Synthesis of 4,6-dimethyldibenzothiophene and 1,2,3,4-tetrahydro-4,6- dimethyldibenzothiophene via Tilak annulation

Article abstract of DOI:10.1002/hlca.201100191

1,2,3,4-Tetrahydro-4,6-dimethyldibenzothiophene was prepared by coupling 2-bromo-3-methylcyclohexanone with 2-methylbenzenethiol and annulating the product with the aid of polyphosphoric acid. A mixture of 1,2,3,4-tetrahydro-4, 6-dimethyldibenzothiophene and 4,6-dimethyldibenzothiophene was prepared by coupling 2-bromo-3-methylcyclohex-2-en-1-one with 2-methylbenzenethiol and annulating the product with the aid of polyphosphoric acid. 2-Bromo-3- methylcyclohexanone was synthesized by conjugate addition of Me₃Al to 2-bromocyclohex-2-en-1-one with CuBr as catalyst and 2-bromo-3-methylcyclohex- 2-en-1-one by bromination-elimination of 3-methylcyclohex-2-en-1-one. 1,2,3,4,4a,9b-Hexahydro-4,6-dimethyldibenzothiophene was prepared by reduction of 1,2,3,4-tetrahydro-4,6-dimethyldibenzothiophene with Zn and CF ₃COOH. Copyright

Full text of DOI:10.1002/hlca.201100191

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Synthesis of 4,6-Dimethyldibenzothiophene and 1,2,3,4-Tetrahydro-4,6-
dimethyldibenzothiophene via Tilak Annulation
by Xiaoying Xua), Xiang Lia)b), Anjie Wanga)b), Yinyong Sunc)d), W. Bernd Schweizere),
and Roel Prinsa)d)*
a) State Key Laboratory of Fine Chemicals, Faculty of Chemical, Environmental and Biological Science
and Technology, Dalian University of Technology, Dalian 116024, P. R. China
b) Liaoning Key Laboratory of Petrochemical Technology and Equipments, Dalian 116024, P. R. China
c) School of Chemical Engineering and Technology, Harbin Institute of Technology, Harbin 150001,
P. R. China
d) Institute of Chemical and Bioengineering, ETH Zurich, Wolfgang-Pauli-Str. 10, 8093 CH-Zꢀrich
(phone: þ 41(44)2528280; fax: þ 41(44)6325490; e-mail: prins@chem.ethz.ch)
e) Laboratory for Organic Chemistry, ETH Zurich, Wolfgang-Pauli-Str. 10, 8093 CH-Zꢀrich
1,2,3,4-Tetrahydro-4,6-dimethyldibenzothiophene was prepared by coupling 2-bromo-3-methylcy-
clohexanone with 2-methylbenzenethiol and annulating the product with the aid of polyphosphoric acid.
A mixture of 1,2,3,4-tetrahydro-4,6-dimethyldibenzothiophene and 4,6-dimethyldibenzothiophene was
prepared by coupling 2-bromo-3-methylcyclohex-2-en-1-one with 2-methylbenzenethiol and annulating
the product with the aid of polyphosphoric acid. 2-Bromo-3-methylcyclohexanone was synthesized by
conjugate addition of Me3Al to 2-bromocyclohex-2-en-1-one with CuBr as catalyst and 2-bromo-3-
methylcyclohex-2-en-1-one by brominationꢀelimination of 3-methylcyclohex-2-en-1-one. 1,2,3,4,4a,9b-
Hexahydro-4,6-dimethyldibenzothiophene was prepared by reduction of 1,2,3,4-tetrahydro-4,6-dime-
thyldibenzothiophene with Zn and CF3COOH.
Introduction. – Many countries have introduced or will soon introduce stringent
legislation regarding the maximum permitted level of sulfur in gasoline and diesel fuels.
Polyaromatic sulfur compounds and their substituted derivatives, such as dibenzothio-
phene and 4,6-dialkyldibenzothiophene, with the alkyl groups adjacent to the S-atom,
are the most refractory compounds in the hydrodesulfurization (HDS) process that is
industrially used to remove sulfur from fuel. Therefore, 4,6-dimethyldibenzothiophene
(4,6-DMDBT; 1) is often used as a model compound in hydrodesulfurization studies
[1]. 1,2,3,4-Tetrahydro-4,6-dimethyldibenzothiophene (TH-4,6-DMDBT; 2a) and
1,2,3,4,4a,9b-hexahydro-4,6-dimethyldibenzothiophene (HH-4,6-DMDBT; 3a) are
crucial intermediates in the complex reaction network of the removal of sulfur from
4,6-DMDBT [2].
To achieve a low level of sulfur in fuels, a detailed knowledge of the mechanism of
the HDS reaction and of the behavior of the reaction intermediates is required.
Compounds 2a and 3a have been synthesized by hydrogenation of 1 [3], but this
method is inefficient, because the conversion of 1 must be kept low to avoid further
reaction of the hydrogenated intermediates to desulfurized hydrocarbons. As a
consequence, laborious column-chromatographic separations of the product mixture
and recycling of unreacted 1 have to be performed. In addition, commercial 4,6-
ꢁ 2011 Verlag Helvetica Chimica Acta AG, Zꢀrich

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DMDBT is expensive. It can be prepared in two steps from dibenzothiophene (DBT)
by lithiation at C(4) and C(6) of DBT and subsequent reaction with MeI [4], but this
reaction gives not only a mixture of mono- and dimethyl-dibenzothiophene, but is also
difficult to apply on a multi-gram scale. However, one needs ca. 40 g of 1 to synthesize
10 g of 2a as well as 10 g of 3a, as needed to study HDS [2]. 4,6-DMDBT (1) has also
been synthesized from 2-bromo-3-nitrotoluene and 2-methylbenzenethiol (4) by
reduction of the NO2 group, followed by diazotation and ring closure by the Pschorr
reaction, in which the diazonium group attacks the ortho-C-atom on the other phenyl
ring [5]. The yield of this cyclization step was, however, low (26%). A future method
for synthesizing 1 could be a Pd-catalyzed domino cyclization reaction of 2-chloro-6-
methylbenzenethiol with 2-bromotoluene, analogous to the domino reaction of anilines
and 1,2-dihaloarenes to carbazoles [6].
The reaction of benzenethiol with 2-halocyclohexanone to 2-(phenylsulfanyl)cy-
clohexanone, followed by the Tilak annulation, is an established reaction scheme that
leads in two simple steps to tetrahydrodibenzothiophene (TH-DBT) [7]. Analogously,
one can react 4 with 2-halo-3-methylcyclohexanone to give 3-methyl-2-[(2-methyl-
phenyl)sulfanyl]cyclohexanone (5a) and let this molecule undergo Tilak annulation to
form 2a (Scheme 1), as shown by some of us in a preliminary communication [8].
Aoyama et al. demonstrated that one could even combine the base-catalyzed coupling
of the a-halo ketone with the arenethiol and the subsequent acid-catalyzed Tilak
cyclization, when the base and acid are supported on separate supports, e.g., Na2CO3/
SiO2 and PPA/SiO2 [9].
Scheme 1
a) Br2, AcOH, H2O, 08 to r.t.; 87%. b) NaOH, EtOH, H2O, reflux, 2.5 h; 75%. c) Polyphosphoric acid
(PPA), 1658, 3 h; 69%. d) Zn, CF3COOH (TFA), r.t., 4 d; 80%.
Here, we describe an approach to synthesize 2a and 2b (TH-2,6-DMDBT) based on
the classic Tilak annulation, the coupling of 2-bromo-3-methylcyclohexanone (6a) and
2-bromo-5-methylcyclohexanone (6b), respectively, with 4. Then, 3a and 3b (HH-2,6-
DMDBT) were prepared by reduction of the corresponding compounds 2a and 2b with
Zn and trifluoroacetic acid (TFA). In a second approach, we synthesized 2a and 1
simultaneously by means of vinylic substitution (SNV) of 2-bromo-3-methylcyclohex-

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en-1-one (7; cf. Scheme 3) with the thiophenol 4, followed by an unconventional Tilak
annulation.
Results and Discussion. – A crucial intermediate in the synthesis of 2a is 6a. We first
tried to synthesize 6a by bromination and iodination of 3-methylcyclohexanone (8) to
2-halo-3-methylcyclohexanone. This reaction is easy to perform, and the literature even
indicated that 2-iodo-3-methylcyclohexanone would be formed preferentially [10].
Unfortunately, but not surprisingly, this turned out not to be the case, and the reaction
led to a mixture of four isomers, cis- and trans-2-iodo-3-methyl-, and cis- and trans-2-
iodo-5-methylcyclohexanone, which were too difficult to separate. Although the
analogous four Br isomers could not be separated either, reaction of the mixture with 4
and cyclization of the resulting products 3-methyl-2-[(2-methylphenyl)sulfanyl]cyclo-
hexanone (5a) and 5-methyl-2-[(2-methylphenyl)sulfanyl]cyclohexanone (5b) led to a
crystalline mixture of 2a and 2b (main product; Scheme 1). Crystallization led to pure
2b but to impure 2a. To synthesize pure 2a, we, therefore, turned our attention to
cyclohexenones.
We investigated the use of cyclohex-2-en-1-one (9), because it could give 6a in only
two steps (Scheme 2 [8]). The first step, the bromination of 9, and the final step, the
hydrolysis of the AlꢀO bond, proved to be easy. However, the conjugate addition of
Me3Al to 2-bromocyclohex-2-en-1-one (10) [11] required safety precautions, and,
therefore, only small batches (2 g) at a time could be prepared [8]. With the thus
obtained 6a (cis/trans-mixture) and 4, the synthesis of 2a presented no problem
(Scheme 1). We tried to synthesize 3a in a similar way by reducing 6a with NaBH4 to 2-
bromo-3-methylcyclohexanol and then react the latter with 4 in the presence of
polyphosphoric acid (PPA). While the reduction of the ketone and the subsequent
coupling of the thiol with 2-bromo-3-methylcyclohexan-1-ol to 3-methyl-2-[(2-meth-
ylphenyl)sulfanyl]cyclohexanol proceeded smoothly, the final ring closure by the
reaction of the OH group with the ortho-C-atom of the phenyl ring was not successful.
As an alternative, we transformed 3-methyl-2-[(2-methylphenyl)sulfanyl]cyclohexanol
to 1-chloro-3-methyl-2-[(2-methylphenyl)sulfanyl]cyclohexane and tried to cyclize the
latter with the aid of AlCl3 or ZnCl2. However, also this last step was not successful.
Apparently, FriedelꢀCrafts reactions are not only difficult for phenols, but also for
benzenethiols. We successfully synthesized 3a, instead, by the reduction of 2a with the
Zn and TFA couple [12]. Similarly, 3b was synthesized by reduction of 2b with Zn and
TFA (Scheme 1).
Scheme 2
a) Br2, CH2Cl2, Et3N, 08 to r.t.; 60%. b) CuBr, PPh3, toluene, Me3Al, ꢀ 608 to r.t.; 75%.
Instead of using 2-bromo-3-methylcyclohexanone in the synthesis of hydrogenated
intermediates of 4,6-dimethyldibenzothiophene, one could try to use 2-bromo-3-

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methylcyclohex-2-en-1-one (7). We prepared 7 by bromination of 3-methylcyclohex-2-
en-1-one (11; Scheme 3), extraction with Et2O, and chromatographic purification on a
silica gel column. Hydrogenation of 7 might, in principle, give 6a, which could be used
for the synthesis of 2a [8]. However, when halogen atoms are present in a,b-
unsaturated aldehydes and ketones, the hydrogenolysis of the CꢀX bond is faster than
the hydrogenation of the C¼C bond. Thus, it was impossible to selectively hydrogenate
7 to 6a. We, therefore, attempted to couple 7 directly with 4 by vinylic substitution
(SNV). The coupling was successful and 3-methyl-2-[(2-methylphenyl)sulfanyl]cyclo-
hex-2-en-1-one (12) formed. The resulting 12 (Fig.) was used to close the thiophene
ring with the aid of PPA to give 2a and 1 (Scheme 3). After separation by silica-gel
column chromatography, 1 was obtained as white needle-like crystals and 2a as a
colorless liquid.
Scheme 3
a) Tetrabutylammonium tribromide (TBATB), CH2Cl2, K2CO3, r.t., 56 h; 67%. b) NaOH, EtOH, H2O,
reflux, 2.5 h; 65%. c) PPA, 1508, in the absence of O2, 3 h; 2a (21%) and 1 (44%).
Figure. Crystal structure of 3-methyl-2-[(2-methylphenyl)sulfanyl]cyclohex-2-en-1-one (12). The ADP
ellipsoids are drawn at the 50% probability level.
In general, SNV reactions of vinyl halides do not proceed as well as SN2 reactions of
alkyl halides. Only when an electron-withdrawing group is present in the b-position
relative to the leaving group (in our study Br) is the rate of vinylic substitution fast [13].
In particular, the keto group in the b-position has been studied in depth [13c], but the
influence of a C¼O group in the a-position has not been studied systematically. To the
best of our knowledge, this reaction has been described only once, as the first step in the

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synthesis of tetracycline [14]. Another example of vinylic substitution with an electron-
withdrawing group in the a-position relative to the leaving group is the recent synthesis
of phenyl(1-styryl)sulfide from 1-styryl bromide and benzenethiol [15].
The replacement of the Br-atom of 7 by the RS group of the 2-methylbenzenethiol
may take place by the conjugate addition of the RS group in b-position to form aryl 3-
vinyl sulfide, which then forms aryl 2-vinyl sulfide by substitution of the Br-atom by the
RS group, i.e., an a,b shift (Scheme 4,a). This substitution reaction may be supported
by the neighboring group effect of the S-atom. Another possible explanation is that the
conjugate addition of the RS group is followed by nucleophilic substitution of the Br-
atom by another RS group. Elimination of the RS group in b-position would then give
cyclohexenone with the RS group in the a-position (Scheme 4,b).
Scheme 4. Possible Mechanisms for the Replacement of the Br-Atom by the Thiol Group
The final cyclization of 12 gave 2a and 1. However, heating 2-(arylsulfanyl)cyclo-
hexanone in the presence of a strong acid leads to cyclization by C,C coupling and the
formation of a C¼C bond [7] to give 2a in our case. If the same reaction were to proceed
with our aryl vinyl sulfide, then an additional double bond would be formed in the
cyclohexene ring, and the product would probably have been dihydro-4,6-DMDBT.
Instead, a mixture of 2a and 1 was obtained. When the reaction time was reduced from
3 to 2 h, two new peaks were observed in the GC, and their mass spectrum revealed that
both correspond to m/z 214. The peaks might belong to the isomers 1,2-dihydro-4,6-
DMDBT and 3,4-dihydro-4,6-DMDBT (Scheme 5). Unfortunately, a pure intermedi-
ate was not obtained, and the accurate structure of the intermediate could not be
determined.
Dihydro-4,6-DMDBTwill be unstable under the reaction conditions and dispropor-
tionate to 2a and 1, but this reaction should have led to a 1:1 mixture, whereas a ca. 1:3
mixture was obtained. This suggests that dihydro-4,6-DMDBT can react to 1 by
dehydrogenation. Dehydrogenation in the absence of a metal catalyst seems unlikely,
but oxidation by air might explain the ca. 1:3 ratio of compounds 2a and 1. Indeed,
when the cyclization of the aryl vinyl sulfide with PPAwas carried out under N2, the 2a/
1 ratio became ca. 1:1, as expected for the stoichiometric reaction from dihydro-4,6-
DMDBT. To improve the yield of 2a, we used HI as the reducing agent, knowing that I2
improves the reverse reaction, i.e., the dehydrogenation of a dihydrothiophene ring

Helvetica Chimica Acta – Vol. 94 (2011)
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Scheme 5. Mechanism of the Tilak cyclization of 12 to 2a and 1
[16][17]. To prepare HI in situ, the cyclization of the aryl vinyl sulfide was carried out
with PPA in the presence of KI. The product contained a ca. 2 :1 mixture 2a/1, but at the
cost of a substantial amount of by-products. This result was obtained when the reaction
was carried out in daylight, but not in the dark. Therefore, iodine radicals and HI,
formed from KI and PPA, may be responsible for the reduction of the dihydro-4,6-
DMDBT to 2a. Oxidizing or reducing agents are thus able to influence the ratio 2a/1
(Scheme 5).
Conclusions. – The Tilak annulation is a convenient way to synthesize 2a and 2b.
The synthesis of 6a can be achieved by the conjugate addition of Me3Al to 10 with a Cu
salt as the catalyst. Coupling 7 with 4 and closing the ring with PPA led to a mixture
2a/1. The ratio of the two products was steered by adding oxidants or reductants. This
synthesis can be carried out under mild conditions, consists of only few steps, and leads
to the simultaneous preparation of 2a and 1. Compounds 3a and 3b can be prepared by
the reduction of 2a and 2b, respectively, with Zn and TFA at room temperature. This
demonstrates that Tilak annulation can also be used for alkylbenzenethiols and b-alkyl
a,b-enones, providing easy access to hydrogenated intermediates of derivatives of
dibenzothiophene with alkyl substituents, which are used as model molecules in
hydrodesulfurization studies [2].
This work was supported by the Natural Science Foundation of China (20503003, 20773020,
20973030, and 21073022), the Ministry of Education of China, the Fundamental Research Funds for the
Central Universities, and Project 111. The authors are grateful to Prof. D. Seebach, the late Prof. L. Lu,
and Mr. L. Bertschi for helpful discussions.

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Experimental Part
General. All reactions were carried out in air, unless mentioned otherwise. Commercially available
reagents and solvents were used without further purification, and were purchased from Acros or
Sinopharm Chemical Reagent Co., Ltd. The progress of all reactions was monitored by TLC using glass
plates pre-coated with silica gel 60 F254 of a thickness of 0.5 mm (Merck). All samples were analyzed on
an Agilent GC (6890N) instrument equipped with HP-5 column (30 m ꢁ 0.25 mm ꢁ 0.25 mm). Column
chromatography (CC): silica gel (SiO2; 200 – 300 mesh) with petroleum ether (PE; b.p. 60 – 908) and
AcOEt as the eluents. M.p.: Electrothermal CN66 M/X-6 apparatus. IR Spectra: Thermo-Nicolet NEXUS
1
670 FT-IR spectrophotometer. H- and 13C-NMR spectra: in CDCl3 with a Varian INVA 400 MHz or a
Bruker Avance 200 MHz spectrometer, with TMS as an internal standard. MS: HP6890 GC/5973 MSD
GC-MS instrument. HR-EI-MS: Waters-Micromass-Autospec-Ultima spectrometer.
Bromination of 3-Methylcyclohexanone (8). Br2 (15.1 g, 90 mmol) was added dropwise to a
vigorously stirred mixture of 10.6 g (90 mmol) of 8 and 1 ml glacial AcOH in 38 ml of H2O. The reaction
vessel was cooled in an ice bath throughout the addition. The mixture was then saturated with NaCl, and
the org. layer was separated. The aq. layer was extracted with Et2O, and the combined org. phase was
washed three times with sat. NaHCO3 sol. and once with brine, dried (MgSO4), and concentrated to give
17.4 g of a yellow oil (87%). GC showed that it contained 30% of 6a and 59% of 6b.
Data of 2-Bromo-3-methylcyclohexanone (6a). EI-MS: 192 (14, [M þ 2]þ), 190 (13, Mþ), 148 (21),
147 (26), 146 (20), 111 (62), 83 (14), 69 (52), 55 (100), 41 (36).
Data of 2-Bromo-5-methylcyclohexanone (6b). EI-MS: 192 (13, [M þ 2]þ), 190 (14, Mþ), 148 (7),
146 (7), 111 (30), 84 (7), 69 (100), 55 (21), 41 (23) [18].
3-Methyl-2-[(2-methylphenyl)sulfanyl]cyclohexanone (5a). 2-Methylbenzenethiol (4; 7.4 g) and
NaOH (2.4 g) were dissolved in a mixture of 15 ml of EtOH and 15 ml of H2O. Compound 6a (12 g)
dissolved in EtOH (20 ml) was added dropwise to this soln., kept under a stream of N2. The mixture was
stirred at r.t. for 30 min and then heated to reflux for 4 h. After cooling, 60 ml of H2O were added. The
lower oily layer was removed, and the aq. phase was extracted with CHCl3. The combined oily layer and
extract were dried (Na2SO4). After evaporation, 11 g (75%) of the cis/trans-product was obtained. EI-
MS: 234 (Mþ, 100), 190 (8), 163 (5), 149 (5), 124 (78), 110 (7), 91 (25), 77 (8), 55 (29), 41 (12) [8].
1,2,3,4-Tetrahydro-4,6-dimethyldibenzo[b,d]thiophene (2a). Compound 5a (11 g) was added to a
round-bottom flask containing 100 g of PPA, and the mixture was slowly heated in an oil bath with
continuous stirring for 3 h at 1658. After cooling, the mixture was poured onto ice. The oily layer was
separated, and the aq. phase was extracted with CHCl3. The oily layer and the extracts were combined,
dried (Na2SO4), and the CHCl3 was distilled off to yield 8 g (69%) of 2a. Yellow oil. 1H-NMR (400 MHz,
CDCl3): 7.41 (d, J ¼ 7.2, 1 H); 7.26 (t, J ¼ 7.6, 1 H); 7.07 (d, J ¼ 7.2, 1 H); 3.06 – 3.08 (m, 1 H); 2.68 – 2.76
(m, 1 H); 2.64 – 2.67 (m, 1 H); 2.52 (s, 3 H); 2.03 – 2.09 (m, 2 H); 1.76 – 1.85 (m, 1 H); 1.52 – 1.55 (m, 1 H);
1.37 (d, J ¼ 7.2, 3 H). 13C-NMR (100 MHz, CDCl3): 143.2; 139.8; 138.6; 131.9; 130.1; 124.4; 124.1; 118.6;
32.9; 31.8; 24.2; 23.1; 21.6; 20.5. EI-MS: 216 (62, Mþ), 201 (100), 188 (29), 186 (14), 171 (13), 149 (15)
[3][8].
1,2,3,4-Tetrahydro-2,6-dimethyldibenzo[b,d]thiophene (2b). The mixture 6a/6b obtained in the
bromination of 8 was reacted with 4 to a mixture 5a/5b in the same way as 6a was reacted with 4 to 5a.
The resulting mixture 5a/5b was reacted with PPA, as 5a was reacted with PPA to 2a. The crude product
mixture 2a/2b was purified by CC on SiO2 with PE (b.p. 60 – 908). The separated compounds were stored
in a refrigerator overnight, after which 2b was obtained as a white solid. The solid was washed with PE
(b.p. 30 – 608), recrystallized from AcOEt, and 2.3 g (32%) white needle-like crystals were obtained. The
fraction that contained 2a could not be crystallized to a pure product. 1H-NMR (400 MHz, CDCl3): 7.41
(d, J ¼ 8, 1 H); 7.24 (m, 1 H); 7.06 (d, J ¼ 8, 1 H); 2.86 – 2.91 (m, 3 H); 2.50 (s, 3 H); 2.24 – 2.29 (m, 1 H);
1.96 – 2.01 (m, 2 H); 1.51 – 1.59 (m, 1 H); 1.14 (d, J ¼ 8, 3 H). 13C-NMR (100 MHz, CDCl3): 139.5; 138.8;
136.3; 131.7; 130.2; 124.2; 123.9; 118.1; 32.3; 31.9; 28.7; 25.5; 21.7; 20.3. EI-MS: 216 (66, Mþ), 201 (14), 174
(100) [19].
1,2,3,4,4a,9b-Hexahydro-4,6-dimethyldibenzo[b,d]thiophene (3a). Compound 2a (0.06 g, 0.3 mmol),
TFA (10 ml), and 1.2 g of Zn powder were added to a round-bottom flask, and the mixture was stirred
with a magnetic stirrer at r.t. for 4 d. The mixture was extracted three times with AcOEt. The combined

Helvetica Chimica Acta – Vol. 94 (2011)
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org. layer was washed with sat. NaHCO3 soln., H2O, and brine, and then dried (Na2SO4) and
concentrated in vacuo to remove the solvent. Twofold purification of the crude product by CC (SiO2; PE/
AcOEt 10 :1) gave 0.03 g (50%) 3a as yellow needle-like crystals. The NOE results show that HꢀC(9b) is
close to HꢀC(4a) in space, that HꢀC(4a) is close to HꢀC(9b) and MeꢀC(4), and that HꢀC(4a),
HꢀC(9b), and MeꢀC(4) are on the same side of the molecule. Thus, product 3a has the (4R,4aS,9bS)- or
(4S,4aR,9bR)-configuration. Comparison of the NMR results of our product 3a with those published by
Kukula et al. of the stereoisomers of HH-4,6-DMDBT [3] confirmed this assignment. 1H-NMR
(400 MHz, CDCl3): 6.98 (t, J ¼ 8, 1 H); 6.87 (d, J ¼ 8, 1 H); 6.82 (d, J ¼ 8, 1 H); 3.32 (br. s, 1 H); 2.79
(dd, J ¼ 8, 4, 1 H); 2.23 (s, 3 H); 2.04 – 2.08 (m, 1 H); 1.28 – 1.44 (m, 3 H); 1.12 – 1.21 (m, 2 H); 0.92 (d,
J ¼ 4, 3 H); 0.64 – 0.73 (m, 1 H). 13C-NMR (100 MHz, CDCl3): 142.3; 141.0; 132.7; 128.2; 124.7; 121.0;
1
59.5; 48.8; 35.3; 33.8; 26.2; 21.6; 21.5; 20.6. H-NMR (NOE): HꢀC(9b)/HꢀC(4a); HꢀC(4a)/HꢀC(9b);
HꢀC(4a)/MeꢀC(4). EI-MS: 218 (100, Mþ), 175 (39), 162 (48), 161 (68), 149 (34), 147 (24), 128 (7), 115
(8).
1,2,3,4,4a,9b-Hexahydro-2,6-dimethyldibenzo[b,d]thiophene (3b). Purification of the crude product
mixture 3a/3b, obtained from the reaction of the mixture 2a/2b with Zn and TFA, by CC (SiO2; PE/
AcOEt 10 :1) gave 3b as a yellow oil; yield (80%). GC/MS analysis of this oil showed at least five peaks,
and GC/MS indicated that all peaks belonged to 3b. The peak with the lowest retention time represented
ca. 90% of the intensity. From the yellow oil, we were able to isolate 10% of stereoisomerically pure 3b.
From a comparison of the NMR results of this product with those published by Kukula et al. for the
stereoisomers of the HH-2,6-DMDBT product, obtained in the Birch reduction of 4,6-DMDBTwith Na
in liquid NH3 [19], we concluded that our product 3b had the (2S,4aS,9bS)-configuration. 1H-NMR
(400 MHz, CDCl3): 7.02 – 7.06 (m, 1 H); 6.97 – 7.01 (m, 1 H); 6.94 – 6.96 (m, 1 H); 3.46 – 3.57 (m, 2 H);
2.29 – 2.37 (m, 1 H); 2.26 (s, 3 H); 1.77 – 1.91 (m, 1 H); 1.53 – 1.57 (m, 2 H); 1.31 – 1.47 (m, 2 H); 0.96 –
1.05 (m, 1 H); 0.93 (d, J ¼ 8, 3 H). 13C-NMR (100 MHz, CDCl3): 141.4; 140.5; 132.7; 127.7; 124.4;
120.9; 50.4; 48.5; 34.8; 33.7; 31.4; 26.8; 22.2; 20.5. EI-MS: 218 (100, Mþ), 175 (23), 162 (56), 161 (87), 149
(30), 147 (26), 128 (9), 115 (9).
2-Bromocyclohex-2-en-1-one (10). A soln. of Br2 (157.5 mmol, 9 ml) in 150 ml of CH2Cl2 was added
dropwise over a period of 3 h to a stirred soln. of 9 (150 mmol, 15 ml) in 400 ml of CH2Cl2 at 08. The soln.
was stirred at 08 for 3 h, then Et3N (250 mmol, 35 ml) was added dropwise, and the mixture was stirred at
r.t. for another 3 h. It was washed with 3% HCl and brine, and dried (MgSO4). Recrystallization from
1
hexane/Et2O gave pure 10 (15 g, 60% yield). H-NMR (200 MHz, CDCl3): 7.47 (t, 1 H); 2.67 (t, 2 H);
2.48 – 2.52 (m, 2 H); 2.10 – 2.15 (m, 2 H). 13C-NMR (50 MHz, CDCl3): 191.3; 151.2; 123.9; 38.4; 28.4; 22.7
[8].
2-Bromo-3-methylcyclohexanone (6a). To a mixture of CuBr (100 mg) and PPh3 (300 mg) were
added 50 ml of dry toluene under N2. The soln. was stirred at r.t. for 30 min and then cooled to ꢀ 608
(acetone and dry ice). Me3Al (12 ml, 2m in toluene) was added dropwise, maintaining the temp. below
ꢀ 608. The soln. was stirred for 5 min, and 3 g of 10 in 50 ml of toluene were added dropwise. The mixture
was stirred below ꢀ 608 for 2 h and then allowed to warm to r.t., until all starting material was consumed.
The soln. was diluted with Me2O, the reaction was quenched with MeOH, and the mixture was
successively washed with 2n HCl and brine. The org. layer was dried (Na2SO4). After evaporation, 6a
(2.4 g, 75%; cis/trans-mixture) was obtained. This procedure was repeated five times to obtain 12 g of
product [8].
2-Bromo-3-methylcyclohex-2-en-1-one (7). A soln. of 11 (1.1 g, 10 mmol) in CH2Cl2 (100 ml) was
cooled in a ice-water bath, and tetrabutylammonium tribromide (TBATB; 24.1 g, 50 mmol) was added at
0 – 58. After 20 min, K2CO3 (8.3 g, 60 mmol) was added, and after another 30 min, the mixture was
brought slowly to r.t. under continuous stirring. After 24 h, more K2CO3 (4.2 g, 30 mmol) was added. The
reaction was complete in 56 h, as shown by the GC spectrum. The mixture was filtered, and the white
solid was washed with CH2Cl2. The combined filtrate was concentrated in vacuo to remove the CH2Cl2,
and the product was extracted from the resulting oil with Et2O. The Et2O was distilled off in vacuum, and
1.5 g of yellow/orange oil was obtained. Purification of the crude product by CC (SiO2; PE/AcOEt 4 :1)
gave 1.3 g (67%) of 7. Colorless liquid. IR (neat): 2922, 2851, 1733, 1683, 1605, 1456, 1426, 1374, 1270,
1172, 1134, 793, 570, 508. 1H-NMR (400 MHz, CDCl3): 2.58 (t, J ¼ 6.8, 2 H); 2.51 – 2.54 (m, 2 H); 2.18 (s,
3 H); 1.98 – 2.04 (m, 2 H) [20].

1762
Helvetica Chimica Acta – Vol. 94 (2011)
3-Methyl-2-[(2-methylphenyl)sulfanyl]cyclohex-2-en-1-one (12). Compound 4 (0.5 g, 4 mmol),
NaOH (0.2 g, 4 mmol), deionized H2O (5 ml), and EtOH (5 ml) were added to a three-neck flask,
and the temp. of the H2O bath was increased to reflux temp. A soln. of 7 (0.8 g, 4 mmol) in EtOH (5 ml)
was added to the refluxed soln. by means of a dropping funnel, after which the soln. was refluxed for 2.5 h.
After cooling, 40 ml of H2O were added, and the mixture was extracted three times with Et2O. The
combined oil layer was washed with H2O and brine, dried (Na2SO4), and concentrated in vacuo to
remove the solvent. Purification of the crude product by CC (SiO2; PE/AcOEt 1:1) gave 0.6 g (65%) of
12. White solid. When the chromatographic purification was omitted, a substantial amount of bis(2-
methylphenyl) disulfide was also obtained. Apparently, the ether extract still contained TBATB, the
bromination agent. This tribromide oxidized the thiol 4 to the disulfide. To determine the structure of 12,
and especially the position of the (2-methylphenyl)sulfanyl group, not only 1H- and 13C-NMR data, but
also HR-MS data were collected. The structure was ultimately established by an X-ray structure
determination1). The unit cell contains two molecules with very similar conformation. The angle between
the best planes through the aryl and cyclohexenone rings is 758 in one molecule and 818 in the other. M.p.
1
93.8 – 95.98. H-NMR (400 MHz, CDCl3): 7.10 – 7.12 (m, 1 H); 7.00 – 7.02 (m, 2 H); 6.78 – 6.80 (m, 1 H);
2.62 (t, J ¼ 6, 2 H); 2.57 (t, J ¼ 6.8, 2 H); 2.41 (s, 3 H); 2.23 (s, 3 H); 2.03 – 2.10 (m, 2 H). 13C-NMR
(100 MHz, CDCl3): 194.7; 169.6; 135.9; 135.8; 130.3; 129.6; 126.4; 125.9; 125.1; 38.5; 34.5; 24.6; 21.9; 20.4.
EI-MS: 232.0921 (100, Mþ), 217.0686 (14), 199.1126 (9), 199.0582 (6), 171.1171 (30), 162.0490 (16),
161.0416 (16), 147.0259 (11), 143.0851 (11), 135.0256 (11), 129.0694 (12), 119.0492 (12), 105.0701 (11),
91.0549 (42), 85.0111 (15), 79.0546 (12), 77.0391 (10), 65.0386(11), 44.9769 (14), 41.0358 (14), 39.0197
(12).
X-Ray Crystal-Structure Determination of 12. Colorless single crystals were obtained by recrystal-
lization from AcOEt. All diagrams and calculations were performed using the maXus computer program
[21]. Data reduction was performed with the Denzo and Scalepak programs [22], and cell refinement
with HKL Scalepack [22], refined using SHELXS-97 [23] (Table).
Table 1. Crystal Data and Details of Structure Refinement of 3-Methyl-2-[(2-methylphenyl)sulfanyl]cy-
clohex-2-en-1-one (12)
Crystallized from
Empirical formula
Formula weight
Crystal color, habit
Crystal dimensions [mm]
Temp. [K]
Crystal system,
Space group
Z
a [ꢂ]
b [ꢂ]
c [ꢂ]
a [8]
AcOEt
C14H16OS
232.345
colorless, cube
0.42 ꢁ 0.39 ꢁ 0.195
173
g [8]
105.3195 (9)
1221.19 (4)
1.264
5.82 – 54.97
0.241
55
9779
5590
V [ꢂ3]
Dx [g mꢀ3
]
2q Range [8]
m(MoKa) [mmꢀ1
2qmax [8]
Measured reflections
Independent reflections
Observed reflections
Final R(gt)(I > 2sI)
wR(gt)(F2)
]
triclinic
ꢀ
P1
4
4693
0.0418
0.1313
7.96950 (10)
10.4833 (2)
15.5639 (3)
90.9897 (9)
102.3762 (9)
Calculated weights
D/smax
D1 (max; min) [eꢂ3]
1/[s2(Io) þ (Io þ Ic)2/900]
0.006
b [8]
0.453; ꢀ 0.307
4,6-Dimethyldibenzo[b,d]thiophene (1). Compound 12 (2.0 g, 8.6 mmol) and PPA (40 g) were added
to a round-bottom flask in the absence of O2, and the mixture was slowly heated to 1508 in an oil bath
1
)
File CCDC-800163 at the Cambridge Crystallograpic Data Centre (CCDC) contains the
supplementary crystallographic information. These data can be obtained free of charge at
www.ccdc.cam.ac.uk/data_request/cif, by sending an e-mail to data_request@ccdc.cam.ac.uk or by
contacting The Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB21EZ,
UK; fax: þ 441223336033.

Helvetica Chimica Acta – Vol. 94 (2011)
1763
under continuous stirring for 3 h. After cooling, ice-H2O was added, and the mixture was extracted three
times with Et2O. The combined org. layer was washed with sat. NaHCO3 soln., H2O, and brine, dried
(Na2SO4), concentrated in vacuo to remove the solvent, and analyzed by GC. The product consisted of
45% 2a, 49% 1, and 6% by-products when the reaction was carried out in the absence of O2, of 24% 2a
and 76% 1 under air, and of 55% 2a, 31% 1, and 14% by-products in the presence of KI. The crude
product was further purified by CC (SiO2; PE (b.p. 60 – 908)). The final yields were 21% (2a) and 44% (1)
in the absence of O2, 19% (2a) and 60% (1) when exposed to air, and 29% (2a) and 19% (1) in the
1
presence of KI. Compound 1 was obtained as white needle-like crystals. M.p. 152.8 – 154.28. H-NMR
(400 MHz, CDCl3): 7.99 (d, J ¼ 8, 2 H); 7.39 (t, J ¼ 7.6, 2 H); 7.25 – 7.28 (m, 2 H); 2.61 (s, 6 H). 13C-NMR
(100 MHz, CDCl3): 139.5; 136.3; 132.4; 127.1; 124.9; 119.5; 20.7. EI-MS: 212 (100, Mþ), 197 (16), 178 (6),
105 (12) [3 – 5].
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Received May 5, 2011