PIFA-Mediated Synthesis of Acylsulfenic Acid Alkyl Esters and Benzoyl Alkyl Disulfides from Thioacids

Article abstract of DOI:10.1055/s-0036-1588070

A simple and convenient approach for the synthesis of acylsulfenic acid alkyl esters and benzoyl alkyl disulfides from thiobenzoic acids is described. This reaction uses commercially available [bis(trifluoroacetoxy)iodo]benzene (PIFA) as an oxidant under mild reaction conditions.

Full text of DOI:10.1055/s-0036-1588070

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2016, 48, A–F
paper
A
C.-H. Tsai et al.
Paper
Synthesis
PIFA-Mediated Synthesis of Acylsulfenic Acid Alkyl Esters and
Benzoyl Alkyl Disulfides from Thioacids
Chia-Hsuan Tsaia
Daggula Mallikarjuna Reddya
Ping-An Hsieha
PIFA (1.0 equiv)
R1OH (2 mL)
O
PIFA (2.0 equiv)
R
O
O
2SH (3.0 equiv)
OR1
S
Ar
S
R2
Ar
SH
Ar
S
r.t., 24 h
DCE, r.t., 24 h
Yi-Chen Liua
Mohanraj Kandasamyb
Wei-Yu Lin*b
9 examples
up to 92% yield
8 examples
up to 61% yield
Chin-Fa Lee*a
a Department of Chemistry, National Chung Hsing University,
Taichung, 402, Taiwan, R.O.C.
cfalee@dragon.nchu.edu.tw
b Department of Medicinal and Applied Chemistry, Kaohsiung
Medical University, Kaohsiung, 806, Taiwan, R.O.C.
wylin@kmu.edu.tw
Received: 06.07.2016
Accepted after revision: 17.08.2016
Published online: 28.09.2016
O
O
O
OMe
S
CH2N2
CH2Cl2
OH
m-CPBA
S
SH
DOI: 10.1055/s-0036-1588070; Art ID: ss-2016-f0475-op
(a)
CH2Cl2
7%
Abstract A simple and convenient approach for the synthesis of acyl-
sulfenic acid alkyl esters and benzoyl alkyl disulfides from thiobenzoic
acids is described. This reaction uses commercially available [bis(trifluo-
roacetoxy)iodo]benzene (PIFA) as an oxidant under mild reaction condi-
tions.
NHAc
O
O
O
S
O
H2N
SMe
S
SH
S
+
25 °C
(b)
Me
(solvent-free)
Key words thioacids, alcohols, thiols, oxidations, PIFA, acylsulfenic
acid alkyl esters, disulfides
67%
O
O
S
OH
Acylsulfenic acids [compounds with the general formu-
la RC(O)SOH] are known as metabolic intermediates for the
transformation of COOH to COSH,1 and derivatives of acyl-
sulfenic acids, especially methyl esters, were found in a cul-
ture medium of Pseudomonas putida.2–4 Hubner and co-
workers5 developed a method for the synthesis of alkyl es-
ters of acylsulfenic acids by treatment of diazomethane
with acylsulfenic acid, which in turn was prepared by oxi-
dation of thioacid in the presence of m-CPBA (Scheme 1, a).
However, this method has substantial disadvantages, such
as low yield and the use of toxic diazomethane as the al-
kylating agent.
Alkyl or acyl disulfides play a particularly vital role in
chemistry and biology.6 Acyl disulfides, in particular mono-
acyl disulfides, have come into use as mediators for peptide
bond formation between unprotected peptide segments.7
Generally, alkyl or acyl disulfides can be synthesized by the
oxidation of thiols or thiocarboxylates under controlled
conditions.8 Alkyl disulfides are generally synthesized by
using 2,2′-dithiobis(benzothiazole),9 where the benzothi-
azole is the resultant fragment in the products. In other
methods, dithio compounds are synthesized from symmet-
rical disulfides by oxidative coupling by using rhodium
DDQ
S
OH
n
SH
+
HS
CH2Cl2
0 °C, 5 min
n
(c)
85% (n = 3)
72% (n = 4)
Scheme 1 Previous methods for the construction of S–O and S–S
bonds
metal,10 with sulfenic acid and thiosulfenate intermediates
as precursors.11 Tajbakhsh and co-workers12 demonstrated
the synthesis of alkyl or acyl disulfides from the corre-
sponding alkyl or acyl halides by using sulfur and quaterna-
ry diammonium borohydrides as reagents under mild con-
ditions. All these methods are limited to the synthesis of ei-
ther symmetrical or unsymmetrical dialkyl or diacyl
disulfides. However, alkyl acyl disulfides have received less
attention in literature. Fujiki et al.13 reported the synthesis
of alkyl benzoyl disulfides from thiobenzoic acids and alkyl
aryl thiosulfonates under solvent-free conditions (Scheme
1, b). The main drawback of this reaction is the use of com-
mercially unavailable alkyl aryl thiosulfonates. Later, Wang
and co-workers14 synthesized alkyl benzoyl disulfides from
thiobenzoic acids and thiols by using DDQ as an oxidant
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F

B
C.-H. Tsai et al.
Paper
Synthesis
(Scheme 1, c). However, this method was generalized to di-
alkyl disulfides, but not to alkyl benzoyl disulfides (only
two examples were reported).
Table 1 Optimization of the Reaction Conditionsa
O
O
O
SH
oxidant, EtOH
temp, time
Recently, our research group developed the syntheses of
aryl sulfides15 and thiophosphates16 by treatment of thiols
with NCS, followed by quenching with Grignard reagents
and dialkyl phosphites, respectively (Scheme 2). As part of
our research interest in sulfur coupling,17 herein we report
a novel approach for the synthesis of acylsulfenic acid alkyl
esters and alkyl benzoyl disulfides via oxidative coupling of
thioacids with alcohols or alkyl sulfides in the presence of
[bis(trifluoroacetoxy)iodo]benzene (PIFA).
S
Et
1a
2a
Entry
Oxidant (equiv)
Temp
Time (h)
Yield (%)b,c
1
2
NBS (1.0)
NCS (1.0)
NIS (1.0)
PIDA (1.0)
PIDA (1.0)
PIDA (1.0)
PIDA (2.0)
PIFA (1.0)
PIFA (1.0)
DDQ (1.0)
AgNO3
r.t.
24
24
24
24
24
24
24
24
48
24
24
24
24
n.d.c
n.d.c
n.d.c
50
r.t.
3
r.t.
4
r.t.
ArMgX
5
50 °C
70 °C
r.t.
49
R-S-Ar
toluene
NCS
6
36
R-SH
O
(R1O)2POH
r.t.
7
49
(R1O)2P-SR
MeCN
8
r.t.
r.t.
61
Scheme 2 NCS-mediated syntheses of aryl sulfides and thiophos-
phates
9
59
10
11
12
13
r.t.
n.d.c
n.d.c
n.d.c
n.d.c
r.t.
For the optimization, we examined the feasibility of us-
ing thiobenzoic acid (1a) as substrate to react with an alco-
hol, to form the S–O bond (Table 1). Firstly, when thioben-
zoic acid (1a) was treated with ethanol in the presence of
NBS, the reaction failed to form the S–O bond (entry 1).
When we treated thiobenzoic acid with ethanol in the pres-
ence of NCS or NIS instead of NBS, this also failed to give S–
O bond formation (entries 2 and 3). Fortunately, when (di-
acetoxyiodo)benzene (PIDA) was used as coupling reagent,
the desired product, benzoylsulfenic acid ethyl ester (2a),
was obtained at room temperature in a 50% isolated yield
(entry 4). Increasing the temperature of the reaction or the
amount of PIDA did not improve the yield of the product
(entries 5, 6, and 7). Best results were obtained when thio-
benzoic acid (1 mmol) was treated with ethanol (2 mL) in
the presence of PIFA (1.0 equiv) at room temperature for 24
hours to afford the product in 61% isolated yield (entry 8).
No improvements were observed by leaving the reaction to
run for a longer time (entry 9). Other oxidants such as DDQ,
AgNO3, PCC and CAN failed to give the desired product (en-
tries 10–13). The decrease in yield of product or failure of
the reaction is due to the formation of undesired ethyl ben-
zoate as byproduct.
PCC
r.t.
CAN
r.t.
a Reaction conditions: 1a (1.0 mmol), oxidant (1.0 equiv), EtOH (2.0 mL),
temp, time, under N2.
b Isolated yield; n.d. = not detected.
c Ethyl benzoate was detected by GC-MS analysis.
O
O
PIFA (1.0 equiv)
ROH (2 mL)
OR
SH
S
r.t., 24 h
1a
2
O
O
O
O
O
S
O
S
S
2b, 55%
2a, 61%
2c, 58%
O
S
O
O
O
O
O
S
S
2f, 50%
2e, 28%
2d, 38%
With these optimized reaction conditions in hand, we
treated thiobenzoic acid (1a) with different types of alco-
hols in the presence of PIFA at ambient temperature and
obtained the corresponding products (2a–h) in moderate to
good yields (Scheme 3). Alcohols such as ethylene glycol,
ethanolamine, and phenols failed to give the desired prod-
ucts.
Next, our attention was focused on the synthesis of di-
sulfides (Table 2). For the optimization, we chose thioben-
zoic acid (1a) as the substrate to react with the alkanethiol.
O
O
O
O
S
S
2g, 48%
2h, 47%
Scheme 3 Scope of the S–O bond formation. Reagents and conditions:
1a (1.0 mmol), PIFA (1.0 equiv), ROH (2.0 mL), r.t., 24 h, under N2; iso-
lated yields are given.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F

C
C.-H. Tsai et al.
Paper
Synthesis
To afford the S–S bonds, the amount of alkanethiol used in
the reaction was minimized, due to the unpleasant smell of
thiols. Thus, we treated thiobenzoic acid (1a) with ethane-
thiol (3.0 equiv) in the presence of PIFA (1.0 equiv) in DCE at
room temperature for 24 hours, to yield the desired benzoyl
ethyl disulfide (3a) in 36% isolated yield (entry 1). The use
of 2.0 equivalents of PIFA as oxidant and 3.0 equivalents of
ethanethiol in this coupling reaction afforded benzoyl ethyl
disulfide (3a) in 92% yield (entry 2). Several other common
solvents such as diethyl ether, THF, DMF, ethyl acetate, 1,4-
dioxane, MTBE, and CH2Cl2 were also tested in the S–S cou-
pling (entries 4–10), but, unfortunately, all of them gave
less satisfactory results. We also detected diethyl disulfide
as byproduct by GC-MS analysis.
thiol benzenethiol failed to give the corresponding acyl allyl
and acyl aryl disulfides; the failure of these reactions are
due to the formation of diallyl and diaryl sulfides.
O
O
PIFA (2.0 equiv)
R1SH (3.0 equiv)
S
SH
S
R1
DCE, r.t., 24 h
R
R
1
3
R = H, Me, t-Bu
O
O
O
S
S
S
S
S
Et
S
C6H13
3a, 92%
3b, 74%
3c, 77%
O
O
O
S
Table 2 Optimization of the S–S Bond Formationa
S
S
S
S
S
C12H23
O
O
PIFA (2.0 equiv)
EtSH (3.0 equiv)
S
3d, 86%
3e, 85%
SH
3f, 33%
S
Et
solvent, r.t., 24 h
O
O
O
S
S
S
1a
S
3a
S
Et
S
C6H13
Et
Entry
Solvent
Yield (%)b
3h, 45%
3g, 52%
3i, 30%
1
2
DCE
36c
92
86d
53
65
11
20
21
30
38
Scheme 4 Scope of the S–S bond formation. Reagents and conditions: 1
(1.0 mmol), PIFA (2.0 equiv), R1SH (3.0 equiv), DCE (3.0 mL), r.t., 24 h,
under N2; isolated yields are given.
DCE
3
DCE
4
CH2Cl2
Et2O
While the exact mechanism of this oxidative coupling is
not clear at this stage, the results seem to be consistent
with the proposed coupling shown in Scheme 5. This cou-
pling is likely to be initiated by PIFA to form either transient
species A (path A) or B (path B) via nucleophilic attack of
thioacid or alcohol or alkanethiol with PIFA. Alcohol or al-
kanethiol will react with intermediate A affording product
5
6
THF
7
DMF
8
1,4-dioxane
EtOAc
MTBE
9
10
a Reaction conditions: 1a (1.0 mmol), PIFA (2.0 equiv), EtSH (3.0 equiv),
solvent, r.t., 24 h, under N2.
O
b Isolated yield.
OCOCF3
EtXH
c PIFA (1.0 equiv) used.
d After 48 h.
Ph
SH
I
Ph
SCOPh
1a
path A
X = O or S
A
With these promising results in hand, we chose a vari-
ety of linear and branched alkanethiols to react with thio-
benzoic acid (1a) in the presence of PIFA to obtain the cor-
responding disulfides 3a–e in very good yields (Scheme 4).
We also identified the formation of dialkyl disulfides as by-
products in the reaction. When phenylmethanethiol was
used, the corresponding disulfide 3f was produced in mod-
erate yield (Scheme 4), the decrease in yield due to the ease
of formation of dibenzyl disulfide as a major byproduct. To
increase the scope of the reaction, we also used other thio-
acids such as 4-methylthiobenzoic acid (1b) and 4-tert-but-
ylthiobenzoic acid (1c) to react with alkanethiols, and ob-
tained disulfides 3g–i in moderate to good yields (Scheme
4). On the other hand, prop-2-ene-1-thiol and the aromatic
OCOCF3
O
I
X
Ph
OCOCF3
Ph
S
Et
2a or 3a
path B
OCOCF3
EtXH
O
I
X = O or S
X
Ph
Ph
SH
Et
1a
B
X = S
EtSH
– PhI
– EtSH
EtSSEt
Scheme 5 Plausible mechanism
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F

D
C.-H. Tsai et al.
Paper
Synthesis
2 or 3 upon removal of iodobenzene. On the other hand, al-
cohol or alkanethiol or thioacid can react with species B to
give either the desired product or the homocoupling prod-
uct (ethyl disulfide in this case).
In summary, we have developed a simple and conve-
nient protocol for the synthesis of acylsulfenic acid alkyl es-
ters and benzoyl alkyl disulfides in moderate to good yields
at ambient temperatures, by using thioacids with commer-
cially available alcohols or alkanethiols and PIFA. We antici-
pate that this strategy of oxidative coupling may lead to a
wide range of applications in synthetic chemistry.
HRMS (EI): m/z [M]+ calcd for C11H14O2S: 210.0715; found: 210.0711.
Benzoylsulfenic Acid Isopropyl Ester (2d)
Colorless liquid; yield: 74.5 mg (38%); Rf = 0.50 (5% EtOAc in hexanes).
1H NMR (400 MHz, CDCl3): δ = 7.75 (d, J = 8.0 Hz, 2 H), 7.55–7.62 (m, 1
H), 7.42–7.48 (m 2 H), 4.00–4.07 (m, 1 H), 1.38 (d, J = 8.8 Hz, 6 H).
13C NMR (100 MHz, CDCl3): δ = 195.5, 134.1, 133.7, 128.9, 125.9, 82.6,
22.3.
HRMS (EI): m/z [M]+ calcd for C10H12O2S: 196.0558; found: 196.0550.
Benzoylsulfenic Acid tert-Butyl Ester (2e)
Colorless liquid; yield: 60.0 mg (28%); Rf = 0.52 (5% EtOAc in hexanes).
1H NMR (400 MHz, CDCl3): δ = 7.79 (d, J = 7.6 Hz, 2 H), 7.56–7.60 (m, 1
Chemicals were purchased from commercial suppliers and used
without further purification. All reactions were carried out under an
inert atmosphere. Flash chromatography was performed on Merck
silica gel 60 (230–400 mesh). NMR spectra were recorded on a Varian
Unity Inova-600 or a Varian Mercury-400 instrument; CDCl3 was
used as solvent. Chemical shifts are reported in parts per million
(ppm) and referenced to the residual solvent resonance. GC-MS anal-
yses were performed on an HP 5890 GC instrument equipped with HP
5972 MS. High-resolution mass spectra were carried out on a Jeol
JMS-HX 110 spectrometer by the services at the National Chung
Hsing University.
H), 7.42–7.49 (m, 2 H), 1.40 (s, 9 H).
13C NMR (100 MHz, CDCl3): δ = 195.8, 134.3, 133.6, 128.9, 126.0, 84.6,
27.5.
HRMS (ESI): m/z [M + Na]+ calcd for C11H14NaO2S: 233.0612; found:
233.0611.
Benzoylsulfenic Acid Cyclohexyl Ester (2f)
Colorless liquid; yield: 118.4 mg (50%); Rf = 0.50 (5% EtOAc in hex-
anes).
1H NMR (400 MHz, CDCl3): δ = 7.75 (d, J = 7.6 Hz, 2 H), 7.57–7.61 (m, 1
H), 7.40–7.46 (m, 2 H), 3.72–3.77 (m, 1 H), 2.10–2.14 (m, 2 H), 1.77–
1.81 (m, 2 H), 1.51–1.60 (m, 3 H), 1.22–1.37 (m, 3 H).
Benzoylsulfenic Acid Alkyl Esters 2; General Procedure
13C NMR (100 MHz, CDCl3): δ = 195.6, 134.1, 133.7, 128.9, 125.9, 87.4,
32.3, 25.3, 23.8.
HRMS (EI): m/z [M]+ calcd for C13H16O2S: 236.0871; found: 236.0866.
An oven-dried Schlenk tube was charged with PIFA (0.430 g, 1.0
mmol) and alcohol (2 mL). To this stirred solution was added thioben-
zoic acid (1a; 1.0 mmol) at r.t., and the mixture was stirred for 24 h.
After completion of the reaction, low volatiles were removed under
vacuum. The residue was purified by column chromatography (silica
gel, hexane–EtOAc) to afford 2.
Benzoylsulfenic Acid Cyclopentyl Ester (2g)
Colorless liquid; yield: 106.7 mg (48%); Rf = 0.48 (5% EtOAc in hex-
anes).
Benzoylsulfenic Acid Ethyl Ester (2a)
1H NMR (400 MHz, CDCl3): δ = 7.74 (d, J = 8.4 Hz, 2 H), 7.56–7.60 (m, 1
H), 7.42–7.46 (m, 2 H), 4.43 (m, 1 H), 1.99–2.04 (m, 2 H), 1.76–1.85
(m, 4 H), 1.57–1.63 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 195.5, 134.1, 133.7, 128.9, 125.9, 91.8,
33.2, 23.3.
Colorless liquid; yield: 111.2 mg (61%); Rf = 0.51 (5% EtOAc in hex-
anes).
1H NMR (400 MHz, CDCl3): δ = 7.64 (d, J = 8.4 Hz, 2 H), 7.45–7.52 (m, 1
H), 7.34–7.40 (m, 2 H), 3.97 (q, J = 7.2 Hz, 2 H), 1.31 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 195.3, 134.0, 133.8, 128.9, 125.9, 75.6,
HRMS (APCI): m/z [M + H]+ calcd for C12H15O2S: 223.0793; found:
223.0777.
15.7.
HRMS (EI): m/z [M]+ calcd for C9H10O2S: 182.0402; found: 182.0396.
Benzoylsulfenic Acid Benzyl Ester (2h)
Benzoylsulfenic Acid Methyl Ester (2b)5
Colorless liquid; yield: 115.0 mg (47%); Rf = 0.49 (5% EtOAc in hex-
anes).
1H NMR (400 MHz, CDCl3): δ = 7.72–7.74 (m, 2 H), 7.56–7.60 (m, 1 H),
7.36–7.56 (m, 7 H), 4.98 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 195.0, 136.2, 133.9, 129.6, 129.0,
128.8, 128.5, 128.3, 125.9, 80.8.
Colorless liquid; yield: 92.5 mg (55%); Rf = 0.49 (5% EtOAc in hexanes).
1H NMR (400 MHz, CDCl3): δ = 7.73 (d, J = 7.2 Hz, 2 H), 7.55–7.62 (m, 1
H), 7.42–7.48 (m, 2 H), 3.93 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 195.1, 133.9, 133.9, 129.0, 125.9, 66.8.
HRMS (EI): m/z [M]+ calcd for C8H8O2S: 168.0245; found: 168.0246.
HRMS (ESI): m/z [M + Na]+ calcd for C11H12NaO2S: 267.0456; found:
267.0455.
Benzoylsulfenic Acid n-Butyl Ester (2c)
Colorless liquid; yield: 122.0 mg (58%); Rf = 0.51 (5% EtOAc in hex-
anes).
Benzoyl Alkyl Disulfides 3; General Procedure
1H NMR (400 MHz, CDCl3): δ = 7.73 (d, J = 6.8 Hz, 2 H), 7.56–7.62 (m, 1
H), 7.42–7.48 (m, 2 H), 4.01 (t, J = 6.8 Hz, 2 H), 1.71–1.77 (m, 2 H),
1.44–1.49 (m, 2 H), 0.94 (t, J = 7.2 Hz, 3 H).
A dry Schlenk tube was charged with PIFA (0.860 g, 2.0 mmol) and
DCE (3 mL). To the stirred solution was added thiobenzoic acid (0.125
mL, 1.0 mmol) and the thiol (3.0 mmol) at r.t., and the mixture was
13C NMR (100 MHz, CDCl3): δ = 195.3, 134.0, 133.7, 128.9, 125.8, 79.9,
32.2, 18.8, 13.7.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F

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C.-H. Tsai et al.
Paper
Synthesis
stirred for 24 h. After completion of the reaction, low volatiles were
removed under vacuum. The resulting residue was purified by col-
umn chromatography (silica gel, hexane–EtOAc) to afford 3.
HRMS (APCI): m/z [M + H]+ calcd for C13H17OS2: 253.0721; found:
253.0710.
Benzoyl Benzyl Disulfide (3f)13
Benzoyl Ethyl Disulfide (3a)
White solid; mp 53–54.0 °C; yield: 86.0 mg (33%); Rf = 0.47 (5% EtOAc
Colorless liquid; yield: 182.2 mg (92%); Rf = 0.50 (5% EtOAc in hex-
in hexanes).
anes).
1H NMR (400 MHz, CDCl3): δ = 7.93 (d, J = 7.2 Hz, 2 H), 7.56–7.60 (m, 1
H), 7.40–7.48 (m, 2 H), 7.23–7.38 (m, 5 H), 3.98 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 189.8, 136.0, 135.6, 133.9, 129.4,
128.8, 128.5, 127.6, 127.6, 42.6.
1H NMR (400 MHz, CDCl3): δ = 7.90 (d, J = 7.2 Hz, 2 H), 7.49–7.55 (m, 1
H), 7.35–7.40 (m, 2 H), 2.71 (q, J = 7.6 Hz, 2 H), 1.23 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 190.4, 135.7, 133.9, 128.8, 127.6, 32.6,
14.2.
HRMS (APCI): m/z [M + H]+ calcd for C14H13OS2: 261.0408; found:
261.0395.
HRMS (APCI): m/z [M + H]+ calcd for C9H11OS2: 199.0251; found:
199.02454.
Ethyl 4-Methylbenzoyl Disulfide (3g)
Benzoyl sec-Butyl Disulfide (3b)
Colorless liquid; yield: 110.3 mg (52%); Rf = 0.51 (5% EtOAc in hex-
Colorless liquid; yield: 167.3 mg (74%); Rf = 0.51 (5% EtOAc in hex-
anes).
anes).
1H NMR (400 MHz, CDCl3): δ = 7.86 (d, J = 8.0 Hz, 2 H), 7.23 (d, J = 8.0
Hz, 2 H), 3.06 (q, J = 7.2 Hz, 2 H), 2.39 (s, 3 H), 1.34 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 191.6, 144.0, 134.7, 129.1, 127.1, 23.3,
1H NMR (400 MHz, CDCl3): δ = 8.00 (d, J = 8.4 Hz, 2 H), 7.56–7.62 (m, 1
H), 7.41–7.49 (m, 2 H), 2.84–2.96 (m, 1 H), 1.64–1.78 (m, 1 H), 1.52–
1.60 (m, 1 H), 1.31 (d, J = 6.4 Hz, 3 H), 1.03 (t, J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 190.4, 135.6, 133.7, 128.7, 127.5, 48.1,
28.8, 19.7, 11.3.
21.6, 14.8.
HRMS (ESI): m/z [M]+ calcd for C10H12OS2: 212.0330; found: 212.1172.
HRMS (APCI): m/z [M + H]+ calcd for C11H15OS2: 227.0564; found:
227.0555.
4-tert-Butylbenzoyl Ethyl Disulfide (3h)
Colorless liquid; yield: 114.2 mg (45%); Rf = 0.50 (5% EtOAc in hex-
anes).
Benzoyl n-Hexyl Disulfide (3c)
1H NMR (400 MHz, CDCl3): δ = 7.90 (d, J = 8.4 Hz, 2 H), 7.45 (d, J = 8.4
Hz, 2 H), 3.06 (q, J = 7.6 Hz, 2 H), 1.26–1.36 (m, 12 H).
13C NMR (100 MHz, CDCl3): δ = 191.6, 156.9, 134.6, 127.0, 125.4, 31.1,
Colorless liquid; yield: 196.0 mg (77%); Rf = 0.49 (5% EtOAc in hex-
anes).
1H NMR (400 MHz, CDCl3): δ = 7.99 (d, J = 6.4 Hz, 2 H), 7.56–7.62 (m, 1
H), 7.42–7.52 (m, 2 H), 2.78 (t, J = 7.6 Hz, 2 H), 1.64–1.71 (m, 2 H),
1.26–1.45 (m, 6 H), 0.88 (t, J = 6.0 Hz, 3 H).
29.7, 23.3, 14.8.
HRMS (APCI): m/z [M + H]+ calcd for C13H19OS2: 255.0877; found:
255.0863.
13C NMR (100 MHz, CDCl3): δ = 190.4, 135.7, 133.9, 128.8, 127.6, 38.7,
31.3, 28.9, 28.1, 22.5, 14.0.
HRMS (APCI): m/z [M + H]+ calcd for C13H19OS2: 255.0877; found:
255.0826.
4-tert-Butylbenzoyl n-Hexyl Disulfide (3i)
Colorless liquid; yield: 93.4 mg (30%); Rf = 0.51 (5% EtOAc in hexanes).
1H NMR (400 MHz, CDCl3): δ = 7.91 (d, J = 8.6 Hz, 2 H), 7.44 (d, J = 8.6
Hz, 2 H), 3.05 (t, J = 7.2 Hz, 2 H), 1.62–1.70 (m, 2 H), 1.26–1.48 (m, 15
H), 0.89 (t, J = 6.0 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 191.5, 156.8, 134.6, 127.1, 125.4, 35.0,
31.3, 31.0, 29.6, 28.8, 28.5, 22.5, 14.0.
Benzoyl n-Dodecyl Disulfide (3d)
Colorless liquid; yield: 290.8 mg (86%); Rf = 0.50 (5% EtOAc in hex-
anes).
1H NMR (400 MHz, CDCl3): δ = 7.98 (d, J = 8.0 Hz, 2 H), 7.56–7.62 (m, 1
H), 7.40–7.48 (m, 2 H), 2.77 (t, J = 6.4 Hz, 2 H), 1.61–1.69 (m, 2 H), 1.40
(t, J = 6.8 Hz, 2 H), 1.25 (br s, 16 H), 0.88 (t, J = 6.8 Hz, 3 H).
HRMS (ESI): m/z [M – H]– calcd for C17H25OS2: 309.1347; found:
309.1737.
13C NMR (100 MHz, CDCl3): δ = 190.0, 135.6, 133.7, 128.6, 127.5, 38.6,
31.7, 29.48, 29.47, 29.42, 29.3, 29.2, 29.0, 28.8, 28.3, 22.5, 14.0.
HRMS (APCI): m/z [M + H]+ calcd for C19H31OS2: 339.1816; found:
Acknowledgment
339.1801.
The Ministry of Science and Technology, Taiwan (MOST104-2113-M-
005-002-, MOST104-2113-M-037-001-MY2), National Chung Hsing
University, and Kaohsiung Medical University are gratefully acknowl-
edged for financial support.
Benzoyl Cyclohexyl Disulfide (3e)13
Colorless liquid; yield: 214.4 mg (85%); Rf = 0.50 (5% EtOAc in hex-
anes).
1H NMR (400 MHz, CDCl3): δ = 8.01 (d, J = 8.0 Hz, 2 H), 7.57–7.61 (m, 1
H), 7.43–7.49 (m, 2 H), 2.82–2.89 (m, 1 H), 2.02–2.06 (m, 2 H), 1.76–
1.81 (m, 2 H), 1.56–1.60 (m, 1 H), 1.35–1.45 (m, 2 H), 1.18–1.33 (m, 3
H).
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0036-1588070.
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
o
nrtogI
f
rmoaitn
13C NMR (100 MHz, CDCl3): δ = 190.4, 135.6, 25.3, 133.7, 128.6, 127.5,
49.4, 32.4, 25.8.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F

F
C.-H. Tsai et al.
Paper
Synthesis
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