On aromatic electrophilic substitution promoted by in situ generated thionium ions

Article abstract of DOI:10.1055/s-0032-1318167

α-Sulfanylated α-arylacetates and -thioacetates were prepared via ethylthiomethylation reaction of aromatic compounds. These aromatic electrophilic substitutions were performed by in situ generation of the thionium ions by reacting trifluoroacetic anhydri

Full text of DOI:10.1055/s-0032-1318167

798▌
PAPER
pOapner Aromatic Electrophilic Substitution Promoted by In Situ Generated
Thionium Ions
α-Sulfanyl-α-arylacetates and -thioacetates
Rosana Ribeiro Amici, Claudio Di Vitta, Liliana Marzorati*
Institute of Chemistry, University of São Paulo, Av. Prof. Lineu Prestes 748, 05508-900 São Paulo, SP, Brazil
Fax +55(11)38155579; E-mail: lmarzora@iq.usp.br
Received: 29.11.2012; Accepted after revision: 14.01.2013
Table 1 Electrophilic Aromatic Substitution Using 1 or 2 as the Elec-
trophile Precursor
Abstract: α-Sulfanylated α-arylacetates and -thioacetates were pre-
pared via ethylthiomethylation reaction of aromatic compounds.
These aromatic electrophilic substitutions were performed by in situ
generation of the thionium ions by reacting trifluoroacetic anhy-
dride and S-ethyl 2-(ethylsulfinyl)ethanethioate or ethyl 2-(ethyl-
sulfinyl)acetate in the presence of Lewis acids. Some mechanistic
features of these ethylthiomethylation reactions are also presented.
O
O
S
O
1) TFAA, 0 °C
S
Et
ArH
+
Et
Et
X
2) SnCl4
0 °C to r.t.
Et
X
Ar
X = S or O
Entry
Ar
Sulfoxide Time
(min)
Product ratio Yielda
Key words: ethylthiomethylation, Pummerer reaction, sulfoxide,
aromatic electrophilic substitution
ortho/para
(%)
1
Ph
1
2
1
2
1
2
1
2
1
2
60
60
30
30
30
30
120
120
30
30
–
66
78
30
23
41
47
55
55
42b
44b
2
Ph
–
The generation of thionium ions via Pummerer reaction
and subsequent intramolecular trapping of such electro-
philes by diverse nucleophiles has been extensively re-
viewed,1–3 and stands as one of the most useful methods
for the construction of heterocyclic rings.4 However, the
intermolecular version of this C–C bond formation meth-
od has received less attention, despite its utility for access-
ing the reactivity and the selectivity of substituted
thionium ions. Sulfoxides of enhanced C–H acidity bear-
ing electron attracting groups at the α-position are well
suited for this kind of investigation as previously reported
by Bates5 and Stamos6 in seminal papers. However, sulf-
oxides bearing an α-COSR or α-SO2R groups remained as
unexplored thionium ion precursors. In order to investi-
gate their performance in the alkylthiomethylation of sub-
stituted arenes, we decided to prepare three derivatives to
be employed in a comparative study, i.e. S-ethyl 2-(ethyl-
sulfinyl)ethanethioate (1), ethyl 2-(ethylsulfinyl)acetate
(2), and (methylsulfinyl)methyl phenyl sulfone (3) (Fig-
ure 1). It should be mentioned that α-sulfanylated carbon-
yl and carboxyl derivatives are versatile intermediates.7
3
MeOC6H4
MeOC6H4
MeC6H4
MeC6H4
ClC6H4
ClC6H4
1-naphthyl
1-naphthyl
1:3
1:3
1:9
1:8
1:8
1:7
–
4
5
6
7
8
9
10
–
a Isolated para-substituted product containing traces of the ortho-
isomer after purification by column chromatography on silica gel.
b Using naphthalene (11 mmol) and anhyd CH2Cl2 (35 mL)
In a previous report,8 S-ethyl 2-(methylsulfinyl)ethaneth-
ioate (MeSOCH2COSEt) and methyl 2-(methylsulfi-
nyl)acetate (MeSOCH2CO2Me) were reacted with
Pummerer mixed activators (Ac2O, TFAA). In the case of
the thioester, the reaction afforded a mixture of
MeSCH(OAc)COSEt and MeSCH(OCOCF3)COSEt, but
for the ester derivative only MeSCH(OAc)CO2Me was
obtained. These experimental facts were rationalized in
terms of the decreased stability of the intermediate thioes-
ter thionium cation as compared to the one generated from
the ester. On the basis of these findings, we expected sulf-
oxide 1 to be more effective as compared to sulfoxide 2,
reacting faster with the substituted arene and leading to
good product yields, even for less-activated substrates.
However, the analysis of results (Table 1) indicates that:
(i) For the same reaction time, both sulfoxides afforded
ethylthiomethylated products in very similar yields and
isomer ratios. (ii) As expected the deactivated chloroben-
O
S
O
O
S
O
S
O
Et
Et
X
Me
Ph
1 X = S
2 X = O
3
Figure 1 Functionalized sulfoxides 1–3
Sulfoxides 1 and 2 were reacted with substituted arenes
and trifluoroacetic anhydride followed by the addition of
tin(IV) chloride (Table 1).
SYNTHESIS 2013, 45, 0798–0802
Advanced online publication: 27.02.2013
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0032-1318167; Art ID: SS-2012-M0904-OP
© Georg Thieme Verlag Stuttgart · New York

PAPER
α-Sulfanyl-α-arylacetates and -thioacetates
799
OMe
OMe
OMe
CO2Et
1) TFAA
0 °C
O
S
O
+
O
Et
+
+
Et
X
2) SnCl4
0 °C to r.t.
OMe
COCF3
XEt
OMe
X = O or S
SEt
4
5
Scheme 1 The reaction between anisole and sulfoxides 1 or 2 (TFAA, SnCl4)
zene substrate required a longer time for complete reac- centage of the product 9 increased, the one referring to the
tion. However, the reactivity pattern for electrophilic Pummerer product decreased, reaching equilibrium after
aromatic substitution reactions seems not to apply to these ca. 50 minutes. On the basis of this experimental result,
Pummerer initiated ethylthiomethylation reactions, con- we reasoned that the Lewis acid might associate to the tri-
sidering that anisole failed to perform better than nonacti- fluorocarboxylate moiety of 8, restoring the thionium cat-
vated or deactivated substrates (entries 3, 4 vs. 1, 2 and 7, ion. In order to test this hypothesis, we exposed the
8).
Pummerer product (generated in situ from sulfoxide 2 and
TFAA) to a mixture of benzene and tin(IV) chloride. This
two-step procedure led quantitatively to ethyl 2-(ethylsul-
fanyl)-2-(phenyl)acetate, adding evidence to our mecha-
nistic proposal. As for the rate of formation of products 6
and 9, sulfoxide 1 reacts faster than sulfoxide 2 (see
Figure 2), as expected considering the relative stability of
their intermediate thiocarbenium ions.
The inferior conversion of anisole into ethylthiomethyl-
ated products as compared to other aromatic compounds
could be explained by the results of the GC/MS analysis
of the crude reactions products of anisole with sulfoxide 1
or 2 (Scheme 1). In both cases the Friedel–Crafts acyla-
tion byproduct 4 (m/z = 135 [CH3OC6H4CO]+) was
formed. However, for the reaction with sulfoxide 2, apart
from 4 and the expected o- and p-ethylthiomethylated
products (m/z = 181 [CH3OC6H4CHSC2H5]+), an extra
byproduct could be identified as being ethyl bis(methoxy-
phenyl)acetate 5 (m/z = 300 [(CH3OC6H4)2CHCO2Et]+;
227 [(CH3OC6H4)2CH]+). Compound 5 would originate
from the nucleophilic displacement of ethanethiol by an-
isole on the thiomethylated product, as previously report-
ed for analogous reactions.5
For reactions of sulfoxides 1 or 2 with chlorobenzene
(Scheme 2), analysis by GC/MS of the crude products al-
lowed for the identification of the following components:
(i) for reactions with sulfoxide 1: S-ethyl 2-(chlorophe-
nyl)-2-(ethylsulfanyl)ethanethiolate (o- + p-isomers) 6,
and S-ethyl 2,2-bis(ethylsulfanyl)ethanethioate (7); (ii)
for reactions with sulfoxide 2: 2-ethoxy-1-(ethylsulfanyl)-
2-oxoethyl 2,2,2-trifluoroacetate (8), ethyl 2-(chlorophe-
nyl)-2-(ethylsulfanyl)acetate (o- + p-isomers) 9, and ethyl
2,2-bis(ethylsulfanyl)acetate (10).
Figure 2 Percentage of compounds 6 and 9 vs. reaction time for the
ethylthiomethylation of chlorobenzene by sulfoxides 1 or 2 (TFAA,
SnCl4)
Mercaptals have been reported as minor byproducts in
Pummerer reactions,9–11 accounting for the presence of
components 7 and 10 in the crude product of ethylthio-
methylation reactions employing sulfoxides 1 or 2, re-
spectively.
The relative proportion of components 6 and 7 and 8–10,
estimated by GC, varied as a function of the reaction time.
After five minutes, all starting sulfoxide was consumed
and, for X = O, mainly transformed into the Pummerer
product 8. However, for longer reaction times, as the per-
Starting our investigation on the in situ generation of thi-
onium ion from sulfoxide 3, we performed the reaction of
3 with trifluoroacetic anhydride in chloroform at room
temperature, but the 1H NMR spectra of the crude product
Cl
Cl
O
S
O
O
XEt
1) TFAA 0 °C
EtS
O
EtS
EtS
O
+
+
Et
+
2) SnCl4
0 °C to r.t.
Et
X
F3CCOO
XEt
XEt
SEt
X = S
X = O
6
9
7
10
8
Scheme 2 The reaction of chlorobenzene and sulfoxides 1 or 2 in the presence (TFAA, SnCl4)
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 798–802

800
R. R. Amici et al.
PAPER
1) TFAA
0 °C
O
S
O
S
O
S
O
O
O
S
O
+
Me
ArH
+
+
S
S
Ph
Ph
S
2) SnCl4
Ph
Ph
Me
Me
Ph
or TiCl4
3
or BF3·OEt2
Ar = Ph, MeC6H4, MeOC6H4
Scheme 3 The reaction of sulfoxide 3 with aromatic compounds in the presence of trifluoroacetic anhydride and Lewis acids
IR (neat): 1670 (C=O), 1050 cm–1 (S=O).
indicated that the conversion was low, and that the expect-
1H NMR (60 MHz, CCl4): δ = 1.30 (t, J = 7.0 Hz, 3 H), 1.35 (t,
J = 7.0 Hz, 3 H), 2.83 (q, J = 7.1 Hz, 2 H), 2.97 (q, J = 7.1 Hz, 2 H),
3.87 (s, 2 H).
ed product was formed in admixture with (methylsulfo-
nyl)methyl phenyl sulfone.12 When the same reaction was
performed at 40 °C, analysis of the 1H NMR spectra of the
crude product indicated that sulfoxide 3 was completely Anal. Calcd for C6H12O2S2: C, 39.97; H, 6.71. Found: C, 40.46; H,
6.67.
converted into the expected Pummerer rearranged prod-
uct, (methylsulfanyl)(phenylsulfonyl)methyl trifluoro-
acetate, although it could not be isolated or purified due to
(Methysulfinyl)methyl Phenyl Sulfone (3)
To a mixture of SeO2 (1.11 g, 10.0 mmol), 30% aq H2O2 (1.2 mL),
extensive decomposition. In view of these facts, we decid- and MeOH (5 mL), was added, dropwise, a soln of (methylsulfa-
nyl)methyl phenyl sulfone16 (2.02 g, 10.0 mmol) dissolved in
MeOH (20 mL). The mixture was stirred for 5 min and then H2O
(100 mL) was added. The mixture was saturated with NaCl and then
extracted with CHCl3. The combined organic extracts were dried
ed to perform the ethylthiomethylation reactions at 40 °C,
employing sulfoxide 3 and the aromatic compound either
neat or dissolved in dichloromethane, and varying the
Lewis acid to be added. However, in all cases instead of
(anhyd MgSO4) and the solvent removed to give a crude product
the expected product, the same three components mixture
was formed, although differing in their relative proportion
(Scheme 3). A separate experiment, exposing the crude
that was recrystallized (EtOH) to give pure sulfoxide 3; yield: 1.74
g (80%); mp 98–100 °C.
1H NMR (200 MHz, CDCl3): δ = 2.91 (s, 3 H), 4.38 (s, 2 H), 7.58–
Pummerer product to a small amount of titanium tetra- 8.02 (m, 5 H).
chloride led to formation of the same product mixture.
This evidence of decomposition prior to nucleophilic at-
tack to the thionium ion seems to preclude the application
of this ethylthiomethylation method to sulfinyl methyl
sulfones.
Anal. Calcd for C8H10S2O3: C, 44.02; H, 4.62. Found: C, 44.04; H,
4.58.
S-Ethyl 2-(Ethylsulfanyl)-2-(phenyl)ethanethioate (Table 1,
Entry 1); Typical Procedure
To a stirred soln of sulfoxide 1 (1.98 g; 11.0 mmol) dissolved in
benzene (40 mL), under N2, was added dropwise over 5 min at 0 °C
and by syringe TFAA (1.55 mL, 11.1 mmol). After 5 min, SnCl4
(1.10 mL, 9.30 mmol) was added dropwise at 0 °C over 5 min. The
temperature of the mixture was allowed to reach r.t., and the mixture
was stirred for an additional 60 min. The mixture was poured into
H2O (20 mL) and extracted with CH2Cl2 (3 × 20 mL). The com-
bined organic extracts were washed with H2O (3 × 15 mL) and
dried (anhyd MgSO4). Removal of solvent afforded crude S-ethyl 2-
(ethylsulfanyl)-2-(phenyl)ethanethioate (2.38 g, 90%). Column
chromatography (silica gel, hexane–acetone, 20:1) gave pure prod-
uct as an oil; yield: 1.74 g (7.30 mmol, 66%).
In summary the present results provide further evidence
for the enhanced reactivity of thionium ions generated
from sulfinyl thioesters in comparison to those from sulfi-
nyl esters. Acylation and mercaptal formation are compet-
itive reactions, leading, apparently, to the same reactivity
independently of the electronic character of the aromatic
ring substituents.
1
Commercial reagents were used without further purification. H
IR (neat): 1661 cm–1 (C=O).
NMR spectra were recorded at 60 or 200 MHz (Varian T-60 or
Bruker AC 200, respectively).
1H NMR (200 MHz, CDCl3): δ = 1.23 (t, J = 7.1 Hz, 3 H), 1.24 (t,
J = 7.1 Hz, 3 H), 2.58 (q, J = 7.1 Hz, 2 H), 2.87 (q, J = 7.1 Hz, 2 H),
4.72 (s, 1 H), 7.28–7.49 (m, 5 H).
13C NMR (50 MHz, CDCl3): δ = 14.1, 14.3, 24.1, 26.4, 60.1, 128.2,
128.6 (2 C), 136.1, 197.4.
13C NMR spectra were recorded at 50 MHz on a Bruker AC200;
both relative to an internal standard (TMS). IR frequencies were de-
termined using a Perkin Elmer FT 238-A instrument, and GC/MS
analysis were performed in a HP 5890/5988 A instrument. Melting
point of sulfoxide 3 was determined with an Electrothermal 9100
melting point apparatus. Ethyl 2-(ethylsulfinyl)acetate (2) was pre-
pared as previously reported.13 Solvents for reactions were purified
according to literature procedures.14
Anal. Calcd for C12H16S2O: C, 59.96; H, 6.71. Found: C, 59.83; H,
7.01.
Ethyl 2-(Ethylsulfanyl)-2-(phenyl)acetate by Ethylthiomethyl-
ation of Benzene; Two-Step Procedure
S-Ethyl 2-(Ethylsulfinyl)ethanethioate (1)
To a mixture of S-ethyl 2-(ethylsulfanyl)ethanethioate15 (1.64 g,
10.0 mmol) and pure AcOH (2.2 mL), at 0 °C, was added, dropwise,
30% aq H2O2 (1.2 mL) and the mixture was stirred at r.t. for 2 h. Af-
ter the addition of CH2Cl2 (13 mL), the organic and aqueous layers
were separated and the organic extract was neutralized with aq
NaHCO3. To the aqueous phase was added NaCl and it was extract-
ed with CH2Cl2 (3 × 15 mL). The combined organic extracts were
dried (anhyd MgSO4). Removal of the solvent gave pure sulfoxide
1; yield: 1.26 g (70%).
To sulfoxide 2 (0.92 g, 5.6 mmol), dissolved in CHCl3 (8.0 mL),
was added, dropwise at 0 °C, TFAA (1.45 mL, 10.4 mmol);8 the
mixture was stirred for 2 h at r.t. The solvent was removed under re-
duced pressure, and anhyd benzene (100 mL) was added, followed
by dropwise addition at 0 °C of SnCl4 (0.55 mL, 4.7 mmol). The
mixture was stirred for 1 h at r.t., and then it was poured into H2O
1
(20 mL), and extracted with CH2Cl2. H NMR spectrum showed
quantitative formation of ethyl 2-(ethylsulfanyl)-2-(phenyl)acetate.
Synthesis 2013, 45, 798–802
© Georg Thieme Verlag Stuttgart · New York

PAPER
α-Sulfanyl-α-arylacetates and -thioacetates
801
S-Ethyl 2-(Ethylsulfanyl)-2-(4-methoxyphenyl)ethanethioate
(Table 1, Entry 3)
Column chromatography (hexane–acetone, 20:1) gave a yellow oil;
yield: 0.89 g (30%).
Anal. Calcd for C12H16S2O: C, 64.25; H, 7.19. Found: C, 64.26; H,
6.82.
Ethyl 2-(Ethylsulfanyl)-2-(4-methoxyphenyl)acetate (Table 1,
Entry 4)
Column chromatography (hexane–EtOAc, 15:1) gave a yellow oil;
yield: 0.64 g (23%).
IR (neat): 1689 cm–1 (C=O).
1H NMR (200 MHz, CDCl3): δ = 1.10–1.40 (m, 6 H), 2.56 (q,
J = 7.3 Hz, 2 H), 2.86 (q, J = 7.3 Hz, 2 H), 3.78 (s, 3 H), 4.70 (s, 1
H), 6.86 (d, J = 8.5 Hz, 2 H), 7.36 (d, J = 8.5 Hz, 2 H).
13C NMR (50 MHz, CDCl3): δ = 14.2, 14.3, 24.1, 26.4, 55.2, 59.4,
114.1, 127.9, 129.8, 159.6, 197.8.
IR (neat): 1711 cm–1 (C=O).
1H NMR (200 MHz, CDCl3): δ = 1.10–1.50 (m, 6 H), 2.43–2.65 (m,
2 H), 3.77 (s, 3 H), 4.13–4.23 (m, 2 H), 4.60 (s, 1 H), 6.86 (d, J = 8.5
Hz, 2 H), 7.39 (d, J = 8.5 Hz, 2 H).
Anal. Calcd for C13H18S2O2: C, 57.74; H, 6.71. Found: C, 57.80; H,
6.60.
13C NMR (50 MHz, CDCl3): δ = 13.9 (2 C), 25.7, 51.2, 55.0, 61.2,
113.8, 128.1, 129.4, 159.3, 170.9.
S-Ethyl 2-(Ethylsulfanyl-2-(4-methylphenyl)ethanethioate
(Table 1, Entry 5)
Column chromatography (toluene–EtOAc, 20:1) gave a yellow oil;
yield: 1.15 g (41%).
Anal. Calcd for C13H18SO3: C, 61.39; H, 7.13. Found: C, 61.49; H,
7.18.
Ethyl 2-(Ethylsulfanyl)-2-(4-methylphenyl)acetate (Table 1,
Entry 6)
Column chromatography (hexane–acetone, 30:1) gave a yellow oil;
yield: 1.23 g (47%).
IR (neat): 1671 cm–1 (C=O).
1H NMR (200 MHz, CDCl3): δ = 1.23 (t, J = 7.4 Hz, 3 H), 1.25 (t,
J = 7.3 Hz, 3 H), 2.33 (s, 3 H), 2.58 (q, J = 7.4 Hz, 2 H), 2.87 (q,
J = 7.3 Hz, 2 H), 4.70 (s, 1 H), 7.19 (d, J = 8.0 Hz, 2 H), 7.33 (d,
J = 8.0 Hz, 2 H).
13C NMR (50 MHz, CDCl3): δ = 14.1, 14.2, 21.1, 24.1, 26.4, 59.8,
128.4, 129.4, 132.9, 138.1, 197.7.
IR (neat): 1711 cm–1 (C=O).
1H NMR (200 MHz, CDCl3): δ = 1.10–1.40 (m, 6 H), 2.33 (s, 3 H),
2.50–2.55 (m, 2 H), 4.16–4.20 (m, 2 H), 4.56 (s, 1 H), 7.14 (d,
J = 7.7 Hz, 2 H), 7.36 (d, J = 7.7 Hz, 2 H).
13C NMR (50 MHz, CDCl3): δ = 14.0 (2 C), 21.0, 25.9, 51.8, 61.4,
128.3, 129.2, 133.3, 137.7, 178.0.
Anal. Calcd for C13H18S2O: C, 61.37; H, 7.13. Found: C, 61.53; H,
7.09.
Anal. Calcd for C13H18SO2: C, 65.51; H, 7.61. Found: C, 65.63; H,
7.67.
S-Ethyl 2-(4-Chlorophenyl)-2-(ethylsulfanyl)ethanethiolate
(p-6) (Table 1, Entry 7)
Column chromatography (hexane–EtOAc, 12:1) gave a yellow oil;
yield: 1.66 g (55%).
Ethyl 2-(4-Chlorophenyl)-2-(ethylsulfanyl)acetate (p-9) (Table
1, Entry 8)
Column chromatography (hexane–EtOAc, 12:1) gave a yellow oil;
yield: 1.57 g (55%).
IR (neat): 1671 cm–1 (C=O).
1H NMR (200 MHz, CDCl3): δ = 1.24 (t, J = 7.3 Hz, 3 H), 1.25 (t,
J = 7.3 Hz, 3 H), 2.56 (q, J = 7.3 Hz, 2 H), 2.89 (q, J = 7.3 Hz, 2 H),
4.69 (s, 1 H), 7.27–7.50 (m, 4 H).
13C NMR (50 MHz, CDCl3): δ = 14.1, 14.3, 24.2, 26.5, 59.3, 128.9,
129.9, 132.1, 134.6, 197.1
IR (neat): 1721 cm–1 (C=O).
1H NMR (200 MHz, CDCl3): δ = 1.23 (t, J = 7.1 Hz, 3 H), 1.25 (t,
J = 7.1 Hz, 3 H), 2.54 (q, J = 7.1 Hz, 2 H), 4.19 (q, J = 7.1 Hz, 2 H),
4.51 (s, 1 H), 7.24–7.50 (m, 4 H).
13C NMR (50 MHz, CDCl3): δ = 14.0 (2 C), 25.9, 51.2, 61.6, 128.6,
129.8, 133.9, 134.9, 170.4.
MS: m/z (%) = 276 (3), 246 (3), 214 (5), 187 (40), 185 (100), 157
(14), 155 (16), 125 (3), 89 (5), 59 (3).
MS: m/z (%) = 260 (12), 258 (267.6), 200 (12), 198 (55), 187 (12),
185 (100), 157 (12), 155 (24), 125 (7), 63 (10).
Anal. Calcd for C12H15ClS2O: C, 52.64; H, 5.15. Found: C, 53.11;
H, 5.51.
Anal. Calcd for C12H15ClSO2: C, 55.70; H, 5.84. Found: C, 53.71;
H, 5.57.
S-Ethyl 2-(Ethylsulfanyl)-2-(naphthalen-1-yl)ethanethioate
(Table 1, Entry 9)
Column chromatography (benzene–acetone, 12:1) gave a yellow
oil; yield: 1.34 g (42%).
IR (neat): 1666 cm–1 (C=O).
1H NMR (200 MHz, CDCl3): δ = 1.16–1.31 (m, 6 H), 2.65–2.70 (m,
2 H), 2.85 (q, J = 7.3 Hz, 2 H), 5.45 (s, 1 H), 7.42–8.13 (m, 7 H).
Ethyl 2-(Ethylsulfanyl)-2-(naphthalen-1-yl)acetate (Table 1,
Entry 10)
Column chromatography (benzene–EtOAc, 20:1) gave a yellow oil;
yield: 1.33 g (44%).
IR (neat): 1726 cm–1 (C=O).
1H NMR (200 MHz, CDCl3): δ = 1.15–1.27 (m, 6 H), 2.47–2.74 (m,
2 H), 4.00–4.30 (m, 2 H), 5.34 (s, 1 H), 7.40–8.18 (m, 7 H).
13C NMR (50 MHz, CDCl3): δ = 14.0 (2 C), 26.3, 48.7, 61.6, 123.1,
125.3, 125.7, 126.4, 126.6, 128.7, 128.9, 133.9, 170.1.
13C NMR (50 MHz, CDCl3): δ = 14.2, 14.3, 24.2, 27.0, 56.7, 123.1,
125.3, 125.7, 126.4, 126.6, 128.7, 128.9, 133.9, 197.1.
Anal. Calcd for C16H18S2O: C, 66.16; H, 6.25. Found: C, 66.50; H,
6.82.
Anal. Calcd for C16H18SO2: C, 70.04; H, 6.61. Found: C, 70.24; H,
6.76.
Ethyl 2-(Ethylsulfanyl)-2-(phenyl)acetate (Table 1, Entry 2)
Column chromatography (hexane–acetone, 20:1) gave a yellow oil;
yield: 2.06 g (78%).
IR (neat): 1726 cm-1 (C=O).
1H NMR (200 MHz, CDCl3): δ = 1.22 (t, J = 7.5 Hz, 3 H), 1.24 (t,
J = 7.2 Hz, 3 H), 2.56 (q, J = 7.5 Hz, 2 H), 4.20 (q, J = 7.2 Hz, 2 H),
4.58 (s, 1 H), 7.42–8.13 (m, 5 H).
S-Ethyl 2,2-Bis(ethylsulfanyl)ethanethioate (7)
MS: m/z (%) = 224 (1), 196 (1), 167 (1), 135 (100), 107 (20), 79 (1),
45 (18).17
Ethyl 2,2-Bis(ethylsulfanyl)acetate (10)
MS: m/z (%) = 208 (15), 148 (22), 135 (100), 107 (30), 91 (32), 75
(32), 45 (25). These data agree with those reported for the same
compound.18
13C NMR (50 MHz, CDCl3): δ = 14.0 (2 C), 25.9, 52.0, 61.5, 127.9,
128.4, 128.5, 136.3, 170.8.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 798–802

802
R. R. Amici et al.
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2-Ethoxy-1-(ethylsulfanyl)-2-oxoethyl 2,2,2-Trifluoroacetate
(9) Kenney, W. J.; Walsh, J. A.; Davenport, D. A. J. Am. Chem.
Soc. 1961, 83, 4019.
(10) Walker, D.; Leib, J. Can. J. Chem. 1962, 40, 1242.
(11) Tamura, Y.; Choi, H. D.; Shindo, H.; Uenishi, J.; Ishibashi,
H. Tetrahedron Lett. 1981, 22, 81.
(8)
MS: m/z (%) = 200 (18), 187 (18), 159 (25), 131 (80), 111 (15), 97
(12), 69 (100), 45 (38).
S-Phenyl Benzenethiolsulfonate
(12) Isolated from the crude product by crystallization. Physical
constants and spectroscopic data agree with those reported in
the literature for the same compound: (a) Durkin, K. A.;
Langler, R. F.; Morrison, N. A. Can. J. Chem. 1988, 66,
3070. This product could originate from a putative
sulfoxonium ion: (b) Annunziata, R.; Cinquini, M.;
Colonna, S. J. Chem. Soc., Perkin Trans. 1 1975, 282.
(13) Wladislaw, B.; Marzorati, L.; Di Vitta, C. Phosphorus,
Sulfur Silicon Relat. Elem. 1991, 62, 225.
(14) Perrin, D. D.; Armarego, W. L. F.; Perrin, D. R. Purification
of Laboratory Chemicals; Pergamon Press: Oxford, 1996.
(15) Purvis, J. E.; Jones, H. O.; Tasker, H. S. J. Chem. Soc. 1910,
97, 2287.
Prepared by reacting benzenesulfinic acid with benzenesulfenyl
chloride,19 according to the literature procedure.20
MS: m/z (%) = 250 (45), 141 (35), 125 (100), 109 (52), 77 (91).
Methyl Phenyl Disulfide
Prepared by reacting methanesulfenyl chloride21 with thiophenol,
according to the literature procedure20 as a colorless liquid; yield:
90%.
1H NMR (200 MHz, CDCl3): δ = 2.43 (s, 3 H), 7.18–7.55 (m, 5 H).
MS: m/z (%) = 156 (100), 141 (63), 110 (18), 109 (38), 77 (18), 69
(12), 65 (20), 50 (11).
(16) Ogura, K.; Yahata, N.; Watanabe, J. Bull. Chem. Soc. Jpn.
1983, 56, 3543.
Acknowledgment
(17) Identical GC/MS data were obtained for one of two
components of the crude mixture for the reaction of
sulfoxide 1 and benzene, in the presence of TFAA and
BF3·Et2O. This component was identified as 7 on the basis of
the methine 1H NMR signal as reported for the same
compound: Ando, W.; Suzuki, J.; Arai, T.; Migita, T.
Tetrahedron 1973, 29, 1507.
We thank Fapesp, CNPq, and CAPES for financial support.
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Synthesis 2013, 45, 798–802
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