Preparation of partially hydrogenated 4,6-dimethyldibenzothiophenes

Article abstract of DOI:10.1002/hlca.200690162

The synthesis of three key intermediates of the hydrogenation pathway in the hydrodesulfurization of 4,6-dimethyldibenzothiophene (4,6-DM-DBT; 1) is described. The hydrogenated derivatives 1,2,3,4-tetrahydro-4,6- dimethyldibenzothiophene (=4,6-dimethyl-1,2,3,4-tetrahydrodibenzothiophene; 4,6-DM-TH-DBT; 2), 1,2,3,4,4a,9b-hexahydro-4,6-dimethyldibenzothiophene (=4,6-dimethyl-1,2,3,4,4a,9b-hexahydrodibenzothiophene; 4,6-DM-HH-DBT; 3), and dodecahydro-4,6-dimethyldibenzothiophene (=4,6-dimethylperhydrodibenzothiophene; 4,6-DM-PH-DBT; 4) were prepared by direct hydrogenation of 1. The reactions were carried out in continuous and batch reactors by using metal sulfide as well as noble-metal catalysts. The influence of the reaction conditions on the formation of the products and the distribution of their stereoisomers was studied in detail. The isomers of the main products were isolated and characterized by NMR, GC/MS/MS, and X-ray crystal-structure diffractometry.

Full text of DOI:10.1002/hlca.200690162

Helvetica Chimica Acta – Vol. 89 (2006)
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Preparation of Partially Hydrogenated 4,6-Dimethyldibenzothiophenes
by Pavel Kukulaa), Volker Gramlichb), and Roel Prins*a)
a) Institute for Chemical and Bioengineering, ETH-Zurich, CH-8093 Zurich
(phone: +41446325490; e-mail: prins@chem.ethz.ch)
b) Laboratory of Crystallography, Department of Materials, ETH-Zurich, CH-8093 Zurich
Dedicated to Professor Giambattista Consiglio on the occasion of his 65th birthday
The synthesis of three key intermediates of the hydrogenation pathway in the hydrodesulfurization
of 4,6-dimethyldibenzothiophene (4,6-DM-DBT; 1) is described. The hydrogenated derivatives 1,2,3,4-
tetrahydro-4,6-dimethyldibenzothiophene (=4,6-dimethyl-1,2,3,4-tetrahydrodibenzothiophene; 4,6-DM-
TH-DBT; 2), 1,2,3,4,4a,9b-hexahydro-4,6-dimethyldibenzothiophene (=4,6-dimethyl-1,2,3,4,4a,9b-hexa-
hydrodibenzothiophene; 4,6-DM-HH-DBT; 3), and dodecahydro-4,6-dimethyldibenzothiophene (=4,6-
dimethylperhydrodibenzothiophene; 4,6-DM-PH-DBT; 4) were prepared by direct hydrogenation of 1.
The reactions were carried out in continuous and batch reactors by using metal sulfide as well as noble-
metal catalysts. The influence of the reaction conditions on the formation of the products and the distri-
bution of their stereoisomers was studied in detail. The isomers of the main products were isolated and
characterized by NMR, GC/MS/MS, and X-ray crystal-structure diffractometry.
Introduction. – Polyaromatic sulfur compounds and their substituted derivatives
have received a lot of attention because they are used as model compounds in hydro-
desulfurization (HDS) studies [1–3]. In particular, derivatives of dibenzothiophene
with the alkyl substituents in the 4- and 6-positions at the aromatic ring, adjacent to
the S-atom, are the most-refractory compounds in the HDS process [4–8]. Environ-
mental regulations decreased the maximum-acceptable amount of sulfur in gasoline
and diesel fuel to 50 ppm in many parts of the world in 2005, and this limit may be
reduced to 10 ppm by the end of the decade. To achieve such a low level of sulfur,
deep HDS technology must be implemented. This comprises not only the development
of new HDS catalysts, but also the investigation of the HDS reaction mechanism.
Extensive research has shown that the HDS of 4,6-dimethyldibenzothiophene (4,6-
DM-DBT; 1) occurs by two reaction pathways (Fig. 1) [4–12]. In the so-called direct
desulfurization (DDS) pathway, the CÀS bonds of the reactant molecule are broken
by hydrogenolysis, which leads to the formation of 3,3’-dimethylbiphenyl (3,3’-DM-
BP). In the hydrogenation (HYD) pathway, the reactant molecule is first hydrogenated
to partially and totally hydrogenated intermediates, the CÀS bonds of which are then
broken in the next step to form the HDS products: 3,3’-dimethylcyclohexylbenzene
(=1-methyl-3-(3-methylcyclohexyl)benzene; 3,3’-DM-CHB), and 3,3’-dimethylbicy-
clohexyl (3,3’-DM-BCH). The hydrogenation of the desulfurized products 3,3’-DM-
BP and 3,3’-DM-CHB does not occur under the same reaction conditions, i.e., in the
presence of S-containing compounds. Therefore, the HDS products can only form
© 2006 Verlag Helvetica Chimica Acta AG, Zürich

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Helvetica Chimica Acta – Vol. 89 (2006)
Fig. 1. Reaction pathways of 4,6-dimethyldibenzothiophene (1) hydrodesulfurization
from the partially or fully hydrogenated dibenzothiophenes. To investigate the reaction
mechanism of the hydrodesulfurization of 1 and give a detailed description of its kinet-
ics, the behavior of the reaction intermediates should be studied as well.
We describe here the synthesis of three key intermediates of the hydrogenation
pathway of the HDS of 1: 1,2,3,4-tetrahydro-4,6-dimethyldibenzothiophene (=4,6-
dimethyl-1,2,3,4-tetrahydrodibenzothiophene; 4,6-DM-TH-DBT; 2), 1,2,3,4,4a,9b-
hexahydro-4,6-dimethyldibenzothiophene (=4,6-dimethyl-1,2,3,4,4a,9b-hexahydrodi-
benzothiophene; 4,6-DM-HH-DBT; 3), and dodecahydro-4,6-dimethyldibenzothio-
phene (=4,6-dimethylperhydrodibenzothiophene; 4,6-DM-PH-DBT; 4). Despite the
importance of these compounds, they have not been described in the literature and,
thus, we report here their preparation and properties.
There are several methodologies for the synthesis of (partially) hydrogenated deriv-
atives of 4,6-dimethyldibenzothiophene (1). One is based on cyclization reactions,
which result in the formation of the thiophene ring. These cyclizations are more or
less variations of the Tilak annulation, which has been studied by several groups
[13–16]. Molecules such as 1,2,3,4-tetrahydrodibenzothiophene and 1,2,3,4-tetrahy-
dro-4-methyldibenzothiophene have been prepared by this method [13][14][16]. This
type of cyclization generally provides only the tetrahydro derivatives of dibenzothio-
phene. Hexahydrodibenzothiophene can be prepared by reduction of the C(4a)=
C(9b) bond of tetrahydrodibenzothiophene by using a Pd/C catalyst and AcOH as
the solvent when the thio moiety is oxidized to a sulfone group [16]. The main draw-
back of this method is the intricate preparation of 2-halogeno-3-methylcyclohexanone,
which is required as the starting material for the cyclization reaction and the synthesis
of 2. Another methodology is the direct reduction of 1. Since we had access to this
costly starting material, by optimizing of the preparation method described by
Kuehn-Caubère et al. [17], we decided to investigate different methods of the direct
reduction of 1. The catalytic hydrogenation, by means of different types of catalysts
and different types of reaction setups (continuous and batch), was studied in detail.

Helvetica Chimica Acta – Vol. 89 (2006)
1625
Results and Discussion. – The said procedure of Kuehn-Caubère et al. [17] involves
the dilithiation of dibenzothiophene with an excess of BuLi at elevated temperature.
The reaction is not easy since the lithiation must be carried out at high temperature,
and the dilithiated intermediate must be trapped quickly with MeI to minimize by-
product formation. Therefore, we added the dilithiated intermediate to the pre-cooled
solution of MeI, and not vice versa. After the workup and crystallization, a good yield
(45%) of almost pure 4,6-DM-DBT (1; >98%) was obtained, and its structure was con-
firmed by NMR and X-ray analyses.
Hydrodesulfurization studies of 1 showed that 2 is the main intermediate in the
hydrogenation pathway. Fig. 2 shows the reaction profile and the product selectivities
in the HDS of 1 over sulfided Mo/g-Al2O3 catalyst at 3408. The conversion reached
only 26% at a space time of 5 g·min/mol, demonstrating very low activity of the molyb-
denum catalyst. At the same time, the product-selectivity plot clearly shows that the
main reaction intermediate is 4,6-DM-TH-DBT (2) and that the selectivity to 2 reaches
62% at the space time t=1 g·min/mol (Fig. 2). The selectivity to 2 was also measured
over sulfided NiMo/g-Al2O3, sulfided CoMo/g-Al2O3, and metallic PtPd/g-Al2O3 cata-
lysts, but in all cases, the selectivity was lower than with sulfided Mo/g-Al2O3. The reac-
tion conditions were, therefore, optimized with a sulfided Mo/g-Al2O3 catalyst (see
Table 1 for results). The reactions were carried out at two different temperatures, at
two different H2S pressures, and at various flows. The conversion of 1 was kept low
because the selectivity to 2 decreased with increasing conversion (Fig. 2). On the
other hand, the low conversion decreased the production rate, made product separation
more difficult, and increased the consumption of costly reactants, especially H2S.
Therefore, the optimum conversion had to be found by varying the temperature, H2S
pressure, and flow.
Increasing the temperature from 310 to 3208 increased the conversion substantially
and slightly decreased the selectivity to hydrogenation products. A lower H2S pressure
hardly influenced the conversion and selectivity. A lower flow rate (higher space time)
was beneficial not only for the conversion of 1, but also for a lower H2S consumption.
Table 2 shows the final optimized reaction conditions used to prepare 2. The reaction
was run continuously for 10 d with a conversion of ca. 25%. The crude product con-
tained ca. 19% hydrogenation products, 14% of which represented the desired 2.
The crude product was collected every other day, and unreacted 1 was separated, puri-
fied by crystallization, and recycled back to the reaction feed. The rest of the product
was adsorbed on silica gel and separated by column chromatography (petroleum
ether). Products were eluted in the following order: HDS products 3,3’-DM-BP, 3,3’-
DM-CHB, and 3,3’-DM-BCH: Rf 0.38–0.32; 2: Rf 0.35; 1: Rf 0.32–0.30; 3: Rf
0.30–0.25; 4: Rf 0.25–0.15. The isolated 4,6-DM-TH-DBT (2) was further purified
by vacuum distillation, and a product of 95% purity was obtained. The main impurities
were two isomers with the C=C bond shifted to the positions C(1),C(9b) and
C(4),C(4a) (i.e., the 2,3,4,4a-tetrahydro- and 1,2,3,9b-tetrahydro-4,6-dimethyldibenzo-
thiophene, resp.; cf. Fig. 3 for locants).
The fractions containing 4,6-DM-HH-DBT (3) were analyzed separately. They con-
sisted of three main isomers, 3a–c, in the percent ratio 53 :19 :28 (3a/3b/3c). The mol-
ecule 3 contains three stereogenic centers, i.e., C(4), C(4a), and C(9b). The H-atoms at
these centers can have the cis or trans configuration relative to each other, leading to

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Helvetica Chimica Acta – Vol. 89 (2006)
Fig. 2. a) Reaction profiles and b) product selectivities in the HDS of 1 over sulfided Mo/g-Al2O3 at
~
&
3408 (^=4,6-DM-DBT (1); «=4,6-DM-TH-DBT (2); =3,3’-DM-BCH; =3,3’-DM-CHB; l=3,
3’-DM-BP)
four different diastereoisomers. Moreover, each diastereoisomer has its antipode and,
thus, 3 can occur in eight different forms, i.e., in four pairs of enantiomers (Fig. 3). The
diastereoisomers of 3 obtained as by-products during the preparation of 4,6-DM-TH-
DBT (2) were partially separated by additional column chromatography and then re-
crystallized from EtOH to obtain pure single diastereoisomers. They were character-
ized by several independent methods: NMR, MS/MS experiments, and X-ray single-
crystal diffractometry. The NMR experiments differentiated the diastereoisomers by
different coupling constants between HÀC(4) and HÀC(4a), and HÀC(4) and HÀ
C(9b) (Table 3). The diastereoisomer 3a displayed one large coupling constant between
HÀC(4) and HÀC(4a), and a small coupling constant between HÀC(4a) and HÀC(9),
suggesting the 4,4a-trans;4a,9b-cis configuration. The diastereoisomer 3b showed two
large coupling constants, suggesting the 4,4a-trans;4a,9b-trans configuration, and the
diastereoisomer 3c showed two small, almost equal, coupling constants, suggesting

Helvetica Chimica Acta – Vol. 89 (2006)
1627
Table 1. Optimization of the Reaction Conditions for the Production of 2 over Mo/g-Al2O3 (various
temperatures, various flows, 35 kPa H2S)
Temperature [8] Flow [ml/min] Conversion [%] HYDa) [%] Selectivityb) [%] SEL-THc) [%]
310
310
310
320
320
320d)
320d)
0.4
0.3
0.2
0.4
0.3
0.3
0.2
6.0
6.5
10.9
7.4
10.3
9.7
24.5
5.4
5.9
9.5
6.6
9.1
92
91
87
89
88
86
78
50
62
68
57
70
77
71
8.4
19.1
a) Concentration of all sulfur-containing hydrogenated products: HYD=% TH+% HH+% PH).
b) Selectivity to hydrogenated products: SEL=% HYD/% conversion·100. c) Selectivity to 4,6-DM-
d
TH-DBT (2): SEL-TH=% TH/% HYD·100. ) 20 kPa H2S.
Table 2. Optimized Reaction Conditions for the Production of 2 from 1
Reaction conditions
Product composition
Production rate of 2
Catalyst: 40 mg sulfided
conversion: 24.6%
selectivity: 78%
flow 0.225 ml/min, 83 mg/hour
~2 g/d
Mo/g-Al2O3
A
Substrate: 1 (45 mg/ml)
Solvent: toluene
hydrogenation: 19.2% (13.7% (2), 4.9% continuous production for 10 d
(3), 0.6% (4))
Temperature: 3208
H2S Pressure: 20 kPa
Total pressure: 5 MPa
HDS: 5.4%
Fig. 3. Structures of all possible stereoisomers of 3
the 4,4a-cis;4a,9b-cis configuration. The fourth diastereoisomer 3d was found only in
trace amounts in the reaction products, too little to be isolated for characterization.
It must have the remaining 4,4a-cis;4a,9b-trans configuration. The NMR results were

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Helvetica Chimica Acta – Vol. 89 (2006)
confirmed by the crystal structures of the diastereoisomers 3a (Fig. 4) and 3c (Fig. 5).
The crystal structure of isomer 3b could not be determined, even though the quality
of the crystals was good, the measured unit cell reasonable, and the found space
group P2(1)2(1)2(1) normal. The disordered structure appeared to be so complicated
that only some of the superimposed fragments of the molecule could be detected.
All refinements turned out to be unstable, and the determination of an appropriate sin-
gle molecule failed. The crystal structures of the diastereoisomers 3a and 3c confirmed
the configurations found by NMR and also established that the saturated ring of 3 has
the chair conformation and that the Me group attached to C(4) is in an equatorial posi-
tion in both cases.
A method, that can also be applied for the differentiation of diastereoisomers is
energetic resolution of the diastereoisomers by comparing their stability during elec-
tron-impact (EI) ionization with their energy content [18]. The main advantage of
Table 3. Relative Configurations of the 4,6-DM-HH-DBT Diastereoisomers 3a–d
J(4,4a)
J(4a,9b)
Configuration at
Energy [kcal/mol]a)
Bond length [Å]a)
C(4),C(4a)
C(4a),C(9b)
C(4a)ÀS
C(5a)ÀS
3a
3b
3c
3d
10.5
13.0
4.7
–
6.2
10.8
4.7
–
trans
trans
cis
cis
trans
cis
21.07
22.32
21.16
24.41
1.91
1.90
1.91
1.90
1.84
1.83
1.83
1.84
cis
trans
a) Calculated with the Hyperchem 5.0 software by using the MM+ force field.
Fig. 4. X-Ray crystal structure of rel-(4R,4aS,9bS)-1,2,3,4,4a,9b-hexahydro-4,6-dimethyldibenzothio-
phene (3a)

Helvetica Chimica Acta – Vol. 89 (2006)
1629
Fig. 5. X-Ray crystal structure of rel-(4R,4aR,9bR)-1,2,3,4,4a,9b-hexahydro-4,6-dimethyldibenzothio-
phene (3c)
this method is the direct coupling of the mass detector, which is used for energetic res-
olution, with chromatographic separation (e.g., GC/MS/MS or HPLC/MS/MS). Thus,
the separation of the diastereoisomers is unnecessary, and mixtures can be analyzed
directly. The method for the differentiation of the 4,6-DM-HH-DBT diastereoisomers
3a–d was optimized by varying the EI ionization and mass-detector (ion trap) param-
eters (temperature, amount of helium, collision-induced dissociation (CID) excitation
time). The diastereoisomers were distinguished by comparing the abundance of the
appropriate parent and daughter ions produced in the course of the CID experiments
differing in collision energy. The MS/MS results showed that the excitation energy of
the diastereoisomers increase in the order 3d<3b<3c<3a. These results were com-
pared with the energy contents of the diastereoisomers, which characterize the stability
of the diastereoisomers (Table 3). The energy contents were obtained from molecular-
mechanics calculations (MM+) with the Hyperchem 5.0 software. The order of the cal-
culated total energies of the diastereoisomers corresponded well with that of the
observed excitation energies. The molecular structures obtained from the theoretical
calculations (Fig. 6) were also in good agreement with the crystal structures (Figs. 4
and 5). The calculations confirmed the chair configuration of the unsaturated ring of
3 in all the diastereoisomers and the equatorial position of the Me group at C(4) in
the diastereoisomers 3a, 3b, and 3c. The diastereoisomer 3d, which has the 4,4a-
cis;4a,9b-trans configuration, has also the chair conformation, but the Me group at
C(4) is in an axial position. The theoretical calculations also showed that the C(4a)À
S(5) bond is significantly longer than the C(5a)ÀS(5) bond (Table 3) and, in certain
cases, it almost exceeded the standard CÀS bond length (1.70–1.90 Å).

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Helvetica Chimica Acta – Vol. 89 (2006)
Fig. 6. Optimized molecular structures of the 4,6-DM-HH-DBT diastereoisomers 3a–d and their mini-
mized energies under standard conditions
In view of the hydrogenation pathway (Fig. 1), the isomers 3a and 3c are obviously
products of the syn-addition of H2 to the C(4a)=C(9b) bond of the partially hydrogen-
ated intermediate 2. In comparison, the isomers 3b and 3d have to be formed by anti
addition of H2 to the C(4a)=C(9b) bond or, and this is more probable, they are formed
by isomerization of 3a and 3c. To establish that the isomerization of the diastereoisom-
ers 3 can occur, the pure compounds 3a and 3c were treated separately under basic as
well as under acidic conditions at high temperature (3008) for 2 h in the autoclave. The
isomerization was also tested in the presence of sulfided NiMo/Al2O3 and metallic 10%
Pd/C catalysts in the presence and absence of H2. It was found that the isomerization
took place only when a catalyst was present (to a greater extent over 10% Pd/C) and
in the presence of H2. Under such reaction conditions, the hydrogenation–dehydrogen-
ation equilibrium reactions occur, and the isomers 3a and 3c can dehydrogenate back to
2. The dehydrogenation takes place preferably at positions C(4a),C(9b) and C(1),C(9b)
because the C=C bond remains conjugated with the unsaturated ring. While dehydro-
genation and hydrogenation at position C(4a),C(9b) again gives the products with a cis
configuration, dehydrogenation at position C(1),C(9b) results in the loss of the 4a,9b-
cis configuration, and the 2,3,4,4a-tetrahydro-4,6-dimethyldibenzothiophene inter-
mediate forms. Subsequent hydrogenation of this tetrahydro intermediate, formed
from the 3a and 3c isomers, results in the other two isomers 3b and 3d, respectively.
The formation of the intermediate with a C(1)=C(9b) bond and its fast subsequent
hydrogenation to the product with the 4a,9b-trans configuration is analogous to the
hydrogenation of naphthalene to cis- and trans-decalin (=cis- and trans-decahydro-

Helvetica Chimica Acta – Vol. 89 (2006)
1631
naphthalene). It was shown [19][20] that cis-decalin is formed by the hydrogenation of
D
9,10-octalin (=1,2,3,4,5,6,7,8-octahydronaphthalene), while trans-decalin is the prod-
uct of D1,9-octalin (=1,2,3,4,4a,5,6,7-octahydronaphthalene).
To prepare larger amounts of 3 and 4, the hydrogenation of 1 was studied in detail
with various noble-metal catalysts. The screening experiments were carried out in a
small 60-ml autoclave by using Pd, Pt, Ru, and Rh catalysts. Noble metals are easily
poisoned by S-containing compounds and, therefore, large amounts of catalysts were
used. The reactions were stopped when H2 consumption stopped. The results show
that the catalysts were indeed strongly deactivated, even when large amounts of cata-
lysts were used, and that a high metal loading had a positive effect in preventing poi-
soning (Table 4). Of all the tested noble metals, 10% Pd/C was the most-active catalyst.
The presence of AcOH markedly increased conversion. Therefore, further reactions
were carried out with AcOH as the solvent. Other parameters, such as temperature
and H2 pressure were optimized as well. High H2 pressure was necessary to shift the
equilibrium as much as possible to the hydrogenation side. The optimal temperature
had to be found because, although the conversion increased with increasing tempera-
ture, the selectivity to hydrogenated S-containing products decreased due to CÀS
bond cleavage and consecutive sulfur removal.
After the screening experiments, a larger autoclave (300 ml) was used to prepare
larger amounts of 3 and 4. During these experiments, the H2 pressure was high (15
MPa) and the influence of temperature and the substrate-to-catalyst ratio on product
selectivity was investigated (Tables 5–7). The main products at 1708 were the 4,6-
DM-HH-DBT diastereoisomers 3 (37% at 42% conversion; Table 5, Entry 1). The per-
cent ratio of the hexahydro-diastereoisomers 3 was 27:10 :63 (3a/3b/3c) (Table 6). At
the same time, the reaction mixture contained only 1.5% of the totally saturated 4,6-
DM-PH-DBT (4). With increasing temperature, there was an increase in the conver-
sion as well as in the amount of 4 (up to 13%; Table 5, Entry 3). On the other hand,
at 2608, the selectivity to hydrogenated products decreased because of the desulfuriza-
Table 4. Results of the Hydrogenation of 4,6-DM-DBT (1) by Using Various Noble-Metal Catalystsa)
Catalyst
Temp [8] Solvent
Conv. [%] TH [%] HH [%] PH [%] HDS [%] SELb) [%]
3% Pd/1%Pt/ 250
Al2O3
AcOH
8.0
3.0
4.5
0.0
0.5
94
AHCTREUNG
5% Pt/Al
5% Ru/C
5% Rh/Al
5% Rh/C
10% Pd/Cc) 150d)
10% Pd/Cc) 150d)
10% Pd/C
10% Pd/C
A
AcOH
cyclohexane
AcOH
decane/HCl
toluene
toluene/AcOH 23.0
11.0
9.0
9.0
45.0
5.0
3.0
4.0
4.0
11.0
2.0
2.0
0.0
2.5
3.4
17.0
2.0
20.0
39.0
35.0
0.0
0.0
0.0
1.0
0.0
0.0
4.0
13.0
8.0
2.5
1.6
16.0
1.0
1.0
27
72
82
64
80
96
87
73
G
170d)
250
AcOH
AcOH
53.0
77.0
3.0
8.0
7.0
21.0
a) Reaction conditions: 250 mg of substrate, 250 mg of catalyst, 20 ml of solvent, 13 MPa H2. b) Selectivity
to hydrogenated products: SEL=(% TH+% HH+% PH)/%conversion·100. c)125 mg of catalyst. d) 8
MPa H2.

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Helvetica Chimica Acta – Vol. 89 (2006)
tion reaction. The percent ratio of the diastereoisomers 3 also changed at higher tem-
perature and a more equilibrated mixture of isomers was obtained: 3a/3b/3c 32 :17:50
(Table 6, Entry 3). This is in good agreement with the isomerization experiments. At
lower temperatures, syn addition of H2 takes place in particular and the major product
is the diastereoisomer 3c. The amount of the other diastereoisomers increased with
increasing temperature due to the hydrogenation–dehydrogenation equilibrium. We
also carried out an experiment in which the reaction time was ten times longer
(Table 6, Entry 4). The conversion remained almost the same, but the percent ratio
of the diastereoisomers shifted to 40 :14 :45 (3a/3b/3c). This result coincides well
with the energy contents of the diastereoisomers as obtained from theoretical calcula-
tions. They showed that 3a and 3c have almost the same energy and are more stable
than 3b (Fig. 6). The calculated energy of the diastereoisomer 3d, which was present
in the reaction mixtures, but only in trace amounts (<0.1%), was ca. 2 kcal/mol higher
than that of diastereoisomer 3b. The highest energy content and, thus, the lowest stabil-
ity of isomer 3d are probably caused by the axial position of the Me group at C(4).
The highest selectivity to 4,6-DM-PH-DBT (4) (33%) was obtained at 2008 by using
a large amount of catalyst (the substrate-to-catalyst molar ratio was decreased to 3;
Table 7, Entry 5). These reaction conditions resulted in high conversion (71%) and a
yield of 24% of 4 (Table 5). The rest of the product consisted mainly of 4,6-DM-HH-
DBT isomers 3 (41%). The products of all the hydrogenation reactions were separated
by double-column chromatography, and the isomers of 3 were purified by crystalliza-
Table 5. Hydrogenation of 1 over 10% Pd/C under Various Reaction Conditionsa)
Entry
Temp. [8]
Conversion [%]
TH [%]
HH [%]
PH [%]
HDS [%]
SEL [%]b)
1
2
3
4
5
170
210
260
200c)
200d)
42
53
61
58
71
1.7
3.6
7.5
3.7
2.6
36.9
40.7
23.5
40.3
40.9
1.5
6.4
13.0
8.9
1.9
2.3
17
5.1
3.8
95.5
95.7
72.1
91.2
94.6
23.7
a) 5 g of substrate, 5 g of catalyst, 180 ml of AcOH, 15 MPa H2, 2 h. b) Selectivity to hydrogenated prod-
ucts: SEL=(% TH+% HH+% PH)/% conversion·100. c)10 g of substrate, 10 g of catalyst, 20 h. d) 10 g
of substrate, 15 g of catalyst, 5 h.
Table 6. Distribution of the 4,6-DM-HH-DBT Diastereoisomers 3 during the Hydrogenation of 1 over
10% Pd/Ca)
Entry
Temp. [8]
Conversion [%]
3a [%]
3b [%]
3c [%]
3d [%]
SEL-HH [%]b)
1
2
3
4
5
170
210
260
200c)
200d)
42
53
61
58
71
26.6
31.0
31.5
39.5
35.5
10.3
11.3
16.6
13.6
5.9
63.1
57.7
49.8
44.7
58.6
–
–
2.1
2.2
–
87.9
76.8
38.5
70.7
57.6
a) 5 g of substrate, 5 g of catalyst, 180 ml of AcOH, 15 MPa H2, 2 h. b) Selectivity to HH isomers: SEL-
HH=% HH/% conversion·100. c)10 g of substrate, 10 g of catalyst, 20 h. d) 10 g of substrate, 15 g of cat-
alyst, 5 h.

Helvetica Chimica Acta – Vol. 89 (2006)
1633
Table 7. Distribution of the 4,6-DM-PH-DBT Diastereoisomers 4 during the Hydrogenation of 1 over 10%
Pd/Ca)
Entry
Temp. [8]
Conversion [%]
4a [%]
4b [%]
4c [%]
4d [%]
SEL-PH [%]b)
1
2
3
4
5
170
210
260
200c)
200d)
42
53
61
58
71
0
4
11
4
7
23
49
34
18
64
47
13
36
53
29
26
27
26
27
3.6
12.1
21.3
15.6
33.4
2
a) 5 g of substrate, 5 g of catalyst, 180 ml of AcOH, 15 MPa H2, 2 h. b) Selectivity to PH isomers: SEL-
PH=% PH/% conversion·100. c)10 g of substrate, 10 g of catalyst, 20 h. d) 10 g of substrate, 15 g of cat-
alyst, 5 h.
tion. The mixture of the 4,6-DM-PH-DBT isomers 4 was further separated by column
chromatography, and the isomers with the highest concentration were isolated and
characterized by NMR spectroscopy.
Compound 4 contains six stereogenic centers and can contain a plane of symmetry.
Therefore, the maximum number of different 4,6-DM-PH-DBT diastereoisomers is 20
(16 pairs of enantiomers and 4 meso forms), and not 25 =32. We observed 10 peaks with
m/z 224 in our product by using GC/MS. Most of these peaks were, however, very small,
meaning that the corresponding isomers were present in the reaction mixture but only
in a very low concentration. We successfully separated four major isomers, 4a–d, and
characterized them by NMR experiments (Table 8). The isomers were differentiated by
the interaction constants between HÀC(4) and HÀC(4a), HÀC(4a) and HÀC(9b), HÀ
C(5a) and HÀC(6), and HÀC(5a) and HÀC(9a). All four isomers had the same cis con-
figuration between C(4a) and C(9b), and trans configuration between C(5a) and C(9a).
The configuration between C(9a) and C(9b) could not be determined because the sig-
nals of HÀC(9a) and HÀC(9b) overlapped with the signals of other H-atoms of the
molecule. The only case, in which the signals were well separated was for isomer 4c.
The NMR signals of its H-atoms were split by four neighboring H-atoms into compli-
cated multiplets. Simulation of the NMR spectrum and comparison with the measured
spectrum established the cis configuration between C(9a) and C(9b) in the 4c isomer.
Both isomers 4b and 4d possess the 5a,6-cis;5a,9a-trans configuration, which suggests
that the Me group at C(6) occupies the axial position. This was confirmed by the
lower chemical shifts of the Me group of the 4b and 4d isomers in the 13C-NMR spectra
(d 12.1 and 12.3, resp.). Isomers 4a and 4c both have Me groups in equatorial positions.
The major isomer formed at low temperature (Table 7, Entry 1) was 4c with 4,4a-
cis;4a,9b-cis;5a,6-trans;5a,9a-trans;9a,9b-cis configuration (Fig. 7). Isomer 4c is proba-
bly formed by consecutive isomerization and cis hydrogenation of 3c, the most abun-
dant isomer of 3 at low temperature. Molecule 3c is not flat, as the starting molecule
1, and the hydrogenated ring is perpendicular to the plane of benzothiophene (Figs.
5 and 6). During the syn-hydrogenation of the second benzene ring, a product with
all-cis-configuration would be expected. In this structure, both hydrogenated rings
would be oriented in the same direction, i.e., perpendicular to the plane of tetrahydro-
thiophene. Both hydrogenated rings would be so close that they would sterically hinder

1634
Helvetica Chimica Acta – Vol. 89 (2006)
Table 8. Relative Configurations of the 4,6-DM-PH-DBT Diastereoisomers 4a–d
J(4,4a) J(4a,9b) J(5a,6) J(5a,9a) Configuration at
C(4),C(4a) C(4a),C(9b) C(5a),C(6) C(5a)C(9a)
4a 10.8
4b 10.8
6.6
5.8
4.3
4.3
10.5
4.0
10.7
4.3
10.5
10.7
9.1
trans
trans
cis
cis
cis
cis
cis
trans
cis
trans
cis
trans
trans
trans
trans
4c
4.3
4.3
4d
11.7
cis
not only each other but also the adsorption through the S-atom. In agreement with this,
the minimal energy (28.50 kcal/mol) calculated for this molecular structure was signifi-
cantly higher than the energy of other 4,6-DM-PH-DBT isomers 4 (between 20 and 26
kcal/mol). Instead of the product with all-cis configuration, the much more stable (21.05
kcal/mol) 4c isomer with 4,4a-cis;4a,9b-cis;5a,6-trans;5a,9a-trans;9a,9b-cis configura-
tion formed (Fig. 7). As shown for isomer 3c, the bond C(4a)ÀS is elongated to such
an extent (Table 3) that it can be easily split, and the configuration around C(4a) can
change from cis,cis to trans,trans. The syn-hydrogenation of the isomer with trans,trans
configuration around C(4a) would then result in the isomer 4c.
Fig. 7. Structure of the main isomer 4c of 4,6-DM-PH-DBT
The major isomer formed at high temperature (Table 7, Entry 3) was 4b followed by
4d. Both have one Me group in the axial position and the 5a,9a-trans configuration. The
isomer 4b may be formed by syn hydrogenation of isomer 3a, which first gives 4,6-DM-
PH-DBT with 4,4a-trans;4a,9b-cis;5a,6-cis;5a,9a-cis;9a,9b-cis configuration. Molecule
3a is not flat and, similar to 3c, the hydrogenated ring is perpendicular to the plane
of the dihydrobenzothiophene ring. Therefore, isomers 3a and 3c can only adsorb
from one side of the benzothiophene ring and, thus, the hydrogenation of 3a and 3c
would always give products with 9a,9b-cis configuration. On the other hand, the molec-
ular calculations showed that products with all-cis configuration at the tetrahydrothio-
phene ring, i.e., HÀC(4a), HÀC(5a), HÀC(9a), HÀC(9b) on the same side, are much
less stable than isomers that have at least one of the H-atoms on the opposite side.
Thus, the product molecules tend to acquire this energetically more stable configura-
tion. This can take place by dehydrogenation and subsequent hydrogenation, similar
as in case of the isomerization of the 4,6-DM-HH-DBT isomers 3a–d, or the hydroge-
nation of naphthalene to cis- and trans-decalin [19][20]. The product of syn hydrogena-
tion of 3a is 4,6-DM-PH-DBT with the 4,4a-trans;4a,9b-cis;5a,6-cis;5a,9a-cis;9a,9b-cis

Helvetica Chimica Acta – Vol. 89 (2006)
1635
configuration (24.04 kcal/mol). This molecule can be dehydrogenated in positions
C(9),C(9a) to 1,2,3,4,4a,5a,6,7,8,9b-decahydro-4,6-dimethyldibenzothiophene, which
is then hydrogenated to the more stable isomer 4b (22.56 kcal/mol). Similarly, isomer
4d may be a product of dehydrogenation–hydrogenation of isomer 3c. The hydrogen-
ated intermediate with all-cis configuration (28.50 kcal/mol) may isomerize by dehy-
drogenation and hydrogenation to the more stable isomer 4d (24.38 kcal/mol). The
last isomer isolated from the reaction mixture was the isomer 4a. It may form by iso-
merization of 4,6-DM-PH-DBT with 4,4a-trans;4a,9b-cis;5a,6-trans;5a,9a-cis;9a,9b-cis
configuration (31.08 kcal/mol). Such an intermediate could only be a product of syn
hydrogenation of 1,2,3,4,6,7,8,9-octahydro-4,6-dimethyldibenzothiophene. However,
it will readily isomerize due to its high energy to the much more stable isomer 4a
(20.64 kcal/mol).
At low temperature, the isomers 4c and 4d (both formed from 3c) were the main
isomers of 4,6-DM-PH-DBT (4) (Table 7, Entry 1). This is in good agreement with
the distribution of the 4,6-DM-HH-DBT isomers 3a–d, which shows that the predom-
inant isomer under the same reaction conditions was isomer 3c (Table 6, Entry 1). With
increasing temperature, the content of isomer 4b (formed from 3a) increased, to the
detriment of isomer 4c. This also agrees with the distribution of the 4,6-DM-HH-
DBT isomers 3, where the content of isomer 3a increased to the detriment of isomer 3c.
At high temperature (Table 7, Entry 3), more-equilibrated mixtures of the 4,6-DM-
PH-DBT isomers 4a–d as well as of the 4,6-DM-HH-DBT isomers 3a–d were pro-
duced by hydrogenation–dehydrogenation reactions on the surface of the noble-
metal catalyst. The isomerization can be caused not only by fast hydrogenation–dehy-
drogenation reactions at higher reaction temperature, but also by splitting and reform-
ing of the C(4a)ÀS(5), C(5a)ÀS(5), or C(9a)ÀC(9b) bonds of the partially hydrogen-
ated thiophene ring.
Conclusions. – We have demonstrated that the direct reduction of 4,6-dimethyldi-
benzothiophene (4,6-DM-DBT; 1) over heterogeneous catalysts can be applied to pre-
pare partially and totally hydrogenated 4,6-dimethyldibenzothiophenes. The three key
intermediates of the hydrogenation pathway of the hydrodesulfurization of 1 were pre-
pared: 1,2,3,4-tetrahydro-4,6-dimethyldibenzothiophene (2), 1,2,3,4,4a,9b-hexahydro-
4,6-dimethyldibenzothiophene (3), and perhydro-4,6-dimethyldibenzothiophene (4).
The products were used to investigate the reaction mechanism and the kinetics of
the hydrodesulfurization of 1 over metallic Pd as well as over sulfided Mo and
NiMo/g-Al2O3 catalysts [21][22]. It was shown that 1 reacts almost exclusively through
the hydrogenation pathway and that the partially and totally hydrogenated intermedi-
ates desulfurize much easier than 1. This is explained by the molecular changes around
the S-atom upon hydrogenation. First, the planarity of 1 is removed and, thus, the steric
encumbrance of the S-atom by the Me groups decreases. Second, the bond between the
S- and C-atoms belonging to the hydrogenated ring elongates significantly. These
results of hydrogenation provide better access to the S-atom and, thus, enhanced
removal of the S-atom from the reaction intermediates.
Special attention was paid to the configuration of the products and the isolation and
characterization of the main isomers formed during hydrogenation reactions. It was
shown that the products of the syn addition of H2 form preferentially when noble-

1636
Helvetica Chimica Acta – Vol. 89 (2006)
metal catalysts were used. The resulting cis isomers readily isomerized to equilibrium
mixtures, especially at higher reaction temperatures, due to fast hydrogenation–dehy-
drogenation reactions. Nevertheless, reasonable amounts of the pure isomers of the
main products, namely 2, 3a, 3c, 4c, and 4d, were separated and purified (from 1 up
to 20 grams). The further study of the HDS mechanism with single diastereoisomers
at a lower reaction temperature provided more information about the nature of the
active sites of the HDS catalysts.
We thank Dr. Marina Egorova and Dr. Adeline Röthlisberger for performing the continuous hydro-
ˇ
ˇ
genation in the plug-flow reactor, Peter Kälin for scaling up the synthesis of 1, Vlastimil Cízek for skill-
ˇ
fully carrying out column chromatography, and Dr. Heinz Rüegger and Dr. Petr Kacer for their kind help
and assistance with the NMR and GC/MS/MS measurements, respectively.
Experimental Part
General. Column chromatography (CC): Fluka silica gel 60 (0.04–0.063 mm); eluent petroleum
ether (b.p. 110–1408). TLC: Merck TLC plates precoated with silica gel 60 F254; visualization by treat-
ment with Mostain soln. GC: HP-5890-II-Plus-Agilent instrument equipped with an HP-1 capillary col-
1
umn; tR in min. H- and 13C-NMR spectroscopy: Bruker-DPX-300 and Bruker-Avance-500 spectrome-
ters; d in ppm, J in Hz. GC/MS: Agilent-GC-MS (HP 6890 MSD) equipped with an HP-5MS column
(30 m×0.25 mm×0.25 mm); in m/z (rel. %). MS/MS Experiments: GC-MS/MS-Saturn-2000-Varian
instrument equipped with CP-Sil-8-CB-Lowbleed/MS column and an ion-trap mass detector; EI ioniza-
tion, trap temp. 808, emission current 10 mA, axial modulation voltage 2.5 V, isolation time for ion prep-
aration 10 ms; dissociation: resonant waveform type, excitation time 2 ms. Elementary analysis: auto-
matic analyzer Perkin Elmer CHN 240C.
X-Ray Diffraction Analyses. The crystal structures of isolated crystalline products were determined
by X-ray single-crystal diffraction analysis by using Oxford-Xcalibur and Picker-Stoe-Dif4 X-ray diffrac-
tometers. The crystallographic data were validated with the PLATON program. Crystal data and details
of structure refinement of 3a and 3c are given in Table 9.
Hydrogenation Procedure. The experiments were performed in the liquid phase in a 60- or 300-ml
stainless-steel autoclave (Premex AG) equipped with a sampling tube and a magnetic gas-inducing impel-
ler. Several noble-metal catalysts on different supports were used in screening experiments: 10 wt-% Pd/
C (Acros); 5 wt-% Pt/Al2O3, 5 wt-% Ru/C, 5 wt-% Rh/C, 5 wt-% Rh/Al2O3 (all Fluka); 3% Pd/1% Pt/
Al2O3 (prepared by incipient wetness impregnation of g-Al2O3 with a 5% aq. soln. of Pd(NH3)(NO3)2,
drying at 1208, and calcining at 5008 for 4 h). The catalyst (usually 250 mg) and solvent (30 ml) were
placed in the reactor, and an appropriate amount of 1 (250 mg) was added. A rather large amount of cat-
alyst with respect to the substrate was required to obtain a reasonable reaction time because of the poi-
soning effect of the S-atom in the substrate molecule. The autoclave was closed, and the air was displaced
first with N2 (3×) and then with H2 (3×). The autoclave was pressurized with H2 to the desired value
(8–13 MPa), and stirring (1000 rpm) and heating to the appropriate temp. (150–2508) were started. Sam-
ples of the reaction mixture were withdrawn during the reaction and analyzed by GC. After the hydro-
genation was complete, the catalyst was filtered off and washed several times with CH2Cl2. The solvent
was evaporated, and the final product was analyzed by GC and GC/MS.
4,6-Dimethyldibenzothiophene (1). To a soln. of dry hexane (200 ml) and N,N,N’,N’-tetramethyl-
ethane-1,2-diamine (TMEDA; 74.4 g, 96 ml) was added dropwise 1.6M BuLi in hexane (400 ml) at 08.
The mixture was stirred for 30 min at 08 and then 30 min at r.t. It was diluted with additional hexane
(400 ml), the dibenzothiophene (39 g) was added, and the mixture was heated to 608 and stirred for 2
h. The yellow suspension was cooled to À158 and added in parts through a Teflon tube (6×4 mm) to a
precooled soln. of MeI (91 g, 20 ml) in hexane (200 ml). The mixture was cooled during this process
by a dry ice/liq. N2/aceton mixture so that the temp. did not exceed À708. Stirring was continued for
12 h, during which the mixture was allowed to reach r.t. The mixture was poured into a flask containing

Helvetica Chimica Acta – Vol. 89 (2006)
1637
Table 9. Crystal Data and Details of Structure Refinement of 4,6-DM-HH-DBT Isomers 3a and 3ca)
3a
3c
Formula
Mr
C14
218.34
A
G
C14
218.34
G
A
System
Space group
Crystal size [mm]
a [Å]
b [Å]
c [Å]
monoclinic
P2(1)/c
0.1×0.1×0.08
7.6530(15)
16.585(3)
10.244(2)
90.00
orthorhombic
Pbca
0.1×0.1×0.07
14.3771(15)
8.8904(7)
19.1231(19)
90.00
a [8]
b [8]
111.06
90.00
g [8]
90.00
1213.4(5)
4
1.195
295(2)
90.00
2444.3(4)
8
1.187
295(2)
V [Å3]
Z
Dx [g·cmÀ3
T [K]
]
m [mmÀ1
F(000)
]
2.057
472
0.230
944
2q Range [8]
5.33–67.07
2333
2165
1830
137
0.8686; 0.1775
0.0782; 0.1924
1.110
0.526; À0.782
4.18–27.59
16023
2820
1896
136
0.0817; 0.2060
0.1170; 0.2275
1.107
0.235; À0.235
Measured reflections
Unique reflections
Observed reflections
Number of variables
R1 and wR2 (I>2s(I))
R1 and wR2 (all data)
Goodness of fit
Final D1 [eÅÀ3
]
a) The isomers 3a and 3c were measured on a Picker-Stoe-Dif4 diffractometer with Cu-Ka radiation and a
Oxford-Excalibur diffractometer with MoKa radiation, resp. Standard data reduction and absorption cor-
rections were applied. Structure solution and refinement was performed with the SHELX program pack-
age. CCDC 296765 (3a) and CCDC 296766 (3c) contain the supplementary crystallographic data for this
paper. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
1.5 l of ice-water and extracted with toluene (3×600 ml). The org. phase was washed with 1M HCl (1×600
ml) and H2O (3×600 ml), dried (MgSO4), and evaporated. The crude product was recrystallized from
THF: 20 g (45%; >98% GC purity) of 1. White needle-like crystals. M.p. 1548 ([17]: m.p. 1548). TLC:
Rf 0.32. GC (inj. 3008; det. 3008; temp. program: 2008 for 2 min, heating rate 108/min, 2808 for 5 min):
tR 4.84. 1H-NMR (CDCl3, 300 MHz): 2.57 (s, MeÀC(4), MeÀC(6)); 7.21 (d, J=7.2, 2 H); 7.38 (t,
J=7.5, 2 H); 7.98 (d, J=7.8, 2 H). 13C-NMR (DEPT, CDCl3, 125 MHz): 20.5 (2q, MeÀC(4), MeÀ
C(6)); 119.3, 124.7, 126.8 (6d); 132.2, 136.0, 139.3 (6s). EI-MS: 212 (100), 197 (15), 105 (13). Anal.
calc. for C14H12S (212.32): C 79.20, H 5.70, S 15.10; found: C 79.23, H 5.78, S 15.23. The X-ray crystal
structure of 1 was identical with the structure published elsewhere [23].
1,2,3,4-Tetrahydro-4,6-dimethyldibenzothiophene (2). The synthesis of 2 from 1 was performed in a
continuous plug-flow fix-bed reactor usually used in hydrodesulfurization experiments [24]. Two types of
catalysts were used, a bimetallic 3 wt-% Pd/1 wt-% Pt/Al2O3 catalyst and a 8 wt-% sulfided Mo/g-Al2O3
catalyst, both prepared by incipient wetness impregnation [21][25]. The reactor was loaded with 40 to 75
mg of catalyst mixed with SiC (8 g) to achieve plug-flow conditions. The molybdenum catalyst was acti-
vated prior to the reaction by in situ sulfidation with a mixture of 10% H2S in H2 (50 N ml/min) at 4008

1638
Helvetica Chimica Acta – Vol. 89 (2006)
and 1 MPa for 4 h. The molybdenum catalyst was more effective in the production of 2 than the Pd/Pt
bimetallic catalyst, and the optimized reaction conditions with the molybdenum catalyst were as follow:
the temp. was decreased to 3208 and the total pressure increased to 5 MPa; the liquid reactants were fed
to the reactor. The gas-phase feed consisted of 130 kPa toluene (as solvent), 2.5 kPa 1 (almost the limit of
solubility; 45 mg/ml), 20 kPa H2S, and ca. 4.85 MPa H2. The reaction was carried out at a space time of
t=4.9 g·min/mol. Under these conditions, the product mixture consisted of 69% of 1, 18% of 2, 6.5% of
3, 0.5% of 4, and 6% of desulfurized products. After partial evaporation of the solvent, unreacted 1 was
recovered by repeated crystallization in toluene. The formed crystals of 1 were filtered, and the remain-
ing mother liquor was added to commercial silica gel and evaporated to dryness. The reaction products
were separated by CC (SiO2, petroleum ether). The fractions containing 2 were further purified by vac-
uum distillation (b.p. 105–1098/26 Pa): 2 of 95% purity. Colorless liquid, which turned slightly yellow with
time. The main impurities (5%) were two isomers with the C=C bond shifted to the positions C(1),C(9b)
and C(4),C(4a), i.e., 2,3,4,4a-tetrahydro- and 1,2,3,9b-tetrahydro-4,6-dimethyldibenzothiophene, resp.
Data of 2: TLC: Rf 0.35. GC (inj. 3008; det. 3008; temp. program: 2008 for 2 min, heating rate 108/min,
1
2808 for 5 min): tR 4.33. H-NMR (CDCl3, 500 MHz): 1.35 (d, J=6.9, MeÀC(4)); 1.48–1.54 (m, 1 HÀ
C(3)); 1.72–1.81 (m, 1 HÀC(2)), 1.97–2.07 (m, 1 HÀC(2), 1 HÀC(3)); 2.50 (s, MeÀC(6)); 2.61–2.67
(m, 1 HÀC(1)); 2.72–2.77 (m, 1 HÀC(1)); 3.01–3.05 (m, HÀC(4)); 7.04 (d, J=7.4, HÀC(7)); 7.24 (t,
J=7.5, HÀC(8)); 7.38 (d, J=7.8, HÀC(9)). 13C-NMR (DEPT, CDCl3, 125 MHz): 20.3 (q, MeÀC(6));
21.5 (t, C(2)); 22.9 (q, MeÀC(4)); 24.0 (t, C(1)); 31.7 (d, C(4)); 32.8 (t, C(3)); 118.4 (d, C(9)); 123.9 (d,
C(8)); 124.2 (d, C(7)); 130.0 (s, C(9b)); 131.7 (s, C(6)); 138.5 (s, C(5a)); 139.6 (s, C(9a)); 143.0 (s,
C(4a)). EI-MS: 216 (78), 201 (100), 188 (36), 186 (17), 171 (17). Anal. calc. for C14H16S (216.35): C
77.72, H 7.45, S 14.82; found: C 77.81, H 7.42, S 14.87.
1,2,3,4,4a,9b-Hexahydro-4,6-dimethyldibenzothiophene (3). Compound 3 was prepared by hydroge-
nation of 1 at high H2 pressure in a 300-ml stainless-steel autoclave. The autoclave was loaded with 10 wt-
% Pd/C catalyst (10 g), 1 (10 g), and AcOH (180 ml; as solvent, crucial for a high conversion). The reac-
tion was carried out at 2008 and 15 MPa H2 for 5 h. The hydrogenation product consisted of 47% of 1, 4%
of 2, 42% of 3, 4% of 4, and 3% of desulfurized products. After cooling the autoclave to r.t., the catalyst
was filtered off. Since a large amount of product remained adsorbed on the catalyst, the catalyst was
refluxed in CHCl3 for 1 h and filtered again. Both filtrates were then evaporated separately, and
unreacted 1 was purified by recrystallization from toluene. The mother liquors were evaporated together
with commercial silica gel, and the reaction products were separated twice by CC as described for 2.
There were three different isomers of 3 in the reaction mixture in the following proportions: 28% of
3a, 9% of 3b, and 63% of 3c. The isomers were partly separated by CC and further purified by crystal-
lization from EtOH to obtain pure white crystalline compounds for full characterization (1H- and 13C-
NMR, MS/MS experiments, X-ray single-crystal diffraction analysis). For crystallographic data and
details of structural determination of isomers 3a and 3c, see above, Table 9.
rel-(4R,4aS,9bS)-1,2,3,4,4a,9b-Hexahydro-4,6-dimethyldibenzothiophene (3a). TLC: Rf 0.27. GC (inj.
3008; det. 3008; temp. program: 2008 for 2 min, heating rate of 108/min, 2808 for 5 min): tR 3.50. M.p.
87–898. 1H-NMR (C6
A
C(4)); 1.15–1.23 (m, J=3.2, 12.7, 1 HÀC(2), HÀC(4)); 1.28–1.45 (m, 1 HÀC(2), 1 HÀC(3), 1 HÀ
C(1)); 2.06 (m, J=2.4, 3.3, 14.2, 1 HÀC(1)); 2.22 (s, MeÀC(6)); 2.78 (dd, J=6.2, 10.5, HÀC(4a)); 3.30
(br. s, HÀC(9b)); 6.80 (d, J=7.4, HÀC(9)); 6.85 (d, J=7.4, HÀC(7)); 6.97 (t, J=7.4, HÀC(8)). 13C-
NMR (DEPT, C6
A
33.7 (t, C(3)); 35.2 (d, C(4)); 48.8 (d, C(9b)); 59.5 (d, C(4a)); 120.9 (d, C(9)); 124.6 (d, C(8)); 128.1 (d,
C(7)); 132.6 (s, C(6)); 141.0 (s, C(9a)); 142.3 (s, C(5a)). EI-MS: 218 (100), 175 (37), 161 (70), 149 (36),
128 (8), 115 (10). Anal. calc. for C14H18S (218.36): C 77.01, H 8.31, S 14.68; found: C 77.10, H 8.27, S 14.71.
rel-(4R,4aS,9bR)-1,2,3,4,4a,9b-Hexahydro-4,6-dimethyldibenzothiophene (3b): TLC: Rf 0.26. GC
(inj. 3008; det. 3008; temp. program: 2008 for 2 min, heating rate 108/min, 2808 for 5 min): tR 3.70. H-
NMR (C
G
1.03–1.18 (m, 1 HÀC(1), 1 HÀC(2)); 1.47–1.50 (m, J=3.5, 13.4, 1 HÀC(3)); 1.54–1.57 (m, 1 HÀ
C(2)); 1.70–1.78 (m, HÀC(4)); 1.98 (dd, J=3.3, 11.0, 1 HÀC(1)); 2.25 (s, MeÀC(6)); 2.73 (ddd,
J=3.1, 10.8, HÀC(9b)); 2.89 (dd, J=10.8, 13.0, HÀC(4a)); 6.81 (d, J=7.3, HÀC(9)); 6.87 (d, J=7.3,
HÀC(7)); 6.95 (t, J=7.4, HÀC(8)). 13C-NMR (DEPT, C6
D6, 125 MHz): 20.7 (q, MeÀC(6)); 22.0 (q,

Helvetica Chimica Acta – Vol. 89 (2006)
1639
MeÀC(4)); 26.0 (t, C(2)); 28.4 (t, C(1)); 35.3 (t, C(3)); 37.5 (d, C(4)); 54.4 (d, C(9b)); 66.0 (d, C(4a));
119.9 (d, C(9)); 124.6 (d, C(8)); 128.4 (d, C(7)); 132.4 (s, C(6)); 141.9 (s, C(9a)); 143.7 (s, C(5a)). EI-
MS: 218 (100), 175 (28), 161 (70), 147 (19), 128 (10), 115 (10). Anal. calc. for C14H18S (218.36): C
77.01, H 8.31, S 14.68; found: C 76.90, H 8.39, S 14.61.
rel-(4R,4aR,9bR)-1,2,3,4,4a,9b-Hexahydro-4,6-dimethyldibenzothiophene (3c): TLC: Rf 0.25. GC
(inj. 3008; det. 3008; temp. program: 2008 for 2 min, heating rate 108/min, 2808 for 5 min): tR 3.56. M.p.
1
72–758. H-NMR (C6
A
(m, 1 HÀC(3)); 1.37–1.41 (m, 1 HÀC(1)); 1.44–1.60 (m, 1 HÀC(3), 1 HÀC(1), 1 HÀC(2), HÀC(4));
2.22 (s, MeÀC(6)); 2.70 (ddd, J=5.3, 5.8, 11.3, HÀC(9b)); 3.96 (t, J=4.9, HÀC(4a)); 6.83 (d, J=7.4,
HÀC(7)); 6.87 (d, J=6.7, HÀC(9)); 6.91 (t, J=7.3, HÀC(8)). 13C-NMR (DEPT, C6
(q, MeÀC(6)); 22.3 (q, MeÀC(4)); 25.1 (t, C(2)); 28.6 (t, C(1)); 28.9 (t, C(3)); 33.6 (d, C(4)); 48.7 (d,
C(9b)); 59.8 (d, C(4a)); 121.3 (d, C(9)); 124.6 (d, C(8)); 128.2 (d, C(7)); 132.8 (s, C(6)); 140.1 (s,
C(9a)); 146.1 (s, C(5a)). EI-MS: 218 (100), 175 (37), 161 (65), 149 (34), 128 (7), 115 (8). Anal. calc. for
C14H18S (218.36): C 77.01, H 8.31, S 14.68; found: C 77.07, H 8.29, S 14.65.
Dodecahydro-4,6-dimethyldibenzothiophene (4). As described for 3, but with a lower S/C ratio (15 g
of 10% Pd/C catalyst were used for reduction of 10 g of 1). Under the same conditions (2008, 15 MPa H2,
5 h), the hydrogenation product contained 29% of 1, 3% of 2, 41% of 3, 23% of 4, and 4% of desulfurized
products. Compound 4 has 20 different diastereoisomers. Under our reaction conditions, we observed ten
of them, but only 4 reached a concentration higher than 0.5%. These were separated by CC as colorless
1
liquids and were characterized by MS, H- and 13C-NMR.
4,4a-trans;4a,9b-cis;5a,6-trans;5a,9a-trans-Dodecahydro-4,6-dimethyldibenzothiophene (4a): TLC:
Rf 0.22. GC (inj. 3008; det. 3008; temp. program: 2008 for 2 min, heating rate 108/min, 2808 for 5 min):
1
tR 3.11. H-NMR (CDCl3, 500 MHz): 0.89 (d, Me); 0.96 (d, Me); 1.05–2.00 (m, 16 H); 2.48 (dd, J(5a,
6)=10.5, J(5a,9a)=10.5, HÀC(5a)); 2.80 (dd, J(4a,4)=10.8, J(4a,9b)=6.6, HÀC(4a)). 13C-NMR
(DEPT, CDCl3, 125 MHz): 21.0, 21.4 (2q); 21.9, 25.9, 26.1, 29.3, 35.0, 35.5 (6t); 40.0, 40.05, 47.2, 47.4,
54.6, 60.4 (6d). EI-MS: 224 (100), 190 (58), 167 (28), 153 (55), 108 (33), 95 (51). Anal. calc. for C14H24S
(224.41): C 74.93, H 10.78, S 14.28; found: C 74.98, H 10.69, S 14.31.
4,4a-trans;4a,9b-cis;5a,6-cis;5a,9a-trans-Dodecahydro-4,6-dimethyldibenzothiophene (4b): TLC: Rf
0.19. GC (inj. 3008; det. 3008; temp. program: 2008 for 2 min, heating rate 108/min, 2808 for 5 min): tR
3.33. 1H-NMR (CDCl3, 500 MHz): 0.89 (d, Me); 1.02 (d, Me); 1.14–2.17 (m, 16 H); 2.73 (dd, J(4a,
4)=10.8, J(4a,9b)=5.7, HÀC(4a)); 3.10 (dd, J(5a,6)=4.0, J(5a,9a)=10.6, HÀC(5a)). 13C-NMR
(DEPT, CDCl3, 125 MHz): 12.1, 20.0 (2q); 21.0, 21.4, 25.5, 26.7, 30.5, 32.5 (6t); 35.0, 39.0, 39.6, 47.3,
54.7, 57.2 (6d). EI-MS: 224 (100), 190 (44), 167 (30), 153 (65), 108 (30), 95 (65). Anal. calc. for C14H24S
(224.41): C 74.93, H 10.78, S 14.28; found: C 75.0, H 10.71, S 14.34.
4,4a-cis;4a,9b-cis;5a,6-trans;5a,9a-trans;9a,9b-cis-Dodecahydro-4,6-dimethyldibenzothiophene (4c):
TLC: Rf 0.17. GC (inj. 3008; det. 3008; temp. program: 2008 for 2 min, heating rate 108/min, 2808 for 5
1
min): tR 3.50. H-NMR (CDCl3, 500 MHz): 0.90 (d, J=6.2, Me); 0.95 (d, J=6.8, Me); 1.02–1.18 (m, 2
H); 1.32–1.45 (m, 3 H); 1.51–1.64 (m, 5 H); 1.72–1.78 (m, 2 H); 1.85–1.93 (m, 2 H); 2.04 (dddd, J(1,
9b)=5.7, 12.0, J(4a,9b)=4.3, J(9a,9b)=5.5, HÀC(9b)); 2.29 (dddd, J(5a,9a)=9.1, J(9a,9b)=5.5, J(9,
9a)=2.2, 7.2, HÀC(9a)); 2.87 (dd, J(5a,6)=10.7, J(5a,9a)=9.1, HÀC(5a)); 3.64 (dd, J(4a,4)=4.3, J(4a,
9b)=4.3, HÀC(4a)). 13C-NMR (DEPT, CDCl3, 125 MHz): 22.0, 22.7 (2q); 23.5, 25.1, 25.7, 26.1, 28.2,
33.2 (6t); 33.9, 40.1, 44.5, 49.4, 53.0, 55.8 (6d). EI-MS: 224 (100), 190 (8), 181 (23), 167 (36), 153 (25),
95 (23). Anal. calc. for C14H24S (224.41): C 74.93, H 10.78, S 14.28; found: C 74.95, H 10.80, S 14.25.
4,4a-cis;4a,9b-cis;5a,6-cis;5a,9a-trans-Dodecahydro-4,6-dimethyldibenzothiophene (4d): TLC: Rf
0.22. GC (inj. 3008; det. 3008; temp. program: 2008 for 2 min, heating rate 108/min, 2808 for 5 min): tR
3.57. 1H-NMR (CDCl3, 500 MHz): 0.94 (d, Me); 1.06 (d, Me); 1.15–2.05 (m, 16 H); 3.27 (dd, J(5a,
6)=4.2, J(5a,9a)=11.7, HÀC(5a)); 3.68 (dd, J(4a,4)=4.3, J(4a,9b)=4.3, HÀC(4a)). 13C-NMR (DEPT,
CDCl3, 125 MHz): 12.3, 20.4 (2q); 21.8, 21.9, 25.1, 28.0, 28.4, 31.0 (6t); 32.6, 34.3, 45.8, 46.1, 52.0, 55.7
(6d). EI-MS: 224 (100), 181 (20), 167 (31), 153 (37), 95 (36). Anal. calc. for C14H24S (224.41): C 74.93,
H 10.78, S 14.28; found: C 75.01, H 10.83, S 14.34.

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REFERENCES
[1] T. Kabe, A. Ishihara, W. Qian, ‘Hydrodesulfurization and Hydrodenitrogenation’, Kodansha Scien-
tific, Wiley-VCH, New York, 1999.
[2] B. C. Gates, H. Topsoe, Polyhedron 1997, 16, 3213.
[3] D. D. Whitehurst, T. Isoda, I. Mochida, Adv. Catal. 1998, 48, 345.
[4] M. J. Girgis, B. C. Gates, Ind. Eng. Chem. Res. 1991, 30, 2021.
[5] M. Houalla, N. K. Nag, A. V. Sapre, D. H. Broderick, B. C. Gates, AIChE J. 1978, 24, 1015.
[6] T. Kabe, A. Ishihara, Q. Zhang, Appl. Catal. A: General 1993, 97, L1.
[7] V. Meille, E. Schulz, M. Lemaire, M. Vrinat, J. Catal. 1997, 170, 29.
[8] M. Macaud, A. Milenkovic, E. Schulz, M. Lemaire, M. Vrinat, J. Catal. 2000, 193, 255.
[9] K. Sakanishi, T. Nagamatsu, I. Mochida, D. D. Whitehurst, J. Mol. Catal. A: Chem. 2000, 155, 101.
[10] P. da Costa, C. Potvin, J.-M. Manoli, J.-L. Lemberton, G. Pérot, G. Djéga-Mariadassou, J. Mol. Catal.
A: Chem. 2002, 184, 323.
[11] S. K. Bej, S. K. Maity, U. T. Turaga, Energy Fuels 2004, 18, 1227.
[12] A. Ishihara, F. Dumeignil, J. Lee, K. Mitsuhashi, E. W. Qian, T. Kabe, Appl. Catal. A: General 2005,
289, 163.
[13] K. Rabindran, B. D. Tilak, Proc. Indian Acad. Sci.,Sect. A 1952, 36, 411.
[14] E. Campaigne, L. Hewitt, J. Ashby, J. Heterocycl. Chem. 1969, 6, 553.
[15] M. L. Tedjamulia, Y. Tominaga, R. N. Castle, M. L. Lee, J. Heterocycl. Chem. 1983, 20, 1485.
[16] J. C. DiCesare, L. B. Thompson, R. J. Andersen, J. Nail, Org. Prep. Proced. Int. 2000, 32, 169.
[17] C. Kuehm-Caubère, S. Adach-Becker, Y. Fort, P. Caubère, Tetrahedron 1996, 52, 9087.
ˇ
[18] J. S. Splitter, F. Turecek, ‘Applications of Mass Spectrometry to Organic Stereochemistry’, VCH
Publishers, New York, 1994.
[19] A. W. Weitkamp, Adv. Catal. 1968, 18, 1.
[20] P. A. Rautanen, J. R. Aittamaa, A. O. I. Krause, Chem. Eng. Sci. 2001, 56, 1247.
[21] A. Röthlisberger, R. Prins, J. Catal. 2005, 235, 229.
[22] M. Egorova, R. Prins, in preparation.
[23] V. Meille, E. Schulz, M. Lemaire, R. Faure, M. Vrinat, Tetrahedron 1996, 52, 3953.
[24] M. Egorova, R. Prins, J. Catal. 2004, 221, 11.
[25] M. Egorova, R. Prins, J. Catal. 2004, 225, 417.
Received February 9,2006