Copper-catalyzed cyanation of disulfides by azobisisobutyronitrile leading to thiocyanates

Article abstract of DOI:10.1039/c4cc04578e

The copper-catalyzed cyanation of disulfides by azobisisobutyronitrile (AIBN) was developed, leading to thiocyanates in moderate to good yields. This procedure tolerates a series of functional groups, such as chloro, nitro, methyl and methoxycarbonyl in the phenyl ring of disulfides. Notably, it enables the use of two ArS units in (ArS)₂. CuI was found to be essential for the in situ formation of cyanide anions. This journal is

Full text of DOI:10.1039/c4cc04578e

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Copper-catalyzed cyanation of disulfides by
azobisisobutyronitrile leading to thiocyanates†
Cite this:DOI: 10.1039/c4cc04578e
Fan Teng,a Jin-Tao Yu,a Haitao Yang,a Yan Jianga and Jiang Cheng*ab
Received 16th June 2014,
Accepted 17th August 2014
DOI: 10.1039/c4cc04578e
www.rsc.org/chemcomm
The copper-catalyzed cyanation of disulfides by azobisisobutyronitrile
(AIBN) was developed, leading to thiocyanates in moderate to good
yields. This procedure tolerates a series of functional groups, such as
chloro, nitro, methyl and methoxycarbonyl in the phenyl ring of
disulfides. Notably, it enables the use of two ArS units in (ArS)2. CuI
was found to be essential for the in situ formation of cyanide anions.
Aryl thiocyanates are not only the subunits of biologically active
compounds1 but also versatile intermediates leading to sulfonyl
cyanides, sulfonic acids, sulfonylchlorides, thiocarbamates, thio-
esters, sulfides and related heterocycles.2 Moreover, thiocyanate
serves as the cyanation reagent with boronic acid.3
Scheme 1 The pathways leading to aryl thiocyanates.
Intriguingly, less attention has been paid to the synthesis of
aryl thiocyanate. Thiocyanation of arene suffered from limited
substrate scope (eqn (1), Scheme 1).4 The reaction of diazonium salts Inspired by our recently developed copper-mediated N-cyanation
with metal thiocyanate, known as Gattermann–Sandmeyer reaction, reaction,10 herein, we wish to report a fundamentally different
required careful control of the reaction conditions (eqn (2), pathway leading to thiocyanates: copper-catalyzed thiocyanation of
Scheme 1).5 The reaction of the aryl metal (or halo) represented a diaryl disulfides by azobisisobutyronitrile (AIBN) (eqn (5), Scheme 1).
versatile pathway leading to aryl thiocyanate (eqn (3), Scheme 1).6 This procedure is characterized by the following features: (1) com-
Alternatively, the cyanation of organosulfur compounds provided a pared with the procedures in eqn (2) and (3), less halo-containing
complement of the aforementioned transformation. For example, waste was produced; (2) AIBN serves as a less toxic cyanide source in
Saito reported the reaction of arenesulfinates (or arenesulfonyl comparison with the procedure in eqn (4).
chlorides) with cyanotrimethylsilane to form aryl thiocyanates
We started our study by using the combination of ArSSAr
(eqn (4), Scheme 1).7 However, the toxicity of cyanide would (Ar = 4-MeOC6H4–, 0.1 mmol), AIBN (0.15 mmol), CuO (10 mol%),
dramatically decrease the practicability of such a transformation. and K2CO3 (0.1 mmol) in MeCN (2 mL) under O2 at 100 1C as the
Fortunately, C-cyanation reaction using a cyanide source other than model reaction. To our delight, arylthionate was isolated in 27%
metal cyanide was well developed.8 Han reported the seminal yield (Table 1, entry 1). Replacing CuO with CuCl2, the yield
copper-mediated direct cyanation of an arene C–H bond by increased to 47% (Table 1, entry 2). CuSO4 was less efficient for
azobisisobutyronitrile (AIBN).9 The cyanation of a heteroatom this transformation (Table 1, entry 4) and CuI was the best,
other than the carbon atom was less studied or reported before. providing phenyl thiocyanate in 55% yield (Table 1, entry 3).
In the absence of copper, the thiocyanation product was isolated
a School of Petrochemical Engineering, Jiangsu Key Laboratory of Advanced
Catalytic Materials & Technology, Jiangsu Province Key Laboratory of Fine
Petrochemical Engineering, Changzhou University, 1 Gehu Road, Changzhou,
213164, P. R. China. E-mail: jiangcheng@cczu.edu.cn
in 10% yield, indicating that copper was essential for the reaction
(Table 1, entry 5).11 Solvent was also crucial for this transformation.
Toluene, DCM, CCl4 and MeOH all resulted in no reaction or low
efficiency (Table 1, entries 6–9). Switching the base from K2CO3 to
NaOH and K3PO4 slightly increased the yields to 61% and 65%,
respectively (Table 1, entries 10 and 12). Fortunately, 81% yield was
obtained by using KHCO3 as base (Table 1, entry 13). Under air, the
b State Key Laboratory of Coordination Chemistry, Nanjing University,
22 Hankou Road, Nanjing, 210093, P. R. China
† Electronic supplementary information (ESI) available: Detailed synthetic pro-
cedures and characterization of new compounds. See DOI: 10.1039/c4cc04578e
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Table 1 Selected results for screening the optimized reaction conditionsa
Entry
Catalyst
Base
Solvent
Yieldb (%)
1
2
3
4
5
6
7
8
CuO
CuCl2
CuI
CuSO4
—
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
NaOH
NaOAc
K3PO4
KHCO3
—
MeCN
MeCN
MeCN
MeCN
MeCN
Toluene
DCM
27
47
55
25
10
o1
10
CCl4
28
9
MeOH
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
o1
10
11
12
13
14
15
16
61
39
65
81 (o1)c (61)d
o5
10
o5
Et3N
DBU
a
Reaction conditions: 1c (0.1 mmol), AIBN (1.5 equiv.), Cu catalyst
(0.1 equiv.), base (1.0 equiv.), solvent (2.0 mL) under O2 for 12 h,
b
c
d
100 1C, sealed tube. Isolated yield. Under N2. Under air.
yield slightly decreased to 61% and no reaction took place under
N2 (Table 1, entry 13). In the absence of base, the procedure
failed to produce any product (Table 1, entry 14). The organic
bases, such as Et3N and DBU, showed low efficiency (Table 1,
entries 15 and 16).
After the establishment of the optimized reaction conditions,
the scope of disulfides was studied, as shown in Fig. 1. This
procedure tolerated chloro, nitro, methoxycarbonyl, methyl,
bromo and acyl oxy groups. For diaryl disulfides, the reaction
was not sensitive to the electron nature of the substrates, as both
4-nitro and 4-methyloxy substrates provided the desired products
in good yields (3c and 3f). However, 3g was isolated in moderate
yield. The chloro and alkenyl groups survived well under the
standard conditions (3e, 3h and 3m), which were applicable for
further functionalization. Diaryl disulfide with free phenolic
hydroxyl failed to deliver the thiocyanation product. However,
after the protection of the hydroxy group, 3i and 3h were isolated
in 73% and 50% yields. Particularly, the di-hetero aryl disulfides,
such as 2,20-dipyridyl disulfide, 2,20-dithio-dibenzothiazole and
4,40-dipyridyl disulfide, worked under the standard conditions,
providing 3j, 3k and 3p in 77%, 37% and 60% yields, respectively.
Notably, dibenzyl disulfide was a good reaction partner, and 3l
was isolated in 56% yield. Dioctyl disulfide provided the cyanation
product 3r in 52% yield.
Fig. 1 Scope of disulfides.a a Reaction conditions: disulfide 1 (0.1 mmol),
CuI (0.02 mmol), AIBN 2 (0.15 mmol), KHCO3 (0.1 mmol), MeCN (2.0 mL),
O2, 100 1C, 12 h. b Disulfide 1 (0.1 mmol), CuI (0.02 mmol), AIBN
(0.15 mmol), K2CO3 (0.15 mmol), MeCN (2.0 mL), O2, 75 1C, 12 h.
Table 2 Detection of cyanide anionsa
Entry
PhSSPh
CuI
KHCO3
Atmosphere
Results
1
2
3
4
5
6
7
O
ꢀ
O
O
ꢀ
ꢀ
ꢀ
O
O
ꢀ
O
O
O
O
O
O
O
ꢀ
ꢀ
ꢀ
ꢀ
O2
O2
O2
O2
O2
N2
Air
+
+
ꢁ
+
+
+
+
a
Detection conditions: CuI (0.1 equiv.). For details, see ESI. ‘‘+’’ means
positive results; ‘‘ꢁ’’ means negative results.
Some experiments were conducted to gain some insight into
the reaction. Firstly, the cyanide anion was detected using an
indicating paper (for details, see ESI†). A further study revealed thiocyanation product was isolated in 38% yield in the presence
that PhSSPh, KHCO3 and O2 were not essential for the in situ of KHCO3 in CH3CN (Scheme 2, eqn (2)), which was comparable
formation of cyanide anions. However, in the absence of CuI, with the result when two equivalents of CuI were employed
no cyanide ion was detected (Table 2).
(Scheme 2, eqn (3)). Moreover, replacing CuI with PhSCu
Next, in the presence of 0.5 mmol of TEMPO, the reaction (10 mol%) under the standard conditions, phenyl thiocyanate
was inhibited, indicating that a radical pathway may be was isolated in 53% yield (Scheme 2, eqn (4)). Furthermore,
involved in the procedure (Scheme 2, eqn (1)). A stoichiometric acetone was detected as the byproduct in the procedure by
amount of PhSCu(I) was subjected to the reaction, and the GC-MS (Scheme 2).
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We thank the National Natural Science Foundation of China
(no. 21272028 and 21202013), ‘‘Innovation & Entrepreneurship
Talents’’ Introduction Plan of Jiangsu Province, the Natural
Science Foundation of Zhejiang Province (no. R4110294), State
Key Laboratory of Coordination Chemistry of Nanjing Univer-
sity, Jiangsu Key Laboratory of Advanced Catalytic Materials &
Technology, Jiangsu Province Key Laboratory of Fine Petro-
chemical Engineering (BM2012110), and the Priority Academic
Program Development of Jiangsu Higher Education Institu-
tions (PAPD) for financial support.
Notes and references
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Scheme 3 The proposed mechanism.
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In the presence of CuI, initially, the PhSꢂ radical is formed by
the homolytic cleavage of the S–S bond. Then the formed PhSꢂ
radical reacts with Cu(I) to form a Cu(II) species 4. Meanwhile,
the sequential cleavage of the NQN bond in AIBN followed by
the loss of one equivalent of N2 provides radical species 5, which
is oxidized to radical species 6 by O2. By the extrusion of one
equivalent of acetone, radical species 6 converts to the cyano
radical. Subsequently, single electron transfer between the cyano
radical and Cu(II) species 4 provides Cu(III) species 7. Finally,
reductive elimination of Cu(III) species 7 delivers the thiocyana-
tion product and regenerates Cu(I).
In conclusion, we have developed a copper-catalyzed cyanation
of disulfides by AIBN leading to thiocyanates. This procedure
employs O2 as the clean terminal oxidant and AIBN as a safe
cyanide source. Thus, it represents a promising pathway to
access thiocyanates and a key progress in cyanation reaction.
11 K2CO3 contains 0.24 ppm of copper, as detected by ICP-MS.
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