Unsymmetrical disulfide and sulfenamide synthesis via reactions of thiosulfonates with thiols or amines

Article abstract of DOI:10.1016/j.tet.2017.02.047

The reactivity of thiosulfonates with nucleophilic reagents was investigated. When reactions of thiosulfonates with thiols were performed, unsymmetrical disulfides were obtained in excellent yields. This procedure could employ numerous aryl or alkyl thiols. On the other hand, reactions of thiosulfonates with amines proceeded in the presence of a copper catalyst. The procedure was performed efficiently in air, and afforded the corresponding sulfenamides.

Full text of DOI:10.1016/j.tet.2017.02.047

Accepted Manuscript
Unsymmetrical disulfide and sulfenamide synthesis via reactions of thiosulfonates
with thiols or amines
Nobukazu Taniguchi
PII:
S0040-4020(17)30186-2
10.1016/j.tet.2017.02.047
TET 28488
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 9 January 2017
Revised Date: 19 February 2017
Accepted Date: 21 February 2017
Please cite this article as: Taniguchi N, Unsymmetrical disulfide and sulfenamide synthesis via reactions
of thiosulfonates with thiols or amines, Tetrahedron (2017), doi: 10.1016/j.tet.2017.02.047.
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Graphical Abstract
Unsymmetrical Disulfide and Sulfenamide
Synthesis via Reactions of Thiosulfonates
with Thiols or Amines
Leave this area blank for abstract info.
Nobukazu Taniguchi
Department of Chemistry, Fukushima Medical University, Fukushima 960-8055 Japan

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1
Tetrahedron
journal homepage: www.elsevier.com
Unsymmetrical Disulfide and Sulfenamide Synthesis via Reactions of
Thiosulfonates with Thiols or Amines
Nobukazu Taniguchia
a Department of Chemistry, Fukushima Medical University, Fukushima 960-8055 Japan
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
The reactivity of thiosulfonates with nucleophilic reagents was investigated. When reactions of
thiosulfonates with thiols were performed, unsymmetrical disulfides were obtained in excellent
yields. This procedure could employ numerous aryl or alkyl thiols. On the other hand, reactions
of thiosulfonates with amines proceeded in the presence of a copper catalyst. The procedure was
performed efficiently in air, and afforded the corresponding sulfenamides.
Available online
Keywords:
Thiosulfonates
2009 Elsevier Ltd. All rights reserved
.
Unsymmetrical disulfides
Sulfenamides
Copper catalyst
Oxidativel reaction
———
Corresponding author. Tel.: +81-24-547-1369; fax: +81-24-547-1369; e-mail: taniguti@fmu.ac.jp

ACCEPTED MANUSCRIPT
2
Tetrahedron
1. Introduction
The development of organosulfur synthesis is an important
research area in organic chemistry.1 In particular, the
construction of carbon-sulfur bonds has been thoroughly
investigated.2 Although numerous methodologies for sulfur-
heteroatom bond formation have been exploited to date, a study
of convenient metal-catalyzed procedures has been recently
reported.3,4
Entry
Solv.
3aa (%)
45
1
DMF
DMA
PhCH3
EtOH
EtOH
EtOH
2
43
3
52
On the other hand, we found that thiosulfonates could be
synthesized by the copper-catalyzed coupling of thiols or
disulfides with sodium sulfinates (Scheme 1).5 The procedure can
be used to efficiently prepare the expected thiosulfonates at one
step.
4
96
5b
6c
40
61
aReaction conditions: The mixture of 1aa (0.3 mmol) and 2a (0.3 mmol) was
treated in EtOH (1.0 mL) at 50 °C in air.
bNa2CO3 (0.3 mmol) was added at 50 °C.
cThe reaction was performed at 30 °C.
Table 2. Unsymmetrical disulfide formation
Scheme 1. Copper-catalyzed synthesis of thiosulfonates using
thiols with sodium sulfinates
R2SH 2
S
R2
O
R1
S
S
R1
S
EtOH, 50 °C
18 h
3
O
The important characteristics of the obtained thiosulfonate are
the polarity of its sulfur-sulfone bond and its odorless quality.
Therefore, it is anticipated that it could be used as a sulfur source
in the synthesis of organosulfur derivatives. However, the
development of such reactions is rarely reported6 and further
research is now desired.
1
Entry
1
R1
R2
3 (%)
4-MeC6H4
4-MeC6H4
C6H5
3aa
3ab
3ac
3ad
3ae
3af
96
80
82
72
88
51
79
73
79
90
12
81
78
78
84
83
70
trace
70
58
85
54
71
2
3
4-MeOC6H4
4-BrC6H4
4-ClC6H4
4-HOC6H4
2-MeC6H4
2-MeOC6H4
2-BrC6H4
HOCH2CH2
H2NCH2CH2
i-Pr
Meanwhile, the formation of unsymmetrical disulfides has
been studied by many researchers.7,8 The most commonly
employed method is a reaction using sodium thiosulfates9 or
thioimides.10 Benzotriazolated thiols are also employed.11
Although a reaction using thiosulfonates is exploited,12 the
previous method can use only limited substrates, and the required
conditions (molar quantities of substrates or additives) depend on
the substrates. A suitable condition has not been established yet.
Therefore, it is not viable from a practical point of view.
4
5
6
7
3ag
3ah
3ai
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
3aj
The greatest problem associated with these procedures is
complex preparation of the starting materials. Also, the formation
of sulfur-nitrogen bonds using these sulfidation reagents has not
yet been achieved.
3ak
3al
n-Bu
3am
3an
3bn
3cn
3dn
3en
3fn
3gn
3am
3hn
3ia
n-Octyl
As an approach to solving these problems, the synthesis of
unsymmetrical disulfides and sulfenamides using thiosulfonates
was investigated.
C6H5
4-MeOC6H4
4-ClC6H4
4-O2NC6H4
2-MeC6H4
2-BrC6H4
n-Bu
2.
Results and discussion
Initially, the preparation of unsymmetrical disulfides was
investigated (Table 1). To establish suitable conditions,
numerous solvents were evaluated. When the reactions in DMF
or DMA were examined, the expected disulfide 3aa was obtained
in about 40% yield with the recovery of thiosulfonate 1a (Entries
1−2). A reaction in PhCH3 also gave similar result (Entry 3).
Fortunately, the use of EtOH as a solvent could afford the
corresponding disulfide in 96% yield with 4-toluenesulfonyl
ethyl ester (Entry 4). The reaction proceeded smoothly at 50 °C.
The addition of Na2CO3 did not promote the reaction
satisfactorily (Entry 5).
4-MeC6H4
n-Octyl
n-Bu
Me
4-MeC6H4
aReaction conditions: The mixture of 1 (0.3 mmol) and 2 (0.3 mmol) was
treated in EtOH (1.0 mL) at 50 °C in air.
On the basis of the developed procedure, preparations of
numerous unsymmetrical disulfides were performed. As shown
in Table 2, when a mixture of thiosulfonates 1 with thiols 2 was
Table 1. Investigation of suitable conditionsa

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3
9
4-O2NC6H4
2-MeC6H4
2-BrC6H4
n-Bu
6gb
6hb
6ib
76
82
72
0
treated in EtOH, the expected disulfides 3 were produced in
excellent yields. The procedure could be performed by using
various combinations of arylthiosulfonates with thiols (Entries
1−20). The effect of steric hindrance was no observed. However,
a reaction using 2-aminoethanethiols gave a lower yield owing to
a formation of complex mixtures (Entry 11).13,14 A reaction using
4-nitrophenylthiosulfonate bearing an electron withdrawing
group hardly proceeded (Entry 18). Not only arylthiosulfonates
but also alkylthiosulfonates could be employed in the reaction
(Entries 21−23). Thus, the procedure afforded the desired
unsymmetrical disulfides in excellent yields. However, a case
using thiols involving an amino-group did not produce the
corresponding disulfide satisfactorily without a formation of
sulfenamides or sulfonamides. This result shows that the
nucleophilic attack of amines on thiosulfonates is impossible.
10
11
12
13
6jb
6kb
PhCH2
0
aReaction conditions: The mixture of 1 (0.3 mmol), 5 (0.6 mmol), and CuI-
bpy (1:1, 10 mol%) was treated in DMSO (0.3 mL) at 60 °C in air.
Consequently, attention was focused toward investigating the
reaction of thiosulfonates with amines. The reaction of
thiosulfonate with diethylamine in DMSO was initially surveyed
(Table 3). When the reaction was attempted in the absence of a
copper catalyst, the expected sulfenamide 6aa was not obtained
(Entry 1). However, the addition of a CuI-bpy(2,2’-bipyridine)
catalyst increased the yield to 54% with the formation of
sulfonamide 7aa. The reaction using 2 equivalents of 5a afforded
sulfenamide 6aa in 77% yield (Entry 3). Regrettably, the use of
other ligands or solvents resulted in low reactivity (Entries 4−7).
Similarly, other copper catalysts could not satisfactorily promote
the reaction (Entries 8−10).
Table 3. A reaction of thiosulfonates with amines
According to the described procedure, numerous sulfenamides
were prepared. As shown in Table 4, when a mixture of
thiosulfonates 1 (0.3 mmol) and amines 5 (0.6 mmol) in DMSO
was treated with CuI-bpy (1:1, 10 mol%), the corresponding
sulfenamides 6 were obtained in excellent yields (Entries 1−11).
The procedure proceeded without the effects of electronic and
Entry
reagent
solvent
6aa
(%)
7aa
(%)
1a
none
EtOH
trace
54
77
31
38
43
15
44
58
50
trace
18
49
26
37
17
0
steric hindrance. Regrettably,
a
reaction using n-
2a
CuI-bpy(1:1, 10 mol%)
CuI-bpy(1:1, 10 mol%)
CuI(10 mol%)
DMSO
DMSO
DMSO
DMSO
DMF
alkylthiosulfonate hardly proceeded owing to the formation of
complex mixtures including disulfide and sulfonamide (Entry
12−13).
3b
4b
5b
6b
7b
8b
9b
10b
To clarify the mechanism, some experiments were then
performed. As shown in Scheme 2, a reaction under nitrogen
atmosphere gave 6aa in 16% yield. It was obvious that the
procedure was promoted by oxygen. Similarly, a reaction in the
presence of a radical scavenger was also investigated (Scheme 3).
The procedure was inhibited by TEMPO. This fact suggests that
the reaction of thiosulfonates with amines proceeds via a radical
process15, and the procedure never proceeds via nucleophilic
attack of amines without the oxidation of thiosulfonates.
CuI-TMEDA(1:1, 10 mol%)
CuI-bpy(1:1, 10 mol%)
CuI-bpy(1:1, 10 mol%)
CuCl-bpy(1:1, 10 mol%)
CuBr-bpy(1:1, 10 mol%)
CuBr2-bpy(1:1, 10 mol%)
PhMe
DMSO
DMSO
DMSO
37
56
46
aReaction conditions: The mixture of 1a (0.3 mmol) and 5a (0.3 mmol) was
treated in solvent (0.3 mL) at 60 °C.
From these results, a plausible mechanism is considered as
follows (Figure 1).16 After the oxidation of thiosulfonate by a
copper catalyst in air, radical intermediates 8 are produced. The
reaction of 8 with amines gives sulfenamides and sulfonyl
radicals 9. Finally, sulfonamides or sulfonyl anion 10 are formed
via sulfonyl radicals react with amines or are reduced by CuI.
b5a (0.6 mmol).
Table 4. A copper-catalyzed synthesis of 3ulfonamides
Et2NH 5a
S
CuI-bpy(1:1, 10 mol%)
NEt2
R1
R2R3NH
Et2NH
6
6 (%)
77
1a
Entry
DMSO, 60 °C, 18 h
under N2
6aa
1
2
3
4
5
6
7
8
4-MeC6H4
6aa
6ab
6ac
6ad
6bb
6cb
6db
6fb
16%
Piperidine
Morpholine
t-BuNH2
Piperidine
81
Scheme 2. A reaction in the absence of oxygen
88
70
Ph
74
4-MeOC6H4
4-BrC6H4
4-ClC6H4
73
77
65

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4
Tetrahedron
Scheme 3. A reaction in the presence of TEMPO
8.0 Hz, 2H), 7.10 (d, J = 8.0 Hz, 2H), 6.82 (d, J = 8.9 Hz, 2H),
3.77 (s, 3H), 2.32 (s, 3H); 13C NMR (67.5 MHz, CDCl3) δ 159.8,
137.6, 134.0, 131.9, 129.8, 129.2, 128.3, 114.6, 55.3, 21.1.
4.2.4. (4-Methylphenyl)(4-bromophenyl) disulfide (3ad). The title
compound was obtained as white solids (84.9 mg, 72%); mp
67−68 °C; [Found: C, 50.13; H, 3.51; C13H11BrS2 required C,
50.16; H, 3.56%]; n(max) (CHCl3) 2975, 1490, 1471, 1386 cm-1;
1H NMR (270 MHz, CDCl3) δ 7.41−7.23 (m, 6H), 7.10 (d, J =
8.2 Hz, 2H), 2.31 (s, 3H); 13C NMR (67.5 MHz, CDCl3) δ 137.8,
136.5, 133.1, 132.0, 129.9, 129.3, 128.6, 121.1, 21.0.
4.2.5. (4-Methylphenyl)(4-chlorophenyl) disulfide (3ae)7e. The
title compound was obtained as white solids (70.2 mg, 88%); mp
57−58 °C; [Found: C, 58.40; H, 4.02; C13H11ClS2 required C,
1
58.52; H, 4.16%]; n(max) (CHCl3) 1490, 1474, 1388 cm-1; H
Figure 1. A plausible reaction mechanism
NMR (270 MHz, CDCl3) δ 7.42−7.34 (m, 4H), 7.27−7.23 (m,
2H), 7.10 (d, J = 8.2 Hz, 2H), 2.31 (s, 3H); 13C NMR (67.5 MHz,
CDCl3) δ 137.9, 135.9, 133.1, 129.9, 129.3, 129.2, 129.1, 128.7,
21.0.
3. Conclusion
In investigating the reactivity of thiosulfonates, two
convenient reactions were exploited. The coupling of
thiosulfonates with thiols could afford unsymmetrical disulfides
in excellent yields. Furthermore, the reaction of thiosulfonates
with amines achieved the synthesis of the desired sulfenamides
with the formation of sulfonamides. The procedure required the
addition of a copper catalyst in air.
4.2.6. (4-Methylphenyl)(4-hydroxyphenyl) disulfide (3af). The
title compound was obtained as white solids (38.1 mg, 51%); mp
108−109 °C; [Found: C, 62.74; H, 4.57; C13H12OS2 required C,
62.87; H, 4.87%]; n(max) (CHCl3) 3428, 1597, 1582, 1494 cm-1;
1H NMR (270 MHz, CDCl3) δ 7.49−7.45 (m, 2H), 7.26−7.20 (m,
4H), 6.79−6.76 (m, 2H), 5.89 (brs, 1H), 2.43 (s, 3H); 13C NMR
(67.5 MHz, CDCl3) δ 158.9, 144.8, 140.0, 138.6, 129.5, 127.6,
118.3, 116.7, 21.7.
4.2.7. (4-Methylphenyl)(2-methylphenyl) disulfide (3ag). The title
compound was obtained as pale yellow liquid (58.7 mg, 79%);
[Found: C, 68.06; H, 5.60; C14H14S2 required C, 68.24; H,
4. Experimental section
4.1 General Procedure and Chemicals.
1
5.73%]; n(max) (neat) 3059, 2919, 1589, 1489, 1464 cm-1; H
All reactions were carried out in air. H and 13C NMR spectra
were recorded at 270 and 67.5 MHz, respectively. Chemical
1
NMR (270 MHz, CDCl3) δ 7.60−7.57 (m, 1H), 7.39−7.34 (m,
2H), 7.15−7.06 (m, 5H), 2.40 (s, 3H), 2.30 (s, 3H); 13C NMR
(67.5 MHz, CDCl3) δ 137.5, 137.0, 135.8, 130.3, 129.8, 128.7,
128.5, 128.2, 127.2, 126.6, 21.0, 20.0.
shifts are reported in
δ ppm referenced to an internal
tetramethylsilane standard for 1H NMR and chloroform-d (δ
77.0) for 13C NMR.
4.2.8. (4-Methylphenyl)(2-methoxyphenyl) disulfide (3ah). The
title compound was obtained as pale yellow liquid (57.5 mg,
73%); [Found: C, 64.29; H, 5.52; C14H14OS2 required C, 64.08;
H, 5.38%]; n(max) (neat) 3007, 2934, 2835, 1579, 1463, 1239
4.2 Typical procedure for unsymmetrical disulfides
preparation from thiosulfonates with thiols: Synthesis of
bis(4-methylphenyl) disulfide (3aa) (Table 2, entry 1)
1
cm-1; H NMR (270 MHz, CDCl3) δ 7.57 (d, J = 7.9 Hz, 1H),
4.2.1. Bis(4-methylphenyl) disulfide (3aa)
7.39 (d, J = 8.2 Hz, 2H), 7.18 (dd, J = 7.9 and 8.2 Hz, 1H), 7.08
(d, J = 8.2 Hz, 2H), 6.91 (dd, J = 7.9 and 8.2 Hz, 1H), 6.83 (d, J
= 8.2 Hz, 1H), 3.85 (s, 3H), 2.29 (s, 3H); 13C NMR (67.5 MHz,
CDCl3) δ 156.5, 137.1, 133.4, 129.7, 128.1, 128.0, 127.9, 125.0,
121.2, 110.6, 55.8, 21.0.
4.2.9. (4-Methylphenyl)(2-bromophenyl) disulfide (3ai)7e: The
title compound was obtained as pale yellow liquid (73.6 mg,
79%); [Found: C, 50.05; H, 3.52; C13H11BrS2 required C, 50.16;
H, 3.56%]; n(max) (neat) 3054, 2919, 1574, 1489, 1442, 1428
cm-1; 1H NMR (270 MHz, CDCl3) δ 7.71−7.67 (m, 1H),
7.51−7.48 (m, 1H), 7.38−7.35 (m, 2H), 7.30−7.24 (m, 1H),
7.11−7.04 (m, 3H), 2.30 (s, 3H); 13C NMR (67.5 MHz, CDCl3) δ
137.6, 137.5, 132.8, 132.5, 129.9, 128.1, 127.9, 127.6, 127.1,
120.9, 21.0.
A mixture of S-4-methylphenyl 4-methylbenzenethiosulfonate
(83.5 mg, 0.3 mmol) and 4-methylphenylthiol (37.2 mg, 0.3
mmol) in EtOH (1.0 mL) was stirred at 50 °C for 18 h in air.
After the residue was dissolved in Et2O, the solution was washed
with H2O and saturated sodium chloride and dried over
anhydrous magnesium sulfate. Chromatography on silica gel
(hexane) gave bis(4-methylphenyl) disulfide 3aa (70.8 mg,
96%)7b: white solid. mp: 45−46 °C; 1H NMR (270 MHz, CDCl3)
δ 7.37 (d, J = 8.2 Hz, 4H), 7.08 (d, J = 8.2 Hz, 4H), 2.29 (s, 6H);
13C NMR (67.5 MHz, CDCl3) δ 137.4, 133.9, 129.7, 128.5, 21.0.
4.2.2. (4-Methylphenyl) phenyl disulfide (3ab)7e. The title
compound was obtained as pale yellow liquid (55.7 mg, 80%);
[Found: C, 67.13; H, 5.08; C13H12S2 required C, 67.20; H,
1
5.21%]; n(max) (neat) 3057, 2919, 1579, 1489, 1438 cm-1; H
NMR (270 MHz, CDCl3) δ 7.50−7.47 (m, 2H), 7.38 (d, J = 8.2
Hz, 2H), 7.31−7.19 (m, 3H), 7.09 (d, J = 8.2 Hz, 2H), 2.30 (s,
3H); 13C NMR (67.5 MHz, CDCl3) δ 137.5, 137.3, 133.6, 129.8,
129.0, 128.3, 127.6, 127.0, 21.0.
4.2.10. (4-Methylphenyl)(2-hydroxyethyl) disulfide (3aj). The title
compound was obtained as pale yellow liquid (54.0 mg, 90%);
[Found: C, 53.83; H, 6.13; C9H12OS2 required C, 53.96; H,
1
6.04%]; n(max) (neat) 3350, 2920, 1489, 1397 cm-1; H NMR
(270 MHz, CDCl3) δ 7.45 (d, J = 8.2 Hz, 2H), 7.14 (d, J = 8.2 Hz,
2H), 3.84 (brs, 2H), 2.88 (t, J = 5.8 Hz, 2H), 2.33 (s, 3H), 1.93
(brs, 1H); 13C NMR (67.5 MHz, CDCl3) δ 137.6, 133.6, 129.9,
128.9, 59.9, 41.2, 21.0.
4.2.3. (4-Methylphenyl)(4-methoxyphenyl) disulfide (3ac). The
title compound was obtained as pale yellow liquid (64.4 mg,
82%); [Found: C, 64.11; H, 5.50; C14H14OS2 required C, 64.08;
1
H, 5.38%]; n(max) (neat) 3003, 2936, 1589, 1490, 1246 cm-1; H
NMR (270 MHz, CDCl3) δ 7.41 (d, J = 8.9 Hz, 2H), 7.38 (d, J =

ACCEPTED MANUSCRIPT
5
4.2.11. (4-Methylphenyl)(i-propyl) disulfide (3al)7b. The title
compound was obtained as colorless liquid (48.1 mg, 81%);
[Found: C, 60.90; H, 7.13; C10H14S2 required C, 60.55; H,
7.11%]; n(max) (neat) 2960, 2992, 2863, 1489, 1448, 1380, 1245
cm-1; 1H NMR (270 MHz, CDCl3) δ 7.42 (d, J = 8.2 Hz, 2H),
7.10 (d, J = 8.2 Hz, 2H), 3.04 (seq., J = 6.9 Hz, 1H), 2.32 (s, 3H),
1.28 (d, J = 6.9 Hz, 6H); 13C NMR (67.5 MHz, CDCl3) δ 136.6,
134.8, 129.6, 127.8, 41.4, 22.4, 20.9.
[Found: C, 50.70; H, 6.33; C14H21BrS2 required C, 50.44; H,
6.35%]; n(max) (neat) 2925, 2853, 1574, 1442 cm-1; 1H NMR
(270 MHz, CDCl3) δ 7.80 (d, J = 8.2 Hz, 1H), 7.50 (d, J = 7.9 Hz,
1H), 7.34 (dd, J = 7.2 and 7.9 Hz, 1H), 7.05 (dd, J = 7.2 and 8.2
Hz, 1H), 2.73 (t, J = 7.2 Hz, 2H), 1.72−1.62 (m, 2H), 1.52−1.25
(m, 10H), 0.87 (d, J = 6.4 Hz, 3H); 13C NMR (67.5 MHz, CDCl3)
δ 138.1, 132.8, 127.8, 127.3, 127.0, 121.1, 38.7, 31.7, 29.1, 29.0,
28.9, 28.5, 22.6, 14.1.
4.2.12. (4-Methylphenyl)(n-butyl) disulfide (3am)7b. The title
compound was obtained as colorless liquid (49.7 mg, 78%);
[Found: C, 62.22; H, 7.65; C11H16S2 required C, 62.21; H,
7.59%]; n(max) (neat) 2957, 2871, 1567, 1489, 1463, 1218 cm-1;
1H NMR (270 MHz, CDCl3) δ 7.43 (d, J = 8.2 Hz, 2H), 7.13 (d, J
= 8.2 Hz, 2H), 2.73 (t, J = 7.2 Hz, 2H), 2.33 (s, 3H), 1.70−1.59
(m, 2H), 1.45−1.32 (m, 2H), 0.88 (t, J = 7.2 Hz, 3H); 13C NMR
(67.5 MHz, CDCl3) δ 136.9, 134.1, 129.7, 128.2, 38.5, 30.8, 21.6,
21.0, 13.6.
4.2.19. (n-Butyl)(n-octyl) disulfide (3hn). The title compound
was obtained as colorless liquid (38.1 mg, 54%); [Found: C,
61.69; H, 10.98; C12H26S2 required C, 61.47; H, 11.18%]; n(max)
1
(neat) 2926, 2855, 1464, 1378, 1270 cm-1; H NMR (270 MHz,
CDCl3) 2.72−2.66 (m, 4Η), 1.72−1.61 (m, 4H), 1.46−1.35 (m,
12H), 0.95−0.86 (m, 6H); 13C NMR (67.5 MHz, CDCl3) δ 39.2,
38.9, 31.8, 31.3, 29.2, 29.2, 29.1, 28.5, 22.6, 21.7, 14.1, 13.7.
4.2.20. (Methyl)(4-methylphenyl) disulfide (3ia). The title
compound was obtained as pale yellow liquid (36.1 mg, 71%);
[Found: C, 56.50; H, 5.87; C8H10S2 required C, 56.42; H, 5.92%];
n(max) (neat) 2927, 1423 cm-1; 1H NMR (270 MHz, CDCl3) 7.43
(d, J = 7.9 Hz, 2H), 7.15 (d, J = 7.9 Hz, 2H), 2.43 (s, 3H), 2.34 (s,
3H); 13C NMR (67.5 MHz, CDCl3) δ 137.3, 133.5, 129.8, 128.7,
22.9, 21.0.
4.2.13. (4-Methylphenyl)(n-octyl) disulfide (3an). The title
compound was obtained as pale yellow liquid (62.9 mg, 78%);
[Found: C, 67.29; H, 9.14; C15H24S2 required C, 67.10; H,
9.01%]; n(max) (neat) 2925, 2854, 1567, 1489, 1464, 1272 cm-1;
1H NMR (270 MHz, CDCl3) δ 7.43 (d, J = 8.2 Hz, 2H), 7.12 (d, J
= 8.2 Hz, 2H), 2.72 (t, J = 7.2 Hz, 2H), 2.32 (s, 3H), 1.71−1.60
(m, 2H), 1.36−1.23 (m, 10H), 0.87 (d, J = 6.8 Hz, 3H); 13C NMR
(67.5 MHz, CDCl3) δ 136.9, 134.2, 129.7, 128.3, 38.9, 31.8, 29.2,
28.7, 28.4, 22.6, 21.0, 14.1.
4.3 Typical procedure for sulfenamide from thiosulfonates
with amines: Synthesis of N-(4-Methylphenylthio)-N,N-
diethyl amine (6aa) (Table 3, entry 1)
4.3.1. N-(4-Methylphenylthio)-N,N-diethyl amine (6aa)
4.2.14. (Phenyl)(n-octyl) disulfide (3bn). The title compound was
obtained as colorless liquid (65.0 mg, 84%); [Found: C, 66.00; H,
8.64; C14H22S2 required C, 66.08; H, 8.71%]; n(max) (neat) 2925,
2853, 1580, 1476, 1438 cm-1; 1H NMR (270 MHz, CDCl3) δ
7.55−7.51 (m, 2H), 7.34−7.20 (m, 3H), 2.73 (t, J = 7.2 Hz, 2H),
1.71−1.60 (m, 2H), 1.32−1.24 (m, 10H), 0.87 (d, J = 6.8 Hz, 3H);
13C NMR (67.5 MHz, CDCl3) δ 137.7, 128.9, 127.4, 126.6, 38.9,
31.8, 29.1, 28.8, 28.4, 22.6, 14.1;
A mixture of S-4-methylphenyl 4-methylbenzenethiosulfonate
(83.5 mg, 0.3 mmol), diethylamine (43.9 mg, 0.6 mmol), CuI
(5.7 mg, 0.03 mmol) and bpy (4.7 mg, 0.03 mmol) in DMSO (0.3
mL) was stirred at 60 °C for 18 h in air. After the residue was
dissolved in Et2O, the solution was washed with H2O and
saturated sodium chloride and dried over anhydrous magnesium
sulfate. The crude product was distilled (150 °C/30Pa) after
chromatography on silica gel (hexane) to give N-(4-
Methylphenylthio)-N,N-diethyl amine 6aa (43.9 mg, 77%)4a:
colorless liquid; [Found: C, 67.53; H, 8.70; N, 7.07; C11H17NS:
C, 67.64; H, 8.77; N, 7.17%]; n(max) (neat) 2970, 2930, 2830,
2848, 1489, 1444, 1374, 1178 cm-1; 1H NMR (270 MHz, CDCl3)
δ 7.26 (d, J = 8.2 Hz, 2H), 7.10 (d, J = 8.2 Hz, 2H), 2.93 (q, J =
7.0 Hz, 4H), 2.32 (s, 3H), 1.19 (t, J = 7.0 Hz, 6H); 13C NMR
(67.5 MHz, CDCl3) δ 136.0, 129.3, 127.4, 124.3, 51.9, 21.0,
13.7.
4.2.15. (4-Methoxyphenyl)(n-octyl) disulfide (3cn). The title
compound was obtained as pale yellow liquid (70.5 mg, 83%);
[Found: C, 63.46; H, 8.54; C15H24OS2 required C, 63.33; H,
1
8.50%]; n(max) (neat) 2925, 2853, 1591, 1491, 1245 cm-1; H
NMR (270 MHz, CDCl3) δ 7.47 (d, J = 8.2 Hz, 2H), 6.86 (d, J =
8.2 Hz, 2H), 3.80 (s, 3H), 2.72 (t, J = 7.2 Hz, 2H), 1.71−1.60 (m,
2H), 1.36−1.24 (m, 10H), 0.87 (d, J = 5.9 Hz, 3H); 13C NMR
(67.5 MHz, CDCl3) δ 159.4, 131.6, 128.6, 114.6, 55.4, 38.9, 31.8,
29.1, 28.7, 28.5, 22.6, 14.1.
4.3.2. N-(4-Methylphenylthio)-N,N-(piperidyl)amine (6ab). The
title compound was obtained as colorless liquid (50.0 mg, 81%);
[Found: C, 69.35; H, 8.26.; N, 6.51; C12H17NS: C, 69.51; H, 8.26;
N, 6.76%]; n(max) (neat) 2934, 2817, 1595, 1489, 1450, 1217
4.2.16. (4-Chlorophenyl)(n-octyl) disulfide (3dn). The title
compound was obtained as colorless liquid (60.6 mg, 70%);
[Found: C, 58.27; H, 7.29; C14H21ClS2 required C, 58.20; H,
1
7.33%]; n(max) (neat) 2925, 2854, 1473, 1387 cm-1; H NMR
1
cm-1; H NMR (270 MHz, CDCl3) 7.38 (d, J = 7.9 Hz, 2H), 7.16
(270 MHz, CDCl3) δ 7.47−7.43 (m, 2H), 7.30−7.25 (m, 2H), 2.72
(t, J = 7.2 Hz, 2H), 1.70−1.59 (m, 2H), 1.36−1.24 (m, 10H), 0.87
(d, J = 6.8 Hz, 3H); 13C NMR (67.5 MHz, CDCl3) δ 136.3, 132.6,
129.0, 128.7, 39.0, 31.8, 29.1, 28.8, 28.4, 22.6, 14.1.
(d, J = 7.9 Hz, 2H), 2.88 (t, J = 5.4 Hz, 4H), 2.35 (s, 3H),
1.65−1.57 (m, 4H), 1.34−1.28 (m, 2H); 13C NMR (67.5 MHz,
CDCl3) δ 138.1, 132.3, 129.2, 124.3, 57.5, 27.3, 23.0, 21.2.
4.3.3. N-(4-Methylphenylthio)-N,N-(morpholyl)amine (6ac). The
title compound was obtained as colorless liquid (51.8 mg, 88%);
[Found: C, 63.09; H, 7.25; N, 6.69; C11H15NOS: C, 63.12; H,
7.22; N, 6.69%]; n(max) (CHCl3) 3012, 2960, 2856, 1596, 1490,
1216 cm-1; 1H NMR (270 MHz, CDCl3) 7.39 (d, J = 8.2 Hz, 2H),
7.18 (d, J = 8.2 Hz, 2H), 3.70-3.66 (m, 4H), 2.35 (s, 3H),
2.90−2.87 (m, 4H); 13C{1H} NMR (67.5 MHz, CDCl3) δ 138.9,
35.4, 133.1, 129.4, 67.6, 55.8, 21.2.
4.3.4. N-(4-Methylphenylthio)-N-(tert-butyl)amine (6ad)4a. The
title compound was obtained as colorless liquid (40.1 mg, 70%);
[Found: C, 67.42; H, 8.70; N, 7.11; C11H17NS: C, 67.64; H, 8.77;
N, 7.17%]; n(max) (neat) 3325, 2969, 1598, 1490, 1458, 1361,
4.2.17. (2-Methylphenyl)(n-octyl) disulfide (3fn). The title
compound was obtained as colorless liquid (56.4 mg, 70%);
[Found: C, 67.19; H, 9.05; C15H24S2 required C, 67.10; H,
1
9.01%]; n(max) (neat) 2925, 2853, 1589, 1463, 1272 cm-1; H
NMR (270 MHz, CDCl3) δ 7.72 (d, J = 7.6 Hz, 1H), 7.21−7.12
(m, 3H), 2.70 (t, J = 7.2 Hz, 2H), 2.40 (s, 3H), 1.69−1.61 (m, 2H),
1.37−1.32 (m, 10H), 0.87 (d, J = 6.8 Hz, 3H); 13C NMR (67.5
MHz, CDCl3) δ 136.9, 136.1, 130.3, 127.8, 126.7, 126.5, 38.7,
31.8, 29.1, 28.8, 28.5, 22.6, 19.9, 14.1.
4.2.18. (2-Bromophenyl)(n-octyl) disulfide (3gn). The title
compound was obtained as colorless liquid (57.7 mg, 58%);

ACCEPTED MANUSCRIPT
6
Tetrahedron
1
1204 cm-1; H NMR (270 MHz, CDCl3) 7.25 (d, J = 8.2 Hz,
MHz, CDCl3) δ 141.6, 132.5, 127.4, 125.8, 124.9, 116.7, 57.4,
2H), 7.08 (d, J = 8.2 Hz, 2H), 2.80 (br, 1H), 2.30 (s, 3H), 1.17 (s,
9H). 13C NMR (67.5 MHz, CDCl3) 140.8, 134.3, 129.2, 122.9,
54.8, 29.2, 20.9.
27.4, 23.3.
Supplementary data
Supplementary data associated with this article can be found in
the online version, at http://
4.3.5. N-(Phenylthio)-N,N-(piperidyl)amine (6bb). The title
compound was obtained as colorless liquid (43.0 mg, 74%);
[Found: C, 68.14; H, 7.79; N, 7.01; C11H15NS: C, 68.35; H, 7.82;
N, 7.25%]; n(max) (neat) 2934, 2849, 2818, 1584, 1475, 1439,
1217 cm-1; 1H NMR (270 MHz, CDCl3) 7.45−7.41 (m, 2H),
7.36−7.30 (m, 2H), 7.26−7.20 (m, 1H), 2.95 (t, J = 5.4 Hz, 4H),
1.67−1.59 (m, 4H), 1.40−1.31 (m, 2H); 13C NMR (67.5 MHz,
CDCl3) δ 136.3, 129.4, 128.5, 127.1, 57.6, 27.3, 23.1.
References and notes
1. (a) Comprehensive Organic Synthesis, Trost, B. M. Fleming, I.
Eds. Pergamon Press Ltd., New York, 1991, Vol. 4.
2. Selected reviews: (a) Metzner, P.; Thuillier, A. Sulfur Reagents in
Organic Synthesis; Katritzky, A. R.; Meth-Cohn, O.; Rees, C. W.
Eds.; Academic Press: San Diego, 1994. (b) Ley, S. V.; Thomas,
A. W. Angew. Chem. Int. Ed. 2003, 42, 5400–5449. (c) Kondo, T.;
Mitsudo, T. Chem. Rev. 2000, 100, 3205–3220. (d) Beletskaya, I.
P.; Ananikov, V. P. Chem. Rev. 2011, 111, 1596–1636. (e)
Partyka, D. V. Chem. Rev. 2011, 111, 1529–1595. (f) Allen, S. E.;
Walvoord, R. R.; Padilla-Salinas, R.; Kozlowski, M. C. Chem.
Rev. 2013, 113, 6234–6458.
4.3.6. N-(4-Methoxyphenylthio)-N,N-(piperidyl)amine (6cb). The
title compound was obtained as colorless liquid (49.1 mg, 73%);
[Found: C, 64.56; H, 7.67; N, 6.21; C12H17NOS: C, 64.53; H,
7.67; N, 6.27%]; n(max) (neat) 2934, 2817, 1587, 1491, 1287,
1246 cm-1; 1H NMR (270 MHz, CDCl3) 7.48 (d, J = 8.9 Hz, 2H),
6.90 (d, J = 8.9 Hz, 2H), 3.83 (s, 3H), 2.81 (t, J =5.4 Hz, 4H),
1.64−1.56 (m, 4H), 1.30−1.21 (m, 2H); 13C NMR (67.5 MHz,
CDCl3) δ 160.5, 137.5, 136.6, 113.8, 57.2, 55.3, 27.3, 22.9.
3. Selected reviews of previous methods: (a) Davis, F. A. J. Org.
Chem. 2006, 71, 8993–9003. (b) Craine, L.; Raban, M. Chem.
Rev. 1989, 89, 689–712.
4. Recent synthesis of sulfur-heteroatom bonds: Selected paper of S-
N bond formation: (a) Taniguchi, N. Synlett 2007, 1917–1920. (b)
Taniguchi, N. Eur. J. Org. Chem. 2010, 2670–2673. (c) Lee, C.;
Lim, Y. N.; Jang, H.-Y. Eur. J. Org. Chem. 2015, 5934–5938. (d)
Sakagami, K.; Jin, X.; Suzuki, K.; Yamaguchi, K.; Mizuno, N.
Chem. Lett. 2016, 45, 173–175. (e) Taniguchi, N. Eur. J. Org.
Chem. 2016, 2157–2162. Selected paper of S-P bond formation:
(a) Zhu, Y.; Chen, T.; Li, S.; Shimada, S.; Han, L.-B. J. Am.
Chem. Soc, 2016, 138, 5825–5828. (b) Kumaraswamy, G.; Raju,
R. Adv. Synth. Catal. 2014, 356, 2591–2598. (c) Bai, J.; Cui, X.;
Wang, H.; Wu, Y. Chem. Comm. 2014, 50, 8860–8863. (d)
Kaboudin, B.; Abedi, Y.; Kato, J.-Y.; Yokomatsu, T. Synthesis
2013, 45, 2323–2327.
4.3.7. N-(4-Bromophenylthio)-N,N-(piperidyl)amine (6db). The
title compound was obtained as pale yellow liquid (62.8 mg,
77%); [Found: C, 48.65; H, 5.24; N, 5.18; C11H14BrNS: C, 48.54;
H, 5.18; N, 5.15%]; n(max) (neat) 2934, 2818, 1566, 1468, 1384,
1216 cm-1; 1H NMR (270 MHz, CDCl3) 7.45 (d, J = 7.9 Hz, 2H),
7.27 (d, J = 7.9 Hz, 2H), 2.93 (t, J = 5.4 Hz, 4H), 1.67−1.59 (m,
4H), 1.42−1.35 (m, 2H); 13C NMR (67.5 MHz, CDCl3) δ 136.1,
131.6, 130.2, 120.7, 57.6, 27.3, 23.1.
4.3.8. N-(4-Chlorophenylthio)-N,N-(piperidyl)amine (6fb). The
title compound was obtained as colorless liquid (44.4 mg, 65%);
[Found: C, 57.80; H, 6.08; N, 5.98; C11H14ClNS: C, 58.01; H,
6.20; N, 6.15%]; n(max) (neat) 2935, 2818, 1568, 1472, 1268 cm-
5. (a) Taniguchi, N. Eur. J. Org. Chem. 2014, 5691–5694. (b)
Taniguchi, N. J. Org. Chem. 2015, 80, 1764–1770.
6. (a) Yoshida, S.; Sugimura, Y.; Hazama, Y.; Nishimura, Y.; Yan,
T.; Shimizu, S.; Hosoya, T.; Chem. Comm. 2015, 51, 16613–
166616. (b) Rao, B.; Tang, J.; Zeng, X. Org. Lett. 2016, 18, 4154–
4157. (c) Mampuys, P.; Zhu, Y.; Sergeyev, S.; Ruijter, E.; Orru,
R. V.; Van Doorslaer, S.; Maes, B. U. Org. Lett. 2016, 18, 2808–
2811.
1
1; H NMR (270 MHz, CDCl3) 7.38−7.25 (m, 4H), 2.93 (t, J =
5.4 Hz, 4H), 1.67−1.59 (m, 4H), 1.41−1.35 (m, 2H); 13C NMR
(67.5 MHz, CDCl3) δ 132.9, 130.4, 129.2, 128.7, 57.6, 27.3,
23.1.
7. Other methods: (a) Mukaiyama, T.; Takahashi, Tetrahedron Lett.
1968, 9, 5907–5908. (b) Furukawa, M.; Suda, T.; Tsukamoto, A.;
Hayashi, S. Synthesis 1975, 165–167. (c) Witt, D.; Antoniow, S.
Synthesis 2007, 363-366. (d) Vandavasi, J. K.; Hu, P.; Chen, C.-
Y.; Wang, J. J. Tetrahedron 2011, 67, 8895–8903. (e) Bao, M.;
Shimizu, M. Tetrahedron 2003, 59, 9655–9659. (f) Xiao, X.;
Feng, M.; Jiang, X. Chem. Comm. 2015, 51, 4208–4211.
8. Metal-catalyzed coupling reactions: (a) Arisawa, M.; Yamaguchi,
M. J. Am. Chem. Soc. 2003, 125, 6624–6625. (b) Tanaka, K.;
Ajiki, K. Tetrahedron Lett. 2004, 45, 5677–5679.
4.3.9. N-(4-Nitrophenylthio)-N,N-(piperidyl)amine (6gb). The
title compound was obtained as yellow solid (54.3 mg, 76%); mp
32−33 °C; [Found: C, 55.40; H, 5.92; N, 11.71; C11H14N2O2S: C,
55.44; H, 5.92; N, 11.76%]; n(max) (CHCl3) 3022, 2939, 2827,
1578, 1511, 1337, 1107 cm-1; 1H NMR (270 MHz, CDCl3)
8.16−8.12 (m, 2H), 7.41−7.36 (m, 2H), 3.09−3.05 (m, 4H),
1.75−1.66 (m, 4H), 1.56−1.50 (m, 2H); 13C NMR (67.5 MHz,
CDCl3) δ 151.8, 123.9, 123.9, 122.2, 57.5, 27.2, 23.1.
9. (a) Swan, J. M. Nature 1957, 180, 643-645. (b) Alonso, M. E.;
Aragona, H. Org. Synth. 1978, 58, 147. (c) Hiver, P.; Dicko, A.;
Paquer, D. Tetrahedron Lett. 1994, 35, 9569–9572.
10. (a) Boustany, K. S.; Sullivan, A. B. Tetrahedron Lett. 1970, 11,
3547–3549. (b) Harpp, D. N.; Ash, D. K.; Back, T. G.; Gleason, J.
G.; Orwig, B. A.; Van Horn, T. F. Tetrahedron Lett. 1970, 11,
3351–3554. (c) Klose, J.; Reese, C. B.; Song, Q. Tetrahedron
1997, 53, 14411–14416. (d) Abe, Y.; Nakabayashi, T.; Tsurugi, J.
Bull. Chem. Soc. Jpn. 1973, 46, 1898–1899.
4.3.10. N-(2-Methylphenylthio)-N,N-(piperidyl)amine (6hb). The
title compound was obtained as colorless liquid (50.7 mg, 82%);
[Found: C, 69.59; H, 8.19; N, 6.64; C12H17NS: C, 69.51; H, 8.26;
N, 6.76%]; n(max) (neat) 3059, 2934, 2816, 1589, 1463, 1217
cm-1; 1H NMR (270 MHz, CDCl3) 7.57 (d, J = 7.9 Hz, 1H),
7.24−7.07 (m, 3H), 2.99 (t, J = 5.4 Hz, 4H), 2.26 (s, 3H),
1.70−1.62 (m, 4H), 1.47−1.41 (m, 2H); 13C NMR (67.5 MHz,
CDCl3) δ 137.8, 134.2, 130.1, 126.0, 125.9, 125.5, 57.6, 27.4,
23.3, 19.3.
11. Hunter, R.; Caira, M.; Stellenboom, N. J. Org. Chem. 2006, 71,
8268–8271.
12. Parsons, T. F.; Buckman, J. D.; Pearson, D. E.; Field, L. J. Org.
Chem. 1965, 30, 1923–1926.
4.3.11. N-(2-Bromophenylthio)-N,N-(piperidyl)amine (6ib). The
title compound was obtained as colorless liquid (58.7 mg, 72%);
[Found: C, 48.15; H, 5.15; N, 5.04; C11H14BrNS: C, 48.54; H,
5.18; N, 5.15%]; n(max) (neat) 2934, 2820, 1574, 1441, 1216 cm-
1; 1H NMR (270 MHz, CDCl3) 7.54 (dd, J = 8.2 and 1.3 Hz, 1H),
7.43 (dd, J = 7.9 and 1.3 Hz, 1H), 7.31 (ddd, J = 7.5, 8.2 and 1.3
Hz, 1H), 6.96 (ddd, J = 7.5, 7.9 and 1.3 Hz, 1H), 3.06 (t, J = 5.4
Hz, 4H), 1.73−1.65 (m, 4H), 1.54−1.45 (m, 2H); 13C NMR (67.5
13. The reaction never gave a corresponding sulfonamide.
14. Field, L.; Buckman, J. D. J. Org. Chem. 1967, 32, 3467–3470.
15. (a) Fossey, J.; Lefort, D.; Sorba, J. Free Radicals in Organic
Chemistry; John Wiley &Sons: New York, 1995. (b) Radicals in
Organic Synthesis; Renaud, P.; Sibi, M. P. Eds.; Wiley-VCH:
Weinheim, 2001.
16. Kochi, J. K.; Organometallic Mechanisms And Catalysis;
Academic Press: San Diego, 1978.