Reactions of toluquinone-cyclopentadiene Diels-Alder epoxide adducts with nucleophiles under heterogeneous conditions

Article abstract of DOI:10.1139/V10-106

Toluquinone-cyclopentadiene Diels-Alder epoxide adducts react with sulfur and oxygen nucleophiles under heterogeneous conditions, leading to products resulting from the epoxide ring opening and from skeletal rearrangement, respectively. Pyrolysis of the s

Full text of DOI:10.1139/V10-106

996
Reactions of toluquinone– cyclopentadiene
Diels –Alder epoxide adducts with nucleophiles
under heterogeneous conditions
´
Andreas A. von Richthofen, Jose E. P. Cardoso Filho, Liliana Marzorati,
Julio Zukerman-Schpector, Edward R.T. Tiekink, and Claudio Di Vitta
Abstract: Toluquinone–cyclopentadiene Diels–Alder epoxide adducts react with sulfur and oxygen nucleophiles under het-
erogeneous conditions, leading to products resulting from the epoxide ring opening and from skeletal rearrangement, re-
spectively. Pyrolysis of the sulfanyl adducts gave the new 3-sulfanyltoluquinones (1).
Key words: toluquinone, phase-transfer catalysis (PTC) conditions, thiolation, epoxide, Diels–Alder.
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Resume : Les epoxydes des adduits de Diels–Alder de la toluquinone et du cyclopentadiene reagissent avec des nucleophi-
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les sulfures et oxygenes, dans des conditions heterogenes pour conduire respectivement a des produits resultats d’une ou-
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verture de l’epoxyde et d’une transposition du squelette. La pyrolyse des adduits sulfanyles conduit aux nouvelles 3-
sulfanyltoluquinones (1).
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Mots-cles : toluquinone, conditions de transfert catalytique de phase (TCP), epoxyde, Diels–Alder.
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[Traduit par la Redaction]
Introduction
Fig. 1. 2-Alkylsulfanyl- and arylsulfanyl-toluquinones (1).
Quinones occur widely in nature as important components
of organisms.1 Natural and synthetic quinone-based com-
pounds are frequently used for therapeutic purposes such as
antitumor and anti-infection agents.2 In particular, benzoqui-
none thioethers possess a variety of biological and toxico-
logical activities.3 In the case of 3-sulfanyltoluquinones (1)
(Fig. 1), it should be mentioned that, although Karrer and
Dutta4 had described the synthesis of the methylsulfanyl de-
rivative 1 (X = SCH3), by reacting p-toluquinone with meth-
anethiol in water, McHale et al.,5 after trying to reproduce
Karrer and Dutta’s work, concluded that the product formed
under these conditions was 6-methylsulfanyltoluquinone in-
stead of 1 (X = SCH3).
Therefore, we decided to synthesize 1 (X = SR or SAr)
according to the route depicted in Scheme 1, which is based
on the pyrolysis of adducts 2.6 Such adducts could be pre-
pared by selective cycloaddition at the unsubstituted C=C
double bond of 3, followed by bromine/SR exchange.
However, in view of the described low yields of 3-bromo-
toluquinone (3),7 we considered an alternative route for ad-
ducts 2, based on the ring opening of epoxides 4 (Scheme 2).
Although the successful ring opening of epoxides 4 (R =
R’ = H) was described8 for 1-phenyl-5-mercaptotetrazole
(HPMT) as nucleophile in the presence of catalytic amounts
of Et3N, leading to adduct 2 (R = R’ = H; X = PMT), the
use of a stoichiometric mixture of Et3N and thiols like
HPMT, 2-mercaptobenzothiazole (HMBT), and p-toluene-
thiol (HPTT) gave the aromatized substituted adducts 5 in
yields ranging from 41% to 50% (Scheme 3) as the result
of the action of the base on the a-carbonyl hydrogens of 2
(R = R’ = H; X = SAr). Aromatization was also observed
when the epoxide 4 (R = R’ = H) was treated with sodium
ethylsulfide in EtOH.9
Considering the successful use of phase-transfer catalysis
(PTC) conditions in suppressing the aromatization reaction,
as described by Ferreira et al.,10 for the substitution of the
chlorine atoms of 6 by methylsulfide anion (Scheme 4), we
Received 24 February 2010. Accepted 2 June 2010. Published on the NRC Research Press Web site at canjchem.nrc.ca on 15 September
2010.
A.A. von Richthofen, J.E.P. Cardoso Filho, L. Marzorati, and C. Di Vitta.1 Chemistry Institute of the University of Sa˜o Paulo, Av.
Prof. Lineu Prestes 748, 05508-000 Sa˜o Paulo, SP, Brazil.
´
J. Zukerman-Schpector. Departamento de Quımica, Universidade Federal de Sa˜o Carlos-CP 676-13565-905 Sa˜o Carlos, SP, Brazil.
E.R.T. Tiekink. Department of Chemistry, University of Malaya, Kuala Lumpur 50603, Malaysia.
1Corresponding author (e-mail: cldvitta@iq.usp.br).
Can. J. Chem. 88: 996–1002 (2010)
doi:10.1139/V10-106
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von Richthofen et al.
997
Scheme 1. Proposed synthesis of 1.
Scheme 2. Proposed alternative synthesis of adducts 2.
Considering that the formation of the bis-sulfanylated ad-
ducts 7 and 8, obtained by using the HSCH3/benzene/NaOH/
H2O system, could arise from the sulfanylation of the two
possible enolic forms of adduct 214 (R = R’ = H; X =
SCH3), we performed the same reaction under more con-
trolled conditions, avoiding the presence of oxygen to mini-
mize the oxidation of methanethiol to methyl disulfide,
which could act as electrophile in the sulfanylation reac-
tion15 of 2 (R = R’ = H; X = SCH3). However, even after
careful degassing of the employed solvents and the reaction
apparatus, adducts 7 and 8 were still produced in compara-
ble yields. Thus, due to the low concentration of the sulfa-
nylating agent (CH3SSCH3, as electrophile) present in the
reaction medium,16 the formation of compounds 7 and 8 via
the mechanism depicted in Scheme 5, involving the thiola-
tion process of the intermediate benzoquinone 9, was sug-
gested. To test this hypothesis, 9 was prepared in 94% yield
by oxidation of 5 (X = SCH3) using Fe3+.17 Under the heter-
ogeneous conditions used for the thiolation of epoxides 2,
quinone 9 reacted rapidly yielding compounds 7 and 8,
although in a 1:1 ratio, in contrast to the observed 2:1 ratio
for the same reaction performed with 2 or 4.18
reasoned that we could successfully apply this methodology
to the route depicted in Scheme 2 to avoid the aromatization
of 2.
Results and discussion
Accordingly, epoxide 4 (R = R’ = H) was dissolved in
benzene and submitted to the reaction with an aqueous solu-
tion of methanethiol and sodium hydroxide, using tetrabuty-
lammonium hydrogensulfate (TBAHS) as catalyst.11 By
monitoring the reaction by TLC, and after complete con-
sumption of the starting epoxide 4 (R = R’ = H), three prod-
ucts were formed, two of them had similar retention factors.
All these products were easily isolated by chromatography.
The minor product (10% yield) was identified by NMR
spectroscopy as the desired sulfurated adduct 2 (R = R’ =
Having in hands the mono-sulfanylated adducts 2 (R = R’ =
H; X = SCH3 or SC6H5), they were heated under vacuum,
yielding the corresponding new toluquinones 1 (X = SCH3
in 80% yield; SC6H5 in 25% yield).
1
H; X = SCH3). The H NMR spectra of the two major prod-
ucts were consistent with the isomeric bis-sulfanylated ad-
ducts 7 (30% yield) and 8 (15% yield) (Fig. 2). In the case
of the major product, a single crystal was also obtained,12 al-
lowing for the unequivocal determination of the cis-endo struc-
ture 7 for this compound (Fig. 3). Owing to the similarity of
the spectroscopic data for compounds 7 and 8, the same kind
of cis-endo structure can be proposed for the latter adduct.
Although under PTC conditions the aromatization side re-
action could be completely suppressed, the selective forma-
tion of the sulfanylated product 2 could not be achieved.
However, by using HSCH3 and a less basic PTC condition
(K2CO3/benzene/TBAHS), the formation of bis-sulfanylated
products was completely avoided and the desired mono-sul-
fanylated adduct 2 (R = R’ = H; X = SCH3) was isolated in
21% yield. Unfortunately, a considerable amount of 5 (X =
SCH3; 24% yield) was also obtained.13 As for other thiols,
when benzenethiol was employed as nucleophile in the ben-
zene/NaOH/H2O system, the mono-sulfanylated adduct 2 (R =
R’ = H; X = SC6H5) was the sole product and could be iso-
lated in 81% yield. Under such conditions, the C6H5S– nu-
cleophile was also selective in the oxirane ring opening of
other similar epoxides 4 (R = H; R’ = CH3 or R = CH3; R’ =
H), leading exclusively to the mono-sulfanylated adducts 2
(R = H; R’ = CH3; X = SC6H5 in 61% yield, and R = CH3;
R’ = H; X = SC6H5 in 40% yield).
In an attempt to explore the use of the heterogeneous con-
dition for the reaction of 4 (R = R’ = H) with other nucleo-
philes, this compound was submitted to the reaction with
methoxide ion in the biphasic system (benzene/H2O). A col-
ourless solid was obtained in 51% yield for which the pres-
ence of a methoxy group incorporated to the structure of the
1
product was evidenced by a singlet at 3.41 ppm in the H
NMR spectrum. However, the lack of signals corresponding
to the norbornene hydrogens led us to the conclusion that
the reaction promoted a structural change also at that moiety
of 4 (R = R’ = H). The absence of the characteristic pale
yellow colour of toluquinone–cyclopentadiene Diels–Alder
adducts indicated the lack of conjugation between the car-
bonyl groups and the C=C double bond, suggesting that one
of the carbonyl groups was no longer present. Accordingly,
the 13C NMR spectrum for the product revealed the presence
of only one C=O group and two olefinic carbons, thus con-
firming the absence of the norbornene system. On the other
hand, the counting of 13 carbons was consistent with a prod-
uct resulting from the incorporation of a methoxy group to
the epoxide 4 (R = R’ = H). Additionally, the summing of
1
14 hydrogens by integration of the H NMR spectrum was
in agreement with this addition of a methoxide anion, and
the same conclusion emerged from the elemental composi-
tion of the product for which the minimal formulae
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998
Can. J. Chem. Vol. 88, 2010
Scheme 3. Reactions of epoxides 4 with nucleophiles under homogeneous conditions.
Scheme 4. Substitution of chlorine atoms of 6 under PTC condi-
tions.
Fig. 4. Molecular structure and X-ray crystal structure of compound
10 showing atom labeling and displacement ellipsoids at the 50%
probability level (arbitrary spheres for the H atoms).
Fig. 2. Bis-sulfanylated products formed by reaction of 4 (R = R’ =
H) with HSCH3/benzene/NaOH/H2O.
Fig. 3. X-ray crystal structure of compound 7 showing atom label-
ing and displacement ellipsoids at the 50% probability level (arbi-
trary spheres for the H atoms).
with the Loftfield mechanism for the Favorskii rearrange-
ment,20 giving an intermediate resulting from displacement
of an oxirane bond by the enolate of C8a. However, in the
second step under heterogeneous conditions, attack of meth-
oxide ion occurs on C4 of the protonated intermediate, lead-
ing to compound 10 instead of the cyclopropanone ring
opening by attack at C1.
It should be mentioned that no reaction was observed em-
ploying nitrogen nucleophiles like H2NCH3, HN(CH3)2, or
aniline under the same heterogeneous conditions.
C13H14O3 could be determined. For this compound, structure
10 (Fig. 4) emerged after a single-crystal X-ray analysis.
Crystallographic data are summarized in Table 1.
At this point, it is worth mentioning the remarkable capa-
bility of the heterogeneous conditions in changing the reac-
tivity of the methoxide ion in comparison to the
homogeneous system. In this sense, in contrast to our result
for the reaction between 4 (R = R’ = H) and sodium ethox-
ide in ethanol, a Favorskii-type ring contraction was de-
scribed by Herz et al.19 Our proposal for the formation of
10 is depicted in Scheme 6. The initial step is in accordance
Conclusion
–
For the reactions of 4 with SCH3, the two-phase system
Published by NRC Research Press

von Richthofen et al.
999
Scheme 5. Proposed mechanism for the formation of 7 and 8 under heterogeneous condition.
Scheme 6. Proposed mechanism for the formation of 10 under heterogeneous condition.
can suppress the aromatization process. The use of sodium
methoxide as nucleophile under similar conditions led to
the product with the conspicuous strained structure 10, with
complete suppression of the Favorskii-type ring contraction
reaction.
The present work reports also the first unequivocal syn-
thesis of 3-sulfanyltoluquinones (1; X = SCH3 or SC6H5).
w = 1/[s2(Fo ) + (0.0429P)2 + 0.534P] where P = (Fo
+
2
2
2Fc )/3) was introduced in each case.24
2
Reaction of 4 with nucleophiles
Using thiols in a liquid–liquid system — General
procedure
A mixture of epoxide 4 (1.0 mmol), benzene (14 mL),
aqueous sodium hydroxide (0.35 mol/L; 14 mL), and thiol
(10 mmol) was vigorously stirred at room temperature until
complete consumption of the epoxide, as indicated by TLC.
For CH3SH, the reaction flask was equipped with a dry-ice
cold finger, and the mixture was saturated with the thiol.
The organic layer was separated and the aqueous layer was
extracted with CH2Cl2. The combined organic extracts were
washed twice with water, dried over anhydrous MgSO4, and
concentrated under vacuum. The crude product was submit-
ted to dry-flash chromatography using a gradient of n-hex-
ane/ethyl acetate as eluant.
Adduct 2 (R = R’ = H; X = SCH3) was isolated as a yel-
low solid. Mp 75–76 8C. dH (200 MHz, CDCl3, Me4Si): 1.42
(d, 1H, J = 8.8 Hz), 1.54 (d, 1H, J = 8.8 Hz), 2.02 (s, 3H),
2.46 (s, 3H), 3.27 (m, 2H), 3.50 (m, 2H), 6.05 (m, 2H). dC
(75 MHz, CDCl3, Me4Si): 13.59, 16.03, 36.77, 42.77, 40.85,
59.74, 77.45, 96.40, 82.99, 87.02, 91.00, 110.21, 112.77. El-
emental analysis (%) (C13H14SO2) calcd.: C 66.6, H 6.0;
found: C 66.4, H 6.1.
Adduct 2 (R = R’ = H; X = SC6H5) was isolated as a
yellow solid. Mp 82–83 8C. dH (200 MHz, CDCl3, Me4Si):
1.42 (d, 1H; J = 6.5 Hz), 1.52 (d, 1H; J = 6.5 Hz), 2.05 (s,
3H), 3.23 (dd, 1H, J1 = 9.0 Hz; J2 = 3.6 Hz), 3.30 (dd, 1H,
J1 = 9.0 Hz; J2 = 3.6 Hz), 3.45 (m, 1H), 3.53 (m, 1H), 6.06
(m, 2H), 7.30 (m, 5H). dC (75 MHz, CDCl3, Me4Si): 15.69,
48.00, 48.16, 48.54, 48.77, 49.48, 127.72, 129.09, 131.32,
133.03, 135.38, 135.99, 150.47, 150.76, 193.73, 196.30. Ele-
mental analysis (%) (C18H16SO2) calcd.: C 72.9, H 5.4;
found: C 72.8, H 5.3.
Experimental
Methods and materials
Melting points were determined on a Koffler micro hot
stage and are uncorrected. NMR spectra were recorded with
a Bruker AC 200 or a Varian INOVA 300 spectrometers
1
against Me4Si (for H NMR) or the central line of the sol-
vent signal (CDCl3 triplet at 77.0 ppm, for 13C NMR). TLC
and dry-flash chromatography were carried out on Merck
silica gel. All reagents and solvents were used as received
from commercial suppliers. Epoxides 4 (R = R’ = H or R =
H; R’ = CH3 or R = CH3; R’ = H) were prepared according
to literature procedures.21
X-ray crystallography for compound 10
A single crystal suitable for X-ray crystallographic analy-
sis was obtained from a slow evaporation of a methanol sol-
ution (see Supplementary data section). Intensity data were
measured at 153 K on a Rigaku AFC12k/SATURN724 dif-
˚
fractometer fitted with Mo Ka radiation (l = 0.71073 A).
Data processing and absorption corrections were accom-
plished with CrystalClear and ABSCOR,22 respectively. De-
tails of cell data, X-ray data collection, and structure
refinement are given in Table 1. The structures were solved
by direct-methods.23 Full-matrix least-squares refinement on
F2 with anisotropic thermal parameters for all non-hydrogen
atoms was performed.24 H atoms were placed on stereo-
chemical grounds and refined with fixed geometry, each rid-
ing on a carrier atom with an isotropic displacement
parameter amounting to 1.2 times (1.5 for methyl-H) the
value of the equivalent isotropic displacement parameter of
the respective carrier atom. A weighing scheme of the form
Adduct 2 (R = H; R’ = CH3; X = SC6H5) was isolated as
a yellow solid. Mp 61–62 8C. dH (200 MHz, CDCl3, Me4Si):
1.36 (s, 3H), 1.51 (dt, 1H, J1 = 10 Hz, J2 = 1.6 Hz), 1.63 (br
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1000
Can. J. Chem. Vol. 88, 2010
Table 1. Crystallographic data and refinement details for compound 10.
Empirical formula
Formula mass
C13H14O3
218.24
Colour, habit
Colourless, plate
Crystal dimensions (mm)
Crystal system
0.25 Â 0.25 Â 0.05
Monclinic
Space group
P21/c
6.0728(10)
16.256(3)
10.474(2)
˚
a (A)
˚
b (A)
˚
c (A)
b (8)
V (A )
Dcalcd. (Mg m–3)
102.119(6)
1010.9(3)
1.434
3
˚
Z
4
Absortion coeff. (m) (mm–1)
F(000)
0.101
464
q range for data collection (8)
Collected/Independent/observed refls.
[I > 2s(I)]
3.43–26.50
5506 (Rsigma = 0.0286)/2085/1941 (Rint
0.0296)
=
Data/restraint/parameters
Goodnes-of-fit on F2
Final R indices [I > 2s(I)]
R indices (all data)
Largest diff. peak and hole (e A )
2085/0/146
1.088
R = 0.0480, wR = 0.1090
R = 0.0515, wR = 0.1116
0.220, – 0.195
–3
˚
d, 1H, J = 10 Hz), 2.08 (s, 3H), 2.84 (d, 1H, J = 4 Hz), 2.98
(br s, 1H), 3.44 (br s, 1H), 5.99 (dd, 1H, J1 = 4.0 Hz; J2 =
2.0 Hz), 6.11 (dd, 1H, J1 = 4.0 Hz; J2 = 2.0 Hz), 7.20–7.42
(m, 5H). dC (75 MHz, CDCl3, Me4Si): 15.3, 26.3, 45.7, 47.9,
52.2, 53.8, 57.2, 127.9, 129.0, 131.8, 132.7, 134.8, 139.2,
149.0, 151.0, 196.1, 196.8. Elemental analysis (%)
(C19H18SO2) calcd.: C 73.5, H 5.8; found: C 73.4, H 6.1.
Adduct 2 (R = CH3; R’ = H; X = SC6H5) was isolated as
a yellow solid. Mp 76–77 8C. dH (200 MHz, CDCl3, Me4Si):
1.50 (s, 3H), 1.52 (m, 1H), 1.62 (br d, 1H, J = 9.6 Hz), 2.07
(s, 3H), 2.82 (d, 1H, J = 4.0 Hz), 3.08 (br s, 1H), 3.37 (br s,
1H), 6.00 (dd, 1H, J1 = 6.5 Hz, J2 = 3.3 Hz), 6.15 (dd, 1H,
J1 = 6.5 Hz, J2 = 3.3 Hz), 7.20–7.35 (m, 5H). dC (75 MHz,
CDCl3, Me4Si): 15.9, 27.3, 46.1, 48.1, 53.0, 58.1, 127.7,
129.1, 131.1, 133.1, 135.3, 138.3, 149.8, 149.9, 193.9,
200.1. Elemental analysis (%) (C19H18SO2) calcd.: C 73.5,
H 5.8; found: C 73.8, H 6.2.
Adduct 7 was isolated as a yellow solid. Mp 69–72 8C.
dH (300 MHz, CDCl3, Me4Si): 1.62 (dt, 1H, J1 = 8.9 Hz; J2 =
1.7 Hz), 1.97 (s, 3H), 2.01–2.06 (m, 1H), 2.11 (s, 3H), 2.46
(s, 3H), 2.86 (d, 1H, J = 3.9 Hz), 3.37 (br s, 1H), 3.51 (br s,
1H), 6.08–6.17 (m, 2H). dC (75 MHz, CDCl3, Me4Si): 12.8,
14.0, 14.9, 15.2, 45.0, 45.8, 46.0, 46.2, 57.7, 59.6, 134.4,
137.5 (2C), 142.9, 154.2, 184.8, 193.0. Elemental analysis
(%) (C14H16S2O2) calcd.: C 60.0, H 5.7; found: C 60.7; H
6.0.
(15 mL), TBAHS (0.030 mmol), and solid anhydrous potas-
sium carbonate (10 mmol) was saturated with methanethiol
in a reaction flask equipped with a dry-ice cold finger. The
mixture was vigorously stirred at room temperature for
2 h.12 Water (15 mL) was added and the organic layer was
separated. The aqueous phase was extracted with CH2Cl2
(3 Â 15 mL), and the combined organic extracts were dried
over anhydrous MgSO4 and concentrated under vacuum.
The crude product was submitted to dry-flash chromatogra-
phy.
Aromatic 5 (X = SCH3) was isolated as a white solid. Mp
121–123 8C after dry-flash chromatography separation us-
ing, as eluant,
a
gradient of n-hexane/acetone. dH
(200 MHz, CDCl3, Me4Si): 2.12–2.26 (m, 2H), 2.15 (s, 3H),
2.41 (s, 3H), 4.06 (br s, 1H), 4.17 (br s, 1H), 6.73 (dd, 1H,
J1 = 5.1 Hz; J2 = 2.9 Hz), 6.84 (dd, 1H, J1 = 5.1 Hz; J2 =
2.9 Hz). dC (75 MHz, CDCl3, Me4Si): 14.1, 18.7, 46.7,
47.2, 69.2, 117.7, 126.3, 133.2, 139.6, 141.6, 142.0, 143.2,
144.8. Elemental analysis (%) (C13H14O2S) calcd.: C 66.6,
H 6.0; found: C 66.9, H 6.1.
Using CH3OH in a liquid–liquid system
A mixture of epoxide 4 (R = R’ = H; 0.75 mmol), ben-
zene (10 mL), water (11 mL), and sodium methoxide
(8.3 mmol) was vigorously stirred at room temperature until
complete consumption of the epoxide, as indicated by TLC.
The organic layer was separated and the aqueous layer was
extracted with CH2Cl2. The combined organic extracts were
washed twice with water, dried over anhydrous MgSO4, and
concentrated under vacuum. The crude product was submit-
ted to dry-flash chromatography separation using a gradient
of n-hexane/ethyl acetate as eluant. Compound 10 was iso-
lated as white crystals. Mp 105–107 8C. dH (300 MHz,
CDCl3, Me4Si): 1.38 (dd, 1H, J1 = 4.5 Hz; J2 = 1.2 Hz),
1.72 (d, 1H, J = 11.9 Hz), 1.78 (d, 1H, J = 11.9 Hz), 1.82
(d, 3H, J = 1.8 Hz), 2.54 (br d, 1H, J = 4.5 Hz), 2.65 (br s,
Adduct 8 was isolated as a yellow solid. Mp 75–76 8C.
dH (300 MHz, CDCl3, Me4Si): 1.63 (dt, 1H, J1 = 9.0 Hz; J2 =
1.9 Hz), 2.04 (br d, 1H, J = 9.1 Hz), 2.07 (s, 3H), 2.11 (s,
3H), 2.43 (s, 3H), 2.89 (d, 1H, J = 3.9 Hz), 3.35 (br s, 1H),
3.50 (br s, 1H), 6.05 (dd, 1H, J1 = 6.0 Hz; J2 = 3.0 Hz), 6.15
(dd, 1H, J1 = 6.0 Hz; J2 = 3.0 Hz).
Using CH3SH in a solid–liquid system
A mixture of epoxide 4 (R = R’ = H; 1.0 mmol), benzene
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von Richthofen et al.
1001
E.; Fournet, A. Bioorg. Med. Chem. 2005, 13 (13), 4153.
doi:10.1016/j.bmc.2005.04.041. PMID:15876538.
(4) Karrer, P.; Dutta, P. C. Helv. Chim. Acta 1948, 31 (7), 2080.
doi:10.1002/hlca.19480310724. PMID:18100036.
(5) McHale, D.; Mamalis, P.; Marcinkiewicz, S.; Green, J. J.
Chem. Soc. 1959, 3358. doi:10.1039/jr9590003358.
(6) Wladislaw, B.; Marzorati, L.; Di Vitta, C. Synthesis 1983,
(06), 464. doi:10.1055/s-1983-30382.
1H), 2.86 (d, 1H, J = 2.1 Hz), 3.41 (s, 3H), 4.63 (br s, 1H),
6.60 (br s, 1H). dC (75 MHz, CDCl3, Me4Si): 15.2, 23.5,
27.0, 29.2, 33.3, 40.7, 49.7, 53.3, 85.8, 102.9, 136.7, 140.6,
195.1. Elemental analysis (%) (C13H14O3) calcd.: C 71.5, H
6.5; found: C 71.3, H 6.2.
Pyrolysis of adduct 2 (R = R’ = H; X = SCH3)
Adduct 2 (R = R’ = H; X = SCH3; 0.25 mmol) was heated
under vacuum (0.1 mm Hg) at 200 8C in a Kugelrohr, and
3-methylsulfanyltoluquinone (1; X = SCH3; 0.20 mmol)
was collected as a red oil. dH (200 MHz, CDCl3, Me4Si):
2.19 (s, 3H), 2.59 (s, 3H), 6.74 (d, 2H, J = 1.2 Hz). dC
(75 MHz, CDCl3, Me4Si): 14.09, 17.22, 136.31, 137.15,
142.75, 145.02, 183.03, 184.03. Elemental analysis (%)
(C8H8SO2) calcd.: C 57.1, H 4.8; found: C 56.8, H 4.8.
3-Phenylsulfanyltoluquinone (1; X = SC6H5; 0.070 mmol)
was obtained by a process similar to the above described as
a red oil, starting from adduct 2 (R = R’ = H; X = SC6H5;
0.28 mmol). dH (200 MHz, CDCl3, Me4Si): 2.21 (s, 3H),
6.78 (s, 2H), 7.29 (m, 5H). dC (75 MHz, CDCl3, Me4Si):
15.08, 127.44, 129.17, 130.70, 133.56, 136.52, 137.10,
142.98, 146.96, 182.34, 185.18. Elemental analysis (%)
(C13H10SO2) calcd.: C 67.8, H 4.4; found: C 67.6, H 4.4.
(7) According to Sato and co-workers (Inoue, S.; Saito, K.;
Kato, K.; Nozaki, S.; Sato, K. J. Chem. Soc. Perkin Trans.1
1974, 2097), toluquinone (3) was obtained in 1.5% yield
starting from the commercially available 2-bromo-3-nitroto-
luene. Hewson et al. (Hewson, A. T.; Sharpe, D. A.; Wads-
worth, A. H. Synthetic Commun. 1989, 19, 2095) obtained 3
in 26% yield by oxidation of N-2-methyl-3-bromophenyl-
phenylsulfonamide; however, no data on yield was reported
by the authors for the preparation of the starting sulfona-
mide.
(8) (a) O’Brien, D. F.; Gates, J. W., Jr. J. Org. Chem. 1965, 30
(8), 2593. doi:10.1021/jo01019a022.; (b) Wilgus, H. S., III;
Frauenglass, E.; Chiesa, P. P.; Nawn, G. H.; Evans, F. J.;
Gates, J. W., Jr. Can. J. Chem. 1966, 44 (5), 603. doi:10.
1139/v66-081.; (c) Youngquist, M. J.; O’Brien, D. F.; Gates,
J. W., Jr. J. Am. Chem. Soc. 1966, 88 (21), 4960. doi:10.
1021/ja00973a032.; (d) O’Brien, D. F. J. Org. Chem. 1968,
33 (1), 262. doi:10.1021/jo01265a052.
(9) Wladislaw, B. Chemistry Institute of University of Sa˜o
Paulo, Sa˜o Paulo, SP, Brazil; unpublished results.
(10) Ferreira, V. F.; Park, A.; Schmitz, F. J.; Valeriote, F. A. Tet-
rahedron 2003, 59 (8), 1349. doi:10.1016/S0040-4020(02)
01591-0.
(11) In the presence or absence of the catalyst, the reaction pro-
ceeds at similar rates, and it probably occurs at the benzene/
water interface.
(12) von Richthofen, A. A.; Cardoso Filho, J. E. P.; Marzorati, L.;
Zukerman-Schpector, J.; Tiekink, E. R. T.; Di Vitta, C. Acta
Cryst. 2010, E66, o1259. doi:10.1107/S1600536810015710 .
(13) The reaction was quenched after 2 h, although without com-
plete consumption of starting epoxide to avoid further aro-
matization.
Supplementary data
Supplementary data for this article (general methods, in-
strumentation, preparation, and diffraction data) are avail-
able on the journal Web site (canjchem.nrc.ca). CCDC
766956 contains the X-ray data in CIF format for this manu-
script. These data can be obtained, free of charge, via www.
ccdc.cam.ac.uk/conts/retrieving.html (or from the Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge
CB2 1EZ, UK; fax +44 1223 336033; or deposit@ccdc.
cam.ac.uk).
Acknowledgements
`
This work was supported by Fundac¸a˜o de Amparo a Pes-
quisa do Estado de Sa˜o Paulo (FAPESP), Coordenac¸a˜o de
´
(14) Adduct 2 (R = R’ = H; X = SCH3) is the precursor of 7 and
8, as proved by the formation of the latter compounds in a
2:1 ratio by treatment of 2 (R = R’ = H; X = SCH3) with
benzene/H2O/NaOH/HSCH3.
Aperfeic¸oamento de Pessoal de Nıvel Superior (CAPES),
´
and Conselho Nacional de Desenvolvimento Cientıfico e
´
Tecnologico (CNPq).
(15) Wladislaw, B.; Marzorati, L.; Di Vitta, C. Org. Prep. Proced.
Int. 2007, 39 (5), 447. doi:10.1080/00304940709458600.
(16) After 24 h of stirring, only 2% of CH3SSCH3 was detected
by GLC in the benzene layer of the heterogeneous system
(benzene/H2O/NaOH/HSCH3).
(17) Aromatic 5 (X = SCH3; 0.080 g; 0.34 mmol) was dissolved
in acetone (2 mL) and to the stirred solution at RT, an aqu-
eous saturated solution of Fe(NO3)3 was dropwised until
complete consumption of the starting material by TLC (Hex-
ane:EtOAc, 6:1). The reaction mixture was poured into
water (10 mL) and extracted with Et2O. After drying
(MgSO4), concentration and purification by dry-flash chro-
matography (Hexane:EtOAc, 20:1), quinone 9, a red oil,
was obtained (0.074 g; 3.2 mmol; 94% yield). dH
(200 MHz, CDCl3, Me4Si): 2.16 (s, 3H), 2.27 (dt, 2H; J1 =
References
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Valderrama, J. A.; Zamorano, C.; Gonzalez, M. F.; Prina,
Published by NRC Research Press

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Can. J. Chem. Vol. 88, 2010
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formed in a 2:1 ratio after 24 h of stirring.
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Published by NRC Research Press