Synthesis, structure, and first reactions of a new class of thiacyclophanes?

Article abstract of DOI:10.1139/cjc-2016-0358

In our effort to prepare [m.n]cyclophanes carrying functional groups in their molecular bridges, the thiacyclophanes 14, 19, 20, and 21 have been prepared by simple routes from the pseudo-gem dibromide 10a and the corresponding bis-thiol 10b. The triply-bridged bis-thia-cyclophanes 14, and 19-21 were characterized by their spectroscopic data as well as by X-ray structural analyses. The meta-isomer 20 was oxidized to the bis-sulfone 23, which on flash vacuum pyrolysis (FVP) yielded a product mixture presumably containing the hydrocarbon 26 with a cleaved molecular bridge. Subjecting 23 to Ramberg-B?cklund conditions (CCl₄, NaOH, phase transfer catalysis) provided the chloride 24 in poor yield (9%), a [2.2]paracyclophane in which the new molecular bridge is fully conjugated.

Full text of DOI:10.1139/cjc-2016-0358

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Synthesis, Structure, and First Reactions of a
New Class of ThiacyclophanesƢ.
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Dedicated to Professor Reginald H. Mitchell
Arunachalam Kannan[a], Henning Hopf*[a], Ina Dix[a, b], Peter G.
Jones[c], and Ludger Ernst[d]
[a]
Institut für Organische Chemie, Technische Universiꢀ
tät Braunschweig, Hagenring 30, Dꢀ38106 Braunschweig
(Germany)
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Fax: (+49)531ꢀ391ꢀ5388
Eꢀmail: h.hopf@tuꢀbs.de
[b]
Current address: Novartis Pharma AG, Forum 1,
Novartis Campus, CHꢀ4056 Basel (Switzerland)
Eꢀmail: ina.dix@novartis.com
[c]
Institut für Anorganische und Analytische Chemie,
Technische Universität Braunschweig, Postfach 3329, Dꢀ
38106 Braunschweig (Germany)
Fax: (+49)531ꢀ391-5387
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Eꢀmail: p.jones@tuꢀbs.de
[d]
NMRꢀLaboratorium der Chemischen Institute,
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Technische Universität Braunschweig, Hagenring 30, Dꢀ
38106 Braunschweig (Germany)

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Fax: (+49)531ꢀ391ꢀ5245
EꢀMail: l.ernst@tuꢀbs.de
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[Ƣ] Cyclophanes, Part 75; for Part 74 see ref.1
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Key words: Cyclophanes, cyclophenes, ring contraction, sulfone
pyrolysis, RambergꢀBäcklund reaction, Xꢀray structural
analysis
Abstract: In our effort to prepare [m.n]cyclophanes carrying
functional groups in their molecular bridges, the
thiacyclophanes 14, 19, 20, and 21 have been prepared by
simple routes from the pseudoꢀgem dibromide 10a and the
corresponding bisꢀthiol 10b. The triplyꢀbridged bisꢀthiaꢀ
cyclophanes 14, and 19ꢀ21 were characterized by their
spectroscopic data as well as by Xꢀray structural analyses.
The metaꢀisomer 20 was oxidized to the bisꢀsulfone 23, which,
on flash vacuum pyrolysis (FVP) yielded a product mixture
presumably containing the hydrocarbon 26 with a cleaved
molecular bridge. Subjecting 23 to RambergꢀBäcklund conditions
(CCl4, NaOH, phase transfer catalysis) provided the chloride 24
in poor yield (9%), a [2.2]paracyclophane in which the new
molecular bridge is fully conjugated.

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Introduction: Compared to the chemical behavior of the
aromatic rings in cyclophanes, much less is known about the
reactivity of the bridges that hold these aromatic moieties
together. Even when studying the electronic interactions
between the latter, most authors are interested in the
intraannular, throughꢀspace interactions between the aromatic
“decks”, rather than the throughꢀbond interactions by way of
the bridges. Indeed, if one exchanges one of the saturated
ethano bridges in [2.2]paracyclohane (1) for an olefinic
double bond, as in [2.2]paracyclophene (2) one would not
expect any πꢀπꢀinteraction (conjugation) at all since, as
indicated in formula 2’ (Scheme 1), the pꢀorbitals of the
olefinic and the adjcacent aromatic units are orthogonal.
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Scheme 1 here please
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Scheme 1: Electronic interactions between the aromatic rings
of [2.2]paracyclophanes.
Increasing the length of the (unsaturated) bridge(s) should
result in a greater flexibility of this structural element and
hence, by allowing more nonꢀorthogonal orientations of the

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respective pꢀorbitals, lead to more conjugation between the
aromatic rings.
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We have recently described the first [2.2]paracyclophane
derivatives possessing such lengthened unsaturated bridges:2
The pseudoꢀgeminally substituted dienyne 3 and the enediyne 4,
as well as its pseudoꢀortho isomer 5 (Scheme 2), were prepared
and some of their chemical properties studied.
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Scheme 2 here please
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Scheme 2: A selection of [2.2]paracyclophane derivatives with
a lengthened unsaturated bridge.
Since the hydrocarbons 3ꢀ5 are not very stable,2 a property
also assumed to be characteristic for the yet unknown 6, we
decided to replace at least one of the double bonds by a

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benzene ring. This could be achieved in two ways: Exchange of
a terminal double bond of the bridge by a benzene ring results
in the generation of benzꢀannelated hydrocarbon 7, whereas the
analogous substitution of the central double bond of 6 by a
benzene ring produces 8a (Scheme 2). Note that the double
bonds in 7 and 8 cannot only be anchored in the orthoꢀposition
as in 8a, but also in the metaꢀ and paraꢀorientation: 8b and
8c, respectively.
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For the preparation of hydrocarbons of type 8 we decided to
proceed as illustrated by the retrosynthetic Scheme 3 for the
model system 8c:
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Scheme 3 here please
Scheme 3: Preparation of the hydrocarbons 8: retrosynthetic
analysis.
One of the most often employed strategies to prepare bridged
aromatic systems involves the preparation of sulfides, which

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are subsequently subjected to ring contraction. This could
start from the sulfide and use the Sꢀanalogous Stevensꢀ
rearrangement3 or oxidize the sulfide first to a sulfone and
then remove the SO2ꢀlinker thermally (“sulfone pyrolysis”)4.
Access to 9 could be provided by either coupling the pseudoꢀ
gem-dibromide 10a or the pseudoꢀgem bisꢀthiol 10b with the
paraꢀxylylene dibromides 11a or bisꢀthiols 11b. To prepare
various isomers of 9 and products derived therefrom, the
appropriate isomers of 10 and 11 have to be used. For the time
being we wish to keep the functional groups in the
[2.2]paracyclophane derivative 10 in the pseudoꢀgem position,
since this guarantees closest proximity of the bridging
elements in this part of the molecules.
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In our first coupling experiment (Scheme 4) we reacted the
pseudoꢀgem dibromide 10a with either the orthoꢀ (12) or the
metaꢀxylylenedithiol 13 in the presence of potassium hydroxide
in benzene/ethanol under high dilution conditions (Scheme 4).

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Scheme 4 here please
Scheme 4: Coupling of the pseudoꢀgem cyclophane 10a with
orthoꢀ, 12, and metaꢀxylylenedithiol, 13.
To our surprise in neither case could the desired bisꢀsulfides
be obtained. Instead in both experiments the triply bridged
[3.2.2]thiacyclophane 14 was obtained in approximately the
same yield.
The compound was characterized by its spectroscopic data (see
Experimental section) and an Xꢀray structural study.
The molecular structure of 14 in the crystal is shown in Fig.
1.
Fig. 1 here please

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Fig. 1. The molecular structure of compound 14 in the crystal.
Ellipsoids represent 50% probability levels. Selected
molecular dimensions (Å and °): C1–C2 1.576(3), C9ꢀC10
1.591(3), C17ꢀS1 1.813(3), C18ꢀS1 1.815(3); C2ꢀC1ꢀC14
112.2(2), C1ꢀC2ꢀC3 113.0(2), C6ꢀC9ꢀC10 113.1(2), C9ꢀC10ꢀC11
112.8(2), S1ꢀC17ꢀC15 114.7(2), S1ꢀC18ꢀC4 116.0(2), C17ꢀS1ꢀC18
102.05(12); C15ꢀC17ꢀS1ꢀC8 58.7(2), C4ꢀC18ꢀS1ꢀC17 ꢀ61.9(2).
The molecule of 14 (Fig. 1) displays approximate mirror
symmetry (r.m.s. deviation 0.29 Å). The introduction of the
extra bridge scarcely alters the distortions that are wellꢀ
known for [2.2]paracyclophane1,5, features of which include
lengthened bridge bonds, widened bridge angles, narrow ring
angles at the bridgehead atoms; see the figure caption and the
Experimental section for individual values. The flattened boat
form adopted by the rings, in which the bridgehead atoms lie

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some 0.13–0.16 Å out of the plane of the other four ring
atoms, is also retained, and the interplanar angle between the
rings (excluding bridgehead atoms) is 2.9°. The bond angles in
the CH2ꢀSꢀCH2 bridge may be compared to values obtained from a
search of the Cambridge Database6 for the moiety CꢀCH2ꢀSꢀCH2ꢀC
with twoꢀcoordinate central sulfur: 113.4° for the angle at
the methylene carbon and 101.4° for the angle at sulfur,
averaged from 1758 individual values.
A reasonable mechanism for the formation of 14 is summarized
in Scheme 5.
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Scheme 5 here please

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Scheme 5: Mechanism of formation of the triplyꢀbridged
cyclophane 14 from 10a and the dipotassium salts of various
xylylenedithiols, 15.
We propose that in the first step the salt 15 attacks the
dibromide 10a in an SN2ꢀsubstitution and yields the monobromide
16. This, in principle, could react similarly for a second
time, but in an intramolecular fashion, to yield the desired
disulfides, e.g. 9. In fact, the required ringꢀclosure takes
place, but with the sterically much closer sulfur atom of the
thioether function as shown in 16. This results in the
generation of the sulfonium ion 17, which in the final step is
cleaved by the potassium salt 15 to provide the isolated
thioether 14. The trisꢀsulfur compound 18, which is also
produced, could participate in the process again to finally
yield the polymeric material which is also observed. We had
previously noted that the yields of this type of coupling
reactions to prepare thiacyclophanes are influenced by the
binding of the respective functional groups: thus, taking a
thiol of one coupling partner and reacting it with the bromide
of the other can yield different results than the combination
in which these two functional groups are reversed.7
We hence decided to replace the pseudoꢀgeminal dibromide 10a
by the dithiol 10b. This derivative was prepared by reacting
10a with thiourea and hydrolysis of the resulting bisꢀisoꢀ

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thiouronium salt in the presence of ethylenediamine in aqueous
dioxane; 10b was produced in 70% yield (Schema 6).
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Scheme 6 here please
Scheme 6: Preparation of the three dithiacyclophanes 19ꢀ21
from 10b.
When 10b was reacted with the orthoꢀ, metaꢀ and paraꢀisomer of
9a, the anticipated bisthioethers 19ꢀ21 were all formed. In
the first two cases the yields were good, in the third case
rather low. We would assume that this isomer is the most
strained and that the transition state for the final
intramolecular coupling process is the least favorable.

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All compounds were characterized by their spectroscopic and
analytical data (see Experimental section), and also by Xꢀray
structural analyses.
The molecular structure of 19 in the crystal is shown in Fig.
2.
Fig. 2 here please
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Fig. 2. The molecular structure of compound 19 in the crystal.
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Ellipsoids represent 30% probability levels. Selected
molecular dimensions (Å and °): C1–C2 1.589(5), C9ꢀC10
1.572(5), C17ꢀS1 1.824(3), C18ꢀS1 1.823(3), C25ꢀS2 1.832(3),
C26ꢀS2 1.819(3); C2ꢀC1ꢀC14 112.1(3), C1ꢀC2ꢀC3 112.4(3), C6ꢀC9ꢀ
C10 111.9(3), C9ꢀC10ꢀC11 114.0(3), S1ꢀC17ꢀC4 111.4(2), S1ꢀC18ꢀ
C19 114.7(2), S2ꢀC26ꢀC15 113.8(2), S2ꢀC25ꢀC20 113.7(2), C17ꢀ
S1ꢀC18 101.5(2), C25ꢀS2ꢀC26 101.05(15), C25ꢀC20ꢀC19 122.8(3),
C18ꢀC19ꢀC20 122.7(3); C4ꢀC17ꢀS1ꢀC18 163.0(2), C17ꢀS1ꢀC18ꢀC19 ꢀ
54.4(3), C15ꢀC26ꢀS2ꢀC25 ꢀ146.3(2), C26ꢀS2ꢀC25ꢀC20 ꢀ34.9(3),
C5ꢀC4ꢀC17ꢀS1 33.9(4), C16ꢀC15ꢀC26ꢀS2 50.8(4).

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In the orthoꢀisomer 19 (Fig. 2), the [2.2]paracyclophane
framework retains its usual features (see above), although the
interplanar angle is slightly increased to 4.2°. The aromatic
ring C19ꢀ24 of the newly introduced bridge is to a good
approximation perpendicular to the two rings of the
paracyclophane unit (this is also the case for the other two
isomers, see below), and shows little sign of strain except
for the slightly widened angles C25ꢀC20ꢀC19 and C18ꢀC19ꢀC20 to
the sulfurꢀcontaining bridges. The conformation of these
bridges is completely different; the atom S1 is directed into
the space between the cyclophane rings [torsion angle C5ꢀC4ꢀ
C17ꢀS1 33.9(4)°], whereas S2 points away from the cyclophane
[C16ꢀC15ꢀC26ꢀS2 50.8(4)°].
The molecular structure of 20 in the crystal is displayed in
Fig. 3.
Fig. 3 here please

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Fig. 3. The molecular structure of compound 20 in the crystal.
Ellipsoids represent 30% probability levels. Selected
molecular dimensions (Å and °): C1–C2 1.585(4), C9ꢀC10
1.585(4), C17ꢀS1 1.820(3), C18ꢀS1 1.826(3), C25ꢀS2 1.835(3),
C26ꢀS2 1.821(3); C2ꢀC1ꢀC14 113.4(2), C1ꢀC2ꢀC3 113.9(2), C6ꢀC9ꢀ
C10 113.3(2), C9ꢀC10ꢀC11 113.3(2), S1ꢀC17ꢀC4 114.2(2), S1ꢀC18ꢀ
C19 112.4(2), S2ꢀC26ꢀC15 113.7(2), S2ꢀC25ꢀC21 113.0(2), C17ꢀ
S1ꢀC18 98.75(15), C25ꢀS2ꢀC26 98.27(15); C4ꢀC17ꢀS1ꢀC18 ꢀ
153.0(2), C17ꢀS1ꢀC18ꢀC19 67.2(3), C15ꢀC26ꢀS2ꢀC25 163.9(2),
C26ꢀS2ꢀC25ꢀC21 ꢀ58.7(3), C3ꢀC4ꢀC17ꢀS1 58.1(3), C14ꢀC15ꢀC26ꢀS2
ꢀ64.2(3).
The molecule of the metaꢀisomer 20 (Fig. 3) is much more
regular than that of 19 and displays approximate mirror
symmetry (r.m.s. deviation 0.15 Å). Both sulfur atoms point
away from the cyclophane core, which again retains its

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customary structural features (see above), although the
interplanar angles between the cyclophane decks is 5.5°. The
additional aromatic ring C19ꢀ24 is not itself distorted, but
incipient strain may be indicated by the fact that the
substituent atoms C18 and C25 are displaced by 0.16 and 0.14 Å
respectively out of the ring plane towards the cyclophane.
The molecular structure of the paraꢀisomer 21 in the crystal
is shown in Fig. 4.
Fig. 4 here please
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Fig. 4. The molecular structure of compound 21 in the crystal
(one of two independent molecules; solvent omitted).
Ellipsoids represent 30% probability levels. Selected
molecular dimensions (Å and °) for this molecule: C1–C2
1.587(4), C9ꢀC10 1.574(5), C17ꢀS1 1.837(3), C18ꢀS1 1.850(3),

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C25ꢀS2 1.829(4), C26ꢀS2 1.831(3); C2ꢀC1ꢀC14 114.1(3), C1ꢀC2ꢀC3
113.9(2), C6ꢀC9ꢀC10 113.3(2), C9ꢀC10ꢀC11 113.3(2), S1ꢀC17ꢀC4
114.2(3), S1ꢀC18ꢀC19 110.9(2), S2ꢀC26ꢀC15 112.1(2), S2ꢀC25ꢀC22
111.7(2), C17ꢀS1ꢀC18 100.52(15), C25ꢀS2ꢀC26 100.7(2); C4ꢀC17ꢀ
S1ꢀC18 173.3(2), C17ꢀS1ꢀC18ꢀC19 ꢀ34.7(3), C15ꢀC26ꢀS2ꢀC25 ꢀ
166.8(2), C26ꢀS2ꢀC25ꢀC22 48.5(3), C3ꢀC4ꢀC17ꢀS1 ꢀ63.8(4), C14ꢀ
C15ꢀC26ꢀS2 55.2(4).
The paraꢀisomer 21 (Fig. 4) crystallizes with two independent
but similar molecules in the asymmetric unit, together with a
cyclohexane molecule that is disordered across an inversion
centre. Both molecules display approximate mirror symmetry,
with r.m.s. deviations 0.14 and 0.10 Å respectively; the fit
of one molecule to the other gives an r.m.s. deviation of 0.11
Å. There are indications that this isomer is the most strained
of the three; the paracyclophane decks are tilted by 7.5°, and
the substituent atoms C18 and C25 are displaced by 0.39 and
0.35 Å respectively out of the plane of the ring C19ꢀ24
towards the cyclophane core.
In another coupling experiment we tried to combine the two
pseudoꢀgemꢀ[2.2]paracyclophanes 10a and 10b with each other.
In the first experiment with potassium hydroxide as the base,
only the thiaphane 14 was obtained in good yield (Scheme 7)

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Scheme 7 here please
Scheme 7: The direct coupling of two pseudoꢀgemꢀ[2.2]paraꢀ
cyclophane derivatives, 10a and 10b.
This was still the main product when we changed to cesium
hydroxide as the base; but in this case we also isolated a
small amount of a disulfide to which we assign the “dimeric”
structure 22 according to its spectroscopic and analytical
data (see Experimental section). Note that in principle two
diastereomers of 22 could be formed, a mesoꢀ and a d,lꢀ
diastereomer. At the present time we cannot distinguish
between these two possibilities. The experiment illustrates,
however, that besides the functionality of the respective
building blocks, the base employed in their coupling can also
play a significant role.
Summarizing our work up to this point, we have been successful
in synthesizing and characterizing new thiacyclophane systems,
the disulfides 19ꢀ21, by simple and effective routes,
compounds which are now ready for further transformation.

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To obtain a first impression concerning their reactivities, we
studied the ring contraction of 20, hoping to obtain a
representative of the hydrocarbons 8 shown in Scheme 2 (the
metaꢀisomer, 8b).
Towards this end the metaꢀderivative 20 was first oxidized to
the bisꢀsulfone 23 in excellent yield with metaꢀ
chloroperbenzoic acid (MCPBA) in dichloromethane in the
presence of acetic acid (Scheme 8).
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Scheme 8 here please
Scheme 8: First reactions with the metaꢀbisꢀsulfide 20: ringꢀ
contractions. Letters aꢀm in formula 24 indicate protons
assigned by NMR (see Experimental).
Neither the conventional RambergꢀBäcklund reaction8 nor
employing the modified version of Chan et al.9, mixing powdered
KOH and aluminum oxide, lead to isolable products.

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Therefore, the reaction was carried out under phaseꢀtransfer
conditions, using carbon tetrachloride as the halogenating
reagent in the first step (Scheme 8). In this case, a diene
was produced indeed, although in low yield (9%). According to
its spectral data (see Experimental section) it bore a
chlorine substituent at one of its double bonds. There are
reports in the literature10 that under these conditions
polyhalhalogenation takes place in the first step of the
RambergꢀBäcklund process causing the formation of vinylhalides
after the sulfur dioxide has been extruded.
The structure of 24 was derived from close inspection of the
coupling patterns in its 1H NMR spectrum and from useful longꢀ
range correlations in its H,HꢀCOSY spectrum. The deshielded
protons, Ha–Hd in formula 24, of the mꢀdisubstituted benzene
ring were easily identified. Protons Hj and Hk with a mutual
coupling of 11.0 Hz indicate a cisꢀC=C double bond. Olefinic
proton Hj displayed longꢀrange correlations with Ha and Hc, so
these latter ones are situated ortho to Hj of the –CHk=CHjꢀ
bond. The slightly broadened singlet of olefinic proton He had
longꢀrange crossꢀpeaks with Ha and Hd, thus determining the
position of the second olefinic bridge, –C(Cl)=CHe–. Proton Hk
of the first bridge correlates with the isolated proton, Hm, of
the “upper” [2.2]paracyclophane deck, while the isolated
proton, Hl, of the “lower” deck shows no correlation with any
olefinic proton because its orthoꢀbenzylic position is

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occupied by the chloro substituent, the presence of which is
evident from the mass spectrum and the elemental analysis.
To prepare the parent system, from which 24 is formally
derived, the hydrocarbon 25, we subjected the bissulfone 23 to
flash vacuum pyrolysis (FVP) at 500ꢀ540 oC. From the
pyrolysate, a hydrocarbon mixture could be isolated by column
chromatography in ca. 22% yield. Acoording to its NMR
spectroscopic data, this must contain components carrying
methyl groups as in 26 (Scheme 8 and Experimental Section). A
rationalization for these signals would involve cleavage of
one ethano bridge of the presumed intermediate 25. Similar
cleavage products have been obtained by pyrolysis of
paracyclophane hydrocarbons, including the parent system 1.
Their formation presumably takes place via diradicals formed
11
by homolysis of an ethano bridge.
We hence assume that 25 is generated as a reaction
intermediate, that does not survive the harsh pyrolysis
conditions in this case.
Conclusions: We have shown that dithiacyclophanes can be
prepared readily by wellꢀestablished routes in high yield.
Exploratory experiments demonstrate that these intermediates
can be converted into novel cyclophanes containing unsaturated
bridges, compounds which are of interest in the study of
conjugation effects between the rings (“decks”) of layered
organic compounds.

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References:
(1) Lehne, V.; Ernst, L.; Hopf, H. Synlett 2016, in press.
(2) Dix, I.; Bondarenko, L.; Jones, P. G.; Ernst, L.; Ibrom,
K.; Grunenberg, J.;, Boese, R.; Hopf, H. Chem. Eur. J. 2014,
20, 16360ꢀ16376.
(3) For a typical example see Mitchell, R. H.; Boekelheide, V.
Tetrahedron Lett. 1970, 1197ꢀ1201.
(4) Vögtle, F.; Rossa L. Angew. Chem. 1979, 91, 534ꢀ549;
Angew. Chem. Int. Ed. Engl. 1979, 18, 515ꢀ529.
(5) Keehn P. M. in Keehn, P. M.; Rosenfeld, S. M. (eds.),
Cyclophanes, Academic Press, New York, 1983, Vol. 1, Chapter
3, pp 69ꢀ238.
(6) Groome, C. R.; Allen, F. H. Angew. Chem. 2014, 126, 675ꢀ
684; Angew. Chem. Int. Ed. 2014, 53, 662ꢀ671.
(7) Bodwell, G.; Ernst, L.; Hopf,H.; Jones, P. G.; McNally, J.
P.; Schomburg, D. Chem. Ber. 1990, 123, 2381ꢀ2386.
(8) Review: Paquette, L. A. Org. Reactions, 1977, 25, 1ꢀ71.
(9) Chan. T. L.; Fong, S.; Li, Y.; Man, T.ꢀO.; Poon, C.ꢀD. J.
Chem. Soc. Chem. Commun. 1994, 1771ꢀ1772.
(10) Yang, F. M.; Lin, S. H. J. Org. Chem. 1997, 62, 2727ꢀ
2731.
(11) Reich, H. J.; Cram, D. J. J. Am. Chem. Soc. 1967, 89,
3078ꢀ3080.
(12) Trampe, S.; Menke, K.; Hopf, H. Chem. Ber. 1977, 110,
371ꢀ372.

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(13) Truesdale, E. A.; Cram, D. J. J. Org. Chem. 1980, 45,
3974ꢀ3981.
Graphical abstract:
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Experimental:
General methods: Chromatography: TLC: Polygram Sil G/UV254
(Macherey and Nagel) – Column chromatography: Merck silica gel
60 (70ꢀ230 mesh). – NMR: solvent: CDCl3 (δC = 77.01 ppm) or
CD2Cl2 (δC = 53.84 ppm), internal standard: TMS for 1H, solvent for
13C; Bruker AM 300 (1H: 300.1 MHz, 13C: 75.5 MHz; Bruker AM 400
(1H: 400.1 MHz, 13C: 100.6 MHz); degree of carbon atom
substitution by DEPTꢀ135. – IR: in solution, as film (neat),
and as KBr pellets on a PerkinꢀElmer 1420 instrument. – UV: in

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ethanol and/or acetonitrile, Beckman UV 5230. – MS: EI (70
eV), Finnigan MAT 8436.
The dibromide 10a was prepared according to the method
described in the literature:12
General procedure for assembling thiacyclophanes: A solution
containing equimolar amounts (1 mmol each) of the appropriate
dibromide and the dithiol in degassed benzene (100 mL) was
added by a syringe pump to a wellꢀstirred solution of
potassium hydroxide (0.14 g, 2.5 mmol) in ethanol (95%, 800
mL) during 8ꢀ10 h. After the addition was complete, the
mixture was stirred for an additional 8 h period. The solvent
was removed in vacuo and the crude product as chromatographed
on silica gel to give the corresponding cyclophane.
4,15-Bis(mercaptomethyl[2.2]paracyclophane (10b): A solution
of 4,15ꢀbis(bromomethyl)[2.2]paracyclophane (10a, 2.44 g, 6.2
mmol) and thiourea (0.95 g, 12.4 mmol) in anhydrous THF (60
mL) was heated to reflux for 12 h. The mixture was cooled to
room temp. and the precipitated isothiouronium salt was
removed by filtration and dried. The salt was dissolved in
water/dioxane (1:2, v/v, 180 mL) under nitrogen and to this
solution was added ethylene diamine (0.57 g, 9.4 mmol). The
mixture was heated to reflux under nitrogen for 12 h, cooled
to room temp., and hydrochloric acid (2 N) was added for
hydrolysis until a pH of 4 was reached. The solvent was

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removed in vacuo, and the crude product was chromatographed
using dichloromethane/hexane (1:1, v/v) as the eluent: 1.30 g
(70%) of 10b as a colorless powder, m. p. 85 oC. – 1H NMR: δ =
1.46 (t, J = 7.0 Hz, 2 H), 2.95ꢀ3.08 (m, 6 H), 3.38 (m,
AA’XX’, N = 9.9 Hz, 2 H), 3.45 (dd, J = 12.8, 6.9 Hz, 2 H),
3.85 (dd, J = 12.8, 6.9 Hz, 2 H), 6.32 (d, J = 1.7 Hz, 2 H),
6.45 (dd, J = 7.7, 1.7 Hz, 2 H), 6.48 ppm (d, J = 7.7 Hz, 2 H).
– 13C NMR: δ = 27.4 (t), 31.7 (t), 34.9 (t), 132.4 (d), 132.5
(d), 135.3 (d), 136.0 (s), 140.01 (s), 140.02 (s). – MS: m/z
(%) = 300 (18, M+), 267 (40), 266 (86), 147 (100). – HRMS:
C18H20S2: calcd.: 300.100; found: 300.100.
Attempted coupling of 10a with o-xylylene dithiol (12):
According to the above general procedure it was attempted to
couple the dibromide 10a (0.40 g, 1.0 mmol) with oꢀxylylene
dithiol (12, 0.17 g, 1.0 mmol). Purification of the obtained
crude reaction product by silica gel chromatography with
dichlormethane/hexae (3:7, v/v) afforded the thiacyclophane 14
as colorless needles (0.21 g, 80%), m. p. 240 oC. The compound
has been described previously,13 but its spectroscopic data are
incomplete in the literature. – 1H NMR: δ = 2.84ꢀ3.07 (m, 6 H),
3.29ꢀ3.41 (m, 4 H), 4.09 (d, J = 14.7 Hz, 2 H), 6.24 (dd, J =
7.9, 1.9 Hz, 2 H), 6.34 (d, J = 7.9 Hz, 2 H), 6.85 ppm (d, J =
1.9 Hz, 2 H). – 13C NMR: δ = 32.3 (t), 32.5 (t), 35.3 (t),
131.7 (d), 134.2 (d), 134.6 (d), 135.0 (s), 138.3 (s), 140.3
(s) ppm.

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Attempted coupling of 10a with m-xylylene dithiol (13): As
above 10a (0.40 g, 1.0 mmol) was attempted to be coupled with
mꢀxylylene dithiol (0.17 g, 1 mmol). Again, only the
intramolecularly generated 14 was obtained (0.19 g, 70%).
Dithiacyclophane 19: According to the above general procedure
was coupled 10b (0.60 g, 2 mmol) with oꢀxylylene dibromide (oꢀ
11, 0.53 g, 2 mmol). The crude product was purified by silica
gel column chromatography with dichloromethane/hexane (3:7,
v/v) to provide 19 as colorless needles (0.50 g, 62%), m. p.
211 oC. ꢀ 1H NMR: δ = 2.74ꢀ3.07 (m, 8 H), 3.48, 3.53 (AB
system, J = 15.1 Hz, 4 H), 3.78 (d, J = 13.9 Hz, 2 H), 4.33
(d, J = 13.9 Hz, 2 H), 6.37 (d, J = 7.7 Hz, 2 H), 6.42 (dd, J
= 7.7, 1.8 Hz, 2 H), 6.63 (d, J = 1.8 Hz, 2 H), 7.35, 7.55
(AA’XX’, N = 9.2 Hz, 4 H). ꢀ 13C NMR: δ = 31.3 (t), 31.7 (t),
33.2 (t), 35.0 (t), 127.6 (d), 131.11 (d), 131.17 (d), 131.25
(d), 133.9 (d), 136.3 (s), 136.6 (s), 137.0 (s), 139.6 ppm
(s). – HRMS: C26H26S2: calcd.: 402.147; found: 402.147.
Dithiacyclophane 20: According to the above general procedure
was coupled 10b (0.60 g, 2 mmol) with mꢀxylylene dibromide (mꢀ
11, 0.53 g, 2 mmol). The crude product was purified by silica
gel column chromatography with dichloromethane/hexane (2:3,
v/v) to provide 20 as a colorless powder (0.64 g, 80%), m. p.
224 oC. ꢀ 1H NMR: δ = 2.52ꢀ2.62 (AA’BB’, 4 H), 2.84ꢀ3.04
(CC’DD’, 4 H), 3.36 (d, J = 12.3 Hz, 2 H), 3.738, 3.774 (AB

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system, J = 13.3 Hz, 4 H), 3.86 (d, J = 12.3 Hz, 2 H), 6.26
(br. s, 2 H), 6.36 (d, J = 7.7 Hz, 2 H), 6.41 (dd, J = 7.7,
1.8 Hz, 2 H), 7.11 (t, J = 1.8 Hz, 1 H), 7.45 (2 H), 7.55 ppm
(1 H) (br. A2B, J = 7.5 Hz). ꢀ 13C NMR: δ = 31.5 (t, 2 C),
34.6 (t, 2 C), 34.9 (t, 2 C), 37.3 (t, 2 C), 128.4 (d, 2 C),
130.5 (d, 1 C), 132.54 (d, 2 C), 132.60 (d, 1 C), 132.72 (d, 2
C), 135.2 (d, 2 C), 135.4 (s, 2 C), 137.3 (s, 2 C), 138.6 (s,
2 C), 139.1 ppm (s, 2 C). – HRMS: C26H26S2: calcd.: 402.147;
found: 402.147.
Dithiacyclophane 21: According to the above general procedure
was coupled 10b (0.60 g, 2 mmol) with pꢀxylylene dibromide (pꢀ
11a, 0.53 g, 2 mmol). The crude product was purified by silica
gel column chromatography with dichloromethane/hexane (2:3,
v/v) to provide 21 as a colorless powder (0.25 g, 32%), m. p.
221 oC (decomp.). ꢀ 1H NMR: δ = 2.61 (d, J = 11.7 Hz, 2 H),
2.81ꢀ2.99 (m, 6 H), 2.84 (d, J = 11.7 Hz, 2 H), 3.23ꢀ3.35 (m,
2 H), 3.89, 3.95 (AB system, J = 12.1 Hz, 4 H), 6.18 (br s, 2
H), 6.39 (dd, J= 7.7, 1.8 Hz, 2 H), 6.45 (d, J = 7.7 Hz, 2 H),
7.23, 7.76 ppm (AA’XX’, N = 2.3 Hz, 4 H). ꢀ 13C NMR: δ = 32.5
(t), 34.2 (t), 34.8 (t), 36.6 (t), 130.3 (d), 130.4 (d), 132.6
(d), 132.9 (d), 135.0 (s), 135.4 (d), 136.9 (s), 138.8 (s),
139.0 (s) ppm. – HRMS: C26H26S2: calcd.: 402.147; found:
402.147.
Coupling of 10b (0.30 g, 1.0 mmol) and 10a (0.40 g, 1.0 mmol):
under the above conditions after chromatography with
dichloromethan/hexane (3:7) the thiacyclophane 14 was obtained

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(0.21 g, 80%, with respect to the thiol 10b): spectroscopic
data as above.
Repeating the experiment (same concentrations of coupling
partners 10a and 10b) in the presence of cesium hydroxide
(0.38 g, 2.5 mmol) yielded after workꢀup (column
chromatography with dichloromethane/hexane = 2:1 (v/v) the
thiacyclophane 14 (0.16 g, 60%) and the dimer 22 (26.0 mg, 5%)
as colorless powder, m.p. 195 oC. – 1H NMR: δ = 2.89ꢀ3.10 (m,
12 H), 3.50ꢀ3.53 (m, 4 H), 4.37 (d, J = 12.7 Hz, 4 H), 4.94
(d, J = 12.7 Hz, 4 H), 6.26 (dd, J = 7.8, 1.7 Hz, 4 H), 6.35
(d, J = 7.8 Hz, 4 H), 6.45 ppm (d, J = 1.7 Hz, 4 H). ꢀ 13C NMR:
δ = 137.6, 136.0, 134.6, 134.4, 134.3, 132.7, 37.4, 35.0, 34.6
ppm. – MS (EI, 70 eV): m/z (%) = 532 (6, M+), 266 (20), 147
(50), 104 (100). – C36H36S2 (532.80): calcd.: C 81.16, H 6.81, S
12.03; found: C 81.19, H 6.80, S 12.06.
Disulfone 23 from disulfide 20: To a solution of the
cyclophane 20 (1.2 g, 3.0 mmol) in a 1:1ꢀmixture of
dichloromethane/glacial acetic acid (300 mL) was added at 0 oC
under stirring a solution of mꢀchloroperbenzoic acid (MCPBA,
70% purity, 3.52 g, 14.3 mmol) in glacial acetic acid (100
mL). The reaction mixture was slowly warmed to room temp., and
stirred for 3 d. The precipitated disulfone was removed by
filtration, washed with trichloromethane, and dried: 1.26 g
(90%) of colorless crystals, m. p. 282 oC. – IR (KBr):
nu(tilde) = 1320 and 1115 cmꢀ1 (vs, SO2). ꢀ 1H NMR (DMSOꢀd6): δ
= 2.50ꢀ2.52 (m, 4 H), 2.96 (m, 4 H), 3.96ꢀ4.18 (m, 4 H), 4.64

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(m, 4 H), 6.33 (br. s, 2 H), 6.50 (d, J = 7.7 Hz, 2 H), 6.57
(dd, J = 7.7, 1.3 Hz, 2 H), 7.62ꢀ7.67 (m, 3 H), 7.98 ppm (br.
s, 1 H). ꢀ 13C NMR: δ = 139.8, 139.3, 135.1, 133.8, 131.9,
131.0, 129.9, 124.7, 61.1, 54.0, 34.2, 31.0 ppm. – MS (EI, 70
eV): m/z (%) = 466 (44, M+), 402 (8), 338 (60), 337 (100), 219
(76), 104 (44). – C26H26O4S2 (466.61): calcd.: C 66.93, H 5.62,
S 13.74; found: C 66.91, H 5.63, S 1372.
Diene 24: To a suspension of the disulfone 23 (0.47 g, 1.0
mmol) in dichloromethane/trichloromethane (50 mL, 2:1, v/v)
was added carbon tetrachloride (0.5 mL), aqueous sodium
hydroxide solution (25 mL, 10%), and cetyltrimethylammonium
chloride (0.18 g, 0.50 mmol). The mixture was heated at reflux
with vigorous stirring for 3 d. After cooling to room temp.,
the organic phase was separated, dried, and the solvent was
removed in vacuo. Column chromatography (silica gel;
hexane/dichloromethane = 8:2) yielded 24 (30.0 mg, 9%) as
colorless crystals, m. p. 120 oC (decomp.) ꢀ 1H NMR (CD2Cl2;
protons are labeled as in formula 24): δ = 2.42ꢀ2.61 (m, 2 H),
2.91ꢀ3.01 (m, 2 H), 3.09ꢀ3.35 (m, 4 H), 5.79 (br. s, 1 H; Hm),
5.90), 6.14 (d, J = 11.0 Hz, 1 H; Hk), 6.66 (d, J = 11.0 Hz, 1
H; Hj), 6.72 (dd, J = 7.3, 1.4 Hz, 1 H; Hi), 6.77 (d, J = 7.3
Hz, 1 H; Hh), 6.80 (br. d, J = 7.3 Hz, 1 H; Hg), 6.85 (dd, J =
7.3, 1.6, 1 H; Hf), 6.94 (br. s, 1 H; He), 7.10 (br. d, J = 7.7
Hz, 1 H; Hd), 7.17 (br. d, J = 7.7 Hz, 1 H; Hc) 7.32 (t, J =
7.7 Hz, 1 H; Hb), 7.51 ppm (td, J = 1.8, 0.6 Hz, 1 H; Ha). ꢀ 13C
NMR (CD2Cl2): δ = 34.7 (t), 34.95 (t), 35.04 (t), 35.08 (t),

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125.7 (d), 126.5 (d), 129.0 (d), 129.3 (d), 130.0 (d), 130.3
(d), 130.6 (d), 131.2 (d), 132.3 (d), 133.9 (d), 135.2 (d),
135.5 (s), 136.0 (s), 136.2 (d), 136.9 (s), 138.11 (s), 138.16
(s), 138.4 (d), 138.9 (s), 139.0 (s, 2 C), 139.3 (s) ppm. – MS
(EI, 70 eV): m/z (%) = 370 (20, M+), 368 (56, M+), 333 (100),
205 (45). – HRMS: calcd. 368.133, found 368.133. – C26H21Cl
(368.90): calcd.: C 84.65, H 5.74, Cl 9.61; found: 84.69, H
5.74.
Flash vacuum pyrolysis of 23: In a flash vacuum pyrolysis
apparatus disulfone 23 (0.47 g, 1.0 mmol) was pyrolyzed at
500ꢀ540 oC and 0.2 torr. The pyrolysate was frozen out on a
cold finger and the product mixture dissolved in
dichloromethane. Chromatography (silica gel; dichloro–
methane/hexane = 1:9) yielded ca. 80 mg (22%) of 26. ꢀ NMR:
Mixture displaying methyl signals at δH = 2.13 and 2.25 ppm and
at δC = 18.9 and 21.0 ppm. ꢀ MS (EI, 70 eV): m/z (%) = 340
(100, M+), 249 (8), 235 (22), 221 (56), 119 (50). – C26H28
(340.50): calcd.: C 91.71, H 8.29; found 91.74 H 8.30.
X-Ray structure determinations
Crystals were mounted in inert oil on glass fibres and
transferred to the cold gas stream of the diffractometer
(Siemens P4 for 21, otherwise Stoe STADIꢀ4). Intensity data
659
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661
were recorded using monochromated Mo Kα radiation (λ =
0.71073 Å). Absorption corrections were not performed. The
structures were refined anisotropically on F2 using the