Iron(III) phthalocyanine-chloride-catalyzed synthesis of sulfones from sulfonylhydrazones

Article abstract of DOI:10.1016/j.tetlet.2016.04.044

In this study, sulfones are synthesized from sulfonylhydrazones catalyzed by iron(III) phthalocyanine chloride. This reaction offers broad substrate scope, occurs under mild conditions, utilized readily available reactants, and forms products in good-to-h

Full text of DOI:10.1016/j.tetlet.2016.04.044

Accepted Manuscript
Iron(III) Phthalocyanine-Chloride-Catalyzed Synthesis of Sulfones from Sul-
fonylhydrazones
Jun-Long Zhao, Shi-Huan Guo, Jun Qiu, Xiao-Feng Gou, Cheng-Wen Hua,
Bang Chen
PII:
S0040-4039(16)30394-X
DOI:
http://dx.doi.org/10.1016/j.tetlet.2016.04.044
TETL 47544
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
26 February 2016
8 April 2016
13 April 2016
Please cite this article as: Zhao, J-L., Guo, S-H., Qiu, J., Gou, X-F., Hua, C-W., Chen, B., Iron(III) Phthalocyanine-
Chloride-Catalyzed Synthesis of Sulfones from Sulfonylhydrazones, Tetrahedron Letters (2016), doi: http://
dx.doi.org/10.1016/j.tetlet.2016.04.044
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1
Tetrahedron Letters
journal h omepage: www.els evier. com
Iron(III) Phthalocyanine-Chloride-Catalyzed Synthesis of Sulfones from
Sulfonylhydrazones
Jun-Long Zhao, Shi-Huan Guo, Jun Qiu, Xiao-Feng Gou, Cheng-Wen Hua, Bang Chen
Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry & Materials Science, Northwest
University, Xi’an 710069, P. R. China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
In this study, sulfones are synthesized from sulfonylhydrazones catalyzed by iron(III)
phthalocyanine chloride. This reaction offers broad substrate scope, occurs under mild
conditions, utilized readily available reactants, and forms products in good-to-high yields.
Crossover experiments reveal that the reaction occurs via an intramolecular process, which is
possibly different from other studies reported previously. The method provides a novel, simple,
and promising strategy for synthesizing functionalized sulfones in the research field of sulfur
chemistry.
Available online
Keywords:
Iron(III) phthalocyanine chloride
Sulfones
2016 Elsevier Ltd. All rights reserved.
Sulfonylhydrazones
Sulfones are ubiquitous bioactive molecules,1 which are
commonly found in several pharmaceutical2 and agrochemical
compounds.3 They are also widely applied as important
intermediates in organic synthesis4 and polymeric compounds.5
Despite their widespread use in these areas, methods commonly
employed for their preparation typically involve either the
oxidation of sulfides6 or the alkylation/arylation of sulfinate salts
(Scheme 1).7 Besides, in recent years, some other methods have
also been developed, such as the use organometallic reagents8 as
well as SO2 and its surrogates.9 However, these methods
generally have limitations in that oxidation methods are often
incompatible with sensitive functional groups found in complex
organic substrates and that the commercial availability of
sulfonate salts is limited. Hence, it is imperative to develop a
simple, convenient, and generally applicable protocol for
synthesizing sulfones.
Sulfonylhydrazones are versatile synthetic intermediates,
which have been used as a source for the in situ synthesis of
diazo compounds in different transition-metal-catalyzed
reactions,10 such as XH (X = C, N, O) insertion reactions,11
cyclopropanation,12 epoxidation,13 and aziridination.14 Recently,
Barluenga and co-workers have reported the metal-free coupling
of tosylhydrazones with boronic acids15 or hydroxyl
compounds,16 which has significantly improved the application
of sulfonylhydrazones. To our delight, when tosylhydrazones
were heated in the presence of iron(III) phthalocyanine chloride
and base, the corresponding sulfones were obtained in high
yields. Although Che and co-workers have previously reported
the same reaction by using a Ru-based catalyst,17 their
observations were not satisfactory, and very poor product yields
were observed with a limited substrate scope. However, recently,
a similar transformation promoted by Cu salts18 and Fe salts19
has been reported. However, these transformations are not
satisfactory; furthermore, either lower yields are obtained, or the
reaction requires a strong base. Herein, we report a practical
iron(III) phthalocyanine-chloride-catalyzed synthesis of sulfones
from sulfonylhydrazones (Scheme 1). Furthermore, we describe
a novel mechanism for their synthesis.
First, the decomposition of tosylhydrazone 1a, which was
derived from acetophenone and tosylhydrazide, was chosen as a
model system for optimizing the reaction conditions, and various
catalysts, bases, solvents, and temperatures were then screened
(Table 1). Initially, we chose iron(III) phthalocyanine chloride as
the catalyst, K2CO3 as the base in 1,4-dioxane at 100 °C for 2 h,
and the desired product 2a was obtained in 43% yield (Table 1,
entry 1). Next, the temperature of the reaction was changed, and
———Scheme 1. Methods for the Preparation of Sulfones
 Corresponding author. Tel.: +86-29-88302687; e-mail: zhaojunlong327@163.com

2
Tetrahedron Letters
the chemical yield dramatically increased to 93% when the
was confirmed to be general and efficient for preparing sulfones.
From the results obtained, the presence of electron-withdrawing
or -donating groups on the aromatic rings does not affect the
reaction, and they are conveniently transformed to their
corresponding sulfones in excellent yields.
reaction temperature was lowered to 80 °C (Table 1, entry 2).
However, with further decrease in the temperature, the yields
also decreased (Table 1, entries 3 and 4). Only a trace amount of
target product 2a was observed in the absence of either iron(III)
phthalocyanine chloride (entry 5) or base (entry 6). Thus, both
iron salt and base are crucial for this transformation. A range of
bases such as Na2CO3, K3PO4, and Et3N were then screened, and
K2CO3 was found to be the most suitable base (Table 1, entries
7–9). The use of some alternative solvents (CH3CN, EtOH, THF,
and DMF, entries 10–13, respectively) and iron salts (FeCl3,
Fe2O3, and Fe(NO3)3, entries 14–16, respectively) also led to
decreased yields or even no reaction. Finally, even with an
increased amount of catalyst, the yield did not improve (Table 1,
entry 17).
Table 2
Decomposition of Tosylhydrazones Derived from Various
Carbonyl Compoundsa
entry R1
R2
Me
Me
Me
Me
Me
i-Pr
H
T (h)
2
yield b (%)
2a, 93
2b, 85
2c, 86
2d, 87
2e, 82
2f, 83
Table 1
1
2
1a, C6H5
Optimization of the Reaction Conditionsa
1b, 3-MeOC6H4
1c, 4-ClC6H4
1d, 4-MeOC6H4
1e, 2-Nap
3
3
3
4
6
5
3
6
1f, C6H5
3
yield b (%)
43
7
1g, C6H5
1
2g, 89
2h, 89
2i, 96
entry
1c
catalyst
FePcCl
FePcCl
FePcCl
FePcCl
----
base
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
----
solvent
8
1h, 4-NO2C6H4
1i, 4-ClC6H4
H
2
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
9
H
3
2
3d
4e
93
10
11
12
13
14
15
16
17
18
19
1j, 4-MeC6H4
1k, 4-MeOC6H4
1l, 4-(CH3)2NC6H4
1m, 4-OHC6H4
1n, 4-FC6H4
H
2
2j, 83
0
H
2
2k, 95
2l, 82
26
H
3
5
trace
trace
22
H
3
2m, 85
2n, 87
2o, 89
2p, 95
2q, 89
2r, 94
2s, 87
6
FePcCl
FePcCl
FePcCl
FePcCl
FePcCl
FePcCl
FePcCl
FePcCl
FeCl3
H
2
7
Na2CO3 1,4-dioxane
1o, 2-FC6H4
H
2
1p, 2-MeOC6H4
1q, 3-NO2C6H4
1r, 2,4-diClC6H4
H
2
8
K3PO4
Et3N
1,4-dioxane
1,4-dioxane
CH3CN
46
H
3
9
trace
15
H
3
10
11
12f
13g
14
15
16
17h
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
1s, 2-MeO-4-
OHC6H4
H
6
EtOH
trace
13
THF
20
21
22
1t, 2-Thienyl
H
H
H
3
3
3
2t, 87
2u, 93
2v, 91
1u, 2-Furanyl
DMF
28
1v, 5-Me-2-Furanyl
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
trace
0
a Reaction conditions: The reaction was conducted using 1 (0.5
mmol), FePcCl (1 mol%), and K2CO3 (2 equiv) in dioxane (4
mL) at 80 °C.
Fe2O3
Fe(NO3)3 K2CO3
FePcCl K2CO3
0
b Isolated yield.
89
Further, we substituted tosylhydrazide with benzenesulfonyl
hydrazide, which could afford the corresponding sulfones in high
yields (Scheme 2).
a Reaction conditions: 1a (0.5 mmol), catalyst (1 mol%),
base (2 equiv), and solvent (4 mL) at 80 °C for 2 h.
b Isolated yield.
c 100 °C.
d Room temperature.
e 60 °C.
f 70 °C.
g 110 °C.
h Catalyst (2 mol%)
a Reaction conditions: The reaction was conducted using 1 (0.5
mmol), FePcCl (1 mol%), and K2CO3 (2 equiv) in dioxane (4
mL) at 80 °C for 3 h.
With the optimized reaction conditions, the scope of the
reaction was investigated (Table 2). Various carbonyl
compounds were investigated for this reaction. Tosylhydrazone
substrates were prepared by the reaction between carbonyl
compounds, such as aldehydes and ketones containing aromatic
or heteroaromatic substituents, and tosylhydrazide. This method
b Isolated yield.
Scheme 2. Decomposition of Benzenesulfonylhydrazones
Derived from Various Carbonyl Compoundsa

3
Sulfonylhydrazones can be readily prepared by mixing
sulfonyl hydrazides with the corresponding aldehydes or ketones.
Hence, we investigated whether the reaction could be directly
conducted in one pot from carbonyl compounds without the
isolation of intermediate sulfonylhydrazones. To our delight,
positive results were observed. After heating carbonyl compound
3 and sulfonyl hydrazide 4 for 2 h at 60 °C, followed by the
addition of base and catalyst FePcCl, the mixture was heated at
80 °C for another 3 h. Product sulfones 2 were obtained with
similar yields, but without the need to isolate the intermediate
sulfonylhydrazones. Table 3 shows selected examples.
a Reaction conditions: 1c (0.5 mmol), 1x (0.5 mmol), FePcCl (2
Table 3
mol%), K2CO3 (4 equiv), and dioxane (8 mL) at 80 °C for 3 h.
One-Pot Synthesis of Sulfones from Carbonyl Compounds with
Sulfonyl Hydrazidesa
b Reaction conditions: 1c (0.5 mmol), 1x (0.5 mmol), FePcCl (2
mol%), K2CO3 (4 equiv), and dioxane (40 mL) at 80 °C for 3 h.
Scheme 3. Study of the Pathway of the Iron(III) Phthalocyanine-
Chloride-Catalyzed Synthesis of Sulfones by a Crossover
Experiment.
Scheme 4 shows the supposed reaction mechanism. First,
hydrazone salt II was formed in the presence of base from
hydrazone I. Subsequently, in the presence of Fe(III)PcCl, II
combined with Fe(III)PcCl and formed compound III.
Compound IV was formed by the intramolecular migration of
compound III. Compound V was then formed by the loss of the
catalyst and release of nitrogen from compound IV. The final
product was formed by proton exchange.
entry
R1
1a, C6H5
R2
Me
R3
4-Tol
4-Tol
4-Tol
4-Tol
4-Tol
Ph
yield b (%)
2a, 91
1
2
3
4
5
6
1c, 4-ClC6H4
Me
H
2c, 82
1h, 4-NO2C6H4
1k, 4-MeOC6H4
1u, 2-Furanyl
1w, 4-ClC6H4
2h, 84
2k, 90
2u, 92
2v, 83
H
H
Me
a Reaction conditions: 1) 3 (0.5 mmol), 4 (1.05 equiv), and 1,4-
dioxane (4 mL), 60 °C, 2 h; 2) FePcCl (1 mol%) and K2CO3
(2 equiv) at 80 °C for 3 h.
b Isolated yield.
N-tosylhydrazones are well known to undergo thermal
decomposition via the Bamford–Stevens reaction in the presence
of base, generating diazo compounds; this reaction occurs via a
carbine intermediate to finally form elimination and dimerization
compounds.20 To obtain additional proof for this mechanistic
proposal and to eliminate the possibility of intramolecular
nitrogen extrusion, we conducted a crossover experiment by
using two sulfonylhydrazones. Thus, tosylhydrazone 1c, derived
from 1-(4-chlorophenyl)ethan-1-one, and benzene sulfonyl
hydrazone 1x, derived from 4-nitrobenzaldehyde, were used in
the established procedure (Scheme 3). The reaction afforded four
combinations of carbonyl and sulfonyl fragments. These four
products were not formed in equimolar amounts, and the
corresponding sulfone produced by a hydrazone accounted for
the majority of the product (Scheme 3, conditions a). Hence, we
speculate that this is an intramolecular process in the presence of
iron(III) phthalocyanine chloride, rather than an intermolecular
process as has been previously proposed.18,19 For confirming this
hypothesis, we decided to increase the amount of solvent for
decreasing the contact between the two hydrazones (Scheme 3,
conditions b). We were pleasantly surprised to observe a slight
increase in the yield of sulfone with the corresponding
hydrazone. This result confirms our hypothesis, and the process
occurs via an intramolecular pathway and not via intermolecular
extrusion.
Scheme 4. Proposed mechanism
In conclusion, we developed a simple, efficient method for
synthesizing sulfones. The reaction used sulfonylhydrazones,
which were easily prepared from carbonyl compounds, to
provide corresponding target products in good-to-excellent
yields. In addition, we proposed a new reaction mechanism for
this transformation. Further applications of this methodology are
currently underway.
Acknowledgments
This study was supported by the Industrial Research Project
of Shaanxi Science and Technology Department (2014K08-29),
Science and Technology Plan Project of Xi’an (CXY1511(7)),
and the Scientific Research Foundation of Northwest University.
Supplementary data
Supplementary data associated with this article can be found,
in the online version, at doi:.
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Graphical Abstract
.
Iron(III) Phthalocyanine-Chloride-Catalyzed Synthesis of
Sulfones from Sulfonylhydrazones
Leave this area blank for abstract info.
Jun-Long Zhao*, Shi-Huan Guo, Jun Qiu, Xiao-Feng Gou, Cheng-Wen Hua, Bang Chen

5
Highlights
Mild conditions
Readily available reactants
Good-to-high yields
New reaction mechanism