Synthesis and structures of 8-benzyl[2.2]metaparacyclophanes

Article abstract of DOI:10.3184/030823410X12795612532727

A convenient preparation of 8-benzyl[2.2]metaparacyclophanes using TiCl₄ catalysed Friedel-Crafts benzylation of arenes with 8-bromomethyl[2.2]metaparacyclophane is described. The structures of these novel 8-benzyl[2.2]metaparacyclophanes in so

Full text of DOI:10.3184/030823410X12795612532727

428 RESEARCH PAPER
AUGUST, 428–431
JOURNAL OF CHEMICAL RESEARCH 2010
Synthesis and structures of 8-benzyl[2.2]metaparacyclophanes
Bigyan Sharma, Naoki Shinoda, Shinpei Miyamoto and Takehiko Yamato*
Department of Applied Chemistry, Faculty of Science and Engineering, Saga University, Honjo-machi 1, Saga 840-8502, Japan
A convenient preparation of 8-benzyl[2.2]metaparacyclophanes using TiCl4 catalysed Friedel–Crafts benzylation of
arenes with 8-bromomethyl[2.2]metaparacyclophane is described. The structures of these novel 8-benzyl[2.2]meta-
paracyclophanes in solution are also discussed.
Keywords: cyclophanes, Friedel–Crafts benzylation, chemical shifts, ring current effect, conformation
[2.2]MPCP ([2.2]metaparacyclophane) was first prepared1 via
acid-catalysed rearrangement of [2.2]paracyclophane. Since
then, [2.2] of MPCP has been prepared by other synthetic
methods.2–9 A versatile procedure, appropriate for the synthesis
of substituted derivatives, makes use of 2,11-dithia[3.3]MPCP
as a precursor.3 The meta-bridged benzene ring of [2.2]MPCP
has been shown to undergo conformational flipping2,3,6,8,10–12
with a substantial energy barrier (ca 80 kJ mol–1), so that
elevated temperatures (about 400 K) were required for the
interconversion to be revealed on NMR time scale. A large part
of this energy barrier is believed to arise from steric destabili-
sation of the transition state in which the 8-hydrogen atom of
the meta-bridged ring impinges into the π-electron cloud of the
para-bridged one.
preparation of 8-(methyl substituted benzyl)[2.2]MPCPs using
TiCl4 catalysed Friedel-Crafts benzylation of arenes with 8-
bromomethyl[2.2]MPCP 2.
Results and discussion
The preparative route of 8-bromomethyl[2.2]MPCP 2 is shown
in Scheme 2 following our previous reported procedure.15,16
Thus bromination of 114,17–21 with N-bromosucccinimide (NBS)
in the presence of benzoyl peroxide under CCl4 reflux for 3 h
afforded the desired 8-bromomethy[2.2]MPCP 2 in 90%
yield.
The TiCl4-catalysed benzylation of various arenes with 8-
bromomethyl-5-tert-butyl[2.2]MPCP 2 was carried out under
various conditions and the results are compiled in Table 1. The
TiCl4-catalysed benzylation of benzene with compound 2 at
20 °C for 5 min led to benzylation reaction affording the
desired 8-benzyl[2.2]MCP 3a in 21% yield along with the
recovery of the starting compound 2 in 79% yield. The pro-
longed reaction time to 2 h under the same reaction conditions
above led to increase the yield of 8-benzyl[2.2]MPCP 3a to
81%.
The TiCl4-catalysed benzylation of methylarenes with com-
pound 2 at 20 °C led to a benzylation reaction within 5 min
affording the desired 8-(methyl substituted benzyl) [2.2]
MPCPs 3b–g in good yields. Methyl functions increased the
yield of the benzylation product because of its high electron-
donating ability which is similar to normal aromatic ben-
zylation.22 Thus, the yields of 3 are comparable for toluene,
o-xylene, m-xylene, p-xylene, and mesitylene, and somewhat
lower for benzene which is the same as TiCl4-catalysed ben-
zylation. The reaction is generally applicable for arenes that
normally undergo Friedel–Crafts benzylation. As shown in
Table 1, the present method provides excellent yields of diphe-
nylmethanes 3, and no concomitant trans-tert-butylation was
observed under the reaction conditions.
The amount of the catalyst used relative to 8-bromomethyl
[2.2]MPCP 2 was between 0.5 and 1.5 by molar ratio. Opti-
mum yields were obtained with 1.5 mole of catalyst, whereas
a 0.5 molar ratio gave only slightly lower yields and the pro-
longed reaction time to complete the present benzylation reac-
tion. It is difficult, however, to assess properly the selectivity
of the reactions and the exact nature of the reaction. The sub-
strate and positional selectivity of the present benzylation
reaction under the TiCl4 catalyst was found to be almost the
same as that obtained by the reaction with benzyl halides under
the TiCl4 catalyst.23
According to X-ray crystallographic studies of [2.2]MPCP,13
the deformations of benzene rings in [2.2]MPCP are similar to
those of the corresponding rings in [2.2]para- and [2.2]meta-
cyclophane, with para- and meta-bridged rings bent in a boat-
and a chair-like form, respectively. The angle between the two
aromatic planes defined by the carbon atoms, 3, 4, 6, and 7, on
one hand, and 12, 13, 15, and 16, on the other, is about 13°.
Note that the angle between the 11, 12, 16-plane and 10, 11-
bond vector (or between 13, 14, 15-plane and 1, 14-bond
vector) is even larger than the analogous angle in [2.2]para-
cyclophane. The para-briged moiety of [2.2]MPCP is thus
more strongly tilted than those of the isomeric compound. The
rotation of the methyl group (which is fixed above the para-
benzene ring) of 8-methyl[2.2]MPCP appears to be hindered,
if not blocked. However, proton resonance measurements
down to –20 °C show no rotation barrier for the molecule in
solution.14
Thus introduction of methyl substituted benzyl groups to
the 8-position of [2.2] of MPCP might increase the rotation
barrier around the [2.2]MPCP-CH2–Ar for the molecule in
solution. It is surprising that there have been no reports on the
preparation of 8-(methyl substituted benzyl)[2.2]MCPs despite
the fact that the chemical shift of the 2, 3, and 4-methyl
1
substituent provides a convenient probe for H NMR studies
of any possible conformational changes. There has been sub-
stantial interest in investigating the structures of 8-(methyl
substituted benzyl)[2.2]MPCPs. We report here the convenient
Scheme 1
* Correspondent. E-mail: yamatot@cc.saga-u.ac.jp
Scheme 2

JOURNAL OF CHEMICAL RESEARCH 2010 429
Table 1 TiCl4 catalysed benzylation of arenes with 2a
Run
ArH
Reaction
time/min
Yield/%b,c
Recovery
of 2
1
2
benzene
toluene
120
5
3a (81) [75]
3b (0.4), 3c
(92) [87]
19
7.6
3
4
5
6
o-xylene
m-xylene
p-xylene
mesitylene
5
5
5
5
3d (93) [90]
3e (95) [91]
3f (98) [92]
3g (99) [93]
7
5
2
1
a [Ar-H]:[2] = 30 : 1 [mol/mol]; [TiCl4]:[2] = 1.5 : 1 [mol/mol].
b The yields were determined by GLC. analysis.
c Isolated yields are shown in square brackets.
Table
2 Chemical shifts of the methylene protons and
Scheme 3
aromatic protons of 8-benzyl[2.2]MPCPs 3a and 8-(methyl
substituted benzyl)[2.2]MPCPs 3b–ga
The structures of 3a–g were determined on the basis of their
Substrate
δCH2
δC-4,6
δC-12,13
δC-15,16
1
elemental analyses and spectral data. The H NMR spectrum
3a
3b
3c
3d
3e
3f
H
3.57
3.47
3.44
3.49
3.34
3.43
3.55
6.77
6.79
6.74
6.75
6.70
6.68
6.79
7.05
7.11
7.06
7.07
7.01
7.00
7.16
5.80
5.82
5.78
5.79
5.73
5.72
5.79
of 3a in CDCl3 shows a singlet at δ 3.57 ppm for methylene
protons of benzyl group at 8-position which is in a strongly
shielding region of opposite para-bridged benzene.24–30 It was
2-Me
4-Me
3,4-(Me)2
2,4-(Me)2
2,5-(Me)2
2,4,6-(Me)3
1
also found that the H NMR spectrum of 3a shows a doublet
(J = 1.0 Hz) at δ 5.80 ppm for internal aromatic C-15 and C-16
protons which are in a strongly shielding region of opposite
meta-bridged benzene ring and δ 7.05 ppm for external aro-
matic C-12 and C-13 protons, respectively. The mass spectral
data for 3a (M+ = 354) strongly support 8-benzyl[2.2]MPCP
structure. Similar findings were observed in compounds
3b–g.
3g
a Determined in CDCl3 using SiMe4 as a reference.
The values of the chemical shifts of the methylene protons
and aromatic protons of 8-benzyl[2.2]MPCPs 3a and 8-(methyl
substituted benzyl)[2.2]MPCPs 3b–g are summarised in
Table 2. The chemical shifts of the methylene protons in 8-
(methyl substituted benzyl)[2.2]MPCPs 3b–3g (δ = 3.34–4.55
ppm) are in an upper field than those (δ = 3.82–4.00 ppm) in
the reference compounds 5a–5g (∆δ = 0.40–0.53 ppm). It was
also found that the chemical shifts of internal aromatic C-15
and C-16 protons (δ = 5.72–5.82 ppm) are also in the upper
field than that of p-xylene (δ = 7.04 ppm) due to being in a
strongly shielding region of opposite meta-bridged benzene
ring (∆δ = 1.22–1.32 ppm). On the other hand, the chemical
shifts of external aromatic C-12 and C-13 protons (δ = 7.00–
7.16 ppm) are almost same as that of p-xylene.
The values of the chemical shifts differences of the methyl
protons and aromatic protons of the 8-(methyl substituted
benzyl) group between [2.2]MPCPs 3 and the reference com-
pounds 5 are also summarised in Table 3. The upper field
chemical shifts are observed for the 2-methyl protons on the
8-(methyl substituted benzyl) group in 3e–3g (∆δ = 0.26–0.38
ppm)butsmallerupperfieldshiftwasobservedin3b(∆δ = 0.07
ppm). Interestingly, the aromatic proton at the 6-position of
8-(methyl substituted benzyl) group in 3b, 3e and 3f was
shifted upper field at δ 5.74–5.96 ppm (∆δ = 0.56–0.65 ppm)
The benzyl protons of the above-prepared 8-(methyl sub-
stituted benzyl)[2.2] of MPCPs 3b–g are also observed as a
1
singlet in H NMR spectra at 25 °C. The conformation of
8-(methyl substituted benzyl)[2.2]MPCPs 3b–g has been
1
evaluated by dynamic H NMR spectroscopy. However, for
instance,themethyleneprotonsof8-(2-tolylmethyl)[2.2]MPCP
3b appear each as a singlet even below –60 °C (CDCl3/CS2
1/3), and the rate of the rotation around the [2.2]MCP-CH2–Ar
of 3b is faster than the NMR time scale above this temperature.
Similar findings were obtained in other 8-(2-methyl substi-
tuted benzyl)[2.2]MPCPs 3e–g. These results indicate that
the rotation barrier around the [2.2]MPCP-CH2–Ar 3e–g are
still quite low in spite of the introduction of methyl group at
the 2-position of the 8-benzyl group.
To study the structures of 8-(methyl substituted benzyl)
[2.2]MPCPs 3b–3g in more detail by using chemical shifts, we
have attemped to prepare the corresponding reference com-
pound 5. In fact, the similar TiCl4-catalysed benzylation of
benzene and methylarenes with 2-bromomethyl-5-tert-butyl-
1,3-dimethylbenzene 4 at 20 °C for 4 h led to a benzylation
reaction within 4 h affording the desired benzylated product
5a–g in good yields.
Scheme 4

430 JOURNAL OF CHEMICAL RESEARCH 2010
Table 3 Chemical shifts of the methyl protons and aromatic
protons of 8-(methyl substituted benzyl) group in [2.2]MPCPs
3a and 3b–ga
3e–g are still quite low in spite of the introduction of methyl
group at the ortho position of the 8-benzyl group. Interestingly,
the 2-methyl protons and aromatic proton at the 6-position of
the 8-(methyl substituted benzyl) group in 3b and 3e–g are
affected by the ring current of both the aromatic ring on the
same side and that of the opposite para-benzene ring. Further
studies on the chemical properties of the 8-(methyl substituted
benzyl) of [2.2]MPCPs 3 are in progress.
Substrate
δ2-Me(∆δ)c
δ6-H(∆δ)c
δ3-H(∆δ)c
3a
3b
3c
3d
3e
3f
H
–
6.68 (0.25)
5.96 (0.56)
6.56 (0.41)
6.36 (0.45)
5.79 (0.65)
5.74 (0.59)
–
7.05 (0.09)
6.93 (0.25)b
6.86 (0.18)
6.81 (0.12)
6.54 (0.25)
6.80 (0.27)
6.61 (0.17)
2-Me
2.35 (0.07)
–
4-Me
3,4-(Me)2
2,4-(Me)2
2,5-(Me)2
2,4,6-(Me)3
–
2.07 (0.30)
1.99 (0.38)
1.82 (0.26)
Experiment
3g
All melting points are uncorrected. 1H NMR spectra were recorded at
300 MHz on a Nippon Denshi JEOL FT-300 NMR spectrometer in
deuteriochloroform with Me4Si as an internal reference. IR spectra
were measured as KBr pellets on a Nippon Denshi JIR-AQ2OM spec-
trometer. 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. G.L.C. analyses were performed by Shimadzu gas chromato-
graph, GC-14A; Silicone OV-1, 2 m; programmed temperature rise,
12 °C/min; carrier gas nitrogen, 25 mL min–1.
a Determined in CDCl3 using SiMe4 as a reference.
b The midpoint value of multiplets.
c (∆δ) = δreference–δMPCP
than those in the unsubstituted 3c and 3d (δ 6.56 and 6.36
ppm) (∆δ = 0.41 and 0.45 ppm). The much larger upfield shifts
are observed in the 8-(2-tolylmethyl)[2.2]MPCPs 3b, 3e and
3f. Thus, the chemical shifts of the aromatic proton at the 6-
position of 8-(2-tolylmethyl) [2.2]MPCPs 3b, 3e and 3f should
be strongly affected by the methyl group at the 2-position of
2-tolylmethyl group. The interaction between the methyl group
at the 2-position and opposite para-benzene ring might be
much more unfavourable for 8-(2-methylbenzyl)[2.2]MPCPs
3b, 3e and 3f. Thus, the steric repulsion of 2-methyl group for
the opposite para-benzene ring and the methylene groups at
the both bridged ethylene chains could shorten the distance
between the aromatic proton at the 6-position and the opposite
para-benzene ring as well as the distance between the methyl
group at the 2-position of 8-(2-methylbenzyl) group and
meta-benzene ring.
From these findings, it is concluded that 8-(2-methyl-
benzyl)[2.2]MPCP 3b has the conformers A and B and that
8-(2-methylbenzyl)[2.2]MPCP 3b might exist preferentially in
conformer A because of steric repulsion between the 2-methyl
group and the bridged ethylene bonds. Accordingly, the 2-
methyl protons and aromatic proton at the 6-position of 2-
methylbenzyl group in 3b are located in the region affected by
the ring current of the aromatic rings on both the same side and
the opposite aromatic rings. Although it is difficult to conclude
from the available results that the structure of di- and trimeth-
ylsubstituterd analogues 3e–g, which showed the slightly dif-
ferent chemical shifts from that of 3b, one might suppose the
increased π-density of the tolylmethyl group by introduction of
electron-donating methyl groups might lead to adopting the
different conformation arising from the interaction between
the aromatic ring of tolylmethyl group and the para-benzene
ring.
The preparation of 5-tert-butyl-8-methyl[2.2]MPCP 115 and 4-tert-
butyl-2,6-dimethylbromomethylbenzene 416,31 have been previously
described.
Bromination of 5-tert-butyl-8-methyl[2.2]metaparacyclophane (1)
with N-bromo of succinimide:After a mixture of 5-tert-butyl-8-methyl
[2.2]metaparacyclophane 1 (3.03 g, 10.88 mmol), N-bromosuccin-
imide (2.32 g, 13.06 mmol), and benzoyl peroxide (100 mg) in carbon
tetrachloride (150 mL) had been refluxed for 7 h, the precipitates
formed were filtered off. The filtrate was washed with 10% sodium
hydroxide and water. The organic layer was dried over sodium sulfate
and evaporated in vacuo to leave a colourless solid which was
recrystallised from hexane to give 8-bromomethyl-5-tert-butyl[2.2]
metaparacyclophane 2 (3.50 g, 90%) as colourless prisms; m.p. 163–
164 °C; δH (CDCl3) 1.32 (9H, s, tBu), 2.65–2.82 (6H, m, CH2), 3.16–
3.20 (2H, m, CH2), 4.23 (2H, s, CH2), 5.77 (2H, d, J = 1.2 Hz, ArH),
6.81 (2H, s, ArH) and 6.96 (2H, d, J = 1.2 Hz, ArH); m/z 356 and 358
(M+) (Found: C, 70.60; H, 7.11. C21H25Br (357.34) requires C, 70.59;
H, 7.05%).
Benzylation of benzene with 8-bromomethyl-5-tert-butyl[2.2]meta-
paracyclophane (2): TiCl4 (0.16 mL butyl[2.2]metaparacyclophane 2
(358 mg, 1.0 mmol) in benzene (2.67 mL, 30 mmol) at 0 °C. After the
reaction mixture had been stirred at room temperature for 2 h, it was
poured into ice-water and extracted with benzene. The extract was
dried over anhydrous sodium sulfate and concentrated. The residue
was subjected to silica-gel (Wako, C-300; 100 g) column chromatog-
raphy using as eluent hexane–benzene (1:1) to give 8-benzyl-5-di-
tert-butyl[2.2]metaparacyclophane 3a (266 mg, 75%) as colourless
prisms (from EtOH), m.p.136–138 °C; δH (CDCl3) 1.32 (9H, s, tBu),
2.52–2.67 (4H, m, CH2), 2.80–2.87 (2H, m, CH2), 3.15–3.23 (2H, m,
CH2), 3.57 (2H, s, Ar-CH2), 5.80 (2H, d, J = 1.0 Hz, H15,16), 6.68 (2H,
d, J = 7.4 Hz, ArH), 6.77 (2H, s, H4,6) and 6.99–7.09 (5H, m, H12,13
,
ArH); m/z 354 (M+) (Found: C, 91.21; H, 8.62. C27H30 (354.54)
requires C, 91.47; H, 8.53%).
Benzylation of arenes with 2 was carried out using the same proce-
dure as described above and product yields are compiled in Table 1.
8-(2-Methylbenzyl)-5-tert-butyl[2.2]metaparacyclophane ( 3b):
Colourless prisms (from EtOH), m.p.147–149 °C; δH (CDCl3) 1.35
(9H, s, tBu), 2.35 (3H, s, Me), 2.47–2.71 (4H, m, CH2), 3.11–3.22
(4H, m, CH2), 3.47 (2H, s, Ar-CH2), 5.82 (2H, d, J = 1.0 Hz, H15,16),
5.96 (1H, d, J = 7.5 Hz, ArH), 6.79 (2H, s, H4,6), 6.81(1H, dd, J = 7.5,
6.6 Hz, ArH), 6.92 (1H, dd, J = 7.5, 6.6 Hz, ArH), 7.03 (1H, d,
J = 7.5 Hz, ArH) and 7.11 (2H, d, J = 1.0 Hz, H12,13); m/z 368 (M+)
(Found: C, 91.11; H, 8.62. C28H32 (368.56) requires C, 91.25; H,
8.75%).
Conclusions
We have demonstrated TiCl4 catalysed Friedel–Crafts ben-
zylation of arenes with 8-bromomethyl[2.2]MPCP 2 to afford
the corresponding 8-benzyl[2.2]MPCPs 3. The rotation barrier
around the 8-(methyl substituted benzyl)[2.2]MPCP 3b and
8-(4-Methylbenzyl)-5-tert-butyl[2.2]metaparacyclophane ( 3c):
Colourless prisms (from EtOH), m.p.140–141 °C; δH (CDCl3) 1.18
(9H, s, tBu), 2.17 (3H, s, Me), 2.40–3.30 (8H, m, CH2), 3.44 (2H, s,
Ar-CH2), 5.78 (2H, d, J = 1.0 Hz, H15,16), 6.56 (2H, d, J = 8.0 Hz,
ArH), 6.74 (2H, s, H4,6), 6.86 (2H, d, J = 8.0 Hz, ArH) and 7.06 (2H,
d, J = 1.0 Hz, H12,13); m/z 368 (M+) (Found: C, 91.20; H, 8.84. C28H32
(368.56) requires C, 91.25; H, 8.75%).
8-(3,4-Dimethylbenzyl)-5-tert-butyl[2.2]metaparacyclophane (3d):
Colourless prisms (from EtOH), m.p.158–160 °C; δH (CDCl3) 1.31
Fig. 1 Structure of 8-(2-methylbenzyl)[2.2]MPCP 3b.

JOURNAL OF CHEMICAL RESEARCH 2010 431
(9H, s, tBu), 2.08 (6H, s, Me), 2.55–2.66 (4H, m, CH2), 2.81–2.88
(2H, m, CH2), 3.12–3.21 (2H, m, CH2), 3.49 (2H, s, Ar-CH2), 5.79
(2H, d, J = 1.0 Hz, H15,16), 6.36 (1H, d, J = 7.8 Hz, ArH), 6.50 (1H, s,
ArH), 6.75 (2H, s, H4,6), 6.81 (1H, d, J = 7.8 Hz, ArH) and 7.07 (2H,
d, J = 1.0 Hz, H12,13); m/z 382 (M+) (Found: C, 90.88; H, 9.05. C29H34
(382.59) requires C, 91.04; H, 8.96%).
8-(2,4-Dimethylbenzyl)-5-tert-butyl[2.2]metaparacyclophane (3e):
Colourless prisms (from EtOH), m.p.134–135 °C; δH (CDCl3) 1.26
(9H, s, tBu), 2.07 (3H, s, Me), 2.22 (3H, s, Me), 2.40–2.60 (8H, m,
CH2), 3.34 (2H, s, Ar-CH2), 5.73 (2H, d, J = 1.0 Hz, H15,16), 5.79 (1H,
d, J = 7.8 Hz, ArH), 6.54 (1H, d, J = 7.8 Hz, ArH), 6.70 (2H, s, H4,6),
6.77 (1H, s, ArH) and 7.01 (2H, d, J = 1.0 Hz, H12,13); m/z 382 (M+)
(Found: C, 90.83; H, 9.04. C29H34 (382.59) requires C, 91.04; H,
8.96%).
(4-tert-Butyl-2,6-dimethylphenyl)(2,4-dimethylphenyl)methane
(5e): Colourless needles (from EtOH), m.p.81–82 °C; δH (CDCl3)
1.33 (9H, s, tBu), 2.17 (6H, s, Me), 2.26 (3H, s, Me), 2.37 (3H, s, Me),
3.82 (2H, s, ArCH2), 6.44 (1H, d, J = 7.8 Hz, ArH), 6.79 (1H, d,
J = 7.8 Hz, ArH), 7.00 (1H, s , ArH) and 7.08 (2H, s, ArH); m/z 280
(M+) (Found: C, 90.10; H, 9.93. C21H28 (280.46) requires C, 89.94; H,
10.06%).
(4-tert-Butyl-2,6-dimethylphenyl)(2,5-dimethylphenyl)methane
(5f): Colourless needles (from EtOH), m.p. 120–122 °C; δH (CDCl3)
1.34 (9H, s, tBu), 2.14 (3H, s, Me), 2.18 (6H, s, Me), 2.37 (3H, s, Me),
3.83 (2H, s, ArCH2), 6.33 (1H, s, ArH), 6.89 (1H, d, J = 7.3 Hz, ArH),
7.07 (1H, d , J = 7.3 Hz, ArH) and 7.08 (2H, s, ArH); m/z 280 (M+)
(Found: C, 90.07; H, 10.13. C21H28 (280.49) requires C, 89.94; H,
10.06%).
(4-tert-Butyl-2,6-dimethylphenyl)(2,4,6-trimethylphenyl)methane
(5g): Colourless needles (from EtOH), m.p. 75–77 °C; δH (CDCl3)
1.28 (9H, s, tBu), 2.08 (6H, s, Me), 2.11 (6H, s, Me), 2.24 (3H, s, Me),
4.00 (2H, s, ArCH2), 6.78 (2H, s, ArH) and 6.95 (2H, s, ArH); m/z 294
(M+) (Found: C, 89.91; H,10.45. C22H30 (294.46) requires C, 89.73; H,
10.27%).
8-(2,5-Dimethylbenzyl)-5-tert-butyl[2.2]metaparacyclophane (3f):
Colourless prisms (from EtOH), m.p.109–111 °C; δH (CDCl3) 1.35
(9H, s, tBu), 1.99 (3H, s, Me), 2.28 (3H, s, Me), 2.50–2.70 (6H, m,
CH2), 3.12–3.16 (2H, m, CH2), 3.43 (2H, s, Ar-CH2), 5.72 (2H, d,
J = 1.0 Hz, H15,16), 5.74 (1H, s, ArH), 6.50 (1H, d, J = 7.5 Hz, ArH),
6.68 (2H, s, H4,6), 6.80 (1H, d, J = 7.5 Hz, ArH), and 7.00 (2H, d,
J = 1.0 Hz, H12,13); m/z 382 (M+) (Found: C, 90.89; H, 8.93. C29H34
(382.59) requires C, 91.04; H, 8.96%).
8-(2,4,6-Trimethylbenzyl)-5-tert-butyl[2.2]metaparacyclophane
(3g): Colourless prisms (from EtOH), m.p.151–153 °C; δH (CDCl3)
1.29 (9H, s, tBu), 1.82 (6H, s, Me), 2.14 (3H, s, Me), 2.41–2.57 (6H,
m, CH2), 3.13–3.55 (2H, m, CH2), 3.55 (2H, s, Ar-CH2), 5.79 (2H, d,
J = 1.0 Hz, H15,16), 6.61 (2H, s, ArH), 6.79 (2H, s, H4,6) and 7.16 (2H,
s, ArH); m/z 396 (M+) (Found: C, 90.91; H, 9.05. C30H36 (396.62)
requires C, 90.85; H, 9.15%).
Benzylation of arenes with 2-bromomethyl-5-tert-butyl-1,3-dimeth-
ylbenzene (4): TiCl4 (0.16 mL, 1.5 mmol) was added to a solution of 4
(255 mg, 1.0 mmol) in benzene (2.67 mL, 30 mmol) at 0 °C. After the
reaction mixture had been stirred at room temperature for 2 h, it was
poured into ice-water and extracted with benzene. The extract was
dried over anhydrous sodium sulfate and concentrated. The residue
was subjected to silica-gel (Wako, C-300; 100 g) column chromatog-
raphy using as eluent hexane–benzene (1:1) to give 4-tert-butyl-2,6-
dimethyldiphenylmethane 5a (192 mg, 76%) as colourless needles
(from EtOH), m.p. 43–45 °C; δH (CDCl3) 1.24 (9H, s, tBu), 2.15 (6H,
s, Me), 3.94 (2H, s, ArCH2), 6.93 (2H, d, J = 8.3 Hz, ArH), 6.99 (2H,
s, ArH), 7.07 (1H, d, J = 8.3 Hz, ArH) and 7.14 (2H, t, J = 7.8 Hz,
ArH); m/z 252 (M+) (Found: C, 90.34; H 9.53. C19H24 (252.40) requires
C, 90.42; H, 9.58%).
Benzylation of 4 with arenes was carried out using the same
procedure as described above and product yields are compiled in
Scheme 4.
(4-tert-Butyl-2,6-dimethylphenyl)(2-methylphenyl)methane (5b):
Colourless needles (from EtOH), m.p. 76–77 °C; δH (CDCl3) 1.34
(9H, s, tBu), 2.18 (6H, s, Me), 2.42 (3H, s, Me), 3.87 (2H, s, ArCH2),
6.52 (1H, d, J = 7.3 Hz, ArH), 7.00 (1H, t , J = 7.8 Hz, ArH), 7.10
(1H, d, J = 8.8 Hz,ArH), 7.09 (2H, s,ArH) and 7.18 (1H, t, J = 7.3 Hz,
ArH); m/z 266 (M+) (Found: C, 90.34; H 9.53. C20H26 (266.43) requires
C, 90.16; H, 9.84%).
(4-tert-Butyl-2,6-dimethylphenyl)(4-methylphenyl)methane (5c):
Colourless needles (from EtOH), m.p. 56–57 °C; δH (CDCl3) 1.31
(9H, s, tBu), 2.23 (6H, s, Me), 2.29 (3H, s, Me), 3.97 (2H, s, ArCH2),
6.97 (2H, d, J = 8.1 Hz, ArH), 7.04 (2H, d, J = 8.1 Hz, ArH) and 7.06
(2H, s, ArH); m/z 266 (M+) (Found: C, 90.39; H, 9.68. C20H26 (266.43)
requires C, 90.16; H, 9.84%).
(4-tert-Butyl-2,6-dimethylphenyl)(3,4-dimethylphenyl)methane
(5d): Colourless needles (from EtOH), 143 °C/ 2 torr, m.p. 38–40 °C;
δH (CDCl3) 1.31 (9H, s, tBu), 2.16 (6H, s, Me), 2.23 (6H, s, Me), 3.93
(2H, s, ArCH2), 6.69 (1H, d, J = 6.8 Hz, ArH), 6.81 (1H, s, ArH), 6.93
(1H, d, J = 6.8 Hz, ArH) and 7.05 (2H, s, ArH); m/z 280 (M+) (Found:
C, 89.79; H, 10.08. C21H28 (280.46) requires C, 89.94; H, 10.06%).
Received 18 May; accepted 25 June 2010
Paper 100142 doi: 10.3184/030823410X12795612532727
Published online: 30 August 2010
References
1
D.J. Cram., D.L. Helgeson, D. Lock and L.A. Singer, J. Am. Chem. Soc.,
1966, 88, 1324.
2
3
4
D.T. Hefelfinger and D.J. Cram, J. Am. Chem. Soc., 1971, 93, 4767.
S.A. Sherrod and R.L. da Costa, Tetrahedron Lett., 1973, 2083.
V. Boekelheide, I.D. Reingold and M. Tuttle, J. Chem. Soc., Chem.
Commun., 1973, 406.
5
6
R.H. Mitchell and V. Boekelheide, J. Am. Chem. Soc., 1974, 96, 1547.
S.A. Sherrod, R.L. da Costa, R.A. Barnes and V. Boekelheide, J. Am.
Chem. Soc., 1974, 96, 1565.
7
R.H. Mitchell, T. Otsubo and V. Boekelheide, Tetrahedron Lett., 1975,
219.
8
9
F. Vögtle, Chem. Ber., 1969, 102, 3077.
P. Neumann and F. Vögtle, Synthesis, 1973, 85.
10 D.T. Hefelfinger and D.J. Cram, J. Am. Chem. Soc., 1970, 92, 1073.
11 D.T. Hefelfinger and D.J. Cram, J. Am. Chem. Soc., 1971, 93, 4767.
12 S. Akabori, S. Hayashi, M. Mawa and K. Shiomi, Tetrahedron Lett., 1969,
3727.
13 A. Renault, C. Cohen-Addad, J. Lajzerowicz-Bonneteau, J.P. Dutasta and
M.J. Cris, Acta Crystallogr., Sect. B, 1987, 43, 480.
14 T.Yamato, J. Matsumoto, K. Tokuhisa, K. Tsuji, K. Suehiro and M. Tashiro,
J. Chem. Soc., Perkin Trans. 1, 1992, 2675.
15 M. Tashiro and T. Yamato, J. Org. Chem., 1981, 46, 1543.
16 M. Tashiro and T. Yamato, J. Org. Chem., 1981, 46, 4556.
17 M. Tashiro and T. Yamato, J. Chem. Soc., Perkin Trans. 1, 1984, 2165.
18 T. Yamato, J. Matsumoto, K. Tokuhisa, M. Shigekuni, K. Suehiro and M.
Tashiro, J. Org. Chem., 1992, 57, 6969.
19 T. Yamato, K. Tokuhisa and H. Tsuzuki, Can. J. Chem., 2000, 78, 238.
20 T. Yamato, K. Noda and H. Tsuzuki, New. J. Chem., 2001, 25, 721.
21 T. Shimizu, K. Hita,A. Paudel, J. Tanaka and T.Yamato, J. Chem. Research,
2009, 246.
22 G.A. Olah, Acc. Chem. Res., 1971, 4, 240.
23 G.A. Olah, S. Kobayashi and M. Tashiro, J. Am. Chem. Soc., 1972, 94,
7448.
24 M. Tashiro and T. Yamato, J. Org. Chem., 1983, 48, 1461.
25 M. Tashiro and T. Yamato, J. Org. Chem., 1985, 50, 2939.
26 B.H. Smith, in Bridged Aromatic Compounds, Academic Press, New York.
1964.
27 F. Vögtle and P. Neumann, Angew. Chem., 1972, 84, 75; Angew. Chem. Int.
Ed. Engl., 1972, 11, 73.
28 F. Vögtle and P. Neumann, Synthesis, 1973, 85.
29 F. Vögtle and G. Höhner, Top. Curr. Chem., 1978, 74, 1.
30 P.M. Keehn and S.M. Rosenfield, Cyclophanes, Academic Press, New
York. vol. 1, 1983.
31 M. Tashiro and T. Yamato, J. Chem. Soc., Perkin Trans. 1, 1979, 176.

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