Molecular rearrangement in the Birch reduction of dibenzothiophenes

Article abstract of DOI:10.1016/j.tetlet.2007.06.026

A molecular rearrangement observed during the Birch reduction of dibenzothiophene and 4,6-dimethyl-dibenzothiophene was explored and a mechanism for the rearrangement has been proposed.

Full text of DOI:10.1016/j.tetlet.2007.06.026

Tetrahedron Letters 48 (2007) 5657–5659
Molecular rearrangement in the Birch reduction of
dibenzothiophenes
Pavel Kukula,* Andreas Dutly, Heinz Ruegger and Roel Prins*
¨
Institute for Chemical and Bioengineering, ETH Zurich, HCI, 8093 Zurich, Switzerland
Received 7 May 2007; revised 31 May 2007; accepted 6 June 2007
Available online 9 June 2007
Abstract—A molecular rearrangement observed during the Birch reduction of dibenzothiophene and 4,6-dimethyl-dibenzothio-
phene was explored and a mechanism for the rearrangement has been proposed.
Ó 2007 Elsevier Ltd. All rights reserved.
The Birch reduction has been a synthetically useful and
+
powerful method for the partial reduction of aromatic
rings for more than 60 years.1 Numerous compounds
have been subjected to reducing conditions that include
alkali metal and ammonia and various modifications
and extensions of the Birch reduction have been devel-
oped.2 The scope of the Birch reduction also covers a
variety of heteroaromatic systems such as pyridines,
indoles, furans and thiophenes.3 Recently, we have been
concerned with the reduction of 4,6-dimethyl-dibenzo-
thiophene to tetra-, hexa- and dodecahydro-4,6-di-
methyl-dibenzothiophenes.4 The Birch reduction has
been tested as a possible route to the partially hydro-
genated 4,6-dimethyl-dibenzothiophenes as well.
S
S
SH
1a
2
3
Figure 1. Birch reduction of dibenzothiophene.
product distribution, for example, the 1,4-dihydro-
derivative 2 arises if a solution of substrate in ether
and ethanol is added to sodium in ammonia, whereas
thiophenol 3 is the major product if the metal is added
last.7
In our case, we were interested in more saturated prod-
ucts with intact C–S bond, such as tetra- and hexahydro-
4,6-dimethyl-dibenzothiophene. To investigate the possi-
bility of further hydrogenation to more saturated prod-
ucts, a large excess of proton source (ethanol) and
continuous addition of sodium to the reaction mixture
were applied. A number of optimization experiments
carried out with 4,6-dimethyl-dibenzothiophene 1b
(Fig. 2) showed that further reduction without C–S
bond cleavage is possible. Reactions were carried out
until full conversion of the starting material and the
product composition was analyzed by GC–MS. The
main products obtained were those with one fully
hydrogenated benzene ring of the dibenzothiophene
structure, that is, various isomers of hexahydro-
dimethyl-dibenzothiophene with molecular weight
218 amu. All products appeared to have the same reten-
tion time and mass spectrum as the appropriate
standards of partially hydrogenated 4,6-dimethyl-di-
benzothiophenes prepared by catalytic hydrogenation.4
The only difference was found in the mass spectrum of
Only a few reports on the Birch reduction of dibenzo-
thiophene and its derivatives are available5–7 and the
unresolved questions concerning the mechanism, nature
of the reactive intermediates and the product distri-
bution still remain. It is known from the literature that
dibenzothiophene 1a is reduced by alkaline metal reduc-
tion in ammonia to 1,4-dihydro-dibenzothiophene 2 as
the major product (Fig. 1).5 Other works claim over-
reduction and cleavage of the C–S bond to the corres-
ponding thiophenol 3 (position of the isolated double
bond not confirmed).6,7 A detailed study suggests that
the order of the reagent addition may be critical to the
Keywords: Birch reduction; Rearrangement; Ring opening; Ring clo-
sure; Sulphur-containing heterocycles; Dibenzothiophene; Hydrode-
sulfurization (HDS).
*
Corresponding authors. Tel.: +41 44 633 4536; fax: +41 44 632 1162
(P.K.); e-mail addresses: pavel.kukula@chem.ethz.ch; roel.prins@
chem.ethz.ch
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.06.026

5658
P. Kukula et al. / Tetrahedron Letters 48 (2007) 5657–5659
+e-
9
1
2
8
9a 9b
+2e-/+2H+
3
+
7
4
4a
5a
6
S
S
S
S
+e-
5
R
R
R
R
R
R
R
1a: R=H
1b: R=Me
R
+e-/+H+
.
.
.
.
.
.
S
S
R
R
R
R
+2e-/+2H+
R
+2e-/+2H+
+H+
R
R
.
.
S
S
S
R
R
R
+H+/+e-/+H+
+H+/+e-/+H+
R
12
R
3
R
1
2
7
11
13
4
10
5
9
S
S
6
S
8
R
R
R
5a: R=H
5b: R=Me
4a: R=H
6a: R=H
6b: R=Me
4b: R=Me
Figure 2. Mechanism of the molecular rearrangement during the Birch reduction of dibenzothiophenes.
tetrahydro-dimethyl-dibenzothiophene (cf. lit.4 with
Supplementary data). The products, isolated from the
reaction mixture, were fully characterized by NMR
experiments (1H, 13C, DEPT, COSY, HETCOR, long
range HETCOR and NOE) and the X-ray crystal struc-
ture of the crystalline products 4b and 5b was measured
(see Supplementary data). It was found that the methyl
group at the hydrogenated ring of tetrahydro-dimethyl-
dibenzothiophene 4b and hexahydro-dimethyl-dibenzo-
thiophene 5b was shifted from position 4- to position
2- (Fig. 2). Moreover, the molecule with expanded
S-containing heterocyclic ring 6b has been identified as
one of the hexahydro isomers. Similar results were
obtained with 1a (Table 1).
proceeded with almost total selectivity since we did
not observe formation of partially hydrogenated 4,6-di-
methyl-dibenzothiophenes. The amount of by-products
did not exceed 10 wt %. The Birch reduction of 1a was
more difficult than that of 1b and a higher amount of
sodium together with longer reaction time had to be
applied in order to reach the same conversion as with 1b.
The molecular rearrangement, which takes place during
the reduction of 1a and 1b, can be explained by cleavage
of the C-4a S-5 bond, rotation of the partially reduced
benzene ring around the C-9a C-9b bond, and subse-
quent addition of the thiophenolate anion to the par-
tially reduced benzene ring (Fig. 2).
The major product of 1a as well as of 1b reduction was
the hexahydro-isomer with the five-membered hetero-
cyclic ring 5a and 5b. The hexahydro-isomers with the
six-membered heterocyclic ring (thiane derivatives) 6a
and 6b were produced to a lower extent. The 5:6 ratio
was significantly higher in the case of methylated di-
benzothiophene, probably because of steric require-
ments of the methyl group on the cyclohexane ring.
Only small concentrations of tetrahydro-dibenzothio-
phenes 4a and 4b were observed. The rearrangement
The first step in the rearrangement is the partial reduc-
tion of one benzene ring of the dibenzothiophene struc-
ture. The 3,9b-dihydro isomer is formed preferentially,
because of the prevailing effect of the electron-donating
S-atom (electron-donating groups stabilize ortho and
meta electron density in the radical anion and thus the
main reduction product will have the least number of
electron-donating and highest number of electron-with-
drawing groups at the bridge heads).8 In the next step,
an electron is added to C-4 or C-9b, which results in
the splitting of the C-4a S-5 bond into a carbene and a
thiophenolate anion, the repulsive interaction of which
induces rotation around the C-9a C-9b bond. The car-
bene is immediately saturated by the addition of two
protons and two electrons. The existence of a carbene
intermediate under Birch reduction conditions has
already been proposed in the literature.9 The thiopheno-
late nucleophile then adds to the double bond of the par-
tially reduced ring10 and the heterocyclic ring closes in
Table 1. Product distribution of the Birch reduction of 1a and 1b
4 (%)
5 (%)
6 (%)
By-productsa (%)
Timeb (h)
1a
1b
8
5
56
71
27
18
9
6
3.5
1.5
a Amount of by-products.
b Time to reach 95% conversion.

P. Kukula et al. / Tetrahedron Letters 48 (2007) 5657–5659
5659
position C-1 or C-2 depending on the dihydro-dibenzo-
thiophene structure. A five- or six-membered hetero-
cyclic ring is thus formed and its further reduction
results in compound 5 or 6, respectively.
sodium sulfate and analyzed by GC–MS. Yield 90%,
typical product composition: 4b (5%), 5b (71%), 6b
(18%) and by-products (6%).
Tetrahydro-4,6-dimethyl-dibenzothiophene 4 can be
formed by reaction of the carbene radical formed from
3,9b-dihydro-4,6-dimethyl-dibenzothiophene. The car-
bene may react with the radical to a double bond, fol-
lowed by immediate reduction by an electron and a
proton. The final tetrahydro product 4 is formed by
addition of the thiophenolate nucleophile to the double
bond of the partially reduced ring, protonation and
isomerization of the double bond under the basic condi-
tions to the more stable C-4a C-9b position.
Supplementary data
Complete experimental and spectroscopic data for this
Letter were submitted as Supplementary data. Supple-
mentary data associated with this article can be found,
in the online version, at doi:10.1016/j.tetlet.2007.06.026.
References and notes
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Our results demonstrate that dibenzothiophenes can be
reduced to tetra- and hexahydro-derivatives by the Birch
reduction. Although C–S bonds are still present in the
final product molecules, the observed methyl group shift
and extension of the S-heterocycle, which takes place dur-
ing the Birch reduction of dibenzothiophenes, indicate
that a molecular rearrangement has taken place, which
can only occur by C–S bond breaking and reclosing.
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Typical experimental procedure for the Birch reduction.
The reaction was carried out in a two-neck 100 ml flask
equipped with a thermometer and reflux cooler. The
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cooled flask kept at À78 °C in a suspension of dry ice
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and the stirring was continued until all the sodium had
dissolved and a blue solution was obtained. After about
10 min the blue colour disappeared and a new portion of
sodium (100 mg, 4.3 mmol) was added. The blue colour
of the reaction mixture was kept by adding new portions
of sodium for about 2 h. The total amount of sodium
added was 1.7 g (73 mmol). When the blue colour of
the reaction mixture had disappeared, solid ammonium
chloride (1 g, 18.7 mmol) was added while stirring and
the solution cleared up. The ammonia was allowed to
evaporate and 50 ml water was cautiously added. The
mixture was extracted three times with 50 ml CH2Cl2,
the extracts were evaporated under vacuum, dried with
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