Synthesis and conformational studies of 9-methoxy- and 9-methyl- 2,11-dithia[3.3]metacyclophanes

Article abstract of DOI:10.3184/030823409X12474221035244

A series of 9-methoxy- and 9-methyl-2,11-dithia[3.3]metacyclophanes are obtained by the coupling reaction of the corresponding 1,3-bis(bromomethyl) benzenes and bis(sulfanylmethyl)benzenes in ethanol under the high dilution conditions. The conformational

Full text of DOI:10.3184/030823409X12474221035244

JOURNAL OF CHEMICAL RESEARCH 2009
AUGUST, 515–519
RESEARCH PAPER 515
Synthesis and conformational studies of 9-methoxy- and 9-methyl-
2,11-dithia[3.3]metacyclophanes
Tomoe Shimizu, Takayuki Maeda, Katsuhiro Hida and Takehiko Yamato*
Department of Applied Chemistry, Faculty of Science and Engineering, Saga University, Honjo-machi 1, Saga-shi,
Saga 840-8502, Japan
A series of 9-methoxy- and 9-methyl-2,11-dithia[3.3]metacyclophanes are obtained by the coupling reaction of the
corresponding 1,3-bis(bromomethyl)benzenes and bis(sulfanylmethyl)benzenes in ethanol under the high dilution
conditions. The conformational studies of 2,11-dithia[3.3]metacyclophanes as well as the ring current interactions
derived from benzene ring are also described.
Keywords: cyclophanes, dithia[3.3]metacyclophanes, conformations, ring current effect, charge transfer complex
For many years, various research groups have been
attracted by the structures of the [3.3]MCP ([3.3]MCP
= [3.3]metacyclophane) skeleton.1–4 When both internal
substituents of a [3.3]phane such as 1 are H, the molecule may
be mobile. Mitchell and his coworkers demonstrated that 9,18-
dimethyl-2,11-dithia[3.3]MCP exists in syn- (syn-2b) and
anti- (anti-2b) conformers, which do not interconvert below
200°C.6–9 As in the case of the [2.2]phanes,2–4 the internal
methyl protons of anti-2b are shielded at d 1.30 ppm by 1.24
from those of syn-2b (d 2.54 ppm), which is relatively normal
for a toluene derivative.
Even one internal methyl substituent is sufficient to allow
the isolation of a discrete syn or anti isomer; for example, in
anti-2a the internal proton (Hi) appears at d 5.50 ppm and
the internal methyl protons (Mei) at d 2.18 ppm. The reduced
shielding of Mei relative to anti-2b indicates that 2a adopts a
different geometry from that of anti-2b.
S
15
18
9
6
S
1
Me
R
Me
9
9
S
S
R
18
18S
S
Vögtle et al.10 have made extensive studies of syn-anti
conversions in other dithia[3.3]MCPs, especially in relation
to the size of the substituents. When electron-withdrawing
groups such as halo, nitro, and cyano are present, the yields
of the syn isomers increase substantially. Very bulky groups,
such as tert-butyl, decrease the yields of syn isomers.
Although the effect on the ratio of syn and anti conformers
of dithia[3.3]MCPs was reported, it is still not clear what the
effects are, not only properties of the internal substituents, but
also having unsymmetrically substituted benzene rings arising
from charge-transfer-type interactions between two benzene
rings as well as steric effects of substituents at the 6 and 15-
positions.
All of the previous compounds are internally unsubstituted
or methyl-substituted dithia[3.3]MCPs and it is surprising
that there are very few reports on the preparation of 9-
methoxy analogues. We report here the synthesis and
stereochemical assignments of 9-methoxy- and 9-methyl-
2,11-dithia[3.3]MCPs using the above method, as well as
studies of their conformation by the ring current interactions
derived from benzene ring.
syn-confomer
anti-confomer
a; R = H
a; R = H
anti-2
syn-2
b; R = Me
b; R = Me
Fig. 1 syn- and anti-Conformers of dithia[3.3]metacyclophane 2.
out under high-dilution conditions in 10% ethanolic KOH in
the presence of a small amount of NaBH4,11–15 giving syn-
9-methoxy-2,11-dithia[3.3]MCPs 6a–e in 16–60% yields,
respectively (Scheme 1).
The structures of 6 were established on the basis of the
base peak molecular ions in their mass spectra, and they were
assigned the syn-stereochemistry syn-6 on the basis of their 1H
NMR spectra by comparison with the known syn-cyclophane
2a, since the 9-proton of syn-6 appears at around d 6.9 ppm
(that for syn-2a is at d 6.82 ppm),5,7,8 i.e. relatively normal for
a benzene, whereas if 6 existed as the anti conformers they
might be expected to be shielded by the opposite ring to ca d
5 ppm. The same shift of the internal methoxy protons at
around d 3.66–3.68 ppm as that of an anisole was observed
in syn-6. Further, the other aryl hydrogens can clearly be seen
to be shielded at d 6.87–6.90 ppm by the adjacent ring, a
common consequence of a face-to-face benzene ring.7 Also the
tert-butyl protons of syn-6a–6d were observed at higher field,
d 1.08–1.19 ppm due to the strong shielding effect of the
benzene ring except syn-6e (d 1.25 ppm). These observations
strongly suggest that compounds 6a–e all adopt syn-
conformations. The chemical shifts (d) of the internal methoxy
protons, the aromatic internal protons at the 18-position and
the tert-butyl protons of syn-9-methoxy-2,11-dithia[3.3]MCPs
syn-6a–e are com piledin Table 1. All the bridged CH2SCH2
protons of the above-prepared cyclophane 6b are observed as
a pair of doublets at d 3.42, 4.22 ppm (J = 14.3 Hz) and d 3.70,
3.79 ppm (J = 14.5 Hz) in 1H NMR spectra at room
temperature. With increasing temperature in DMSO-d6,
Results and discussion
2,6-Bis(sulfanylmethyl)anisoles 4 were prepared by treatment
of the corresponding 2,6-bis(bromomethyl) 4-substituted
anisoles 3 with thiourea and potassium hydroxide in
ethanol.11–15 5-tert-Butyl-1,3-bis(bromomethyl)benzene 5 was
prepared by bromination of 5-tert-butyl-1,3-dimethylbenzene
with N-bromosuccinimide in the presence of 2,2'-azobis(2,4-
dimethylpentanenitrile) in a methylene dichloride solution
according to our reported procedure.11,13
The cyclisations of 5-tert-butyl-1,3-bis(bromomethyl)
benzene 5 and 2,6-bis(sulfanylmethyl)anisoles 4 were carried
* Correspondent. E-mail: yamatot@cc.saga-u.ac.jp

516ꢀ JOURNALꢀOFꢀCHEMICALꢀRESEARCHꢀ2009
Table 1 Chemical shifts (d) of the internal methoxy protons, aromatic internal proton at 18 position and tert-butyl protons of syn-
9-methoxy-2,11-dithia[3.3]MCPs syn-6a–e and anti-9-methyl-2,11-dithia[3.3]MCPs anti-8a–ba
Compound
Methoxy and methyl protons
Aromatic proton at 18-position
tert-Butyl protons
Assignment
6a
6b
6c
6d
6e
8a
8b
3.68
3.66
3.67
3.66
3.67
2.17
2.00
6.90
6.93
6.93
6.87
6.90
5.65
5.00
1.18
1.19
syn
syn
syn
syn
syn
anti
anti
1.10
1.08, 1.14
1.25
1.31
1.24, 1.28
aDetermined in CDCl3 by using SiMe4 as a reference and expressed in ppm.
OMe
OMe
R
1) thiourea
XCH2
HSCH2
CH2SH
CH2X
2) KOH, NaBH4
EtOH
reflux
R
(30%)
(73%)
(51%)
(60%)
(20%)
4 a; R = H
b; R = Me
c; R = Et
3a; R = H, X = Br
b; R = Me, X = Cl
c; R = Et, X = Cl
d; R = tBu, X = Br
e; R = X = Br
d; R = tBu
e; R = Br
6
9
OMe
R
KOH,
S2
CH2Br
BrCH2
NaBH4
4
+
EtOH
tBu15
18
S11
tBu
5
syn -6 a; R = H
b; R = Me
c; R = Et
(48%)
(52%)
(48%)
(60%)
(16%)
d; R = tBu
e; R = Br
Scheme 1
theꢀ doubletsꢀ doꢀ notꢀ coalescencꢀ belowꢀ 150ꢀ°C,ꢀ respectively,ꢀ
and the energy barriers of flipping are both above 25 kcalꢀ
mol-1.8,9,10 Similar findings were obtained in dithia[3.3]MCPs
6a, 6c–6e.ꢀ Theseꢀ observationsꢀ stronglyꢀ suggestꢀ thatꢀ
compoundsꢀ6ꢀadoptꢀrigidꢀsyn-conformation.
theꢀ internalꢀ methylꢀ protonsꢀ appearedꢀ at dꢀ 2.18ꢀ andꢀ 2.00ꢀ
ppm differentꢀ fromꢀ thoseꢀ observedꢀ inꢀ 9,18-dimethyl-2,11-
dithia[3.3]MCP anti-2b (d 1.33 ppm). No ring current effects
of the opposing benzene was observed. These findings might
beꢀattributableꢀtoꢀtheꢀdifferentꢀstructureꢀbetweenꢀanti-8ꢀandꢀ
anti-2b.ꢀ Theꢀ internalꢀ aromaticꢀ protonꢀ atꢀ theꢀ 18-positionꢀ
ofꢀ anti-8 isꢀ observedꢀ atꢀ dꢀ 5.00–5.65ꢀ ppm.ꢀ Theꢀ tert-butylꢀ
protonsꢀ ofꢀ anti-8 was also observed at much lower fieldꢀ
(d 1.24–1.31 ppm) than that of syn-6d atꢀdꢀ1.08ꢀppm.ꢀTheseꢀ
observationsꢀstronglyꢀsuggestꢀcompoundsꢀanti-8a andꢀanti-8b
adoptꢀanꢀanti-conformation.ꢀDependentꢀonꢀtheꢀOMeꢀandꢀMeꢀ
substitution, different yields (inversion of selectivity) of anti-ꢀ
andꢀsyn-conformersꢀwereꢀformed.ꢀThusꢀ9-methoxyꢀanaloguesꢀ
areꢀexclusivelyꢀformedꢀasꢀsyn-conformers,ꢀbutꢀotherꢀ9-methylꢀ
analoguesꢀareꢀexclusivelyꢀformedꢀas anti-conformers.
In contrast, the cyclisation of 1,3-bis(bromomethyl)-5-tert-
butylbenzeneꢀ 5 and 2,6-bis(sulfanylmethyl)toluenes 7a andꢀ
7bꢀ wereꢀ carriedꢀ outꢀ underꢀ highꢀ dilutionꢀ conditionsꢀ inꢀ 10%ꢀ
ethanolicꢀKOHꢀinꢀtheꢀpresenceꢀofꢀaꢀsmallꢀamountꢀofꢀNaBH4,ꢀ
givingꢀexclusivelyꢀanti-9-methyl-2,11-dithia[3.3]MCPs anti-
8aꢀandꢀanti-8bꢀinꢀ60ꢀandꢀ85%ꢀyields,ꢀrespectively (Scheme 2).
Theꢀassignmentsꢀofꢀstructureꢀforꢀtheꢀantiꢀandꢀsynꢀconformersꢀ
wereꢀ readilyꢀ apparentꢀ fromꢀ theirꢀ 1H NMR spectra (Table
1).ꢀ Theꢀ 1Hꢀ NMRꢀ spectraꢀ ofꢀ conformer anti-8aꢀ andꢀ anti-8bꢀ
showꢀ theꢀ internalꢀ aromaticꢀ protonꢀ atꢀ theꢀ 18-positionꢀ atꢀ dꢀ
5.65ꢀandꢀ5.00ꢀppm,ꢀrespectively.ꢀThus,ꢀtheꢀinternalꢀaromaticꢀ
protonꢀofꢀtheꢀanti conformers shows an upfield shift due to
theꢀ ringꢀ currentꢀ ofꢀ theꢀ oppositeꢀ aromaticꢀ ring.3,4ꢀ However,ꢀ
These findings suggest that in the case of 9-methoxy
analogueꢀ theꢀ through-spaceꢀ interactionꢀ betweenꢀ theꢀ non-
bondingꢀ electronꢀ pairsꢀ ofꢀ theꢀ oxygenꢀ atomꢀ ofꢀ theꢀ methoxyꢀ
Me
6
9
R
Me
S2
HSCH2
CH2SH
KOH, NaBH4
EtOH
+
5
18
tBu
15
R
S
11
a; R= H
7
b; R= tBu
a; R= H (60%)
anti-8
b; R= tBu
(85%)
Scheme 2

JOURNAL OF CHEMICAL RESEARCH 2009 517
NC
NC
CN
CN
R
OMe
C
C
S
tBu
R
OMe
S
S
NC
NC
CN
tBu
C
C
S
CN
A
B
Fig. 3 Possible structures of charge-transfer complex for
syn-15-tert-butyl-9-methoxy-2,11-dithia[3.3]MCPs syn-6a–e
with TCNE.
cyclophanes having symmmetric donor-sites, unsymmetric
cyclophanes containing non-equivalent donor-sites such as 4-
acetyl- and 4-methoxy[2.2]paracyclophanes25 can be expected
to form two isomeric one-to-one complexes with TCNE,
i.e., pseudo-configurational isomers.26 An important factor
for determining which isomeric compex is more predominant
or exclusive is the magnitude of ionisation potentials of the
constituent donor moieties. Similarly, two possible pseudo-
configurational isomers A and B are also expected for the
one-to-one complex of syn-15-tert-butyl-9-methoxy-2,11-
dithia[3.3]MCPs syn-6 as shown in Fig. 3.
In studying the electron spectra of syn-6–TCNE complexes,
it is advantageous also to examine the spectra of TCNE
complex of 6,15-di-tert-butyl-9,18-dimethoxy-2,11-dithia-
[3.3]MCP (11). In contrast to 15-tert-butyl-9-methoxy-2,11-
dithia[3.3]MCP (syn-6a), which exhibits a charge-transfer
absorption band with TCNE at 521 nm (log e = 1.307), a
mixture of TCNE and 11 exhibits no band in the visible
region. However, the charge-transfer absorption band of the
reference compound 2,6-dimethylanisole (9) with TCNE
was observed at 455 nm (log e = 1.287).27 Complexing with
TCNE is considered to be difficult in the case of 11 owing
to the cyclophane structure as well as the steric hindrance of
the methoxy group at the 8-position, in spite of the increased
p-basicity of the benzene ring due to the methoxy groups.
Thus the observed charge-transfer bands of the syn-6–TCNE
complexes should be attributed to the internally unsubstituted
benzene-site one. Although the charge-transfer of the 5-tert-
butyl-1,3-dimethylbenzene 10–TCNE complex exhibits
an absorption peak at 422 nm, that of syn-6a is shifted to
521 nm. Such a red shift could be due to the benzene ring
at the other side of the molecule which tends to work as a
p-electron donor.
Fig. 2 Reaction intermediate for the cyclisation to form
dithia[3.3]MCPs.
group and the opposite aromatic p-electrons of the anti-
conformer may disfavour the formation of the latter as shown
in Fig. 2. In contrast, in the case of a 9-methyl analogue the
aromatic p–p interaction between the two opposite benzene
rings and the steric crowding at the internal positions 9 and
18 may inhibit the formation of the syn-conformer in the
[3.3]MCP system and that in turn the C–H–p interaction16
between the methyl and the opposite aromatic p-electrons
may favour the formation of an anti-conformer during the
cyclisation process. C–H–p interactions involving aliphatic CH
moieties are well documented16 as being either conformation
controlling intramolecular processes or involving crystal-
structure controlling intermolecular forces, especially for
inclusion complexes of calixarene derivatives.17–23
A solution of 15-tert-butyl-9-methoxy-2,11-dithia[3.3]MCP
(syn-6a) and TCNE in CH2Cl2 presents a reddish brown
colour and the charge-transfer band at 521 nm (log e = 1.307)
was observed in its UV spectrum. This absorption is due to
the formation of 1:1 charge-transfer complex among the
electron donor, syn-6a and the electron acceptor, TCNE. The
position of absorption maximum and the shape of absorption
curve remain unchanged when a 4–12-fold excess of TCNE
was added. The charge transfer band positions of other 15-
tert-butyl-9-methoxy-2,11-dithia[3.3]MCPs (syn-6b, syn-6c
and syn-6e), 2,6-dimethylanisole 9 and 5-tert-butyl-1,3-
dimethylbenzene 10 with TCNE complexes are summarised
in Table 2.
TCNE complexes have often been used in studies on
the relative p-base strength of various methyl-substituted
benzenes.24 The p-basicity of the donor molecules increases
with an increase in the number of substituted methyl groups
and/or stacking benzene rings and an increase in the face-to-
face overlapping between aromatic nuclei. In contrast to the
Similar redshifts were observed in the 15-tert-butyl-
8-methoxy-6-substituted-2,11-dithia[3.3]MCPs syn-6b and
syn-6c, each of which possesses an electron-donating group,
tBu
6
Table 2 Charge-transfer bands of π–π salts of syn-6a, b, c, e
OMe
a
9 OMe
and reference compounds 9, 10 with TCNE in CH2Cl2
Me
Me
Me
Me
2
S
S
11
Compounds
R
lCT (nm)
log e
OMe
18
syn-6a
syn-6b
syn-6c
syn-6e
9
H
521
520
522
470
455
422
1.307
1.364
1.414
1.386
1.287
1.364
tBu
Me
Et
Br
–
9
10
15
tBu
10
–
11
aThe complexes were prepared in CH2Cl2 using equimolar
quantities of substrate and TCNE at 25ꢀ°C.
Fig. 4 Reference compounds 9, 10 and 11.

518 JOURNAL OF CHEMICAL RESEARCH 2009
OS2 (M+) 277.94348. Found 277.94333 (Found: C, 38.84; H, 3.85.
C9H11BrOS2 (279.21) requires C, 38.72; H, 3.97%).
such as a methyl or ethyl group at the 6-position, respectively,
due to the increased transannular p-electron donation
from the non-complexed to the complexed benzene ring.
In contrast, the charge-transfer band of syn-6e, having an
electron-withdrawing bromine atom at the 6-position, would
certainly be shifted less than that of syn-6a, so that the
overall transannular effect of the uncomplexed ring would
be electron withdrawing. These findings strongly support the
attribution of the observed charge-transfer bands of the syn-8-
methoxy[3.3]MCP (syn-6)–TCNE complexes to the internally
unsubstituted benzene-site complex.
Cyclisation reaction of 4 and 5 to give dithia[3.3]metacyclophanes 6;
typical procedure
A solution of 1,3-bis(bromomethyl)-5-tert-butylbenzene 5 (2.0 g,
4.5 mmol) and 2,6-bis(sulfanylmethyl)anisole 4a (811 mg, 4.5 mmol)
in benzene (100 mL) was added dropwise from a Hershberg funnel
with stirring under nitrogen to a solution of potassium hydroxide
(700 mg, 12.4 mmol) and sodium borohydride (100 mg, 2.5 mmol)
in ethanol (3.0 L). When addition was complete (6 h), the reaction
mixture was concentrated in vacuo and the residue was extracted with
CH2Cl2 (500 mL). The CH2Cl2 extract was washed with water and
dried (Na2SO4), and concentrated. The residue was chromatographed
over silica gel (Walo, C-300; 100 g) with hexane–CH2Cl2 1:1
as eluent to give a colourless solid, which was recrystallised from
hexane to yield the desired 15-tert-butyl-9-methoxy-2,11-dithia[3.3]
metacyclophane (syn-6a) (773 mg, 48%) as prisms (from hexane),
m.p. 103–105°C; nmax(KBr)/cm-1 2900, 1590, 1430, 1166, 1008;
dH(CDCl3) 1.18 (9H, s, tBu), 3.46 (2H, d, J = 14.1 Hz, 1,12-CH2),
3.68 (3H, s, OMe), 3.69 (2H, d, J = 14.4 Hz, 3,10-CH2), 3.79 (2H,
d, J = 14.4 Hz, 3,10-CH2), 4.25 (2H, d, J = 14.1 Hz, 1,12-CH2),
6.60 (1H, t, J = 7.8 Hz, 15-ArH), 6.90 (1H, s, 9-ArH), 6.91 (2H, d,
J = 7.8 Hz, 14,16-ArH) and 6.92 (2H, s, 5,7-ArH); m/z 358 (M+);
HRMS (CI): m/z Calc. for C21H26OS2 (M+) 358.1425; Found
358.1431 (Found: C, 70.47; H, 7.38. C21H26OS2 (358.56) requires C,
70.34; H, 7.31%).
Compounds syn-6b–syn-6e were prepared in the same manner as
described for syn-6a. The yields are compiled in Scheme 1.
15-tert-Butyl-9-methoxy-6-methyl-2,11-dithia[3.3]metacyclophane
(syn-6b). Prisms (from hexane), m.p. 110–112°C; nmax(KBr)/cm-1
2930, 1590, 1160 and 898; dH (CDCl3) 1.19 (9H, s, tBu), 1.99 (3H,
s, Me), 3.42 (2H, d, J = 14.3 Hz, 3,10-CH2), 3.66 (3H, s, OMe), 3.70
(2H, d, J = 14.5 Hz, 1,12-CH2), 3.79 (2H, d, J = 14.5 Hz, 1,12-CH2),
4.22 (2H, d, J = 14.3 Hz, 3,10-CH2), 6.70 (2H, s, 14,16-ArH) and
6.93 (3H, s, 5,7,18-ArH); m/z 372 (M+); HRMS (CI): m/z Calcd for
C22H28OS2 (M+) 372.1582. Found 372.1568 (Found: C, 70.74; H,
7.65. C22H28OS2 (372.59) requires C, 70.92; H, 7.57%).
Conclusions
In conclusion, we have demonstrated for the first time a
through-space interaction between the non-bonding electron
pairs of the oxygen atom of the methoxy group and the
opposite aromatic p-electrons which may disfavour formation
of the anti-conformer during the coupling reaction of the
corresponding 5-tert-butyl-2,6-bis(bromomethyl)benzene 5
and 4-tert-butyl-2,6-bis(sulfanylmethyl)anisole 4 to afford
syn-9-methoxy-2,11-dithia[3.3]MCPs syn-6 exclusively.
In contrast, the corresponding 9-methyl analogues anti-8 are
exclusively formed as anti-conformers. Dependent on the OMe
and Me substitution, different yields (inversion of selectivity)
of syn- and anti-conformers were formed. The substituent
effect at the 6-position does exist in the complexation of syn-
8-methoxy-2,11-dithia[3.3]MCPs (syn-6) with TCNE and
that a through-space electronic interaction of the opposite
uncomplexed benzene ring must be considered. Further
chemical properties and the charge-transfer complexes of
the present novel unsymmetrically substituted syn-[3.3]MCP
derivatives are currently under study in our laboratory.
syn-15-tert-Butyl-6-ethyl-9-methoxy-2,11-dithia[3.3]metacyclo-
phane (syn-6c): Prisms (from hexane), m.p. 70–72°C; nmax(KBr)/cm-1
2904, 1592, 1432, 1208, 1116, 1002 and 870; dH (CDCl3) 1.02 (3H,
t, J = 7.7 Hz, CH2CH3), 1.17 (9H, s, tBu), 2.30 (2H, q, J = 7.7 Hz,
CH2CH3), 3.45 (2H, d, J = 14.4 Hz, 3, 10-CH2), 3.67 (3H, s, OMe),
3.68 (2H, d, J = 14.7 Hz, 1,12-CH2), 3.79 (2H, d, J = 14.7 Hz,
1,12-CH2), 4.22 (2H, d, J = 14.4 Hz, 3,10-CH2), 6.72 (2H, s, 14,16-
ArH), 6.91 (2H, s, 5,7-ArH) and 6.93 (1H, s, 18-ArH); m/z 386
(M+); HRMS (CI): m/z Calcd for C23H30OS2 (M+) 386.1738. Found
386.1723 (Found: C, 71.64; H, 7.83. C23H30OS2 (386.62) requires C,
71.45; H, 7.82%).
Experimental
1
All melting points are uncorrected. H NMR spectra were recorded
at 300 MHz on a Nippon Denshi JEOL FT-300 NMR spectrometer
in deuteriochloroform with Me4Si as an internal reference. UV-vis
spectra were recorded on a Perkin Elmer Lambda 19 UV/VIS/NIR
spectrometer. Mass spectra were obtained on a Nippon Denshi
JMS-HX110A Ultrahigh Performance Mass Spectrometer at 75 eV
using a direct-inlet system. Elemental analyses were performed by
Yanaco MT-5.
syn-6,15-Di-tert-butyl-9-methoxy-2,11-dithia[3.3]metacyclo-
phane (syn-6d): Prisms (from hexane), m.p. 115–117°C; dH(CDCl3)
1.08 (9H, s, tBu), 1.14 (9H, s, tBu), 3.46 (2H, d, J = 15.0 Hz, CH2),
3.60 (2H, d, J = 15.0 Hz, CH2), 3.66 (3H, s, OMe), 3.78 (2H, d,
J = 15.0 Hz, CH2), 4.19 (2H, d, J = 15.0 Hz, CH2) and 6.84–6.90
(5H, m, ArH); m/z 414 (M+) (Found: C, 72.19; H, 8.17. C25H34OS2
(414.67) requires C, 72.41; H, 8.27%).
syn-6-Bromo-15-tert-butyl-9-methoxy-2,11-dithia[3.3]metacyclo-
phane (syn-6e): Prisms (from hexane), m.p. 153–154°C; nmax(KBr)/
cm-1 2908, 1574, 1420, 1200, 1002 and 846; dH (CDCl3) 1.25 (9H, s,
tBu), 3.40 (2H, d, J = 14.3 Hz, 3,10-CH2), 3.67 (3H, s, OMe), 3.70
(2 H, d, J = 14.6 Hz, 1,12-CH2), 3.77 (2H, d, J = 14.6 Hz, 1,12-CH2),
4.19 (2H, d, J = 14.3 Hz, 3,10-CH2), 6.90 (1H, s, 18-ArH), 6.98 (2H,
s, 14,16-ArH) and 7.02 (2H, s, 5,7-ArH); m/z 436, 438 (M+); HRMS
(CI): m/z Calcd for C21H25BrOS2 (M+) 436.05303. Found 436.05179
(Found: C, 57.49; H, 5.67. C21H25BrOS2 (437.46) requires C, 57.66;
H, 5.76%).
Similarly, compounds anti-8a and anti-8b were synthesised in the
same manner as described in 60 and 85% yields, respectively.
anti-15-tert-Butyl-9-methyl-2,11-dithia[3.3]metacyclophane (anti-
8a): 60% as prisms (from hexane); m.p. 83–84°C; dH (CDCl3) 1.31
(9H, s, tBu), 2.17 (3H, s, Me), 3.55 (2H, d, J = 15.0 Hz, CH2), 3.71
(2H, d, J = 15.0 Hz, CH2), 3.78 (2H, d, J = 13.8 Hz, CH2), 3.94 (2H,
d, J = 13.8 Hz, CH2), 5.65 (1H, broad s, internal-H18), 6.78 (2H, t,
J = 7.5 Hz, ArH), 6.84 (2H, s, ArH) and 6.97 (1H, t, J = 7.5 Hz, ArH);
m/z 342 (M+) (Found: C, 73.91; H, 7.53. C21H26S2 (342.56) requires
C, 73.63; H, 7.65%).
Materials
Preparations of 2,6-bis(halomethyl)-4-substituted anisoles 3a–e,
2,6-bis(sulfanylmethyl)-4-substituted anisoles 4a, 4b, 4d28 and
5-tert-butyl-1,3-bis(bromomethyl)benzene
5
were previously
described.11,13 TheTCNE was recrystallised twice from chlorobenzene
and sublimed twice at 125°C (4 mmHg).
2,6-Bis(sulfanylmethyl)-4-ethylanisole (4c). A solution of 3c
(1.20 g, 5.1 mmol) and thiourea (854 mg, 11.22 mmol) in ethanol
(18 mL) was refluxed for 8 h under an atmosphere of nitrogen. After
the reaction mixture was cooled to room temperature and KOH
(858 mg, 15.3mmol)andNaBH4 (38.6mg, 1.02 mmol)wasadded.The
solution was refluxed for 10 h, acidified with aqueous 10% HCl and
extracted with CH2Cl2 (100 mL ¥ 2). The CH2Cl2 extract was washed
with water (100 mL) followed by saturated aqueous NaCl (100 mL),
and dried (Na2SO4) and evaporated in vacuo to leave a colourless
solid. Recrystallisation from hexane gave the 4c as a colourless
liquid (592 mg, 51%), b.p.133–134°C/3 torr; nmax/cm-1 (NaCl) 3040,
2924, 2540, 1428, 1216, 1122, 994 and 870; dH (CDCl3) 1.22 (3H, t,
J = 7.5 Hz, CH2CH3), 1.90 (2H, t, J = 7.4 Hz, SH), 2.59 (2H, q,
J = 7.5 Hz, CH2CH3), 3.75 (4H, t, J = 7.4 Hz, CH2SH), 3.87 (3H, s,
OCH3) and 7.06 (2H, s, ArH); m/z 228 (M+); HRMS (CI): m/z Calcd
for C11H16OS2 (M+) 228.06427. Found 228.06387 (Found: C, 57.74;
H, 7.03. C11H16OS2 (228.37) requires C, 57.86; H, 7.06%).
Compound 4e was prepared in the same manner as described for
4c in 20% yield.
2,6-Bis(sulfanylmethyl)-4-bromoanisole (4e): Colourless liquid,
b.p.165–167°C/10 torr; nmax/cm-1 (NaCl) 3040, 2912, 2540, 1570,
1420, 1202, 984 and 848; dH (CDCl3) 1.91 (2H, t, J = 7.7 Hz, SH),
3.72 (4H, d, J = 7.7 Hz, CH2SH), 3.87 (3H, s, OCH3) and 7.38 (2H,
s, ArH); m/z 278, 280 (M+); HRMS (CI): m/z Calcd for C9H11Br
anti-6,15-Di-tert-butyl-9-methyl-2,11-dithia[3.3]metacyclo-
phane (anti-8b): 85% as prisms (from hexane); m.p. 101–102°C;
d
H (CDCl3) 1.24 (9H, s, tBu), 1.28 (9H, s, tBu), 2.00 (3H, s, Me), 3.54

JOURNAL OF CHEMICAL RESEARCH 2009 519
12 M. Tashiro, K. Koya and T. Yamato, J. Am. Chem. Soc., 1982, 104, 3707.
13 M. Tashiro and T. Yamato, J. Org. Chem., 1985, 50, 2939.
14 T. Yamato, T. Arimura and M. Tashiro, J. Chem. Soc., Perkin Trans. 1,
1987, 1.
15 M. Tashiro, A. Tsuge, T. Sawada, T. Makishima, S. Horie, T. Arimura,
S. Mataka and T. Yamato, J. Org. Chem., 1990, 55, 2404.
16 M. Nishio and M. Horita, Tetrahedron, 1989, 45, 7201.
17 C.D. Andreetti, R. Ungaro and A. Pochini, J. Chem. Soc., Chem.
Commun., 1979, 1005.
(2H, d, J = 15.0 Hz, CH2), 3.70 (2H, d, J = 15.0 Hz, CH2), 3.77 (2H,
d, J = 15.0 Hz, CH2), 3.93 (2H, d, J = 15.0 Hz, CH2), 5.00 (1H, broad
s, internal-H18), 6.88 (2H, s, ArH) and 7.08 (2H, s, ArH); m/z 398
(M+) (Found: C, 75.19; H, 8.53. C25H34S2 requires C, 75.32;
H, 8.60%).
Received 22 April 2009; accepted 26 June 2009
Paper 09/0600 doi: 10.3184/030823409X12474221035244
Published online: 10 August 2009
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