Syntheses, X-ray structures and conformational studies of tetraoxa[n.n]metacyclophanes

Article abstract of DOI:10.1039/a705995g

New types of macrocyclic ligands with tetraoxa[n.n]metacyclophane molecular skeletons have been synthesized. The structures of 14,28-dibromo-1,8,15,22-tetraoxa[8.8]metacyclophane 2a, 16,32-dibromo-1,10,17,26-tetraoxa[10.10]metacyclophane 2b, 14,28-dibromo

Full text of DOI:10.1039/a705995g

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Syntheses, X-ray structures and conformational studies of
tetraoxa[n.n]metacyclophanes
Takuji Ogawa,*,† Tomoaki Kishimoto, Keijiro Kobayashi and Noboru Ono
Department of Chemistry, Faculty of Science, Ehime University, Matsuyama 790, Japan
New types of macrocyclic ligands with tetraoxa[n.n]metacyclophane molecular skeletons have been
synthesized. The structures of 14,28-dibromo-1,8,15,22-tetraoxa[8.8]metacyclophane 2a, 16,32-dibromo-
1,10,17,26-tetraoxa[10.10]metacyclophane 2b, 14,28-dibromo-2,7,16,21-tetraoxa[8.8]metacyclophane 3a,
16,32-dibromo-2,9,18,25-tetraoxa[10.10]metacyclophane 3c, 18,36-dibromo-2,11,20,29-tetraoxa[12.12]-
metacyclophane 3d, 20,40-dibromo-2,13,22,33-tetraoxa[14.14]metacyclophane 3e and 14,28-diiodo-
2,7,16,21-tetraoxa[8.8]metacyclophane 9a have been determined by single-crystal X-ray structure
analyses. In compounds 2a and 2b, two bromide atoms face each other within the macrocyclic ring
while in compounds 3c, 3d and 3e the bromine atoms face in opposite directions, outwards from the
macrocyclic ring. In the smaller ring compounds 3a and 9a the structure was intermediate between these
two types.
Substitution of the bromine atoms via lithiation has been achieved smoothly with iodine and methyl
iodide as the electrophiles to afford disubstituted compounds in good yields, while with trimethylsilyl
chloride as the electrophile the mono-substituted compound has been obtained.
Table 1 Synthesis of tetraoxa[m.m]metacyclophanes 1, 2 and 3
Tetraoxa[n.n]metacyclophanes 1 and their bromides 2 and 3 are
important macrocyclic ligands because the hydrogen atom
between the two oxygen atoms (for 1) or the two bromine
atoms (for 2 and 3) have the possibility of being substituted
with various heteroatoms via lithiation. Thus heteroatoms so
introduced are protected from the outer environment by the
surrounding alkane chain, while at the same time being forced
by the conformational demand of the ring into close proximity.
Thus, such compounds have potential in providing a good
steric protection,1 in situations where two heteroatoms may
interact in a special way or enter into unstable bonding. At the
same time such macrocyclic compounds can work as unique
host molecules.2 Consequently we were interested in the prep-
aration of these tetraoxa[n.n]metacyclophanes and accordingly,
have studied their conformation. As for the structure of small
[n.n]metacyclophanes in which n is <3, there have been many
reports presenting X-ray crystallographic analyses and such
structures can be predicted relatively easily.3 This is not so for
larger cyclophanes, where structural predictions are still dif-
ficult, both for solid compounds and especially for those in the
solution state.
Carbon chain
length n
m
Mp (ЊC)
Yield (%)
1a
1b
1c
1d
2a
2b
2c
2d
3a
3b
3c
3d
3e
3f
6
8
10
12
6
8
122
112
107
95
178
168
145
122
137
93
14.0
11.6
8.5
4.7
15.7
19
10
12
14
8
10
12
14
8
8
10
12
4
5
6
8
10
12
16
22
16.8
17.5
26.8
10.6a
13.5a
24.5
9
10
12
14
16
125
115
84
94
a Overall yields of the two-step reactions from compound 4.
tetraoxa[n.n]metacyclophanes 1, 2 and 3 could be prepared in
moderate yields (Table 1).
In this paper we describe the syntheses and X-ray crystallo-
graphic determination of the structure of tetraoxa[n.n]meta-
cyclophanes in the solid state in addition to a theoretical predic-
tion of the conformation by using semi-empirical molecular
orbital calculations and molecular mechanics/molecular
dynamics calculations. At the same time, we present some
examples of the substitution of the inner bromides with hetero-
atoms and carbon functionalities.
X-Ray crystallographic structure determinations of the
cyclophanes
Some tetraoxa[n.n]metacyclophanes crystallized out to give
good single crystals which were suitable for X-ray crystallo-
graphic analyses. The molecular structures of the dibromides 2a
(tetraoxa[8.8]metacyclophane), 2b (tetraoxa[10.10]metacyclo-
phane), 3a (tetraoxa[8.8]metacyclophane), 3c (tetraoxa[10.10]-
metacyclophane),3d(tetraoxa[12.12]metacyclophane),3e(tetra-
oxa[14.14]metacyclophane) and diiodide 9a (tetraoxa[8.8]meta-
cyclophane) in the solid state were determined as shown in Figs.
1–7, respectively. In 2a, two conformers were included in the
unit cell, however since the difference in the structure of these
two conformers was not significant, only one of them is
depicted in the Figure. In Table 2, the crystallographic param-
eters are summarized.
Results and discussion
Attempts to prepare tetraoxa[n.n]metacyclophanes 1, 2 and 3 in
a one-step method starting from resorcinol derivatives or the
tribromide 4 resulted in complex product mixtures of cyclic and
acyclic compounds of various sizes. These compounds were
therefore prepared by a two-step method via acyclic intermedi-
ates such as 5, 6 or 7, as shown in Scheme 1. In this way, the
In all these tetraoxa[n.n]metacyclophanes so far examined,
the aromatic rings were essentially parallel to each other, with
no overlapping of these rings being observed in projection. The
structures are characterized as ‘sigmoidal’ structures when seen
from the side of the aromatic ring plane, as depicted in the
† Present address: Institute for Fundamental Research of Organic
Chemistry(IFOC), KyushuUniversity, Hakozaki, Higashi-ku, Fukuoka
812-81, Japan
J. Chem. Soc., Perkin Trans. 1, 1998
529

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OH
O
O
(CH2)n
O
O
O
O
(CH2)n Br
i
ii
OH
iii
(CH2)n
(CH2)n Br
5
1
OH
Br
O
O
(CH2)n Br
Br
O
O
(CH2)n
Br
O
O
Br
Br
OH
iv
i
v
Br
Br
OH
(CH2)n Br
(CH2)n
OH
6
2
O
(CH2)n OH
Br
O
(CH2)n
O
vi
vii
Br
O
Br
Br
Br
O
Br
(CH2)n OH
(CH2)n
O
4
7
3
O
(CH2)n
O
O
I
(CH2)n
(CH2)n
O
I
viii
viii
I
I
2
8
3
9
O
O
(CH2)n
O
O
O
O
(CH2)n
O
(CH2)n
SiMe3
(CH2)n
O
ix
x
Me
Me
2
10
2
11
O
(CH2)n
O
O
O
Scheme 1 Reagents and conditions: i, Br(CH2)nBr, K2CO3, acetone, reflux 3 days; ii, resorcinol, K2CO3, acetone; iii, Br2, CCl4; iv, Na2SO3, H2O;
v, 2-bromoresorcinol; vi, HO(CH2)nOH, Na, THF; vii, 4, NaH, THF, reflux 7 days; viii, BuLi, I2; ix, BuLi, MeI; x, BuLi, Me3SiCl
lower sections of Figs. 1–7. The solid-state structures of
[n.n]paracyclophanes (n = 7–11) were reported to have a ‘box-
like’ structure in which the two aromatic rings are parallel with
almost complete overlapping in projection.4 Bis(5-
methoxycarbonyl-1,3-phenylene)-(3x ϩ 2)-crown-x which can
be regarded as polyoxa[n.n]metacyclophanes (n = 10 and 13)
also have ‘sigmoidal’ structures with the aromatic rings essen-
tially parallel to each other, overlap only partially in projec-
tion.5 It may be reasonable to assume that ‘large’ [n.n]metacyclo-
phane type compounds prefer the ‘sigmoidal’ structure in the
solid state.
One distinguishing point in the structures is that in 2a and 2b,
the two bromine atoms face each other within the macrocyclic
ring and the intramolecular distances between them is relatively
small; 3.90 and 4.29 Å for 2a and 3.48 Å for 2b. For conveni-
ence, we named this type of conformation Type C as classified
in Fig. 8. In contrast, in 3c, 3d and 3e the two bromine atoms
face in opposite directions, outwards from the macrocyclic ring,
with the intramolecular distances between them being relatively
large; 12.03 Å for 3d and 14.24 Å for 3e. This type of conform-
ation was named Type E (Fig. 8). In the smaller ring com-
pounds 3a and 9a, the structures were intermediate between
these two types and are designated as Type D (Fig. 8). The
reason for this extreme difference in the conformation observed
in these compounds is not clear at present.
of the bromine atom (3.90 Å), while that in 2b is 3.48 Å, this
being shorter than the sum of the van der Waals radii. These
results indicate that the two bromine atoms of these compounds
can interact strongly, at least in the solid state.
Calculation of the stable conformations of the cyclophanes by
semi-empirical molecular orbital and molecular mechanics
methods
The structure of a compound in solution is often different from
that in the crystal state, the latter not always being the most
stable one. In order to estimate the possibility of particular
structures occurring in solution and to discuss the structures in
the crystal state, energies of possible conformers were calcu-
lated by the semi-empirical molecular orbital and molecular
mechanics methods.
Possible stable conformations were obtained by repeating
molecular dynamics and molecular mechanics calculations
(MM2) starting from various initial structures,6 the resulting
conformations being roughly classified as type A, B, C, D or E,
as depicted in Fig. 8. Type A represents structures in which two
aromatic rings are situated nearly perpendicular to each other.
In Type B, the two aromatic rings are almost parallel and the
bromine atoms face the same direction, known as the ‘syn’
structure. In Type C, the two aromatic rings are almost parallel
and the two bromine atoms face each other within the macro-
cyclic ring, known as the ‘anti ’ structure. In Type E, the two
aromatic rings are almost parallel and the two bromine atoms
The distance between the two bromine atoms in one con-
former of 2a is the same as the sum of the van der Waals radii
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J. Chem. Soc., Perkin Trans. 1, 1998

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Fig.
3
X-Ray crystal structure of 14,28-dibromo-2,7,16,21-tetra-
oxa[8.8]metacyclophane 3a
Fig.
1
X-Ray crystal structure of 14,28-dibromo-1,8,15,22-tetra-
oxa[8.8]metacyclophane 2a
Fig. 2 X-Ray crystal structure of 16,32-dibromo-1,10,17,26-tetra-
oxa[10.10]metacyclophane 2b
Fig.
4
X-Ray crystal structure of 14,28-diiodo-2,7,16,21-tetra-
oxa[8.8]metacyclophane 9a
J. Chem. Soc., Perkin Trans. 1, 1998
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Fig. 6 X-Ray crystal structure of 18,36-dibromo-2,11,20,29-tetra-
oxa[12.12]metacyclophane 3d
differs from those in solution or the gas phase, it is unlikely that
the structure in the crystal state is the least stable of those
calculated in the gas phase. We can therefore conclude that
molecular mechanics calculations are more reliable than AM1
to provide the correct geometry for these types of cyclophanes.
Moreover, since in all the cases measured here molecular
mechanics calculations were able to predict the structure in the
crystalline state, it seems reasonable to expect that this method
can be generally applied for the prediction of the structures of
these types of compounds in the solid state.
Fig.
5
X-Ray crystal structure of 16,32-dibromo-2,9,18,25-tetra-
oxa[10.10]metacyclophane 3c
face opposite directions, outwards from the macrocyclic ring.
Type D is intermediate between Type C and Type E.
Molecular orbital calculations (AM1) were performed start-
ing from each of the optimized structures.7 Although the
optimized structures from the molecular orbital method were
not the same as those obtained by MM2, the difference was
negligible and the essential characteristics of the structure
remained the same.
Substitution of the bromine atoms with heteroatoms and carbon
atoms
An attempt was made to substitute the bromine atoms of these
cyclophanes with other functionalities via lithiation with butyl-
lithium followed by the addition of electrophiles. When the
cyclophanes 2a and 2b were lithiated by butyllithium followed
by the addition of iodine, the corresponding iodides 8a and 8b
were obtained in yields of 82.2 and 67.7%, respectively. Com-
pound 3a also gave the diiodide 9a in the same way in a yield of
71.7%. Dimethylated compound 10 could be obtained in a yield
of 84.5% from 2a by using methyl iodide as the electrophile.
Use of trimethylsilyl chloride as the electrophile in the reaction
with 2a, gave only the mono-trimethylsilylated compound 11
(71.7%), one bromine atom being substituted with hydrogen.
Probably because of steric hindrance, the second trimethylsilyl
molecule had difficulty in reacting with the other aryllithiums,
which reacted with water during the work-up procedure.
Reactions of 2a–2d and 3a–3f with trichlorophosphine and
trichlorobismuthine as the electrophiles also afforded debromi-
nated compounds after work-up together with small amounts
of some unidentified products, although the mass spectrum
of the reaction mixture showed incorporation of these hetero-
atoms within the molecules.
In Figs. 9 and 10, calculated energy differences from the most
stable conformers in each compound are summarized. Dark
bars present MM2 energy differences, while white bars show
AM1 energy differences from the most stable conformers in
each compound. Shadowed characters with asterisks indicate
the structures observed by X-ray crystallography. In all the
compounds the most stable conformers calculated by MM2
corresponded to the structures observed by X-ray crystal-
lography. The agreement of AM1 energies with those of MM2
is poor, and the most stable conformers calculated by AM1 did
not reproduce the results obtained by X-ray crystallography
in any way at all. It has already been reported by Professor
Fukazawa that molecular mechanics calculations provide better
geometry for macrocyclic compounds than do semi-empirical
MO calculations.3b In the present calculations the AM1 method
showed the X-ray structure to be the least stable structure for
compounds 2b, 3a and 9a. Molecular orbital or molecular
mechanics methods essentially calculate the molecular struc-
tures in the gas phase. Although the solid-state structure often
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Fig. 7 X-Ray crystal structure of 20,40-dibromo-2,13,22,33-tetra-
oxa[14.14]metacyclophane 3e
The van der Waals radii of the iodine group and the methyl
group are both 2.00 Å,8 while the estimated van der Waals
radius of the trimethylsilyl group calculated by the sum of the
C᎐Si bond length and the van der Waals radius of the methyl
group is 3.86 Å. The estimated van der Waals radius of the
dichlorophosphino group is calculated to be 3.91 Å. According
to the above results, groups with van der Waals radii not larger
than 2.00 Å can undergo substitution of both bromine atoms
without difficulty, while those with radii not larger than 3.9 Å
can substitute only one bromine atom; groups with radii larger
than 3.9 Å seem to have difficulty in substituting these cyclo-
phanes efficiently.
Herein we have shown the syntheses of a series of tetraoxa-
[n.n]metacyclophanes 1, 2 and 3. An X-ray crystallographic
study of them revealed that compounds 2a and 2b had Type C
structures, compounds 3c, 3d and 3e had Type E structures, while
compounds 3a and 9a had type D structures. Whilst molecular
mechanics calculations reproduced these structures quite nicely,
semi-empirical molecular orbital calculations could not. The
substitution of the bromine atoms was achieved smoothly with
sterically small electrophiles such as I and Me, while larger elec-
trophiles encountered difficulties in giving the products.
Fig. 8 Conformation type classification as exemplified by 2a. In
Type A, the two aromatic rings are situated nearly perpendicular to
each other. In Type B, the two aromatic rings are almost parallel and
the bromine atoms face the same direction. In Type C, the two aromatic
rings are almost parallel and the two bromine atoms face each other
within the macrocyclic ring. In Type E, the two aromatic rings are
almost parallel and the two bromine atoms face opposite directions
outwards from the macrocyclic ring. Type D is intermediate between
Type C and Type E.
values are given in Hz. IR and UV–VIS spectra were recorded
with a Hitachi 270-30 and Shimadzu UV-2200 spectrometer,
respectively. Mass spectra were taken on a Hitachi M-80B.
2-Bromoresorcinol was prepared by a reported method.9
Experimental
Mps were measured by a Yanako micro-melting point appar-
atus and are uncorrected. 1H NMR spectra were measured on a
JEOL-JNM-GSX270 or JNM-EX 400 spectrometer and J
1,3-Bis(6-bromohexyloxy)benzene 5a
A solution of resorcinol (1.29 g, 11.7 mmol), 1,6-dibromo-
J. Chem. Soc., Perkin Trans. 1, 1998
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Table 2 X-Ray crystallographic data for compounds 2a, 2b, 3a, 3c, 3d, 3e and 9a
Compound
2a
2b
3a
3c
3d
3e
9a
Formula
M
Crystal system
Space group
a/Å
b/Å
c/Å
C24H30O4Br2
542.31
Monoclinic
P21/c
12.358(4)
12.939(3)
15.352(3)
90
92.60(2)
90
C28H38O4Br2
598.41
Monoclinic
P21/a
9.268(3)
12.644(2)
12.478(4)
90
101.38(3)
90
C24H30O4Br2
542.31
Orthorhombic Triclinic
C28H38O4Br2
598.41
C32H46O4Br2
654.52
C37.5H56O4.5Br2 C24H30O4I2
738.66
636.31
Monoclinic
P21/n
Triclinic
Triclinic
¯
¯
¯
Pbca
P1
P1
P1
12.601(3)
21.778(2)
8.578(2)
90
90
90
11.888(3)
12.019(2)
10.185(3)
103.09(2)
95.30(3)
104.87(2)
1352(1)
25
13.005(3)
13.819(6)
4.799(2)
92.10(3)
91.53(3)
113.67(3)
788.5(5)
25
14.366(7)
15.065(6)
4.828(2)
95.79(3)
93.71(4)
70.64(4)
980.3(7)
17
7.586(1)
23.312(3)
7.846(1)
90
116.132(8)
90
α/Њ
β/Њ
γ/Њ
V/Å3
2452.2(9)
24
1433.4(7)
25
2353.9(7)
25
1245.7(3)
25
Reflection used for unit cell
determination
2θ Range/Њ
Z
29.5–30.0
4
1.469
1104
33.41
ω–2θ
55.0
23.5–25.6
2
1.386
616
28.27
ω–2θ
55.0
22.9–25.6
4
1.530
1104
34.35
ω–2θ
55.0
22.9–25.6
2
1.469
616
30.37
ω–2θ
55.0
26.0–30.0
1
1.378
340
26.11
ω–2θ
55.1
29.6–30.0
1
1.251
387
24.3–25.9
2
1.696
624
Dc/g cmϪ3
F(000)
µ/cmϪ1
21.09
ω–2θ
55.0
25.22
ω–2θ
55.0
Scan mode
Max. θ/Њ
Unique data
Obs. Data
No. of variables
R, Rw
Goodness of fit
∆ρmax/e ÅϪ3
∆ρmin/e ÅϪ3
5856
2915
3097
6192
3366
4471
2937
I > 3σ(I) 2353 I > 1σ(I) 1325 I > 1σ(I) 1068 I > 2σ(I) 2778 I > 3σ(I) 1576 I > 3σ(I) 2219 I > 2σ(I) 1571
272
0.045, 0.067
1.31
0.45
Ϫ0.52
155
0.064, 0.100
1.14
0.70
Ϫ0.53
137
0.069, 0.086
1.14
1.01
Ϫ0.70
308
0.054, 0.071
1.05
0.45
Ϫ0.45
173
0.041, 0.054
1.11
0.35
Ϫ0.32
196
0.075, 0.115
1.08
136
0.041, 0.042
1.21
1.86
Ϫ0.52
0.45
Ϫ0.64
Fig. 9 Energies above the energy of the global minima of metacyclo-
phanes 2. For each compound, optimization was performed starting
from various initial structures, and the final structures were classified as
A, B, C, D and E, as depicted in Fig. 8. When more than two optimized
structures in one compound had a similar conformation, the most
stable one was selected as the representative one. Dark bars are for
MM2 energy differences, while white bars show AM1 energy differences
from the most stable conformers of each compound. Shadowed char-
acters with asterisks indicate the structures observed by X-ray
crystallography.
Fig. 10 Energies above the energy of the global minima of metacyclo-
phanes 3 and 9a. For each compound, optimization was performed
starting from various initial structures, and the final structures were
classified as A, B, C, D and E, as depicted in Fig. 8. When more than
two optimized structures in one compound had a similar conformation,
the most stable one was selected as the representative. Dark bars are for
MM2 energy differences, while white bars show AM1 energy differences
from the most stable conformers of each compound. Shadowed char-
acters with asterisks indicate the structure observed by X-ray
crystallography.
hexane (8.59 g, 35.2 mmol) and K2CO3 (4.15 g, 30.0 mmol)
in acetone (50 cm3) was refluxed for 3 days with stirring, after
which the solvent was removed in vacuo. Water was added
to the residue which was then extracted with ethyl acetate.
The extract was washed with 10% aqueous NaOH, dried
(Na2SO4) and evaporated. The residue was purified by passage
through a silica-gel column using hexane–CH2Cl2 as the
eluent; yield 54%; mp 42 ЊC; δH(CDCl3) 1.45–1.52 (m, 8H),
1.70–1.92 (m, 8H), 3.40 (t, 4H, J 6.8), 3.92 (t, 4H, J 6.4), 6.42–
6.50 (m, 3H) and 7.10–7.17 (m, 1H); δC(CDCl3) 25.21, 27.82,
28.99, 32.59, 33.68, 67.55, 101.32, 106.54, 129.68 and 160.17;
m/z (EI) 438 (M ϩ 4, 20%), 436 (M ϩ 2, 48), 432 Mϩ, 20) and
110 (100); νmax(KBr)/cmϪ1 2935, 1614, 1578, 1464, 1288, 1186,
850 and 650 (Found: C, 49.7; H, 6.7. C18H28O2Br2 requires C,
49.6; H, 6.5%).
534
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1,3-Bis(8-bromooctyloxy)benzene 5b
106.49, 129.72 and 160.32; m/z (EI) 496 (Mϩ, 16%) and 110
By a method similar to that used for the preparation of 5a, 5b
(41.4%) was obtained, mp 57 ЊC; δH(CDCl3) 1.30–1.50 (m,
16H), 1.70–1.92 (m, 8H), 3.40 (t, 4H, J 6.9), 3.92 (t, 4H, J 6.6),
6.40–6.50 (m, 3H) and 7.10–7.18 (m, 1H); δC(CDCl3) 25.94,
28.07, 28.66, 29.16, 29.20, 32.75, 33.87, 67.81, 101.40, 106.60,
129.72 and 160.30; m/z (EI) 494 (M ϩ 4, 7%), 492 (M ϩ 2, 13),
490 (Mϩ, 7) and 110 (100); νmax(KBr)/cmϪ1 2932, 1614, 1464
and 1180 (Found: C, 53.7; H, 7.4. C22H36O2Br2 requires C, 53.7;
H, 7.4%).
(100); νmax(KBr)/cmϪ1 2900, 2820, 1580, 1480, 1460, 1270, 1160,
1140, 1040, 810 and 770 (Found: C, 77.4; H, 9.7. C32H48O4
requires C, 77.4; H, 9.7%).
1,3-Bis(6-bromohexyloxy)-2-bromobenzene 6a
A stirred solution of 2-bromoresorcinol (18.8 g, 100 mmol),
1,6-dibromohexane (97.58 g, 400 mmol) and K2CO3 (41.5 g,
300 mmol) in acetone (600 cm3) was refluxed for 3 days after
which solvent was removed in vacuo. Water was added to the
residue which was then extracted with ethyl acetate. The extract
was washed with 10% aqueous NaOH, dried (Na2SO4) and
evaporated. The residue was purified by passage through a
silica-gel column using hexane–ethyl acetate as eluent; yield
61%; mp 67 ЊC; δH(CDCl3) 1.22–1.64 (m, 8H), 1.76–2.00 (m,
8H), 3.43 (t, 4H, J 6.7), 4.02 (t, 4H, J 6.3), 6.53 (d, 2H, J 8.6)
and 7.16 (t, 1H, J 8.6); δC(CDCl3) 25.20, 27.79, 28.88, 32.63,
33.75, 68.98, 102.12, 105.71, 127.95 and 156.65; m/z (EI) 518
(M ϩ 6, 19%), 516 (M ϩ 4, 42), 514 (M ϩ 2, 42), 512 (Mϩ, 19)
and 188 (100); νmax(KBr)/cmϪ1 2948, 2908, 1594, 1478, 1402,
1254, 1088, 1038, 764, 708 and 646 (Found: C, 42.15; H, 5.2.
C18H27O2Br3 requires C, 42.0; H, 5.3%).
1,3-Bis(10-bromodecyloxy)benzene 5c
By a method similar to that used for the preparation of 5a, 5c
(49.9%) was obtained, mp 67 ЊC; δH(CDCl3) 1.25–1.52 (m,
24H), 1.70–1.91 (m, 8H), 3.40 (t, 4H, J 6.9), 3.92 (t, 4H, J 6.6),
6.40–6.50 (m, 3H) and 7.10–7.18 (m, 1H); δC(CDCl3) 25.86,
27.97, 28.56, 29.09, 29.16, 29.18, 29.27, 32.63, 33.68, 67.61,
101.17, 106.32, 129.46 and 160.13; m/z (EI) 550 (M ϩ 4, 12%),
548 (M ϩ 2, 22), 546 (Mϩ, 12) and 110 (100) (Found: C, 57.1;
H, 8.1. C26H44O2Br2 requires C, 56.9; H, 8.1%).
1,3-Bis(12-bromododecyloxy)benzene 5d
By a method similar to that used for the preparation of 5a, 5d
(38.4%) was obtained, mp 72 ЊC; δH(CDCl3) 1.72–1.90 (m, 8H),
3.41 (t, 4H, J 6.8), 3.92 (t, 4H, J 6.6), 6.44–6.50 (m, 3H) and
7.10–7.20 (m, 1H); δC(CDCl3) 26.00, 28.13, 28.72, 29.23, 29.34,
29.38, 29.47, 32.80, 33.98, 67.88, 101.36, 106.54, 129.68 and
160.31; m/z (EI) 607 (M ϩ 4, 8%), 604 (M ϩ 2, 14), 602 (Mϩ, 8)
and 110 (100) (Found: C, 59.6; H, 8.7. C30H52O2Br2 requires C,
59.6; H, 8.7%).
1,3-Bis(8-bromooctyloxy)-2-bromobenzene 6b
Yield 47%; mp 61 ЊC; δH(CDCl3) 1.30–1.60 (m, 16H), 1.72–1.94
(m, 8H), 3.41 (t, 4H, J 6.9), 4.02 (t, 4H, J 6.4), 6.52 (d, 2H, J 8.3)
and 7.16 (t, 1H, J 8.3); δC(CDCl3) 25.89, 28.05, 28.64, 29.07,
32.76, 33.87, 69.17, 102.17, 105.66, 127.91 and 156.75; m/z (EI)
574 (M ϩ 6, 4%), 572 (M ϩ 4, 12), 570 (M ϩ 2, 12), 568 (Mϩ, 4)
and 188 (100); νmax(KBr)/cmϪ1 2940, 1602, 1478, 1438, 1252,
1092, 1036 and 640 (Found: C, 46.3; H, 6.0. C22H35O2Br3
requires C, 46.3; H, 6.2%).
1,8,15,22-Tetraoxa[8.8]metacyclophane 1a
A stirred solution of resorcinol (2.85 g, 25.9 mmol), compound
5a (7.54 g, 17.3 mmol) and K2CO3 (7.14 g, 51.8 mmol) in
acetone (500 cm3) was refluxed for 7 days after which solvent
was removed in vacuo. Water was added to the residue which
was then extracted with ethyl acetate. The extract was
washed with 10% aqueous NaOH, dried (Na2SO4) and evapor-
ated. The residue was purified by passage through a silica-
gel column using hexane–CH2Cl2 as the eluent; yield 6.1%;
mp 116 ЊC (lit.,10 114 ЊC); δH(CDCl3) 1.50–1.62 (m, 8H),
1.65–1.90 (m, 8H), 3.97 (t, 8H, J 6.1), 6.40–6.50 (m, 6H)
and 7.10–7.18 (m, 2H); δC(CDCl3) 25.14, 28.26, 67.35,
101.59, 106.49, 129.74 and 160.31; m/z (CI) 385 (M ϩ 1, 100%)
and 110 (14); νmax(KBr)/cmϪ1 2940, 1498, 1282, 1184 and
822 (Found: C, 74.7; H, 8.3. C24H32O4 requires C, 75.0; H,
8.4%).
1,3-Bis(10-bromodecyloxy)-2-bromobenzene 6c
Yield 41%; mp 69 ЊC; δH(CDCl3) 1.00–1.90 (m, 36H), 3.40 (t,
4H, J 6.9), 4.01 (t, 4H, J 6.4), 6.52 (d, 2H, J 8.4) and 7.15 (t, 1H,
J 8.4); δC(CDCl3) 25.90, 28.10, 28.66, 29.05, 29.18, 29.27, 29.35,
32.76, 33.90, 69.13, 102.08, 105.58, 127.86 and 156.71; m/z (EI)
630 (M ϩ 6, 6%), 628 (M ϩ 4, 10), 626 (M ϩ 2, 11), 624 (Mϩ, 5)
and 188 (100); νmax(KBr)/cmϪ1 2920, 1588, 1400, 1216, 1062,
764, 660 and 616 (Found: C, 49.7; H, 6.9. C26H43O2Br3 requires
C, 49.8; H, 6.9%).
1,3-Bis(12-bromododecyloxy)-2-bromobenzene 6d
Yield 40%; mp 76 ЊC; δH(CDCl3) 1.20–1.58 (m, 32H), 1.75–1.92
(m, 8H), 3.40 (t, 4H, J 6.9), 4.01 (t, 4H, J 6.6), 6.52 (d, 2H, J
8.2) and 7.15 (t, 1H, J 8.2); δC(CDCl3) 25.95, 28.14, 28.73,
29.10, 29.27, 29.39, 29.47, 32.80, 33.94, 69.25, 102.13, 105.62,
127.87 and 156.76; m/z (EI) 686 (M ϩ 6, 4%), 684 (M ϩ 4, 12),
682 (M ϩ 2, 11), 680 (Mϩ, 4) and 188 (100); νmax(KBr)/cmϪ1
3432, 2844, 1568, 1400, 1250, 1092, 1046, 766, 728, 660 and 616
(Found: C, 52.5; H, 7.5. C30H51O2Br3 requires C, 52.7; H,
7.5%).
1,10,17,26-Tetraoxa[10.10]metacyclophane 1b
Yield 11.6%; mp 112 ЊC; δH(CDCl3) 1.30–1.54 (m, 16H), 1.70–
1.82 (m, 8H), 3.95 (t, 8H, J 6.2), 6.42–6.50 (m, 6H) and 7.10–
7.17 (m, 2H); δC(CDCl3) 25.14, 28.26, 67.35, 101.59, 106.49,
129.74 and 160.31; m/z (EI) 440 (Mϩ, 92%) and 110 (100);
νmax(KBr)/cmϪ1 2900, 2840, 1720, 1582, 1470, 1440, 1390, 1278,
1170, 1140, 1080, 1030, 820 and 780 (Found: C, 76.0; H, 9.2.
C28H40O4 requires C, 76.3; H, 9.1%).
14,28-Dibromo-1,8,15,22-tetraoxa[8.8]metacyclophane 2a
A stirred solution of 2-bromoresorcinol (9.45 g, 50 mmol), the
dibromide 6a (20.5 g, 40 mmol) and K2CO3 (17.3 g, 125 mmol)
in acetone (2400 cm3) was refluxed for 8 days after which solv-
ent was removed in vacuo. Water was added to the residue which
was then extracted with ethyl acetate. The extract was washed
with 10% aqueous NaOH, dried (Na2SO4) and evaporated. The
residue was purified by passage through a silica-gel column
using hexane–ethyl acetate as the eluent; yield 15.7%; mp
178 ЊC; δH(CDCl3) 1.60–1.76 (m, 8H), 1.76–1.94 (m, 8H), 4.07
(t, 8H, J 5.7), 6.50 (d, 4H, J 8.3) and 7.12 (t, 2H, J 8.3);
δC(CDCl3) 25.51, 28.8, 68.32, 103.02, 105.55, 127.49 and
156.55; m/z (EI) 544 (M ϩ 4, 20%), 542 (M ϩ 2, 38), 514 (Mϩ,
19) and 83 (100); νmax(KBr)/cmϪ1 2940, 2876, 1596, 1478, 1394,
1296, 1232, 1104, 1036, 752 and 664 (Found: C, 53.1; H, 5.6.
C24H30O4Br2 requires C, 53.1; H, 5.6%).
1,12,19,30-Tetraoxa[12.12]metacyclophane 1c
Yield 8.5%; mp 107 ЊC (lit.,11 106 ЊC); δH(CDCl3) 1.30–1.55 (m,
24H), 1.70–1.85 (m, 8H), 3.94 (t, 8H, J 6.2), 6.40–6.50 (m, 6H)
and 7.10–7.20 (m, 2H); δC(CDCl3) 25.87, 29.00, 29.11, 67.77,
101.65, 106.49, 129.72 and 160.32; m/z (EI) 496 (Mϩ, 16%) and
110 (100); νmax(KBr)/cmϪ1 2900, 2820, 1580, 1480, 1460, 1270,
1160, 1140, 1040, 810 and 770 (Found: C, 77.4; H, 9.7. C32H48O4
requires C, 77.4; H, 9.7%).
1,14,21,34-Tetraoxa[14.14]metacyclophane 1d
Yield 4.7%; mp 95 ЊC; δH(CDCl3) 1.30–1.55 (m, 24H), 1.70–
1.85 (m, 8H), 3.94 (t, 8H, J 6.2), 6.40–6.50 (m, 6H) and 7.10–
7.20 (m, 2H); δC(CDCl3) 25.87, 29.00, 29.11, 67.77, 101.65,
J. Chem. Soc., Perkin Trans. 1, 1998
535

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16,32-Dibromo-1,10,17,26-tetraoxa[10.10]metacyclophane 2b
Yield 19.0%; mp 167 ЊC; δH(CDCl3) 1.10–1.90 (m, 24H), 4.03 (t,
8H, J 5.3), 6.51 (d, 4H, J 8.2) and 7.14 (t, 2H, J 8.4); δC(CDCl3)
26.41, 29.41, 29.57, 69.39, 102.75, 105.56, 127.69 and 156.85;
m/z (CI) 601 (M ϩ 5, 28%), 599 (M ϩ 3, 3), 596 (Mϩ, 28) and
83 (100) (Found: C, 56.0; H, 6.4. C28H38O4Br2 requires C, 56.2;
H, 6.4%).
20-Trimethylsilyl-1,14,21,34-tetraoxa[14.14]metacyclophane 11
A dry THF (35 cm3) solution of 2d (213 mg, 0.3 mmol) was
treated with butyllithium (1.2 mmol) added at Ϫ78 ЊC. The
solution was then stirred at the same temperature for 3 h after
which trimethylsilyl chloride (1.2 mmol) was added to it. The
solution was then allowed to warm to room temperature for 12
h, after which it was evaporated, diluted with water and
extracted with chloroform. The extract was dried (Na2SO4) and
evaporated in vacuo to give the crude product, which was puri-
fied by recrystallization from chloroform–hexane; yield 71.7%,
mp 111 ЊC; δH(CDCl3) 0.32 (s, 9H), 1.25–1.40 (m, 24H), 1.70–
1.82 (m, 8H), 3.85–4.00 (m, 8H), 6.42–6.50 (m, 5H) and 7.10–
7.25 (m, 2H); δC(CDCl3) 1.95, 25.91, 26.42, 29.07, 29.13, 29.20,
29.23, 29.27, 29.39, 67.81, 67.91, 101.48, 103.28, 106.55, 113.55,
129.71, 131.06, 160.33 and 164.89; νmax(KBr)/cmϪ1 2916, 1596,
1476, 1280, 1174, 1092, 1026 and 782 (Found: C, 74.8; H, 10.4.
C39H64O4Si requires C, 74.95; H, 10.3%).
18,36-Dibromo-1,12,19,30-tetraoxa[12.12]metacyclophane 2c
Yield 16.4%; mp 145 ЊC; δH(CDCl3) 1.28–1.44 (m, 16H),
1.44–1.62 (m, 8H), 1.72–1.88 (m, 8H), 4.02 (t, 8H, J 5.7),
6.51 (d, 4H, J 8.2) and 7.14 (t, 2H, J 8.4); δC(CDCl3) 26.12,
29.11, 29.17, 29.28, 69.09, 102.28, 105.44, 127.79 and 156.82;
m/z (EI) 656 (M ϩ 4, 44%), 654 (M ϩ 2, 78), 652 (Mϩ, 38)
and 83 (100); νmax(KBr)/cmϪ1 2924, 1592, 1394, 1100 and 762
(Found: C, 58.7; H, 7.1. C32H46O4Br2 requires C, 58.7; H,
7.1%).
20,40-Dibromo-1,14,21,34-tetraoxa[14.14]metacyclophane 2d
Yield 22.1%; mp 122 ЊC; δH(CDCl3) 1.22–1.42 (m, 24H), 1.42–
1.60 (m, 8H), 1.72–1.87 (m, 8H), 4.02 (t, 8H, J 5.8), 6.51 (d,
4H, J 8.2), 7.15 (t, 2H, J 8.4); δC(CDCl3) 26.16, 29.15, 29.34,
29.41, 69.12, 102.31, 105.55, 127.82 and 156.79; m/z (EI) 712
(M ϩ 4, 62%), 710 (M ϩ 2, 100), 708 (Mϩ, 42) and 83
(100); νmax(KBr)/cmϪ1 2924, 1590, 1460, 1296, 1098 and 762
(Found: C, 61.1; H, 7.9. C36H54O4Br2 requires C, 60.9; H,
7.7%).
General procedure for the preparation of the diols 7
Sodium metal (3.45 g, 150 mmol) was added to the dried
polymethylenediol (1.2 mol) in a 300-cm3 flask under an argon
atmosphere. When all the sodium metal had dissolved, the tri-
bromide 4 (10.3 g, 30 mmol) in dry THF (30 cm3) was added
dropwise to the solution. The mixture was stirred and heated at
ca. 60 ЊC for 48 h, after which it was neutralized with concen-
trated hydrochloric acid and evaporated. Unchanged polymeth-
ylenediol was recovered by distillation under reduced pressure
and the residue was purified by column chromatography on sil-
ica gel using hexane–ethyl acetate (1:1) as the eluent to give the
product. Since for 7d (n = 8) and 7e (n = 10) the separations from
the starting polymethylenediols were difficult because the polar-
ities of the materials are very similar, they were used for the next
step reaction without further purification.
14,28-Diiodo-1,8,15,22-tetraoxa[8.8]metacyclophane 8a
A dry THF (75 cm3) solution of 2a (0.75 g, 1.5 mmol) in a 100-
cm3 flask, was treated with butyllithium (6 mmol) at Ϫ78 ЊC.
The solution was stirred at the same temperature for 3 h, after
which iodine (1.65 g, 6.75 mmol) in dry THF (15 cm3) was
added dropwise to it; the solution was then allowed to warm to
room temperature after which it was stirred for 12 h. The excess
iodine was reduced by the addition of saturated aq. sodium
sulfite to the mixture which was then extracted with chloro-
form. The extract was dried (MgSO4) and evaporated in vacuo
and the residue was purified by recrystallization from CCl4–
hexane to give colourless crystals (82.2%), mp 202 ЊC;
δH(CDCl3) 1.60–1.90 (m, 16H), 4.08 (t, 8H, J 5.2), 6.42 (d, 4H,
J 8.2) and 7.15 (t, 2H, J 8.2); δC(CDCl3) 25.20, 28.97, 67.79,
80.44, 104.63, 129.05 and 158.76; m/z (EI) 636 (Mϩ, 100%) and
509 (75); νmax(KBr)/cmϪ1 2950, 1600, 1470, 1400, 1285, 1120,
1080 and 780 (Found: C, 45.2; H, 5.0. C24H30O4I2 requires C,
45.3; H, 4.75%).
1,3-Bis(4-hydroxybutoxymethyl)-2-bromobenzene 7a
Yield 80.9%; yellow crystals, mp 64–65.5 ЊC; δH(CDCl3) 1.65–
1.76 (m, 8H), 2.37 (s, 2H, OH), 3.59 (t, 4H, J 6.0), 3.64 (t, 4H,
J 6.3), 4.59 (s, 4H), 7.31 (dd, 1H, J 8.9 and 5.8) and 7.37–7.42
(m, 2H); δC(CDCl3) 25.95, 29.22, 61.79, 70.47, 72.06, 122.59,
126.84, 127.65 and 137.64; m/z (CI) 361 (M ϩ 1, 33%), 345
(MHϩ Ϫ H2O, 9) and 271 [Mϩ Ϫ O(CH2)4OH, 100]; νmax(KBr)/
cmϪ1 3304, 2950, 2968, 1446, 1360, 1130, 968 and 775 (Found:
C, 53.1; H, 6.9. C16H25O4Br requires C, 53.2; H, 7.0%).
1,3-Bis(5-hydroxypentyloxymethyl)-2-bromobenzene 7b
Yield 72.3%, yellow crystals; mp 49–51 ЊC; δH(CDCl3) 1.44–
1.80 (m, 14H, alkane and OH), 3.56 (t, 4H, J 6.4), 3.63 (t, 4H,
J 6.4), 4.57 (s, 4H), 7.31 (dd, 1H, J 8.5 and 6.1) and 7.36–7.42
(m, 2H); δC(CDCl3) 21.94, 28.94, 31.84, 61.57, 70.40, 71.84,
122.29, 126.63, 127.36 and 137.57; m/z (CI) 389 (M ϩ 1, 27%),
285 [Mϩ Ϫ O(CH2)5OH, 21], 199 (30), 182 (100) and 105 (23);
νmax(KBr)/cmϪ1 3320, 2940, 2856, 1140, 1030 and 784 (Found:
C, 55.4; H, 7.4. C18H29O4Br requires C, 55.5; H, 7.5%).
16,32-Diiodo-1,10,17,26-tetraoxa[10.10]metacyclophane 8b
Yield 67.7%; mp 162 ЊC; δH(CDCl3) 1.40–1.58 (m, 8H), 1.58–
1.75 (m, 8H), 1.75–1.88 (m, 8H), 4.02 (t, 8H, J 5.3), 6.43 (d, 4H,
J 8.2) and 7.16 (t, 2H, J 8.2); δC(CDCl3) 26.29, 29.33, 29.54,
69.20, 79.89, 104.84, 129.24 and 158.97; m/z (EI) 692 (Mϩ,
100%), 565 (8), 438 (6) and 236 (62) (Found: C, 48.7; H, 5.6.
C28H38O4I2 requires C, 48.6; H, 5.5%).
1,3-Bis(6-hydroxyhexyloxymethyl)-2-bromobenzene 7c
14,28-Dimethyl-1,8,15,22-tetraoxa[8.8]metacyclophane 10
A dry THF (5 cm3) solution of 2a (54 mg, 0.1 mmol), was
treated with butyllithium (0.4 mmol) added at Ϫ78 ЊC. The
solution was then stirred at the same temperature for 3 h, after
which methyl iodide (0.8 mmol) was added to it. The solution
was then allowed to warm to room temperature for 12 h after
which it was evaporated, and diluted with water and extracted
with chloroform. The extract was dried (Na2SO4) and evapor-
ated in vacuo to give the crude product, which was purified by
recrystallization from chloroform–hexane; yield 84.5%, mp
165 ЊC; δH(CDCl3) 1.40–1.80 (m, 22H), 3.85–4.00 (m, 8H), 6.47
(d, 4H, J 8.2) and 7.07 (t, 2H, J 8.2); δC(CDCl3) 8.12, 26.22,
29.32, 67.33, 103.81, 115.06, 125.74 and 157.75; m/z (EI) 412
(Mϩ, 100%), 207 (38) and 124 (95) (Found: C, 75.4; H, 8.7.
C26H36O4 requires C, 75.7; H, 8.8%).
Yield 69.4%, yellow crystals; mp 45–48 ЊC; δH(CDCl3) 1.40–2.02
(m, 18H, alkane and OH), 3.55 (t, 4H, J 6.4), 3.63 (t, 4H, J 6.6),
4.57 (s, 4H, benzyl), 7.24 (dd, 1H, J 8.5 and 6.1) and 7.30–7.35
(m, 2H); δC(CDCl3) 25.23, 25.62, 29.27, 32.17, 61.87, 70.52,
71.93, 122.40, 126.73, 127.43 and 137.72; m/z (CI) 417 (M ϩ 1,
31%), 299 [Mϩ Ϫ O(CH2)6OH, 32], 199 (28) and 183 (100);
νmax(KBr)/cmϪ1 3324, 2940, 2860, 1360, 1136 and 784 (Found:
C, 57.45; H, 7.85. C20H33O4Br requires C, 57.55; H, 8.0%).
1,3-Bis(12-hydroxydodecyloxymethyl)-2-bromobenzene 7f
Yield 67.1%, pale yellow solid; mp 69–71 ЊC; δH(CDCl3) 1.23–
1.68 (m, 42H, alkane and OH), 3.54 (t, 4H, J 6.6), 3.63 (t, 4H,
J 6.6), 4.57 (s, 4H, benzyl), 7.31 (dd, 1H, J 8.6 and 6.0) and
7.38–7.42 (m, 2H); δC(CDCl3) 25.46, 25.81, 29.09, 29.13, 29.24,
29.28, 32.26, 61.90, 70.63, 71.87, 122.12, 126.63, 127.23 and
536
J. Chem. Soc., Perkin Trans. 1, 1998

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137.71; m/z (CI) 585 (M ϩ 1, 11%), 383 [Mϩ Ϫ O (CH2)12OH,
29], 201 (64), 183 (60) and 105 (100); νmax(KBr)/cmϪ1 3264,
2920, 2848, 1470, 1130 and 1059 (Found: C, 65.5; H, 9.7.
C24H30O4Br2 requires C, 65.6; H, 9.8%).
1.43 (m, 32H), 1.59–1.66 (m, 8H), 3.54 (t, 8H, J 6.4), 4.56 (s,
8H), 7.28–7.34 (dd, 2H, J 6.3 and 8.7) and 7.40 (d, 4H, J 6.7);
δC(CDCl3) 26.1, 29.1, 29.18, 29.24, 29.6, 70.7, 72.3, 122.8,
127.0, 127.7 and 138.2; m/z (CI) 769 (Mϩ ϩ 5, 2%), 767
(Mϩ ϩ 3, 12), 765 (Mϩ ϩ 1, 5), 685 (6), 565 (6), 485 (5), 383
(33), 285 (19), 185 (91), 183 (100) and 105 (63); νmax(KBr)/cmϪ1
2924, 2852, 1470, 1360, 1132, 1026 and 790 (Found: C, 62.5; H,
8.35. C40H62O4Br2 requires C, 62.7; H, 8.15%).
General procedure for the preparation of 3
The tribromide 4 (0.69 g, 2.0 mmol) and the diol 7 (2.0
mmol) in dry THF (20 cm3) were added dropwise to a sus-
pension of sodium hydride (0.4 g, ca. 10 mmol) in dry THF
(110 cm3) under an argon atmosphere. The mixture was
refluxed for 7 days after which it was concentrated in vacuo,
neutralized with 10% hydrochloric acid and extracted with
chloroform. The organic layer was washed with saturated aq.
NaCl, dried (MgSO4) and evaporated under reduced pressure.
The residue was purified by column chromatography on
silica gel using 5% ethyl acetate in hexane as the eluent to
give the product.
14,28-Diiodo-2,7,16,21-tetraoxa[8.8]metacyclophane 9a
14,28-Dibromo-2,7,16,21-tetraoxa[8.8]metacyclophane 3a (0.5
mmol, 271 mg) was dried in a 50-cm3 flask in vacuo by heating
to ca. 100 ЊC. After the flask had been flushed with dry argon, it
was charged with dry THF (25 cm3) to dissolve compound 3a;
butyllithium (1.5 mmol) was then added at Ϫ56 ЊC to the flask.
The mixture was stirred at Ϫ56 ЊC for 4 h after which an excess
of iodine (3.9 g, ca. 15 mmol) in dry THF (2 cm3) was added to
it. The reaction mixture was allowed to warm to room temper-
ature during about 3 h after which excess of iodine was reduced
by the addition of saturated aq. sodium sulfite. The mixture was
extracted with chloroform and the extract dried (MgSO4) and
evaporated in vacuo. The residual oil was purified by passage
through a silica-gel column with 5% ethyl acetate–hexane as the
eluent; yield 71.7%, colourless crystals; mp 134–135 ЊC;
δH(CDCl3) 1.74–1.78 (m, 8H), 3.52 (t, 8H, J 6.0), 4.41 (s, 8H)
and 7.22 (s, 6H); δC(CDCl3) 26.1, 69.7, 76.9, 102.7, 127.7, 128.1
and 141.2; m/z (EI) 636 (Mϩ, 15%), 546 (28), 492 (48), 231 (100)
and 104 (74); νmax(KBr)/cmϪ1 2944, 2904, 2860, 1356, 1130,
1090, 1146 and 800 (Found: C, 45.4; H, 4.9. C24H30O4I2 requires
C, 45.3; H, 4.75%).
14,28-Dibromo-2,7,16,21-tetraoxa[8.8]metacyclophane 3a
Yield 16.8%, colourless crystals; mp 135–137 ЊC; δH(CDCl3)
1.65–1.75 (m, 8H), 3.53 (t, 8H), 4.46 (s, 8H, benzyl), 7.20 (dd,
2H, J 8.7 and 6.0) and 7.27–7.29 (m, 4H); δC(CDCl3) 25.8, 69.6,
72.0, 123.5, 126.7, 128.1 and 137.9; m/z (CI) 545 (Mϩ ϩ 5,
39%), 543 (Mϩ ϩ 3, 78), 541 (Mϩ ϩ 1, 40), 399 (98), 271 (46),
185 (99), 183 (100) and 105 (69); νmax(KBr)/cmϪ1 2948, 2910,
2864, 1354, 1120, 1086, 1050 and 804 (Found: C, 53.1; H, 5.8.
C24H30O4Br2 requires C, 53.2; H, 5.6%).
15,30-Dibromo-2,8,17,23-tetraoxa[9.9]metacyclophane 3b
Yield 17.5%, colourless crystals; mp 91.5–93 ЊC; δH(CDCl3)
1.53–1.63 (m, 12H), 3.52 (t, 8H, J 5.8), 4.52 (s, 8H, benzyl), 7.17
(dd, 2H, J 8.4 and 7.0) and 7.34 (d, 4H, J 7.6); δC(CDCl3) 22.4,
28.7, 69.9, 72.2, 124.0, 126.9, 128.7 and 138.1; m/z (CI) 573
(Mϩ ϩ 5, 5%), 571 (Mϩ ϩ 3, 12), 569 (Mϩ ϩ 1, 5), 467 (36), 367
(34), 285 (29), 183 (100) and 104 (41); νmax(KBr)/cmϪ1 2950,
2908, 2870, 1136, 1120, 1094 and 780 (Found: C, 54.6; H, 5.9.
C26H34O4Br2 requires C, 54.75; H, 6.0%).
Crystallographic analyses of cyclophanes
Intensity data were recorded on a Rigaku AFC5R or a
RASA7R diffractometer with graphite-monochromated Mo-
Kα radiation and a 12 kW rotating anode generator. Data were
corrected for Lorenz polarization and absorption effects. The
structure was solved by the Patterson method or direct
methods.12 The non-hydrogen atoms were refined anisotropic-
ally. Neutral atom-scattering factors were taken from Crom-
mer and Waber.13 Anomalous dispersion effects were included
in Fc;14 the values for DfЈ and DfЉ were those of Cromer.15 All
the calculations were performed using the TEXSAN16 crystal-
lographic software package of Molecular Structure Corpor-
ation. The ORTEP17 programs were used to obtain Figs. 1–7.
Crystal data and experimental details are listed in Table 2.
Full crystallographic details, excluding structure factor tables,
have been deposited at the Cambridge Crystallographic Data
Centre (CCDC). For details of the deposition scheme, see
‘Instructions for Authors’, J. Chem. Soc., Perkin Trans. 1,
available via the RSC Web pages (http://chemistry.rsc.org/
authors). Any request to the CCDC for this material should
quote the full literature citation and the reference number
207/166.
16,32-Dibromo-2,9,18,25-tetraoxa[10.10]metacyclophane 3c
Yield 26.8%, colourless crystals; mp 123–125 ЊC; δH(CDCl3)
1.35–1.55 (m, 8H), 1.63–1.67 (m, 8H) 3.52 (t, 8H, J 6.1), 4.55 (s,
8H, benzyl), 7.10 (t, 2H, J 7.5) and 7.31 (d, 4H, J 7.32);
δC(CDCl3) 25.5, 29.3, 70.1, 72.2, 122.9, 126.9, 127.8 and 138.1;
m/z (CI) 601 (Mϩ ϩ 5, 5%), 599 (Mϩ ϩ 3, 8), 597 (Mϩ ϩ 1, 5),
519 (12), 481 (28), 367 (21), 299 (20), 185 (94), 183 (100) and 104
(46); νmax(KBr)/cmϪ1 2900, 2856, 1352, 1126 and 780 (Found: C,
56.2; H, 6.5. C28H38O4Br2 requires C, 56.2; H, 6.4%).
18,36-Dibromo-2,11,20,29-tetraoxa[12.12]metacyclophane 3d
Yield from 4 was 10.6%, colourless crystals; mp 114–115 ЊC;
δH(CDCl3) 1.34–1.40 (m, 16H), 1.58–1.65 (t, 8H, J 6.26), 4.57 (s,
8H, benzyl), 7.24–7.29 (m, 2H) and 7.38 (d, 4H, J 7.94);
δC(CDCl3) 25.8, 28.9, 29.5, 70.5, 72.2, 122.6, 127.0, 127.6 and
138.2; m/z (CI) 657 (Mϩ ϩ 5, 3%), 655 (Mϩ ϩ 3, 5), 653
(Mϩ ϩ 1, 3), 573 (6), 509 (8), 367 (23), 327 (16), 185 (100) and
183 (98); νmax(KBr)/cmϪ1 2932, 2908, 2860, 1472, 1394, 1350,
1132 and 774 (Found: C, 58.6; H, 7.2. C32H46O4Br2 requires C,
58.7; H, 7.1%).
Details of calculations
Molecular mechanics and molecular dynamics calculations
were performed using the Chem3D Plus software package on a
Macintosh.6 Semi-empirical calculations were performed using
MOPAC ver. 6.01 on a CONVEX C3440.7 No assumptions
were made concerning the symmetry of the compounds. The
results are tabulated in Table 3. Details of the calculations are
available as supplementary material (SUPPL. NO. 57336, 92
pp.). For details of the Supplementary Publications Scheme
see ‘Instructions for Authors’, J. Chem. Soc., Perkin Trans. 1,
available via the RSC Web page (http://www.rsc.org/authors).
20,40-Dibromo-2,13,22,33-tetraoxa[14.14]metacyclophane 3e
Yield from 4 was 13.5%, colourless crystals; mp 82.5–84 ЊC;
δH(CDCl3) 1.23–1.39 (m, 24H), 1.55–1.66 (m, 8H), 3.54 (t, 8H, J
6.26), 4.56 (s, 8H), 7.28–7.34 (dd, 2H, J 6.6 and 8.5) and 7.40 (d,
4H, J 6.7); δC(CDCl3) 26.0, 28.9, 29.0, 29.5, 70.7, 72.2, 122.7,
126.7, 127.7 and 138.2; m/z (CI) 762 (Mϩ ϩ 2, 7%), 537 (10),
355 (36), 185 (87) and 105 (100); νmax(KBr)/cmϪ1 2924, 2852,
1368, 1348, 1132, 1024 and 786 (Found: C, 60.85; H, 7.7.
C36H54O4Br2 requires C, 60.4; H, 7.8%).
Acknowledgements
We thank the Ministry of Education, Science and Culture of
Japan for financial support of this work by a Grant-in-Aid for
Science and Research (No. 06640769).
22,44-Dibromo-2,15,24,37-tetraoxa[16.16]metacyclophane 3f
Yield 24.5%, colourless crystals; mp 93–94 ЊC; δH(CDCl3) 1.27–
J. Chem. Soc., Perkin Trans. 1, 1998
537

View Article Online
Table 3 Calculated energies and energy differences from the global minima for metacyclophanes 2, 3 and 9
Compound
Typea
∆AM1b/kcal molϪ1
∆MM2c/kcal molϪ1
AM1d/kcal molϪ1
MM2e/kcal molϪ1
2a
C1*
C2*
A
D
B
0.00
0.15
8.77
1.40
4.54
2.54
0.00
0.50
0.73
0.00
1.80
2.99
9.99
0.00
1.94
2.70
1.49
2.31
0.25
1.63
0.00
2.43
0.49
1.58
0.00
0.56
3.83
2.04
0.00
1.55
3.86
1.60
0.00
0.31
1.49
0.67
1.89
3.49
0.00
1.79
5.21
3.55
23.68
0.00
0.00
0.72
1.88
7.19
9.58
0.00
5.19
8.21
9.41
0.00
5.88
5.98
6.76
0.00
4.52
7.97
9.17
0.00
4.59
10.41
15.48
0.00
3.64
10.54
15.80
0.00
0.02
2.74
14.82
0.00
2.09
4.24
4.86
12.72
0.00
0.17
1.03
3.82
15.94
0.00
1.82
3.11
5.46
17.42
Ϫ121.81
Ϫ121.66
Ϫ113.04
Ϫ120.41
Ϫ117.27
Ϫ143.68
Ϫ146.22
Ϫ145.72
Ϫ145.49
Ϫ175.30
Ϫ173.50
Ϫ172.31
Ϫ165.31
Ϫ202.08
Ϫ200.14
Ϫ199.38
Ϫ200.59
Ϫ111.59
Ϫ113.65
Ϫ112.27
Ϫ113.90
Ϫ137.02
Ϫ138.96
Ϫ137.87
Ϫ139.45
Ϫ150.91
Ϫ147.65
Ϫ149.43
Ϫ151.47
Ϫ164.65
Ϫ162.34
Ϫ164.60
Ϫ166.20
Ϫ165.89
Ϫ193.26
Ϫ194.08
Ϫ192.86
Ϫ191.26
Ϫ194.75
Ϫ220.47
Ϫ217.05
Ϫ218.71
Ϫ198.58
Ϫ222.26
27.04
27.76
28.92
34.23
36.62
29.84
35.03
38.05
39.25
34.66
40.54
40.64
41.42
38.24
42.76
46.21
47.41
19.66
24.25
30.07
35.14
20.44
24.08
30.98
36.24
23.41
23.43
26.14
38.23
24.39
26.48
28.63
29.25
37.11
28.42
28.59
29.45
32.24
44.36
30.03
31.85
33.14
35.49
47.45
2b
2c
2d
9a
3a
3b
3c
C*
A
E
B
C
B
E
A
C
A
B
E
D*
B
A
C
D*
B
A
C
B
A
D
C
E*
B
D
A
C
E*
B
D
A
C
E*
B
D
A
C
3d
3e
a Conformational type as depicted in Fig. 8. The asterisks indicate the conformation type observed in the X-ray structure. b Energy above the energy
of the global minimum for each compounds calculated by AM1 method. c Energy above the energy of the global minimum for each compounds
calculated by MM2 method. d Heat of formation energies calculated by AM1. e Total energies calculated by MM2.
8 A. Bondi, J. Phys. Chem., 1964, 68, 441; L. Pauling, The Nature of the
Chemical Bond, 3rd edn. Cornell University Press, Ithaca, N. Y., 1961.
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Received 15th August 1997
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538
J. Chem. Soc., Perkin Trans. 1, 1998