Copper-catalyzed synthesis of aryldiazo sulfones from arylhydrazines and sulfonyl chlorides under mild conditions

Article abstract of DOI:10.1039/c5nj01760b

In this paper, aryldiazo sulfones are prepared from tandem sulfonylation/dehydrogenation reactions of arylhydrazines and sulfonyl chlorides. The transformations proceed well in the presence of catalytic CuSO₄·5H₂O, leading to aryldiazo sulfones in good to excellent yields. It is believed that this protocol represents a safe and convenient model for the synthesis of these versatile aryldiazo sulfones under mild conditions.

Full text of DOI:10.1039/c5nj01760b

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Copper-Catalyzed Synthesis of Aryldiazo Sulfones from
Arylhydrazines and Sulfonyl Chlorides under Mild Conditions
Jin-Biao Liu,*ac Fu-Jiao Chen,a En Liu,a Jin-Hui Lia and Guanyinsheng Qiu*b
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
sulfones remain rare. Traditionally, aryldiazo sulfones are often
In this paper, the aryldiazo sulfones are prepared from tandem
sulfonylation/dehydrogenation reactions of arylhydrazines and
sulfonyl chlorides. The transformations proceed well in the
presence of catalytic CuSO4·5H2O, leading to the aryldiazo sulfones
in good to excellent yields. It is believed that this protocol
represents a safe and convenient model for the synthesis of these
versatile aryldiazo sulfones under mild conditions.
derived from the reaction of aryldiazonium salts with sulfinic acid
salts (Scheme 1a).5 On the other hand, according to our previous
results on hydrazine chemistry, we know that palladium catalysis
enabled aryl hydrazines as excellent aryl source, resulting in diaryl
compounds12b (Scheme 1b). In these transformations, aryldiazo
sulfones were proposed as the key intermediates. And sulfonyl
chloride was a crucial additive, guaranteeing the formation of
aryldiazo sulfones. In view of high importance of aryldiazo sulfones
and insights into the mechanism of our previous reactions, we
envisioned that the reactions of arylhydrazines and sulfonyl
chloride could produce aryldiazo sulfones efficiently under copper
catalysis (instead of palladium catalysis), and the generated
aryldiazo sulfones was able to survive in the presence of copper
(Scheme 1c).
As important building blocks, aryldiazo salts have received
extensively attention in the community of organic chemists during
the past century.1 Presently, it still remains high interests in these
aryldiazonium salts-based transformations (especially, transitional
metal-catalyzed cross-coupling reactions). However, aryldiazonium
salts are often dangerously explosive and prone to decomposition
upon storage. Therefore, it has been one of hot topics in organic
chemistry to synthesize diazonium salts with good stability and
storage safety and further apply them into the synthesis of useful
architectures. To date, aryldiazonium tetrafluoro-borates,2
(1a): traditional synthesis of aryldiazo sulfones
Ar N2BF4
+
RSO2Na
Ar-N2-SO2R
aryldiazonium
hexafluorophosphates,3
and
aryldiazonium
arylsufonates4 have been described as excellent candidates in
aryldiazonium salts-based transformations in the bench level or
even in industrial stage.
(1b): our previous work
[Pd]
Ar NHNH2
Ar-Ar
+
RSO2Cl
To the best of our knowledge, aryldiazo sulfone is a kind of
potential diazonium salts. According to the findings on their
thermal6 and photochemical7 behavior, aryldiazo sulfones show
relatively high stability and storage safety, even with acids8 and
bases.9 What’s more, aryldiazo sulfones have been demonstrated as
electrophilic partners in cycloadditions to construct N-containing
cyclic compounds,10 and in some transition-metal-catalyzed cross-
coupling reactions.11 Although with broad applications, studies on
new methodology development for the synthesis of aryldiazo
(1c): this work
[Cu]
Ar NHNH2
Ar-N2-SO2R
+
RSO2Cl
Scheme 1 Reaction Design.
Initially, the model reaction of phenylhydrazine 1a and p-
toluenesulfonyl chloride (TsCl) 2a was carried out in the presence of
20 mol% Cu(OAc)2·H2O as catalyst, 3.0 equiv Et3N as base, and
CH2Cl2 as solvent. Under aerobic conditions, the reaction was
stirred at room temperature for 4 h, giving rise to the desired
product 3a in 50% yield (Table 1, entry 1). This reaction represented
a formal tandem sulfonylation/dehydrogenation. Encouraged by
this result, other Cu sourses were evaluated [CuCl2·2H2O, CuCl,
CuSO4·5H2O and Cu(OTf)2] (entries 2-5). It is pleased to find that
CuSO4·5H2O was the best choice, affording 70% yield of the product
a.School of Metallurgy and Chemical Engineering, Jiangxi University of Science and
technology, 86 Hongqi Road, Ganzhou 341000, China. E-mail:
liujbgood@hotmail.com;
b.College of Biological, Chemical Science and Engineering, Jiaxing University, 118
Jiahang Road, Jiaxing 314001, China. E-mail: 11110220028@fudan.edu.cn;
c. Key Laboratory of Functional Small Organic Molecule, Ministry of Education,
Jiangxi Normal University, Nanchang 330022, China.
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3a (entry 4). Other transition-metal catalysts were also examined in with 2a proceeded smoothly, giving arylazosulfones (3) with high
the reaction: the reactions using FeSO4·5H2O and ZnSO4 only efficiency. However, the efficiency of the reaction was relatively
afforded less than 10% desired products (entries
6 and 7); sensitive to the substituents on the aromatic rings in different
Ni(NO3)2·6H2O completely shut down this reaction (entry 8). The arylhydrazines (entries 1-13). Arylhydrazine with an electron-
effect of bases in this reaction was then investigated (entries 9-13), withdrawing group on the aromatic ring gave a better yield than
and the use of K2CO3 as the base improved the yield to 88% (entry that bearing an electron-donating group on the aromatic ring. For
11 versus entries 4, 9-10, and 12-13). Solvents evaluation revealed example, the substrates with an electron-donating group, such as
that no better yields were provided when using MeOH, DMSO, THF CH3 or CH3O on the phenyl ring reacted with 2a to afford the
and toluene as solvents (entries 14-17). Reducing copper catalyst corresponding products in 70-79% yields (entries 2-5). But when
loading to 10 mol% resulted in a comparable yield (entry 18 versus arylhydrazines with an electron-withdrawing group (Cl, Br, F or
entry 11). However, further reduction of copper catalyst loading to CF3O) on the phenyl ring reacted with 2a, more than 85% yields of
5 mol % made a significant effect on the yield of the product, the desired products were obtained (entries 6-12). Interestingly, the
forming aryldiazo sulfone 3a in 66% yield (entry 19). It seems that steric hindrance effect of the ortho-substituents of the substrate 1
the oxygen might play an important role as an oxidant in the was negligible for this reaction. For instance, the compounds 1h
dehydrogenation process, because a significant drop in yield was and1i could react smoothly in 90% and 94% yields, respectively
observed under N2 atmosphere (entry 20). Control experiment (entries 8 and 9). Then several other sulfonyl chlorides with
under oxygen gave a comparable outcome with that of under air different substitutions were next explored (entries 14-18). For the
(entry 21).
phenylsulfonyl chloride 2b, the reactions were all successfully
proceeded with 1a, 1b or 1f to afford the products in high yields
(entries 14-16). What’s more, methanesulfonyl chloride (MsCl) 2d
could also produce the azosulfone 3r in 70% yield under the
standard conditions (entry 18). However, the 2c with NO2
substituent delievered the desired compound 3q with low yield, in
34% (entry 17). Other hydrazines such as alkyl hydrazines and tosyl
hydrazine were not compatible for the reactions, probably due to
too high reactivities (data not shown in Table 2).
Table 1 Optimization of reaction conditions.a
conditions
Ph
N
N
Ts
+
TsCl
Ph NHNH2
rt., 1-4h
1a
2a
3a
entry
catalyst/base
solvent
yieldb [%]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18c
19d
20e
21f
Cu(OAc)2·H2O/Et3N
CuCl2·2H2O/Et3N
CuCl/Et3N
CuSO4·5H2O/Et3N
Cu(OTf)2/Et3N
FeSO4·5H2O/Et3N
ZnSO4/Et3N
Ni(NO3)2·6H2O/Et3N
CuSO4·5H2O/DBU
CuSO4·5H2O/DABCO
CuSO4·5H2O/K2CO3
CuSO4·5H2O/ Na2CO3
CuSO4·5H2O/KOH
CuSO4·5H2O/K2CO3
CuSO4·5H2O/K2CO3
CuSO4·5H2O/K2CO3
CuSO4·5H2O/K2CO3
CuSO4·5H2O/K2CO3
CuSO4·5H2O/K2CO3
CuSO4·5H2O/K2CO3
CuSO4·5H2O/K2CO3
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
MeOH
DMSO
THF
50
46
24
70
60
<10
<10
trace
30
65
88
76
24
trace
38
28
46
87
66
40
Table 2 Copper-catalyzed synthesis of aryldiazo sulfones.a
entry
1
R
H (1a)
R’
3
3a
3b
3c
3d
3e
3f
yieldb [%]
87
2
4-Me (1b)
3-Me (1c)
3,5-diMe (1d)
4-OMe (1e)
4-Cl (1f)
3-Cl (1g)
2-Cl (1h)
2,4,6-triCl (1i)
4-Br (1j)
4-F (1k)
4-OCF3 (1l)
4-Ms (1m)
1a
78
3
80
4
75
5
79
6
90
toluene
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
4-MePh
(2a)
7
3g
3h
3i
88
8
91
9
92
86
aReaction conditions: 1a (0.5mmol), 2a (0.5mmol), catalyst (20
mol%), base (3.0 equiv), solvent (3 mL), 1-4 h. bIsolated yields of
3a. cCuSO4·5H2O (10 mol%). dCuSO4·5H2O (5 mol%). eUnder N2.
fUnder O2.
10
11
12
13
14
15
16
17
18
3j
88
3k
3l
90
85
3m
3n
3o
3p
3q
3r
82
80
With the optimized conditions in hand (10 mol% CuSO4·5H2O
ascatalyst, CH2Cl2 as solvent, at room temperature for 1-4 h), the
substrate scope for the reactions of arylhydrazines (1) with sulfonyl
1b
Ph (2b)
84
1f
85
1a
4-NO2Ph (2c)
Me (2d)
30
chlorides (2) was studied (Table 2). For
a wide range of
arylhydrazines with either electron-rich or electron-poor aryl
1a
70
aReaction conditions: 1 (0.5 mmol), 2 (0.5 mmol), CuSO4·5H2O (10
groups, the corresponding tandem sulfonylation/dehydrogenation
2 | J. Name., 2012, 00, 1-3
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mol%), K2CO3 (3.0 equiv), CH2Cl2 (3 mL), 1-4 h. bIsolated yields of 3.
In summary,
preparation of
a
simple and effective procedure for the
aryldiazo
sulfones
by
Cu-catalyzed
sulfonylation/dehydrogenation of arylhydrazines and sulfonyl
chlorides is presented. As a readily available and effective coupling
partner, aryldiazo sulfone exhibits excellent generality in the
aforementioned Pd/Cu-catalyzed coupling reactions. Future studies
will be focused on extending the synthetic applications.
To illustrate the synthetic utility of these versatile intermediates
in organic chemistry, aryldiazo sulfone 3a was applied to various
Pd/Cu-catalyzed reactions (Scheme 2). Interestingly, arydiazo
sulfone 3a could react with dicarbonyl compound, producing
another aryldiazo 4a (Scheme 2a). By changing to catalyst Cu(OAc)2
and base triethylamine, arydiazosulfone 3a converted into N,N-
diphenylhydrazine 4b in 83% yield (Scheme 2b). In particular,
aryldiazo sulfone 3a could react with terminal alkyne in the
presence of 5 mol% Pd(OAc)2, giving the desired 1,2-diphenylethyne
4c in 60% yield (Scheme 2c).
Fig. 1 Proposed mechanism.
Experimental
A mixture of arylhydrazine 1 (0.5 mmol), sulfonyl chloride 2 (0.5
mmol), CuSO4·5H2O (10 mol %), and K2CO3 (3.0 equiv), was stirred
at room temperature in CH2Cl2 (3 mL) for 1-4 h. After completion of
the reaction (indicated by TLC), the mixture was quenched with
saturated NaCl solution, extracted with EtOAc, and dried over
Na2SO4. The crude product was purified by flash column
chromatography to provide the corresponding product 3.
Scheme 2 Synthetic utility of aryldiazo sulfone.
Meanwhile, to understand the mechanism, two control
experiments were carried out (Scheme 3). Firstly, we conceived that
phenylhydrazine derivatives 1a’ would be the key intermediate for
this sulfonylation/dehydrogenation process. As described in
Scheme 3a, N’-tosyl phenylhydrazine 1a’ could be
oxydehydrogenated by Cu(II) affording 3a in 89% yield. Secondly,
when TEMPO was added to the reaction under the standard
conditions, a comparable yield of 3a was observed as well. This
Acknowledgements
This work was supported by the Science and Technology Project of
Jiangxi Provincial Education Department (No. GJJ14450), and the
Open Project Program of Key Laboratory of Functional Small
Organic Molecule, Ministry of Education, Jiangxi Normal University
(No. KLFS-KF-201406). We also thank Dr. Wangqing Kong (EPFL,
Switzerland) for English polishment of this article.
result
probably
indicated
that
the
copper-promoted
oxydehydrogenation did not involve a radical route.
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Graphical Abstract
A
simple and effective procedure for the preparation of aryldiazo sulfones by Cu-catalyzed
sulfonylation/dehydrogenation is presented.
O
Ar N N S R
O
[Cu]
+
RSO2Cl
Ar NHNH2
rt./air