On the ring-contraction of 1,4-dithiins to 1,3-dithiole derivatives

Article abstract of DOI:10.1016/S0040-4039(00)02147-X

The effect of different factors (pK_a of the base, nature of the counterion and dissociation of the ion pairs) on the course of the base-induced rearrangement of 1,4-dithiins to 1,3-dithiole derivatives is discussed. Ab initio calculations account for the driving force of these isomerisations.

Full text of DOI:10.1016/S0040-4039(00)02147-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 875–877
On the ring-contraction of 1,4-dithiins to 1,3-dithiole derivatives
Raquel Andreu, Javier Gar´ın,* Jesu´s Orduna and Jose´ M. Royo
Departamento de Qu´ımica Orga´nica, ICMA, Universidad de Zaragoza-CSIC, E-50009 Zaragoza, Spain
Received 18 October 2000; accepted 21 November 2000
Abstract—The effect of different factors (pKa of the base, nature of the counterion and dissociation of the ion pairs) on the course
of the base-induced rearrangement of 1,4-dithiins to 1,3-dithiole derivatives is discussed. Ab initio calculations account for the
driving force of these isomerisations. © 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
paper we report the effect of different factors on the
course of this rearrangement and the results obtained
with other monocyclic and benzo-fused 1,4-dithiin
derivatives. An explanation for the driving force of
these rearrangements is also proposed.
1,4-Dithiins have attracted much attention because of
their structural and electronic properties, their ability to
act as electron donors and the wide variety of synthetic
transformations they undergo.1 On the other hand,
there are only scant reports in the literature concerning
the metallation of these heterocycles and they show
widely different results. Thus, while some 1,4-dithiin
derivatives can be metallated with LDA,2 BuLi3 or even
weaker bases, such as KOt-Bu,4 NaOMe5 or tetra-
butylammonium hydroxide,6 others can be recovered
unchanged after treatment with BuLi.3c,7 Moreover, the
metallated species, when generated, can react in several
ways, giving rise to substitution,2,3a,b ring-opening3a,c or
ring-contraction (isomerisation)2,4–6 products.
2. The ring-contraction of TTN and 1,4-dithiins to
TTF and 1,4-dithiafulvenes
The fact that KOt-Bu, unlike NaOEt, is able to iso-
merise 1 to 2 has been ascribed4 to the higher pKa of
t-BuOH compared to EtOH (ca. 19 and 16, respec-
tively). This reasonable guess is, nevertheless, an over-
simplification as demonstrated by the following
experiments (refluxing THF was used in every case): (a)
1 was recovered unchanged after treatment with NaH;
(b) treatment of 1 with KOEt led to complete destruc-
tion of TTN and afforded a complex mixture from
which TTF was isolated in 16% yield; and (c) reaction
of 1 with KOH (28 h) led to an 87:13 mixture of 1/2 (as
1,4,5,8-Tetrathianaphthalene (TTN, 1)2c,4,8 is a most
interesting 1,4-dithiin derivative since its base-induced
isomerisation affords tetrathiafulvalene (TTF, 2) in
very good yield (Scheme 1). To that end, both LDA2
and KOt-Bu4 have been successfully used, whereas
NaOEt is unable to carry out the isomerisation.4 In this
1
determined by H NMR) in 64% yield, whereas the use
of NaOH led to recovery of the starting material. It is
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
1
1a
1b
2a
2
Scheme 1.
Keywords: dithioles; isomerisation; sulfur heterocycles; thiafulvalenes.
* Corresponding author. Fax: +34-976-761194; e-mail: jgarin@posta.unizar.es
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)02147-X

876
R. Andreu et al. / Tetrahedron Letters 42 (2001) 875–877
Table 1. Effect of cations and added crowns on the 1 to 2
S
S
H
H
H
S
S
S
S
isomerisationa
S
7
S
Base
Crown
Time (h)
Temp (°C)
1/2b
0:100c
100:0
100:0
77:23
80:20
70:30
90:10
7a
8
8a
KOt-Bu
NaOt-Bu
LiOt-Bu
NaOt-Bu
NaOt-Bu
NaOt-Bu
LiOt-Bu
–
–
–
0.5
1
7
2
2
Reflux
Reflux
Reflux
25
25
50
Scheme 3.
18-c-6
15-c-5
15-c-5
15-c-5
prepared and their reactions with KOt-Bu (5 equiv.) in
refluxing THF afforded the corresponding 1,4-dithiaful-
venes 5a–c12 and 6,11,13 respectively, in medium to good
yields (Scheme 2). On the other hand, very low conver-
sions (for 3b and 3c) or no isomerisation at all (for 3a
and 4) were observed when excess NaOt-Bu and longer
reaction times (11–24 h) were used, thus confirming the
importance of the cation in these rearrangements.
14
6
Reflux
a Experimental conditions: 1 (1 mmol) and base (5 mmol) in THF (7
ml).
b Molar ratio determined by 1H NMR.
c 99% yield (lit.4).
also noteworthy that 1 did not rearrange to 2 when
TBA OH in refluxing MeCN was used, a system which
is reported to isomerise some 1,4-dithiin derivatives to
1,4-dithiafulvenes, even at room temperature.6 Thus,
the extent of the isomerisation seems to be not only
dependent on the pKa of the base, but also on the
counterion. This factor was ascertained by the lack of
reaction of 1 with either NaOt-Bu or LiOt-Bu in
refluxing THF (for 1 and 7 h, respectively). These bases
with smaller cations form larger aggregates than those
with larger cations (such as K+) and the enhanced
dissociation of the ion pairs in the latter case leads to
an increase of the reactivity of the base.9 This point was
further confirmed by addition of crown ethers to the
reaction medium; some representative results are col-
lected in Table 1 and show that complexation of Na+ or
Li+ ions by the crowns leads to partial conversion of 1
to 2.
3. The driving force of the rearrangement
The fact that 1 rearranges to 2 has been accounted for
by the greater thermodynamic stability of the latter;4,14
nevertheless, no clear conclusion has been presented for
the analogous isomerisation of compounds 4 to 6, since
semi-empirical calculations show that both isomers are
close in energy.6 Here we suggest an alternative expla-
nation which accounts for all experimental facts.
These rearrangements are supposed to proceed by an
E1cB mechanism, since trapping of the metallated spe-
cies with electrophilic reagents is sometimes possi-
ble.2,3a,b Thus, we have carried out ab initio
calculations15 at the HF/6-311+G**//HF/6-311+G**
level16 on compounds 1, 1a, 2, 2a and model com-
pounds 7, 7a, 8 and 8a (Scheme 3). Concerning the
isomerisation of 1 to 2, not only 2 is more stable than
1, but DG (1a“2a)=−13.55 kcal mol−1. For the iso-
merisation of 7 to 8, DG=−3.26 kcal mol−1 but, more
important, the protonation of 8a is more exergonic
than that of 7a by 12.5 kcal mol−1, which implies that 7
is a stronger acid by ca. 9 pKa units. Therefore, in the
case of compounds 3 it can be assumed that the equi-
librium established between the corresponding anions is
driven to the right by the protonation of the anion of 5,
which is a strongly favoured step (Scheme 4). More-
over, this explanation accounts for the fact that all of
these rearrangements take place in the presence of the
conjugated acid of the base.2,4–6
These results are in line with the different course of the
lithiation reactions of 1 with LDA in THF or Et2O (70
and 0% yield of 2, respectively), formation of contact
ion pairs in the latter solvent being considered to inhibit
the rearrangement.2a,b A similar conclusion can be
drawn from our experiments: for the rearrangement to
be synthetically useful, an alkoxide with pKa]19 is
needed, provided the ion pairs are dissociated enough
in the reaction medium. These conditions are fulfilled
by KOt-Bu in THF, so we decided to use this combina-
tion in the attempted isomerisation of other 1,4-dithi-
ins. To that end, compounds 3a–c10 and 411 were
r. time (h)
S
S
Ar
Ar
S
S
KOt-Bu
5a: 75%
5b: 65%
5c: 50%
0.5
1
THF, ∆
Ar
Ar
6
3a-c
5a-c
S
Ph
Ph
S
KOt-Bu
84%
S
THF, ∆
S
1 h
4
6
Ar = Ph (a); 4-ClC6H4 (b); 4-NO2C6H4 (c)
Scheme 2.

R. Andreu et al. / Tetrahedron Letters 42 (2001) 875–877
877
S
S
Ar
S
S
Ar
S
S
BH
B
Ar
3
5
Ar
Ar
Ar
Scheme 4.
78, 4783–4787; (b) Parham, W. E.; Kneller, M. T. J. Org.
Chem. 1958, 23, 1702–1705.
To sum up, the pKa of the base and the dissociation of
the ion pairs play a key role on the ring-contraction of
1,4-dithiin derivatives. It is the combination of these
two factors that makes KOt-Bu the reagent of choice
for carrying out these rearrangements. Moreover, the
greater thermodynamic stability of 1,3-dithiole deriva-
tives, together with the weaker acidity of dithiafulvenes,
account for the course of these rearrangements.
8. (a) Mizuno, M.; Cava, M. P.; Garito, A. F. J. Org.
Chem. 1976, 41, 1484–1485; (b) Varma, K. S.; Sasaki, N.;
Clark, R. A.; Underhill, A. E.; Simonsen, O.; Becher, J.;
Bøwadt, S. J. Heterocyclic Chem. 1988, 25, 783–787; (c)
Andreu, R.; Gar´ın, J.; Orduna, J.; Royo, J. M. Tetra-
hedron Lett. 2000, 41, 5207–5210.
9. Msayib, K. J.; Watt, C. I. F. Chem. Soc. Rev. 1992, 21,
237–243.
10. Buess, C. M.; Brandt, V. O.; Srivastava, R. C.; Carper,
Acknowledgements
V. R. J. Heterocyclic Chem. 1972, 9, 887–889.
11. Staab, H. A.; Draeger, B. Chem. Ber. 1972, 105, 2320–
2333.
Financial support from DGESIC (MAT1999-1009-C02-
02) is gratefully acknowledged.
12. (a) Compounds 5a and 5b were obtained as (E)-isomers;
for the sake of comparison, pure (Z)-5a was also inde-
pendently prepared. See: Shafiee, A.; Lalezari, I. J. Hete-
rocyclic Chem. 1973, 10, 11–14; (b) 5c (Clausen, R. P.;
Becher, J. Tetrahedron 1996, 52, 3171–3188) was obtained
as a ca. 1:1 (E/Z) mixture.
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