H ) NBr can promote the reaction, but
4
4
9 4
provide the desired product in yields ranging from 32% to 62% (entries 14–16). Other oxi-
dants such as THBP, H O , and K S O were not active in the reaction and normally
2
2
2 2 8
resulted in very poor yields (entries 17–19). The amounts of mCPBA and NaBr were also
evaluated. As a result, 1.3 equiv and 1.2 equiv were found to be the suitable amounts for
mCPBA and NaBr, respectively (entries 11 and 20–26). Finally, a suitable amount of 2a was
determined and 1.8 was the best choice (entries 24 and 27–29). Under the optimized con-
ditions, the reaction processed smoothly and completed in 4 h (entries 28 and 30–32).
However, in the absence of NaBr or mCPBA, no product was detected (entries 33 and 34).
Based on the extensive screening process, we arrived at the optimal reaction conditions
(
Scheme 1). Next, the one-pot sulfonylation of 1.0 equiv of benzotriazoles (1) with 1.8
equiv of sodium sulfinates (2), 1.2 equiv of NaBr, and 1.3 equiv of mCPBA in EtOAc/
MeOH (4:1) at room temperature for 4 h was investigated. As a consequence, a series of
corresponding N-sulfonylbenzotriazoles (3) were obtained. The results are summarized
in Table 2.
As shown in Table 2, the sulfonylation was compatible with the studied benzotriazoles 1,
affording the corresponding sulfonylbenzotriazoles 3 in moderate to good yields (Table 2,
entries 1–12). It was 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-chlorobenzo-
triazole 1c were used in the reaction, these monosubstituted benzotriazoles typically gave
5
-substituted and 6-substituted mixture products. Because the mixtures were difficult to
isolate, the ratios of 5-substituted products to 6-substituted products were finally deter-
1
mined to be nearly 1:1 by H NMR analysis (entries 4–9). Under the same reaction con-
ditions, 1,2,4-triazole 1e was also treated with 2a, but the product 3m was obtained with

1
434
S. WU ET AL.
Table 1. Optimization of the sulfonylation of benzotriazole.
Sodium benzenesulfinate
(equiv.)
mCPBA
NaBr
a
Entry
(equiv.)
(equiv.)
Solvent
EtOAc
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
9
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
1.5
1.8
2.5
1.8
1.8
1.8
1.8
1.8
1.0
1.0
1.0
1.0
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
6
32
5
28
0
8
CH Cl
MeCN
2 2
1.0
1.0
1.0
1.0
2
H O
1.0
1.0
CF
MeOH
EtOAc/MeOH(5:1)
CH CN/MeOH(5:1)
EtOAc/H O(5:1)
3
CH
2
OH
1.0
1.0
12
72
53
15
38
78
55
39
32
45
62
0
1.0
1.0
1.0
1.0
3
1.0
1.0
2
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
1.0
1.0
EtOAc/MeOH(10:1)
EtOAc/MeOH(4:1)
EtOAc/MeOH(10:3)
EtOAc/MeOH(5:2)
EtOAc/MeOH(4:1)
EtOAc/MeOH(4:1)
EtOAc/MeOH(4:1)
EtOAc/MeOH(4:1)
EtOAc/MeOH(4:1)
EtOAc/MeOH(4:1)
EtOAc/MeOH(4:1)
EtOAc/MeOH(4:1)
EtOAc/MeOH(4:1)
EtOAc/MeOH(4:1)
EtOAc/MeOH(4:1)
EtOAc/MeOH(4:1)
EtOAc/MeOH(4:1)
EtOAc/MeOH(4:1)
EtOAc/MeOH(4:1)
EtOAc/MeOH(4:1)
EtOAc/MeOH(4:1)
EtOAc/MeOH(4:1)
EtOAc/MeOH(4:1)
EtOAc/MeOH(4:1)
EtOAc/MeOH(4:1)
1.0
1.0
1.0
1.0
1.0
1.0
1.0
KBr (1.0)
1.0
4
NH Br (1.0)
1.0
(C
4
H
9
)
4
NBr (1.0)
1.0
THBP(1.0)
H
2
2
S
O
2
2
(1.0)
(1.0)
1.0
8
K
O
8
1.0
10
82
84
78
72
90
90
90
80
90
90
90
90
85
0
1.2
1.3
1.4
1.5
1.3
1.3
1.3
1.3
1.3
1.3
1.3
1.3
1.3
1.3
—
1.0
1.0
1.0
1.0
1.2
1.3
1.5
1.2
1.2
1.2
1.2
1.2
4
3
12
12
1.2
—
1.2
0
a
Isolated yield.
a somewhat lower yield 38% (entry 13). To explore the efficiency and generally of our
methodology, indole was treated under the same reaction conditions. However, the reac-
tion resulted in 2-sulfonylated product via a radical addition and then elimination pro-
[
19]
cess.
5-Nitroindazole and tetrazole, which have two or four nitrogen atom
Scheme 1. Sulfonylation of benzotriazoles.

SYNTHETIC COMMUNICATIONS®
1435
Table 2. Preparation of N-sulfonylbenzotriazoles 3.
a
r
Benzotriazole 1
Sodiumsulfinate 2
Product 3
Yield (%)
1
PhSO
2
Na2a
90
70
50
2
3
1a
1a
2
MeSO Na2c
4
5
6
2a
70
62
40
1b
1b
2b
2c
7
8
9
2a
2b
2c
78
72
48
1c
1c
10
2a
82
1
1
2
1d
1d
2b
2c
3k
68
45
1
13
2a
38
a
Isolated yields.

1
436
S. WU ET AL.
Scheme 2. Proposed mechanism for the sulfonylation of benzotriazoles.
heterocycles, respectively, were also checked, but the desired N-sulfonylated products were
not obtained. Therefore, the new and convenient N-sulfonylation was suitable for triazoles.
A proposed mechanism for the sulfonylation of benzotriazoles is shown in Scheme 2.
Initially, NaBr is oxidized by mCPBA into bromine, which reacts with sodium sulfinate
easily to form sulfonyl bromide. The in situ–generated sulfonyl bromide, similar to sulfonyl
iodide, is then subjected to homolysis to give sulfonyl and bromine radicals as a result
[
19–21]
of its instability.
Finally, the bromine radical or sulfonyl radical attacks the
hydrogen of benzotriazole to produce the benzotriazole radical, which reacts with sulfonyl
radical to afford the N-sulfonylbenzotriazole. To identify the mechanism, a radical scaven-
ger, 2,2,6,6-tetramethylpiperidine1-oxyl (TEMPO) was added in the reaction and no
sulfonylbenzotriazole was detected, demonstrating that a radical mechanism was involved.
That 5-methylbenzotriazole 1b and 5-chlorobenzotriazole 1c resulted in the mixture
products, also indicating the benzotriazole radical was formed during the reaction.
Conclusions
In summary, we have developed a new and convenient procedure for the preparation of
sulfonylbenzotriazoles from benzotriazoles with sodium sulfinates, sodium bromide, and
mCPBA at room temperature. This sulfonylation of benzotriazoles has some advantages
such as mild reaction conditions, simple procedure, and good yields.
Experimental
1
Infrared (IR) spectra were recorded on a Thermo-Nicolet 6700 instrument, H NMR and
1
3
C NMR spectra were measured on a Bruker-AVANCE Ⅲ (500 MHz) spectrometer, and
mass spectra were determined on Waters-GCT Premier, Thermo-DECAX-60000 LCQ
Deca XP, and Thermo-ITQ 1100 mass spectrometers. Benzotriazoles, sodium sulfinates,
sodium bromide, mCPBA, and solvents were commercially available.
General procedure for the sulfonylation of benzotriazoles with the
in situ–generated sulfonyl bromides
In EtOAc/MeOH (4:1) mixed solvent (2 mL), benzotriazole 1a (0.3 mmol), sodium
benzenesulfinate 2a (0.54 mmol), NaBr (0.36 mmol), and mCPBA (0.39 mmol) were added
successively. The suspension mixture was vigorously stirred at room temperature for 4 h.
Upon completion, the reaction was quenched by addition of saturated aqueous Na S O
2
2 3
(
2 mL), saturated aqueous Na CO (8 mL), and H O (5 mL). The mixture was extracted
2 3 2
with CH Cl (3 � 5 mL) and the combined organic phase was dried over anhydrous
2
2

SYNTHETIC COMMUNICATIONS®
1437
Na SO , filtered, and concentrated under reduced pressure. The residue was then purified
2
4
by thin-layer chromatography (TLC; 3:1 (v/v) petroleum ether/ethyl acetate) to furnish
1
-phenylsulfonylbenzotriazole 3a (70 mg, 90%).
[
11]
Pale yellow solid; mp 122–123 °C (lit.
123–125 °C). IR (KBr): 3094.1, 3068.9,
À 1
1
1
586.0, 1479.9, 1385.9, 1194.3, 954.8, 726.2, 589.2 cm . H NMR (500 MHz, CDCl ):
3
δ ¼ 8.15–8.11 (m, 3H), 8.09 (d, J ¼ 8.4 Hz, 1H), 7.70–7.64 (m, 2H), 7.57–7.53 (m, 2H),
1
3
7
1
.52–7.47 (m, 1H). C NMR (125 MHz, CDCl ): δ ¼ 145.4, 137.0, 135.2, 131.6, 130.3,
3
þ
29.6, 127.8, 125.9, 120.5, 111.9. MS (ESI): m/z (%) 260 ([MþH] , 100).
References
[
[
[
[
[
[
[
[
[
1] Katritzky, A. R.; Zhang, G.; Wu, J. Synth. Commun. 1994, 24, 205.
2] Katritzky, A. R.; He, H.-Y.; Suzuki, K. J. Org. Chem. 2000, 65, 8210.
3] Katritzky, A. R.; Shobana, N.; Pernak, J.; Afridi, A. S.; Fan, W.-Q. Tetrahedron 1992, 48, 7817.
4] Katritzky, A. R.; Abdel-Fattah, A. A. A.; Vakulenko, A. V.; Tao, H. J. Org. Chem. 2005, 70, 9191.
5] Yamamoto, S.; Okutsu, E.; Ohzeki, T. US Patent 20050147931, 2005.
6] Kong, S. T.; Sakizadeh, K. US Patent 20050084808, 2005.
7] Takayoshi, O. Jpn. Kokai Tokkyo Koho, JP 2004109239, 2004.
8] Yamamoto, S.; Okutsu, E.; Ohzeki, T. US Patent 20030224307, 2003.
9] Koji, K.; Toshihide, E. Jpn. Kokai Tokkyo Koho, JP 2002278020, 2002.
10] Kong, S. H.; Sakizadeh, K.; Labelle, G. E.; Spahl, E. J.; Skoug, P. G. Eur. Patent 1048975, 2000.
[
[
11] Hergert, L. Y.; Nieto, M. J.; Becerra, M. C.; Albesa, I.; Mazzieri, M. R. Lett. Drug Des. Discov.
2
008, 5, 313.
[
[
12] Soundararajan, R.; Balasubramanian, T. R. Chem. and Ind. (London) 1985, 3, 92.
13] Neikova, N.; Simov, D.; Karparov, A.; Velichkova, E.; Galabov, A. Farmatsiya (Sofia, Bulgaria)
1
981, 31, 48.
[
[
[
[
[
[
14] Purygin, P. P.; Ivanov, I. P.; Laletina, Z. P.; Selezneva, E. S. Khim. Farm. Zh. 1983, 17, 1319.
15] Sasse, K.; Wegler, R.; Grewe, F. Brit. Patent 885843, 1961.
16] Katritzky, A. R.; Rodriguez-Garcia, V.; Nair, S. K. J. Org. Chem. 2004, 69, 1849.
17] Otto, R.; Ostrop, H. Ann. 1867, 141, 365.
18] Otto, R.; von Gruber, O. Ann. 1867, 142, 92.
19] Katrun, P.; Mueangkaew, C.; Pohmakotr, M.; Reutrakul, V.; Jaipetch, T.; Soorukram, D.;
Kuhakarn, C. J. Org. Chem. 2014, 79, 1778.
[
[
20] Truce, W. E.; Wolf, G. C. J. Org. Chem. 1971, 36, 1727.
21] Correa, C. M. M. D. S.; Waters, W. A. J. Chem. Soc. C. 1968, 1874.