A simple method for the preparation of arylselanyl anilines

Article abstract of DOI:10.1080/00397911.2018.1513531

In the presence of I₂, a simple method for the preparation of arylselanyl anilines from anilines and diselenides is developed. This metal-free iodine-promoted procedure proceeds efficiently under mild reaction conditions, providing a series of

Full text of DOI:10.1080/00397911.2018.1513531

Synthetic Communications
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ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
A simple method for the preparation of arylselanyl
anilines
Zhongshi Zhou & Xuehan He
To cite this article: Zhongshi Zhou & Xuehan He (2018): A simple method for the preparation of
arylselanyl anilines, Synthetic Communications, DOI: 10.1080/00397911.2018.1513531
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https://doi.org/10.1080/00397911.2018.1513531
A simple method for the preparation of arylselanyl anilines
Zhongshi Zhoua and Xuehan Heb
aCollege of Biological and Environmental Sciences, Zhejiang Shuren University, Hangzhou, P. R. China;
bZhejiang Institute of Geology and Mineral Resource, Hangzhou, P. R. China
ABSTRACT
ARTICLE HISTORY
Received 10 February 2018
In the presence of I2, a simple method for the preparation of arylse-
lanyl anilines from anilines and diselenides is developed. This metal-
free iodine-promoted procedure proceeds efficiently under mild reac-
tion conditions, providing a series of arylselanyl anilines with high
regioselectivity, and mostly in moderate to good yields.
KEYWORDS
Aniline; arylselanyl aniline;
diselenide; I2-promoted
GRAPHICAL ABSTRACT
A Simple Method for the Preparation of Arylselanyl Anilines
Introduction
Arylselanyl anilines are important organoselenium compounds, they can be prepared by a
traditional selenenylation of electron-rich aromatic compounds with some pre-prepared
selenenylating reagents, such as N-phenylselenosaccharin (NPSSac) and (phenylse1eno)di-
methylsulfonium tetrafluoroborate.[1–2] They were also synthesized by the palladium cata-
lyzed reaction of aryl iodide or triflate with Bu3SnSePh.[3–4] Using PhSeCl as selenenylating
~
reagent in glycerol, Lenardao and coworkers reported a green procedure to access arylse-
lanyl anilines.[5] However, this method should be done in inert gas due to the moisture-
sensitive nature of PhSeCl. An alternative method is the use of cheaper and more stable
diaryl diselenides. Under conventional heating or microwave heating, the CuI-catalyzed
reaction of anilines or haloaromatics with diaryl diselenides can provide arylselanyl ani-
lines.[6–7] Recently, using DMSO as oxidant, Braga’s group developed a metal-free and solv-
ent-free iodine-catalyzed protocol for the preparation of arylselanyl anilines under
microwave irradiation.[8] In this reaction, the in situ generated active electrophilic selenium
species ArSeI, which was formed by the reaction of I2 with diaryl diselenide, played a key
role. However, this greener methodology needed a special reactor (Microwave monomode
CEM reactor) and was not effective at room temperature. Similarly, near the same time,
CONTACT Zhongshi Zhou
zhoushanzsu@163.com
College of Biological and Environmental Sciences, Zhejiang
Shuren University, Hangzhou 310015, P. R. China.
ß 2018 Taylor & Francis Group, LLC

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Z. ZHOU AND X. HE
Yan’s group demonstrated another way of using KI as catalyst and H2O2 as oxidant for
obtaining arylselanyl anilines.[9] This protocol was suitable for the selenation of N,N-disub-
stituted anilines and N-substituted anilines, but when the unsubstituted aniline was used as
substrate, it was difficult to get the desired product. More recently, the Rose Bengal-cata-
lyzed photo-induced synthesis of arylselanyl anilines was reported by Braga’s group.[10] The
above approaches, though effective for obtaining arylselanyl aniline, have some limitations
such as the use of special reactors, pre-functionalized reagents and metal catalysts, as well
as, long reaction times and high reaction temperatures. Consequently, the development of
simple and general methods for the preparation of arylselanyl aniline is still desired.
Recently, iodine-catalyzed or iodine-promoted reactions have been increasingly
explored due to its eco-friendly and metal-like behaviors.[11–17] Considering ArSeI is the
key intermediate for the preparation of arylselanyl aniline[8,9] and that it can be pre-
pared from the reaction of diaryl diselenide with molecular iodine,[18] we have investi-
gated the reaction of anilines with diaryl diselenides in the presence of I2. Although the
Braga’s study has disclosed the iodine-promoted conditions, this reaction needs DMSO
as oxidant and has to be carried out under microwave heating.[8] Compared with it, our
protocol is effective at room temperature, which is simple and mild.
Results and discussion
The Optimization study on the reaction was initiated by using N,N-dimethylaniline 1a
with diphenyl diselenide 2a in the presence of I2 at room temperature. As depicted in
Table 1, the effect of solvent was first examined. The reaction can be carried out in sev-
eral solvents, and afford the desired product N,N-dimethyl-4-(phenylselanyl)aniline 3a
in 11–62% yields, showing that EtOH was the most suitable solvent for the reaction
(Table 1, entries 1–8). Then, the amount of I2 was optimized, and 1.0 equiv proved to
be the best choice (entries 2, 10–15). However, in the absence of I2, 3a was not formed
(entry 9). As a control experiment, when HI took the place of I2, the reaction gave 23%
yield of 3a (entry 16). Finally, both the optimal amount of 1a and the suitable reaction
time were determined: 1.2 equiv of 1a was suitable for the reaction and in 6 h the reac-
tion was completed (entries 2, 17–23).
Having established the optimal conditions, the selenation of 1.2 equiv of anilines 1
with 1.0 equiv of diselenides 2 and I2 in EtOH at room temperature for 6 h was investi-
gated, and as a result, a series of arylselanyl anilines 3 were afforded. As shown from
Table 2, several N,N-disubstituted anilines can react with 2a easily, resulting in the cor-
responding 4-arylselanyl anilines 3a-3d in good yields (Table 2, entries 1-4). However,
N,N-dibenzylaniline 1e let only to 21% yield of desired product 3e due to the sterically
hindered structure (entry 5). To extend the scope of our methodology, two unsubsti-
tuted anilines 1f, 1 g and two N-substituded anilines 1 h, 1i were chosen as representa-
tives to treat with 2a, and obtained the corresponding products 3f-3i in moderate to
good yields (entries 6–9), indicating that this protocol is suitable for a wide variety of
anilines. Other diaryl diselenides such as 2 b and 2c, whether having an electron-donat-
ing group or an electron-withdrawing group on benzene ring, usually had no significant
influence on their reactivity and provided the corresponding products in good yields
(entries 10–11). Under the optimal conditions, dibenzyl diselenide 2d, similar to 2a, an
aliphatic diselenide was also effective in the reaction, giving the product 3 l in 75% yield

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Table 1. Optimization of the selenation of N,N-dimethylaniline promoted by I2.
Entry
N,N-Dimethylaniline (equiv.)
I2 (equiv.)
Solvent
Time (h)
Yield (%)a
1
2
3
4
5
6
7
8
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.0
1.5
2.0
1.2
1.2
1.2
1.2
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0
CH3CN
CH3OH
EtOH
EtOAc
THF
CH2Cl2
DMF
CF3CH2OH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
15
20
10
6
46
38
62
25
32
19
11
50
0
13
31
77
82
80
81
23
63
77
80
78
86
83
67
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
0.1
0.3
0.8
1.0
1.5
2.0
HI (1.0)
1.0
1.0
1.0
1.0
1.0
1.0
1.0
4
aIsolated yields.
(entry 12). From the results it is obvious that except 3 g all obtained arylselanyl anilines
are 4-arylselanyl anilines, showing this selenation has a high regioselectivity.
To explore the mechanism, a radical scavenger, 2,6-di-tert-butyl-4-methylphenol
(BHT), was added to the reaction of 1a with 2a and I2 under the optimized conditions.
It was found that BHT was not effective to the selenation, and after 6 h 3a was obtained
in 81% yield, which indicated that the reaction may not undergo a radical pathway.
Therefore, a plausible eletrophilic substitution mechanism promoted by I2 is shown in
Scheme 1: thus, I2 first reacts with diselenide 2 smoothly to form ArSeI.[18] The in situ
generated active electrophilic selenium species then reacts with aniline, according 4-aryl-
selanyl aniline with high regioselectivity and good yield through an electrophilic aro-
matic substitution. The by-product HI can also be oxidized by air into I2.
Conclusions
We have developed a simple iodine-promoted procedure for the synthesis of 4-arylse-
lanyl anilines. This metal-free reaction proceeded smoothly at room temperature and
was completed in only 6 h, which provided a series of corresponding compounds with
high regioselectivity and in moderate to good yields. Compared with the known meth-
ods, this protocol has some advantages such as milder reaction conditions and is suit-
able for a wide variety of anilines.

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Z. ZHOU AND X. HE
Table 2. Preparation of arylselanyl anilines 3.
Experimental section
General: Melting points were measured with an XT-4 melting point apparatus and were
1
uncorrected. H NMR and 13C NMR spectra were measured on a Bruker-AVANCE III
(500 MHz) spectrometer and mass spectra were determined on Waters-GCT Premier.
Anilines, diselenides, I2, and solvents were commercially available.
General procedure for the preparation of arylselanyl anilines promoted by I2: in
EtOH (2.0 mL), aniline 1 (0.36 mmol), diselenide 2 (0.15 mmol) and I2 (0.15 mmol)
were added successively. The mixture was vigorously stirred at r. t. for 6 h. Upon com-
pletion, aqueous solution of Na2S2O3 (sat., 2 mL), aqueous solution of Na2CO3 (sat.,
5 mL) and H2O (10 mL) were added to the mixture, respectively. The mixture was
extracted with CH2Cl2 (3 Â 10 mL) and the combined organic phase was dried over

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5
Scheme 1. Proposed mechanism for the selenation of anilines promoted by I2.
anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was
then purified by flash chromatography using petroleum ether as the eluent to furnish
arylselanyl anilines 3.
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