Reactions of p-benzoquinone with sulfur nucleophiles

Article abstract of DOI:10.1055/s-2008-1032186

The orientations of the reactions of p-benzoquinone with nucleophiles are discussed. The one-pot reaction of p-benzoquinone with alkanethiols gave the 2-, 2,6-, and 2,5-conjugate addition products. Novel 2,6- and 2,5- bis(alkylsulfanyl)-, 2,3,5-tris(alkylsulfanyl)-, and 2,3,5,6- tetrakis(alkylsulfanyl)-p-benzoquinones, and their corresponding hydroquinones, were obtained in good yields through a sequential addition/in situ oxidation protocol for further testing as polymerization inhibitors in rubber and petroleum products. The structures of five 2,5- and 2,6-disubstituted isomers were established by X-ray crystallography. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1032186

PAPER
777
Reactions of p-Benzoquinone with Sulfur Nucleophiles
R
eactions of
p-Ben
l
zoquin
a
one
w
ith
S
n
ulfur NucleophilesR. Katritzky,*a Dmytro Fedoseyenko,a Prabhu P. Mohapatra,a Peter J. Steelb
a
Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, USA
Chemistry Department, University of Canterbury, Christchurch 8140, New Zealand
Fax +1(352)3929199; E-mail: katritzky@chem.ufl.edu
b
Received 20 July 2007; revised 10 December 2007
cule to afford the 2,3,5-trisubstituted adduct. Finally, the
tris-adduct may react with one equivalent of a further nu-
cleophile to give the 2,3,5,6-tetrasubstituted p-benzo-
quinone.
Abstract: The orientations of the reactions of p-benzoquinone with
nucleophiles are discussed. The one-pot reaction of p-benzoquinone
with alkanethiols gave the 2-, 2,6-, and 2,5-conjugate addition prod-
ucts. Novel 2,6- and 2,5-bis(alkylsulfanyl)-, 2,3,5-tris(alkylsulfa-
nyl)-, and 2,3,5,6-tetrakis(alkylsulfanyl)-p-benzoquinones, and
their corresponding hydroquinones, were obtained in good yields
through a sequential addition/in situ oxidation protocol for further
testing as polymerization inhibitors in rubber and petroleum prod-
ucts. The structures of five 2,5- and 2,6-disubstituted isomers were
established by X-ray crystallography.
Conjugate additions of heteroaromatic nitrogen nucleo-
philes, such as pyridines,12 imidazoles, and benzimid-
azole,13 to p-benzoquinone give the 2-monosubstituted,
2,3- and 2,5-disubstituted, and 2,3,5-trisubstituted hydro-
quinones (Scheme 1). However, the conjugate addition of
a secondary amine to p-benzoquinone is reported to pro-
duce only the 2,5-disubstituted hydroquinone
(Scheme 1).14
Key words: p-benzoquinone, thiols, conjugate additions, hydro-
quinones, polymerization inhibitors
The reactions of pyrazole, 4-nitropyrazole, 3,5-dimeth-
ylpyrazole, 4-chloro-3,5-dimethylpyrazole, and 3-(2-py-
ridyl)pyrazole with p-benzoquinone gave the mono- and
2,3-bis-adducts; only in the case of pyrazole was the 2,5-
bis-adduct, 2,5-dipyrazol-1-ylbenzene-1,4-diol, also
formed (Scheme 1).12b,c The reactions of imidazole, 2-
methylimidazole, and benzimidazole with p-benzoqui-
none in dioxane gave the mono- and 2,3- and 2,5-bis-
adducts.13 As in the reactions of pyrazoles,15,16 the pre-
ferential formation of 2,3- versus 2,5-disubstituted deri-
vatives occurs with hindered imidazoles.13
Derivatives of benzoquinone and hydroquinone are wide-
ly studied in organic synthesis as reagents1 and electron-
accepting components for the synthesis of charge-transfer
complexes and radical ion salts.2 Naturally occurring
quinones and hydroquinones are subunits in many biolog-
ical compounds3 and possess a variety of biological prop-
erties, including antitumoral,4 HIV transcriptase
inhibition,5 and immunomodulation properties.6 Sulfur-
substituted quinones and hydroquinones are effective ox-
idation inhibitors and are widely used for the stabilization
of petroleum products.7 2,5-Bis(methylsulfanyl)-p-benzo-
quinone has been used to prepare sulfur–quinone polyure-
thane coatings for protecting iron surfaces.8 Metal–
carbonyl derivatives of sulfur-containing quinones and
hydroquinones have been synthesized for studying their
electrochemical properties.9 2-Amino-5-sulfanyl-substi-
tuted benzoquinones and hydroquinones are used as addi-
tives in rubber to prevent degradation and in gasoline and
lubricating oil to inhibit polymerization.10 2-Sulfinyl-
substituted quinones are used as cocatalysts in palladium-
catalyzed reactions to improve stereoselectivity.11
There are various well-known examples of the conjugate
addition of one molecule of a sulfur nucleophile to p-ben-
zoquinone (Scheme 2).17 However, double conjugate ad-
ditions of sulfur nucleophiles to p-benzoquinone are rare.
We found only one such example reported: the reaction of
thiophenol and p-benzoquinone gave both 2,5- and 2,6-
bis(phenylsulfanyl)-p-benzoquinone, and the structures of
the products were established by X-ray crystallography
(Scheme 2).18
Conjugate additions of carbon nucleophiles to p-benzo-
quinone generally give the 2-mono- and 2,5- and 2,6-dis-
ubstituted products (Scheme 3) in a similar manner to the
reactions with thiols.19 The reaction of p-benzoquinone
with indole in the presence of either 2 mol% bismuth(III)
triflate or 5 mol% indium(III) bromide in acetonitrile at
room temperature gave 2,5-diindol-3-yl-substituted hyd-
roquinone (Scheme 3).19a,b p-Benzoquinone on reaction
with palladium(II) acetate in acetic acid containing
arenes, such as benzene, p-xylene, and 1,4-dichloroben-
zene, at reflux temperature gave the corresponding 2-aryl-,
2,5-diaryl-, and 2,6-diaryl-p-benzoquinones (Scheme 3).19e
The reaction of p-benzoquinone with 4-hydroxycoumarin
in aqueous acetic acid gave the 3-(p-benzoquinon-2-yl)-
substituted 4-hydroxycoumarin, which reacted further
The conjugate additions of nitrogen, sulfur, oxygen, and
carbon nucleophiles to p-benzoquinone give initially the
2-substituted mono-adducts. Depending on the character
of the nucleophile, the oxidation potential of the mono-
adduct, and the possible reversible formation of a
charge-transfer complex, the initially formed mono-
adduct may undergo further nucleophilic addition to give
the 2,3-, 2,5-, and/or 2,6-disubstituted adducts. These bis-
adducts can in turn react with a third nucleophilic mole-
SYNTHESIS 2008, No. 5, pp 0777–0787
x
x
.
x
x
.2
0
0
8
Advanced online publication: 18.02.2008
DOI: 10.1055/s-2008-1032186; Art ID: M05407SS
© Georg Thieme Verlag Stuttgart · New York

778
A. R. Katritzky et al.
PAPER
OH
OH
+
N
N
OH
O–
85%
R
R
R
R
R
OH
N
N
OH
OH
N
N
OH
N
N
R
N
OH
N
N
R
H
N
R
R
+
+
R
R
R
N
N
+
R
R
N
N
N
N
N
N
OH
OH
OH
R
R
R
R
R = Me
R = H
57%
21%
29%
79%
14%
traces
N
R
R
R
N
N
N
N
OH
OH
OH
OH
OH
O
O
R
N
H
N
N
N
N
+
+
N
OH
N
R
R
R = H
R = Me
31%
10%
28%
85%
41%
5%
OH
OH
N
OH
N
OH
N
N
N
N
N
N
+
N
+
H
N
N
N
OH
OH
48%
32%
20%
OH
H
N
N
N
OH
46%
Scheme 1
with pyridine to give a unique 2,3-disubstituted zwitteri- (1) with cyclohexanethiol (2a) in ethanol at room temper-
onic adduct;15,17c similarly, the reaction of 3-(p-benzo- ature for 12 hours gave seven isolated products, 2-(cyclo-
quinon-2-yl)-substituted 4-hydroxycoumarin with 4- hexylsulfanyl)benzene-1,4-diol (3a),10a 2-(cyclohexyl-
hydroxycoumarin gave selectively a 2,3-disubstituted sulfanyl)-p-benzoquinone (4a),11b benzene-1,4-diol (5),
quinone product16 (Scheme 3).
2,6-bis(cyclohexylsulfanyl)benzene-1,4-diol (6a), 2,6-
bis(cyclohexylsulfanyl)-p-benzoquinone (7a), 2,5-bis(cy-
clohexylsulfanyl)benzene-1,4-diol (8a), and 2,5-bis(cy-
clohexylsulfanyl)-p-benzoquinone (9a), in yields of 5%,
2%, 36%, 1%, 12%, 1%, and 19%, respectively
(Scheme 5). The products were purified by repeated silica
gel column chromatography and recrystallization tech-
niques. The monosubstituted quinone 4a was separated
from the disubstituted quinones 7a and 9a by recrystalli-
zation from methanol. The isomeric disubstituted qui-
nones 7a and 9a have the same Rf value in thin-layer
chromatography and these products were purified by suc-
cessive recrystallization from a mixture of methanol and
Conjugate additions of oxygen nucleophiles, such as eth-
anol and phenol, to p-benzoquinone or activated quinones
give only the 2,5-disubstituted products in addition to the
2-monosubstituted adducts in some cases (Scheme 4).20
Herein, we report the synthesis of some novel 2,5- and
2,6-bis(alkylsulfanyl)-, 2,3,5-tris(alkylsulfanyl)-, and
2,3,5,6-tetrakis(alkylsulfanyl)-p-benzoquinones,
their corresponding hydroquinones, in good yields by se-
quential addition and in situ oxidation.
and
During our ongoing research in the area of rubber addi-
tives,10a,b,17l we found that the reaction of p-benzoquinone
Synthesis 2008, No. 5, 777–787 © Thieme Stuttgart · New York

PAPER
Reactions of p-Benzoquinone with Sulfur Nucleophiles
779
OH
OH
O
SO2Ph
S
S
OH
OH
NH3Cl
O
+
S
CO2R
HS
O
PhSO2H
S
S
NH3Cl
CO2R
SH
O
O
SH
O
OH
SH
S
S
OH
OH
S
HS
CO2Et
OAc
OH
+
OAc
O
O
CO2Et
AcO
O
O
N
O
S
AcHN
OAc
SH
S
R
S
OAc
O
O
AcO
SPy
O
O
O
AcHN
S
R
Scheme 2
chloroform. The mixture of disubstituted hydroquinones for 12 hours gave seven isolated products identified as
6a and 8a, along with a small amount of trisubstituted hy- methyl
3-[(2,5-dihydroxyphenyl)sulfanyl]propanoate
droquinone 11a (see Scheme 8), was very difficult to sep- (3b),10a methyl 3-[(3,6-dioxocyclohexa-1,4-dienyl)sulfa-
arate; therefore, the products were obtained in their pure nyl]propanoate (4b),10a byproduct 5, 2,6-disubstituted hy-
form by alternative methods for characterization pur- droquinone 6b, 2,6-disubstituted quinone 7b, 2,5-
poses. The novel products 6a–9a were fully characterized disubstituted hydroquinone 8b, and 2,5-disubstituted
1
by H and 13C NMR spectroscopy, as well as elemental quinone 9b in yields of 5%, 3%, 37%, 1%, 13%, 2%, and
analysis. The structure of 2,5-disubstituted quinone 9a 16%, respectively (Scheme 6). The novel products 6b–9b
was proved by X-ray crystallography (Figure 1).
were fully characterized by 1H and 13C NMR spectrosco-
py, as well as elemental analysis. The structures of 2,6-
disubstituted quinone 7b and 2,5-disubstituted quinone 9b
were unambiguously proved by X-ray crystallography
(Figure 2 and Figure 3).
Figure 1 X-ray crystal structure of 2,5-disubstituted quinone 9a
The one-pot formation of products 3a, 4a, 5, and 6a–9a
can be explained as follows: Single conjugate addition of
thiol 2a to quinone 1 leads to the formation of hydro-
quinone 3a, which then undergoes in situ oxidation with
quinone 1 to give the monosubstituted quinone 4a and the
reduced byproduct 5. The monosubstituted quinone 4a
then becomes the substrate for the second conjugate addi-
tion of thiol 2a to give a mixture of isomeric disubstituted
hydroquinones 6a and 8a; each of these products then un-
dergoes in situ oxidation to give a mixture of isomeric di-
substituted quinones 7a and 9a.
Figure 2 X-ray crystal structure of 2,6-disubstituted quinone 7b;
the conformation of one methyl group is disordered
Similarly, the reaction of p-benzoquinone (1) with methyl
3-sulfanylpropanoate (2b) in ethanol at room temperature
Figure 3 X-ray crystal structure of 2,5-disubstituted quinone 9b
Synthesis 2008, No. 5, 777–787 © Thieme Stuttgart · New York

780
A. R. Katritzky et al.
PAPER
NH
OH
OH
N
H
HN
O
O
O
O
O
O
+
+
Pd(OAc)2
41%
12%
6%
Me
Me
Me
Me
Me
Me
O
O
O
O
O
Me
Me
Me
+
+
Me
Me
Me
Pd(OAc)2
25%
Cl
O
13%
Cl
O
8%
O
Cl
Cl
Cl
O
O
O
Cl
Cl
+
+
Cl
Cl
Cl
Cl
Pd(OAc)2
O
50%
3%
O
2%
O
Cl
OH
O
O
O
OH
OH
O
O
O
O
O
O
R1
R1
O
R1
R2
OH
O
R2
COR2
O
O
– 2 H2O
O
R2
R2OC
OH
O
R1
O
R1
CN
OH
NCCH2COR
R
O
O
R
CN
OH
Scheme 3
The yields of quinones 4a and 4b, 7a and 7b, and 9a and (Scheme 6). The further reaction of quinone 4a with thiol
9b were significantly improved by simply changing the 2a in methanol at 60 °C for 0.5 hours gave a mixture of the
solvent from ethanol to methanol. The reaction of quinone isomeric disubstituted quinones 7a and 9a in 33% yield.
1 with thiol 2a in methanol at room temperature for one Similarly, the reaction of 4b with 2b in methanol at 60 °C
hour gave monosubstituted quinone 4a in 50% yield for 0.5 hours gave the isomeric disubstituted quinones 7b
(Scheme 5). Similarly, the reaction of quinone 1 with and 9b in 28% total yield. Hydroquinones 3a and 3b, 6a
methyl 3-sulfanylpropanoate (2b) in methanol at room and 6b, and 8a and 8b were found to be unstable to air ox-
temperature for one hour gave product 4b in 70% yield idation; however, they could be obtained in higher yields
Synthesis 2008, No. 5, 777–787 © Thieme Stuttgart · New York

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Reactions of p-Benzoquinone with Sulfur Nucleophiles
781
O
O
O
OH
O
R
O
Me
OH
O
O
R = H
R
Me
O
+
EtOH
O
O
O
R = CO2Me
O
R = H
O
O
R
O
Me
O
Me
O
Scheme 4
O
OH
OH
OH
OH
OH
OH
SH
S
S
S
S
EtOH
+
+
+
+
r.t.
12 h
O
O
1
2a
3a (5%)
4a (2%)
5 (36%)
6a (1%)
OH
O
O
S
S
S
S
+
+
+
S
S
OH
O
O
7a (12%)
8a (1%)
9a (19%)
O
O
OH
OH
SH
S
MeOH
2
+
+
r.t.
1 h
O
O
1
2a
4a (50%)
Scheme 5
and pure form as white microcrystals by reduction of the quinone 10a and 2,5-disubstituted quinone 10b were
corresponding quinones with zinc dust in methanol. Using proved by X-ray crystallography (Figure 4 and Figure 5).
this method, the reduction of 4b gave 3b in 55% yield and
that of 7a gave 6a in 70% yield.
Encouraged by the above results, we tried to obtain un-
symmetrical 2,5- and 2,6-disulfanyl-substituted p-benzo-
quinones and their corresponding hydroquinones by the
sequential addition of two different thiols. Thus, the reac-
tion of 2-(cyclohexylsulfanyl)-substituted quinone 4a
with methyl 3-sulfanylpropanoate (2b) in methanol at 60
°C for 5 minutes gave two novel asymmetrically substitut-
ed products, namely methyl 3-[5-(cyclohexylsulfanyl)-
3,6-dioxocyclohexa-1,4-dienylsulfanyl]propanoate (10a)
and methyl 3-[4-(cyclohexylsulfanyl)-3,6-dioxocyclo-
hexa-1,4-dienylsulfanyl]propanoate (10b), each in 13%
yield (Scheme 7). The structures of 2,6-disubstituted
Figure 4 X-ray crystal structure of 2,6-disubstituted quinone 10a
Figure 5 X-ray crystal structure of 2,5-disubstituted quinone 10b
Synthesis 2008, No. 5, 777–787 © Thieme Stuttgart · New York

782
A. R. Katritzky et al.
PAPER
O
O
OH
OH
OH
OH
O
S
S
S
S
EtOH
SH
+
+
+
+
O
O
O
O
r.t.
12 h
O
O
O
O
OH
6b (1%)
O
O
O
O
OH
1
2b
3b (5%)
4b (3%)
5 (37%)
O
O
O
OH
OH
S
S
S
S
O
O
+
+
+
O
O
O
O
S
S
O
O
O
O
O
O
7b (13%)
8b (2%)
9b (16%)
O
O
S
OH
SH
MeOH
2
+
+
O
r.t.
1 h
O
O
O
O
O
OH
4b (70%)
1
2b
Scheme 6
O
O
O
O
O
O
O
S
S
S
S
SH
O
MeOH
+
+
O
60 °C
5 min
O
O
S
O
4a
2b
10a (13%)
10b (13%)
Scheme 7
O
OH
S
O
S
S
S
S
S
S
O
OH
+
S
O
13a (65%)
11a (73%)
9a
+
SH
O
OH
OH
S
S
S
S
S
S
S
S
2a
O
14a (80%)
12a (5%)
Scheme 8
After obtaining the disubstituted quinones, we used them 2,6-isomers. Thus, the reaction of 2,5-bis(cyclohexylsul-
to prepare the 2,3,5-tri- and 2,3,5,6-tetrasubstituted deriv- fanyl)-substituted quinone 9a and thiol 2a in methanol at
atives (Schemes 8 and 9). We found that the 2,5-disubsti- 65 °C for two hours gave 2,3,5-tris(cyclohexylsulfa-
tuted quinones are more convenient for the synthesis of nyl)benzene-1,4-diol (11a) and 2,3,5,6-tetrakis(cyclohex-
2,3,5-trisubstituted hydroquinones, probably because they ylsulfanyl)benzene-1,4-diol (12a) in 73% and 5% yield,
are less soluble and more stabile toward oxidation than the respectively (Scheme 8). The further reaction of hydro-
Synthesis 2008, No. 5, 777–787 © Thieme Stuttgart · New York

PAPER
Reactions of p-Benzoquinone with Sulfur Nucleophiles
783
O
OH
OH
O
O
S
S
O
S
S
O
O
O
O
S
O
O
O
O
O
O
S
O
S
O
O
11b (17%)
13b (72%)
S
+
9b
O
O
OH
S
O
O
O
S
O
O
S
S
O
O
O
O
O
S
S
O
S
S
O
+
OH
O
O
O
O
HS
O
O
O
O
12b (17%)
14b (96%)
O
2b
Scheme 9
quinone 11a with p-benzoquinone in methanol at room
temperature for one hour gave 2,3,5-tris(cyclohexylsulfa-
nyl)-p-benzoquinone (13a) in 65% yield. Similarly, the
oxidation reaction of the tetrasubstituted product 12a over
a period of four hours gave 2,3,5,6-tetrakis(cyclohexyl-
sulfanyl)-p-benzoquinone (14a) in 80% yield (Scheme 8).
We believe that along with p-benzoquinone, atmospheric
air may also have played a role in the above oxidation of
hydroquinones.
O
O
O
O
O
OH
OH
O
Nu
Nu
addition
oxidation
+
NuH
Scheme 10
Likewise, the reaction of 2,5-disubstituted quinone 9b and
thiol 2b in methanol at 65 °C for 0.2 hours gave 2,3,5-
trisubstituted hydroquinone 11b and 2,3,5,6-tetrasubsti-
tuted hydroquinone 12b, each in 17% yield (Scheme 9).
Alternatively, the reaction of 13b with p-benzoquinone in
methanol at room temperature for two hours gave 12b in
66% yield. The oxidation of 11b with p-benzoquinone in
methanol at reflux for 10 minutes gave the corresponding
quinone 13b in 72% yield. Similarly, the reaction of 12b
with p-benzoquinone in methanol at reflux for 20 minutes
gave the tetrasubstituted quinone 14b in 96% yield
(Scheme 9).
with p-benzoquinone, both the quinones and their corre-
sponding hydroquinones formed in varying yields, proba-
bly because of their comparable oxidation potentials
(Schemes 5 and 6).
Frontier molecular orbital (FMO) and resonance theories
have been employed to explain and predict substituent ef-
fects on the orientations of nucleophilic additions and cy-
cloadditions to p-benzoquinones.21 The proposed order of
reactivity for the second conjugate addition to a p-benzo-
quinone with a donor substituent (D) at the 2-position is
C-5 > C-6 >> C-3, whereas for a p-benzoquinone with an
acceptor substituent (A) at the 2-position the order is C-3
>> C-6 > C-5 (Figure 6).21
It is well established that the formation of quinones versus
hydroquinones for reactions involving different nucleo-
philes can be explained through a mechanism in which
both addition and oxidation processes occur.12c The addi-
tion of one mole of a nucleophile to p-benzoquinone first
produces the monosubstituted hydroquinone that can then
undergo oxidation with excess quinone to finally afford
O
O
2
1
2
3
D
A
6 2
6 2
5
3
5
3
3
1
the
monosubstituted
p-benzoquinone
product
O
O
(Scheme 10). Therefore, the oxidation potential of the in-
termediate hydroquinone compared with that of the oxi-
dant will determine the nature of the final product.
Figure 6 Sites of nucleophilic attack on substituted benzoquinones;
the sites are numbered (circled) in order of decreasing reactivity
In the case of reactions involving nitrogen nucleophiles,
the hydroquinone formed by addition has a higher oxida-
tion potential than that of p-benzoquinone and, therefore,
the adduct is not oxidized by an excess of the quinone re-
agent.12c Thus, the additions of nitrogen nucleophiles to p-
benzoquinone give only the hydroquinones (Scheme 1).
In the above-presented reactions of different alkanethiols
The reaction of p-benzoquinone (1) with cyclohexane-
thiol (2a) gave the corresponding disubstituted quinones
2,5-isomer 9a and 2,6-isomer 7a in a ratio of 1.52 (deter-
mined by NMR spectroscopy). However, the reaction of
p-benzoquinone (1) with methyl 3-sulfanylpropanoate
(2b) gave the disubstituted products 2,5-isomer 9b and
Synthesis 2008, No. 5, 777–787 © Thieme Stuttgart · New York

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A. R. Katritzky et al.
PAPER
2.07–2.02 (m, 2 H), 1.82–1.80 (m, 2 H), 1.67–1.65 (m, 1 H), 1.53–
1.37 (m, 5 H).
2,6-isomer 7b in a lower ratio of 1.25 (Schemes 5 and 6).
Evidently, cyclohexanethiol has more donor properties
compared with methyl 3-sulfanylpropanoate. Thus, this 13C NMR (75 MHz, CDCl3): d = 184.0 (2 C), 152.0, 137.2, 136.2,
124.7, 42.5, 31.8, 25.6, 25.4.
slight difference in the reactivity of these two thiols is in
accordance with FMO and resonance theories.
Alternatively, 4a was prepared from p-benzoquinone (1) (21.6 g,
0.2 mol) following a literature procedure;11b yield: 10.7 g (50%).
In conclusion, the reactions of p-benzoquinone with al-
kanethiols gave the 2-, 2,6-, and 2,5-conjugate addition
products in one pot. Novel 2,6- and 2,5-bis(alkylsulfanyl)-,
2,3,5-tris(alkylsulfanyl)-, and 2,3,5,6-tetrakis(alkylsulfa-
nyl)-p-benzoquinones, and their corresponding hydro-
quinones, were obtained in good yields through a
sequential addition and oxidation protocol.
2,6-Bis(cyclohexylsulfanyl)benzene-1,4-diol (6a)
Compound 6a was purified by column chromatography (first frac-
tion eluted with hexanes).
Yield: 0.4 g (1%); colorless oil.
1H NMR (300 MHz, CDCl3): d = 6.85 (s, 3 H), 4.99 (s, 1 H), 3.10–
2.90 (m, 2 H), 2.00–1.20 (m, 20 H).
13C NMR (75 MHz, CDCl3): d = 150.7, 148.0, 121.2, 119.5, 48.8,
1H and 13C NMR spectroscopic data were recorded in CDCl3 with
TMS (0.00 ppm) and CDCl3 (77.0 ppm) as internal standards, re-
spectively. Supplementary crystallographic data (CCDC-635867
through CCDC-635871) are also available.22
46.8, 33.5, 33.3, 26.0, 25.6, 25.4.
Anal. Calcd for C18H26O2S2: C, 63.86; H, 7.74. Found: C, 63.96; H,
7.99.
Alternatively, 6a was prepared by the reduction of 7a (0.06 g,
0.0001 mol); yield: 0.04 g (70%).
Cyclohexylsulfanyl-Substituted Quinones and Hydroquinones
3a, 4a, and 6a–9a
2,6-Bis(cyclohexylsulfanyl)-p-benzoquinone (7a)
Compound 7a was purified by recrystallization (CHCl3–MeOH).
To a solution of p-benzoquinone (1) (16.2 g, 149.8 mmol) in EtOH
(100 mL) was added cyclohexanethiol (2a) (17.4 mL, 149.8 mmol),
and the mixture was stirred for 12 h at r.t. The red crystals that
formed were filtered, washed with hexanes (100 mL), and succes-
sively recrystallized (MeOH, followed by CHCl3–MeOH) to give
quinones 4a, 7a, and 9a. The filtrate was concentrated, and the res-
idue was purified by column chromatography (silica gel, hexanes
then hexanes–CH2Cl2, 1:1) followed by recrystallization (hexanes–
CH2Cl2) to give hydroquinones 3a, 6a, and 8a.
Yield: 6.0 g (12%); red crystals; mp 145–146 °C.
1H NMR (300 MHz, CDCl3): d = 6.34 (s, 2 H), 3.13–3.05 (m, 2 H),
2.06–2.02 (m, 4 H), 1.82–1.80 (m, 4 H), 1.68–1.63 (m, 2 H), 1.56–
1.31 (m, 10 H).
13C NMR (75 MHz, CDCl3): d = 182.0, 151.4, 125.7, 43.0, 32.2,
25.9, 25.7.
Anal. Calcd for C18H24O2S2: C, 64.25; H, 7.19. Found: C, 63.86; H,
7.37.
Reduction of Quinones To Give Hydroquinones; General Pro-
cedure
Alternatively, 7a was prepared from 4a (2.22 g, 0.010 mol) and 2a
(0.58 g, 0.005 mol) in MeOH (50 mL) at 60 °C for 0.5 h. Yield: 0.22
g (13%). Quinone 9a was also obtained in the reaction. Yield: 0.45
g (20%). The ratio of the 2,5- and 2,6-isomers was found to be 1.52
by NMR spectroscopy.
To a solution of the quinone (1 g) in MeOH (20 mL) was added Zn
dust (1 g), and the mixture was stirred vigorously at reflux. Then,
sat. NH4Cl soln was added dropwise until the color of the mixture
had disappeared (10 min). The mixture was cooled, filtered, and
washed with MeOH (10 mL). The combined solution was evaporat-
ed, the residue was extracted with CHCl3 (100 mL), and the solvent
was evaporated to give the corresponding hydroquinone.
2,5-Bis(cyclohexylsulfanyl)benzene-1,4-diol (8a)
Compound 8a was purified by column chromatography (first frac-
tion eluted with hexanes).
2-(Cyclohexylsulfanyl)benzene-1,4-diol (3a)
Compound 3a was purified by column chromatography (silica gel,
hexanes–CH2Cl2, 1:1) followed by recrystallization (hexanes–
CH2Cl2).
Yield: 1.76 g (5%); white crystals; mp 76–78 °C (Lit.10a mp 25–27
°C).
1H NMR (300 MHz, CDCl3): d = 6.97 (d, J = 2.8 Hz, 1 H), 6.87 (d,
J = 8.6 Hz, 1 H), 6.77 (dd, J = 8.6, 2.8 Hz, 1 H), 6.49 (br s, 1 H),
5.00 (br s, 1 H), 2.86–2.77 (m, 1 H), 1.93–1.89 (m, 2 H), 1.76–1.72
(m, 2 H), 1.60–1.56 (m, 1 H), 1.38–1.15 (m, 5 H).
Yield: 0.4 g (1%); white crystals; mp 95–96 °C.
1H NMR (300 MHz, CDCl3): d = 7.09 (s, 2 H), 6.37 (s, 2 H), 2.90–
2.82 (m, 2 H), 1.95–1.91 (m, 4 H), 1.77–1.73 (m, 4 H), 1.62–1.56
(m, 2 H), 1.41–1.17 (m, 10 H).
13C NMR (75 MHz, CDCl3): d = 150.4, 121.0, 120.5, 48.9, 33.5,
26.1, 25.5.
Anal. Calcd for C18H26O2S2: C, 63.86; H, 7.74. Found: C, 63.38; H,
7.89.
13C NMR (75 MHz, CDCl3): d = 151.6, 148.8, 122.8, 118.6, 118.2,
115.1, 49.0, 33.7, 26.3, 25.7.
2,5-Bis(cyclohexylsulfanyl)-p-benzoquinone (9a)
Compound 9a was purified by recrystallization (CHCl3–MeOH).
Alternatively, 3a was prepared by the reduction of 4a (1.0 g, 0.004
mol); yield: 0.5 g (50%).
Yield: 6.0 g (19%); red crystals; mp 203–205 °C.
1H NMR (300 MHz, CDCl3): d = 6.42 (s, 2 H), 3.13–3.05 (m, 2 H),
2.06–2.02 (m, 4 H), 1.82–1.80 (m, 4 H), 1.66–1.63 (m, 2 H), 1.57–
1.31 (m, 10 H).
13C NMR (75 MHz, CDCl3): d = 180.9, 154.0, 124.2, 42.9, 32.1,
25.9, 25.7.
2-(Cyclohexylsulfanyl)-p-benzoquinone (4a)
Compound 4a was purified by recrystallization (MeOH).
Yield: 0.8 g (2%); orange crystals; mp 114–116 °C (Lit.11b mp 114–
116 °C).
Anal. Calcd for C18H24O2S2: C, 64.25; H, 7.19. Found: C, 63.86; H,
7.37.
1H NMR (300 MHz, CDCl3): d = 6.81 (d, J = 9.9 Hz, 1 H), 6.72 (dd,
J = 9.9, 2.4 Hz, 1 H), 6.42 (d, J = 2.4 Hz, 1 H), 3.17–3.06 (m, 1 H),
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PAPER
Reactions of p-Benzoquinone with Sulfur Nucleophiles
785
Alternatively, 9a was prepared along with 7a from 4a as described
above.
Methyl 3-{5-[2-(Methoxycarbonyl)ethylsulfanyl]-3,6-dioxo-
cyclohexa-1,4-dienylsulfanyl}propanoate (7b)
Compound 7b was purified by recrystallization (CHCl3–MeOH).
[2-(Methoxycarbonyl)ethyl]sulfanyl-Substituted Quinones and
Hydroquinones 3b, 4b, and 6b–9b
Yield: 6.3 g (13%); red crystals; mp 95–96 °C.
1H NMR (300 MHz, CDCl3): d = 6.37 (s, 2 H), 3.73 (s, 6 H), 3.07
(t, J = 7.3 Hz, 4 H), 2.73 (t, J = 7.3 Hz, 4 H).
13C NMR (75 MHz, CDCl3): d = 181.2, 171.3, 151.2, 125.8, 52.4,
32.1, 25.4.
To a solution of p-benzoquinone (1) (16.2 g, 149.8 mmol) in EtOH
(100 mL) was added methyl 3-sulfanylpropanoate (2b) (18.0 g,
149.8 mmol), and the mixture was stirred for 12 h at r.t. The red
crystals that formed were filtered, washed with hexanes (50 mL),
and successively recrystallized (MeOH, followed by CHCl3–
MeOH) to give quinones 4b, 7b, and 9b. The filtrate was concen-
trated, and the residue was purified by column chromatography (sil-
ica gel, hexanes then hexanes–CH2Cl2, 1:1) followed by
recrystallization (hexane–CH2Cl2) to give hydroquinones 3b, 6b,
and 8b.
Anal. Calcd for C14H16O6S2: C, 48.82; H, 4.68. Found: C, 48.60; H,
4.57.
Alternatively, 7b was prepared from 4b (6.03 g, 0.027 mol) and 2b
(1.60 g, 0.013 mol) in MeOH at 60 °C for 0.5 h; yield: 0.8 g (17%).
Methyl 3-{2,5-Dihydroxy-4-[2-(methoxycarbonyl)ethylsulfa-
nyl]phenylsulfanyl}propanoate (8b)
Compound 8b was purified by column chromatography (first frac-
tion eluted with hexanes).
Methyl 3-[(2,5-Dihydroxyphenyl)sulfanyl]propanoate (3b)
Compound 3b was purified by column chromatography (silica gel,
hexanes–CH2Cl2, 1:1) followed by recrystallization (hexanes–
CH2Cl2).
Yield: 1.99 g (5%); white microcrystals; mp 48–50 °C (Lit.10a mp
21–25 °C).
1H NMR (300 MHz, CDCl3): d = 6.97 (d, J = 2.9 Hz, 1 H), 6.86 (d,
J = 8.8 Hz, 1 H), 6.81 (dd, J = 8.6, 2.7 Hz, 1 H), 6.52 (s, 1 H), 6.21
(s, 1 H), 3.70 (s, 3 H), 2.95 (t, J = 7.0 Hz, 2 H), 2.57 (t, J = 7.0 Hz,
2 H).
Yield: 1.6 g (2%); white crystals; mp 118–120 °C.
1H NMR (300 MHz, CDCl3): d = 7.04 (s, 2 H), 6.35 (s, 2 H), 3.64
(s, 6 H), 2.92 (t, J = 7.0 Hz, 4 H), 2.51 (t, J = 7.0 Hz, 4 H).
13C NMR (75 MHz, CDCl3): d = 219.8, 172.1, 150.4, 120.9, 52.0,
33.9, 31.1.
Anal. Calcd for C14H18O6S2: C, 48.54; H, 5.24. Found: C, 48.36; H,
5.20.
13C NMR (75 MHz, CDCl3): d = 172.8, 150.9, 149.1, 121.7, 118.7,
117.9, 115.7, 52.1, 34.0, 30.9.
Alternatively, 8b was prepared by the reduction of 9b (0.52 g, 1.5
mmol).
Alternatively, 3b was prepared by the reduction of 4b (1.00 g, 0.004
mol).
Yield: 0.39 g (75%).
Yield: 0.55 g (55%).
Methyl 3-{4-[2-(Methoxycarbonyl)ethylsulfanyl]-3,6-dioxo-
cyclohexa-1,4-dienylsulfanyl}propanoate (9b)
Compound 9b was purified by recrystallization (CHCl3–MeOH).
Methyl 3-[(3,6-Dioxocyclohexa-1,4-dienyl)sulfanyl]propanoate
(4b)
Compound 4b was purified by recrystallization (MeOH).
Yield: 1.0 g (3%); red crystals; mp 87–89 °C (Lit.10a mp 91–94 °C).
1H NMR (300 MHz, CDCl3): d = 6.82 (d, J = 10.0 Hz, 1 H), 6.74
(dd, J = 10.0, 2.2 Hz, 1 H), 6.43 (d, J = 2.3 Hz, 1 H), 3.73 (s, 3 H),
3.07 (t, J = 7.3 Hz, 2 H), 2.74 (t, J = 7.3 Hz, 2 H).
Yield: 9.7 g (16%); yellow crystals; mp 164–166 °C.
1H NMR (300 MHz, CDCl3): d = 6.43 (s, 2 H), 3.73 (s, 6 H), 3.06
(t, J = 7.3 Hz, 4 H), 2.73 (t, J = 7.3 Hz, 4 H).
13C NMR (75 MHz, CDCl3): d = 180.2, 171.3, 154.1, 124.2, 52.4,
32.1, 25.4.
13C NMR (75 MHz, CDCl3): d = 183.8, 183.6, 171.1, 151.9, 137.4,
136.1, 124.9, 52.2, 31.9, 25.0.
Anal. Calcd for C14H16O6S2: C, 48.82; H, 4.68. Found: C, 48.60; H,
4.57.
Alternatively, 9b was prepared from 4b (6.03 g, 0.027 mol) and 2b
(1.60 g, 0.013 mol) in MeOH at 60 °C for 0.5 h; yield: 0.5 g (11%).
Alternatively, 4b was prepared from p-benzoquinone (1) (21.6 g,
0.2 mol) and 2b (11.1 g, 0.1 mol) in MeOH at r.t. for 1 h; yield: 15.1
g (70%).
Asymmetrically Substituted Quinones 10
To a stirred solution of 4a (4.44 g, 0.02 mol) in MeOH (100 mL) at
60 °C was added 2b (1.20 g, 0.01 mol) over a period of 5 min. After
cooling to r.t. for 1 h, the solution was filtered to give a crude mix-
ture of the 2,5- and 2,6-isomers (0.88 g, 26%).
Methyl 3-{2,5-Dihydroxy-3-[2-(methoxycarbonyl)ethylsulfa-
nyl]phenylsulfanyl}propanoate (6b)
Compound 6b was purified by column chromatography (first frac-
tion eluted with hexanes); 6b quickly oxidized and became a red
color when exposed to air.
Methyl 3-[5-(Cyclohexylsulfanyl)-3,6-dioxocyclohexa-1,4-di-
enylsulfanyl]propanoate (10a)
Fractional crystallization gave 10a.
Yield: 0.66 g (1%); colorless oil.
1H NMR (300 MHz, CDCl3): d = 7.00 (s, 3 H), 6.35 (s, 1 H), 3.81
(s, 6 H), 3.18 (t, J = 6.9 Hz, 4 H), 2.73 (t, J = 6.9 Hz, 4 H).
13C NMR (75 MHz, CDCl3): d = 172.5, 149.6, 149.0, 120.6, 120.2,
119.9, 53.4, 52.0, 34.0, 33.8, 30.8, 29.2.
Yield: 0.45 g (13%); red crystals; mp 96–98 °C.
1H NMR (300 MHz, CDCl3): d = 6.35 (dd, J = 4.7, 2.2 Hz, 2 H),
3.73 (s, 3 H), 3.13–3.04 (m, 3 H), 2.73 (t, J = 7.3 Hz, 2 H), 2.06–
2.02 (m, 2 H), 1.82–1.79 (m, 2 H), 1.68–1.31 (m, 6 H).
13C NMR (75 MHz, CDCl3): d = 181.6, 181.2, 151.4, 151.2, 125.7
(2 C), 124.3, 124.1, 52.4, 43.1, 42.9, 32.1, 25.9, 25.7, 25.4, 25.3.
Anal. Calcd for C14H18O6S2: C, 48.54; H, 5.24. Found: C, 48.82; H,
5.37.
Alternatively, 6b was prepared by the reduction of 7b (0.52 g, 1.5
mmol); yield: 0.42 g (80%).
Anal. Calcd for C16H20O4S2: C, 56.45; H, 5.92. Found: C, 56.52;
H, 6.02.
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786
A. R. Katritzky et al.
PAPER
2,3,5,6-Tetrakis(cyclohexylsulfanyl)-p-benzoquinone (14a)
A mixture of 12a (50 mg, 0.09 mol) and p-benzoquinone (1) (10
mg, 0.09 mol) in MeOH (20 mL) was stirred at r.t. for 4 h. Then,
MeOH was removed, and the residue was extracted with CH2Cl2
(50 mL), washed with H2O (50 mL), and dried (Na2SO4) to give 14a
after recrystallization (n-pentane–Et2O).
Methyl 3-[4-(Cyclohexylsulfanyl)-3,6-dioxocyclohexa-1,4-di-
enylsulfanyl]propanoate (10b)
Compound 10b, isolated along with 10a, was purified by fractional
crystallization (MeOH).
Yield: 0.45 g (13%); red crystals; mp 136–137 °C.
1H NMR (300 MHz, CDCl3): d = 6.42 (d, J = 2.3 Hz, 2 H), 3.73 (s,
3 H), 3.13–3.04 (m, 3 H), 2.73 (t, J = 7.3 Hz, 2 H), 2.06–2.02 (m, 2
H), 1.82–1.74 (m, 2 H), 1.68–1.28 (m, 6 H).
13C NMR (75 MHz, CDCl3): d = 180.6, 180.3, 171.3, 154.2, 153.8,
124.3, 124.0, 52.4, 42.9, 32.1, 25.8, 25.7, 25.3.
Yield: 0.04 g (80%); red crystals; mp 155–156 °C.
1H NMR (300 MHz, CDCl3): d = 3.74–3.65 (m, 4 H), 1.92–1.57 (m,
20 H), 1.47–1.21 (m, 20 H).
13C NMR (75 MHz, CDCl3): d = 174.7, 147.2, 46.7, 37.6, 34.3, 26.2,
25.7.
Anal. Calcd for C16H20O4S2: C, 56.45; H, 5.92. Found: C, 56.10; H,
5.93.
Anal. Calcd for C30H44O2S4: C, 63.78; H, 7.85. Found: C, 63.82; H,
8.00.
2,3,5-Tris(cyclohexylsulfanyl)benzene-1,4-diol (11a)
To a solution of 9a (0.1 g, 0.3 mmol) in MeOH (10 mL) was added
2a (35 mg, 0.3 mmol). The mixture was stirred at 65 °C for 2 h and
then at r.t. until all the red crystals of the quinone dissolved (48 h)
and the solution became colorless. The volatiles were removed and
the residue was crystallized (n-pentane) to give 11a.
Tri- and Tetrasubstituted Hydroquinones 11b and 12b
A solution of 9b (0.5 g, 1.5 mmol) in MeOH (15 mL) was added to
2b (0.18 g, 1.5 mmol), and the mixture was stirred at 65 °C for 0.2
h. The volatiles were removed and the residue was subjected to col-
umn chromatography (silica gel, CHCl3) to give the separated pure
products.
Yield: 0.1 g (73%); green crystals; mp 88–90 °C.
1H NMR (300 MHz, CDCl3): d = 7.06 (s, 1 H), 6.98 (s, 1 H), 6.71
Methyl 3-{2,5-Dihydroxy-3,6-bis[2-(methoxycarbonyl)ethylsul-
fanyl]phenylsulfanyl}propanoate (11b)
Yield: 0.12 g (17%); brown oil.
1H NMR (300 MHz, CDCl3): d = 7.16 (s, 1 H), 6.98 (s, 1 H), 6.83
(s, 1 H), 3.71 (s, 3 H), 3.70 (s, 3 H), 3.68 (s, 3 H), 3.18 (t, J = 7.4
Hz, 2 H), 3.06 (dt, J = 17.2, 7.0 Hz, 4 H), 2.69 (t, J = 7.4 Hz, 2 H),
2.55 (dt, J = 10.6, 3.7 Hz, 4 H).
(s, 1 H), 3.25–2.98 (m, 3 H), 2.03–1.59 (m, 15 H), 1.48–1.21 (m, 15
H).
13C NMR (75 MHz, CDCl3): d = 151.7, 150.4, 124.4, 123.4, 121.0,
117.0, 49.5, 49.1, 44.9, 33.7, 33.3, 26.3, 26.2, 25.9, 25.8.
Anal. Calcd for C24H36O2S3: C, 63.67; H, 8.40. Found: C, 63.92; H,
8.40.
13C NMR (75 MHz, CDCl3): d = 172.3, 172.2, 172.0, 152.1, 150.1,
125.9, 122.6, 120.0, 116.9, 52.1 (2 C), 52.0, 33.9, 33.8, 33.7, 31.6,
31.2, 27.3.
2,3,5,6-Tetrakis(cyclohexylsulfanyl)benzene-1,4-diol (12a)
A solution of 9a (0.65 g, 0.002 mol) in CH2Cl2 (5 mL) was added to
a solution of 2a (0.23 g, 0.002 mol) in MeOH (50 mL) at 65 °C for
2 h, and then the mixture was allowed to stand overnight at r.t. The
mixture was filtered to remove the red crystals of 9a. The filtrate
was evaporated and the residue was separated by column chroma-
tography (silica gel, hexanes then hexanes–CH2Cl2, 2:1 to 1:1) to
give 12a.
Anal. Calcd for C18H24O8S3: C, 46.54; H, 5.21. Found: C, 46.47; H,
5.32.
Methyl 3-{2,5-Dihydroxy-3,4,6-tris[2-(methoxycarbonyl)ethyl-
sulfanyl]phenylsulfanyl}propanoate (12b)
Yield: 0.15 g (17%); brown crystals; mp 58–59 °C.
1H NMR (300 MHz, CDCl3): d = 7.43 (s, 2 H), 3.68 (s, 12 H), 3.17
(t, J = 7.1 Hz, 8 H), 2.57 (t, J = 7.0 Hz, 8 H).
13C NMR (75 MHz, CDCl3): d = 152.8, 125.5, 52.1, 34.3, 30.6.
Yield: 0.05 g (5%); pale orange crystals; mp 185–186 °C.
1H NMR (300 MHz, CDCl3): d = 7.40 (s, 2 H), 3.36–3.29 (m, 4 H),
1.86–1.85 (m, 8 H), 1.76–1.73 (m, 8 H), 1.61–1.60 (m, 4 H), 1.39–
1.22 (m, 20 H).
Anal. Calcd for C22H30O10S4: C, 45.35; H, 5.19. Found: C, 45.35; H,
5.14.
13C NMR (75 MHz, CDCl3): d = 152.6, 124.9, 47.8, 33.3, 26.0, 25.7.
Anal. Calcd for C30H46O2S4: C, 63.55; H, 8.18. Found: C, 63.20; H,
8.41.
Alternatively, the reaction of 13b (0.30 g, 6.5 mmol) with p-benzo-
quinone (1) (0.08 g, 6.5 mmol) in MeOH (10 mL) at r.t. for 2 h and
then at 0 °C for 6 h gave 12b; yield: 0.25 g (66%).
2,3,5-Tris(cyclohexylsulfanyl)-p-benzoquinone (13a)
A mixture of 11a (0.23 g, 0.5 mmol) and p-benzoquinone (1) (0.05
g, 0.5 mmol) in MeOH (20 mL) was stirred at r.t. for 1 h. Then,
MeOH was evaporated, and the residue was extracted with CHCl3
(50 mL), washed with H2O (50 mL), and dried (Na2SO4) to give a
brown oil, which was recrystallized (hexanes) to give 13a.
Methyl 3-{2,4-Bis[2-(methoxycarbonyl)ethylsulfanyl]-3,6-di-
oxocyclohexa-1,4-dienylsulfanyl}propanoate (13b)
A mixture of 11b (0.50 g, 1.07 mmol) and p-benzoquinone (1) (0.45
g, 1.07 mmol) in MeOH (50 mL) was refluxed for 10 min. Then,
MeOH was evaporated, and the residue was extracted with CH2Cl2
(50 mL), washed with H2O (2 × 20 mL), dried (Na2SO4), and evap-
orated to give 13b.
Yield: 0.15 g (65%); red crystals; mp 71–73 °C.
1H NMR (300 MHz, CDCl3): d = 6.37 (s, 1 H), 3.98–3.89 (m, 1 H),
3.77–3.67 (m, 1 H), 3.08–3.00 (m, 1 H), 2.04–1.15 (m, 30 H).
Yield: 0.36 g (72%); red oil.
13C NMR (75 MHz, CDCl3): d = 178.2, 177.8, 153.0, 148.9, 143.7,
125.5, 47.0, 46.8, 46.4, 42.9, 34.0, 33.8, 32.0, 25.9, 25.8, 25.7, 25.5,
25.4.
1H NMR (300 MHz, CDCl3): d = 6.32 (s, 1 H), 3.67 (s, 3 H), 3.63
(s, 3 H), 3.62 (s, 3 H), 3.40 (t, J = 7.1 Hz, 2 H), 3.26 (t, J = 7.1 Hz,
2 H), 2.99 (t, J = 7.3 Hz, 2 H), 2.69–2.59 (m, 6 H).
13C NMR (75 MHz, CDCl3): d = 180.0, 177.5, 171.8, 171.1, 169.9,
153.0, 125.7, 124.0, 112.3, 103.6, 52.2, 52.0, 37.4, 35.2, 31.9, 29.8,
29.5, 25.3.
Anal. Calcd for C24H34O2S3: C, 63.95; H, 7.60. Found: C, 63.83; H,
7.93.
Anal. Calcd for C18H22O8S3: C, 46.74; H, 4.79. Found: C, 47.10; H,
4.83.
Synthesis 2008, No. 5, 777–787 © Thieme Stuttgart · New York

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Reactions of p-Benzoquinone with Sulfur Nucleophiles
787
Methyl 3-{2,4,5-Tris[2-(methoxycarbonyl)ethylsulfanyl]-3,6-di-
oxocyclohexa-1,4-dienylsulfanyl}propanoate (14b)
A mixture of 12b (0.25 g, 0.43 mmol) and p-benzoquinone (1) (0.05
g, 0.43 mmol) in MeOH (10 mL) was stirred at reflux for 20 min.
The solvent was evaporated, and the residue was diluted with
CHCl3 (50 mL), washed with H2O (2 × 20 mL), dried (Na2SO4), and
evaporated to give 14b.
(12) (a) Schmidt, A.; Mordhorst, T. ARKIVOC 2003, (xiv), 233.
(b) Catalan, J.; Fabero, F.; Guijarro, M. S.; Claramunt, R.
M.; Santa Maria, M. D.; Foces-Foces, M. de la C.; Cano, F.
H.; Elguero, J.; Sastre, R. J. Am. Chem. Soc. 1990, 112, 747.
(c) Ballesteros, P.; Claramunt, R. M.; Escolastico, C.; Maria,
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(13) Escolastico, C.; Santa Maria, M. D.; Claramunt, R. M.;
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Yield: 0.24 g (96%); red crystals; mp 58–59 °C.
1H NMR (300 MHz, CDCl3): d = 2.43 (s, 12 H), 2.08 (t, J = 7.0 Hz,
8 H), 1.45 (t, J = 7.0 Hz, 8 H).
13C NMR (75 MHz, CDCl3): d = 174.0, 171.7, 145.8, 51.9, 35.1,
29.1.
Anal. Calcd for C22H28O10S4: C, 45.50; H, 4.86. Found: C, 45.85; H,
4.89.
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(22) These data can be obtained free of charge from the
Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
Synthesis 2008, No. 5, 777–787 © Thieme Stuttgart · New York