p-Toluenesulfonic acid-promoted autocatalytic hydrolyzation of 1-tosyl-1,2,3-triazoles

Article abstract of DOI:10.1080/00397911.2018.1440316

The first example of autocatalytic hydrolyzation of 4-aryl-1-tosyl-1,2,3-triazoles induced by p-toluenesulfonic acid was reported, providing an effective and metal-free synthetic approach to deliver a broad range of new 4-aryl-2H-1,2,3-triazoles in good yields. The kinetic profile of this hydrolyzation suggested that this reaction has exponential autocatalytic behavior.

Full text of DOI:10.1080/00397911.2018.1440316

Synthetic Communications
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p-Toluenesulfonic acid-promoted autocatalytic
hydrolyzation of 1-tosyl-1,2,3-triazoles
Haohao Dong, Dongdong Zhang, Renjie Fang, Qingyang Du, Zhuoya Dong,
Hao Wei, Min Shi & Feijun Wang
To cite this article: Haohao Dong, Dongdong Zhang, Renjie Fang, Qingyang Du,
Zhuoya Dong, Hao Wei, Min Shi & Feijun Wang (2018): p-Toluenesulfonic acid-promoted
autocatalytic hydrolyzation of 1-tosyl-1,2,3-triazoles, Synthetic Communications, DOI:
10.1080/00397911.2018.1440316
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https://doi.org/10.1080/00397911.2018.1440316
p-Toluenesulfonic acid-promoted autocatalytic hydrolyzation
of 1-tosyl-1,2,3-triazoles
Haohao Donga, Dongdong Zhanga, Renjie Fanga, Qingyang Dua, Zhuoya Donga,
Hao Weib, Min Shia,c, and Feijun Wanga
aKey Laboratory for Advanced Materials, School of Chemistry & Molecular Engineering, East China University of
b
Science and Technology, Shanghai, P. R. China; Key Laboratory for Thin Film and Microfabrication Technology
of Ministry of Education, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong
c
University, Shanghai, P. R. China; State Key Laboratory of Organometallic Chemistry, Chinese Academy of
Sciences, Shanghai Institute of Organic Chemistry, Shanghai, P. R. China
ABSTRACT
ARTICLE HISTORY
Received 3 December 2017
The first example of autocatalytic hydrolyzation of 4-aryl-1-tosyl-1,2,
3-triazoles induced by p-toluenesulfonic acid was reported, providing
an effective and metal-free synthetic approach to deliver a broad
range of new 4-aryl-2H-1,2,3-triazoles in good yields. The kinetic
profile of this hydrolyzation suggested that this reaction has
exponential autocatalytic behavior.
KEYWORDS
1,2,3-Triazoles; autocatalytic
hydrolyzation; brønsted acid
GRAPHICAL ABSTRACT
Introduction
Autocatalysis is widely presented in nature and is central to containment-based, metabolic,
and genetic theories on the origins of life.[1] Consequently, the development of autocataly-
tic processes is a prominent objective in chemical research.[2] Many reported autocatalytic
processes are primarily based on template-directed self-replication[3] under the presence of
template triggers such as oligonucleotides,[4] peptides,[5] amino acids,[6] and unnatural
molecules such as those used in Collum ortholithiation[7] or Soai reaction.[8] To satisfy
CONTACT Feijun Wang
Molecular Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237,
P. R. China; Hao Wei haowei@sjtu.edu.cn Key Laboratory for Thin Film and Microfabrication Technology of Ministry of
feijunwang@ecust.edu.cn;
Key Laboratory for Advanced Materials, School of Chemistry &
Education, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road,
Shanghai 200240, P. R. China.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/lsyc.
Supplemental data for this article can be accessed on the publisher’s website.
© 2018 Taylor & Francis

2
H. DONG ET AL.
Scheme 1. Autocatalytic hydrolysis.
the rapidly increasing demand for knowledge of the propagation of life, the intrinsic
properties of many other biological processes[1] and the fascinating prospects for catalytic
science[9] and materials science,[10] the challenges of the development of novel strategy to
design new autocatalytic processes have become an important topic.
Acid-catalyzed ester hydrolysis is a classic example in autocatalysis.[1] However, the
obtained acid with high pKa, for example, 12.6 for acetic acid,[11] cannot be used as an
effective acid catalyst and might limit the synthetic utility of this autocatalytic strategy
(Scheme 1). Brønsted acid can activate a series of functional groups such as carbonyl,
imino, alkenyl, alkynyl, and hydroxyl to receive the attack of nucleophilic reagents.[12]
Therefore, instead of an acyl group in ester, we envisioned that the functional groups such
as tosyl (Ts), which are the potential functional groups for the generation of Brønsted acid
were used to develop their autocatalytic hydrolysis. 1-Tosyl-1H-1,2,3-triazole 1 bearing a
tosyl group and having the N2-nucleophilicity[13] of 1,2,3-triazole ring, which is easily
prepared from the copper(I)-catalyzed “Click” reaction,[14] has recently received much
attention because of its useful transformations through α-imino metal carbenes[15] and
might be an ideal molecule to replace an ester.
Initiated by the remarkable discovery of click chemistry, the 1,2,3-triazoles have
attracted great interest for its widespread applications,[14] especially in medicinal
chemistry,[16] material chemistry,[17] and synthetic organic chemistry.[18] Within the
1,2,3-triazole categories, the 2H-1,2,3-triazoles are an important class which can be used
as valuable intermediates for a series of important transformations[19] and ligands for
metal coordination chemistry.[20] However, their potential applications are still far less
exploited than they could be due to the lack of a general approach to their synthesis.
In the past decades, many approaches for the synthesis of 4-aryl-NH-1,2,3-triazoles have
been developed. In general, methods for the synthesis of 4-aryl-NH-1,2,3-triazoles are
usually confined to the cycloaddition of activated alkynes and alkenes[21] or the
deprotection of an N1-substituted group.[22] However, these strategies suffer from
the use of volatile and toxic hydrazoic acid or metal catalyst under harsh reaction
conditions.

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3
Results and discussion
To address these challenges, an autocatalytic strategy was introduced to achieve high yields
of 2H-1,2,3-triazoles, utilizing the p-toluenesulfonic acid-promoted hydrolyzation of
4-aryl-1-tosyl-1,2,3-triazoles. This represents an effective and matel-free synthetic method
to deliver 2H-1,2,3-triazoles in good yields.
Initially, hydrolysis of 4-phenyl-1-tosyl-1,2,3-triazole 1a as the model substrate was
performed in water. The result is summarized in Table 1. To our delight, under the
presence of 1 mol% TsOH catalyst, 1a was completely hydrolyzed at 80 °C after 4 h,
affording 4-phenyl-2H-1,2,3-triazole 2a in >99% yield (Table 1, entry 2). Reducing the tem-
perature to 60 °C, remarkably, a low yield of 2a was obtained (entry 4), and tosyl migration
product 3a[23] was surprisingly isolated. With the extension of reaction time to 45 h, the
quantitative yield of 2a could be obtained. Further reducing the temperature to 40 °C, even
reacting for 7 d, only 31% yield of 2a was obtained (entry 6). From the optimization of
hydrolyzation conditions, it was generally found that higher reaction temperature and
the addition of TsOH can significantly promote the hydrolysis of 1a. Lower yields of 1a
were obtained without the addition of TsOH catalyst (entries 1, 3, and 5) than those in
the presence of 1 mol% TsOH.
With the optimized reaction conditions on hand, the substrate scope was further
explored. Various substituted 1-tosyl-1,2,3-triazoles 1 were tested (Table 2), affording
the desired 2H-1,2,3-triazole 2 in good yields. The electronic property of substituents on
the phenyl ring of 1 had little influence on this reaction. In addition, the hydrolysis of
1-(4-methylphenylsulfonyl) benzotriazole 1j proceeded smoothly, and benzotriazole 2j
was obtained in up to 97% yield (entry 9).
To verify this reaction having an autocatalytic behavior, a kinetic study of hydrolysis of
1a was performed in water with the addition of 1 mol% TsOH at 80 °C. From the compari-
1
son of H NMR spectra of 1a and 2a, it was found that 1a has a signal for Ha at 8.3 ppm,
while 2a has a signal for Hb at 8.0 ppm. Therefore, the hydrolyzed reaction mixture can be
1
1
directly analyzed by H NMR. These crude H NMR spectra, as shown in Figure 1, were
obtained for every 0.5 h. The consumption of Ha-signal and the enhancement of Hb-signal
can be observed along with the extension of reaction time. It is noteworthy that the
Table 1. Optimization of hydrolysis of 4-phenyl-1-tosyl-1,2,3-triazole 1aa.
Entry
Temperature (°C)
x
t
2aYieldb (%)
3aYield (%)
1
2
3
4
5
6
80
80
60
60
40
40
–
1%
–
1%
–
1%
4 h
90
–
4 h
>99
–
24 h
24 h
7 d
48 (>99)c
63 (>99)c
25
14
12
Trace
Trace
7 d
31
aThe reaction of 1a (1.0 mmol) and TsOH (x mol%) in water (10 mL) was stirred at different reaction temperatures for
different hours.
bIsolated yields are reported.
cReacted for 45 h.

4
H. DONG ET AL.
Table 2. Scope of hydrolysis of 1-tosyl-1,2,3-triazoles 1a.
Entry
1,2,3-Triazole
R
Yieldb (%)
1
2
2b
2-F-C6H4
3-F-C6H4
82
80
81
75
78
70
85
88
97
80
2c
3
2d
4-F-C6H4
4
2e
4-Cl-C6H4
4-Br-C6H4
4-CN-C6H4
4-CH3-C6H4
4-OCH3-C6H4
5
2f
6
2g
7
2h
8
2i
Benzotriazole 2j
2k
9
10
n-Pr
a1,2,3-Triazole 1 (1.0 mmol) and TsOH (1 mol%) in water (10 mL) were stirred at 80 °C for 4 h.
bIsolated yields are reported.
Hb-signal was too low to be found from 0 to 1 h, and only one set of peaks for 2a was found
1
at 4 h. The H NMR spectrum suggests that the hydrolysis of 1a was completely finished.
1
According to these crude H NMR spectra, the yield of 2a can be preliminarily obtained.
The kinetic profile as shown in Figure 2 suggests that the hydrolysis of 1a has an
exponential autocatalytic behavior.
With the p-toluenesulfonic acid-promoted autocatalytic hydrolyzation of 4-aryl-1-tosyl-
1,2,3-triazoles on hand, we also envisioned that 1-tosyl-1H-1,2,3-triazole 1a could be
reacted with alcohols to give the autocatalytic amination through the TsOH-promoted
formation of carbocations from alcohols and subsequently nucleophilic attack of the
Figure 1. The crude 1H NMR spectroscopy of hydrolysis of 1a.

SYNTHETIC COMMUNICATIONS®
5
Figure 2. Evidence of autocatalysis in the hydrolysis of 1a.
1,2,3-triazole ring. 1-Tosyl-1H-1,2,3-triazole 1a was used to react with 1,3-diphenyl-2-
propen-1-ol 4, and the desired N2-allylated 2H-1,2,3-triazole 5 was easily obtained in
80%. Furthermore, the kinetic profile in the reaction of 1-tosyl-1H-1,2,3-triazole 1a with
alcohol 4 in the presence of 0.1 mol% TsOH was investigated. It is worth noting that this
curve (Fig. 3) represents an exponential autocatalytic behavior according to the ratio of 5
1
and 4, which was monitored by H NMR spectroscopy.
Figure 3. The kinetic study of the reaction of 1a with alcohol 4.

6
H. DONG ET AL.
Experimental section
Procedure for the preparation of 4-aryl-2H-1,2,3-triazole
4-Aryl-1-tosyl-1,2,3-triazole (1.0 mmol) was loaded in a 25-mL reaction tube charged with
10 mL of deionized water. Then, p-toluenesulfonic acid (1.0 mol%) was added into the
reaction tube. The resulting mixture was heated at 80 °C for 4 h. The reaction mixture
was cooled to room temperature, exacted with dichloromethane, dried over anhydrous
Na2SO4, concentrated in vacuo, and purified through flash chromatography.
Procedure for the preparation of 5
4-Phenyl-1-tosyl-1,2,3-triazole (0.2 mmol) and 1,3-dipheny-2-propen-1-ol 4 were loaded in
a 10-mL reaction tube charged with 1.0 mL DCE. Then, p-toluenesulfonic acid (0.1 mol%)
was added into the reaction tube. The resulting mixture was heated at 80 °C for 48 h. The
reaction mixture was cooled to room temperature, then concentrated in vacuo and purified
through flash chromatography.
Conclusion
In conclusion, p-toluenesulfonic acid (TsOH)-promoted autocatalytic hydrolysis of 1-tosyl-
1H-1,2,3-triazoles with high efficiency was developed and reported, presenting a metal-free
and practical way to the synthesis of 2H-1,2,3-triazoles. Currently, only limited reports
relating to organocatalyst-based autocatalytic reactions were observed.[24] Further appli-
cation of TsOH-promoted autocatalytic transformation of 1-tosyl-1,2,3-triazoles based
on the catalytic activities of TsOH was also reported.
Funding
We are grateful for the financial support from the National Natural Science Foundation of China
(21372075, 81670958, and 81371178), the Shanghai Pujiang Program (16PJD017 and 16PJD027),
and the Medical-Engineering Crossover Fund of Shanghai Jiao Tong University (YG2015MS23
and YG2016MS71).
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