300 JOURNAL OF CHEMICAL RESEARCH 2009
Me
Zn(Hg), HCl
5c
toluene-H2O
Me
reflux for 24 h
HOOC
10c
(60%)
Zn(Hg), HCl
5d
toluene-H2O
reflux for 24 h
Me
Me
+
O
Me
Me
O
HOOC
(38%)
11d
10d (17%)
Scheme 4
Materials
with the opposing benzene ring, therefore accelerating the
reaction like the formylation of tert-butyl[n.2]MCPs.23,24
However, only one tert-butyl group is ipso-acylated because
of deactivation of the second aromatic ring by the acyl group
introduced (intermediate B).
The preparations of 5,13-di-tert-butyl-8,16-dimethyl[2.2]metacyclo-
phane 119, and 5-tert-butyl-1,2,3-trimethylbenzene 821 have been
previously described.
Titanium tetrachloride catalysed acylation of 5,13-di-tert-butyl-8,16-
dimethyl [2.2]metacyclophane (1); typical procedure
Clemmensen reduction of 5c with Zn–Hg afforded the
desired 10c in 60% yield. In contrast, in the case of 5d the
desired product 10d was obtained only in 17% yield along with
5-tert-butyl-13-(3-oxo-1,3-dihydroisobenzofuran-1-yl)-8,16-
dimethyl[2.2]metacyclophane 11d was obtained in 38% yield.
The structure of 11d was assigned on the basis of elemental
A solution of TiCl4 (1.2 ml, 10.92 mmol) in CH2Cl2 (1 mL) at 0°C
was added to a solution of 5,13-di-tert-butyl-8,16-dimethyl[2.2]meta-
cyclophane (1) (181 mg, 0.52 mmol) and acetic anhydride (0.16 mL,
1.56 mmol) in CH2Cl2 (4 mL). After the reaction mixture was stirred
at 0°C for 2 h, it was poured into ice-water (10 mL). The organic
layer was extracted with CH2Cl2 (10 mL ¥ 2). The extract was washed
with water (5 mL), dried (Na2SO4), and concentrated. The residue
was column chromatographed over silica gel with hexane, hexane:
benzene 1:1, and benzene as eluent to give 30 mg (17%) of 7 and 144
mg (70%) of 5a, respectively.
1
analyses and spectral data. The H NMR spectrum of 11d
shows two kinds of methyl protons, each as a singlet and
the methyl protons shifted strongly up-field at d –0.26
and 0.35 ppm in comparison with those of 10d (d 0.54 and
0.58 ppm). In contrast, the cyclophane aromatic protons of 11d
are observed as four sets of doublet (J = 1.8 Hz) at much lower
fields (d 7.00, 7.02, 7.24 and 7.45 ppm) than those of 10d at
d 6.85 and 7.08 ppm as a singlet. The methine proton was
also observed at d 7.32 ppm as a singlet. The above data show
that the structure of 11d is the 8,16-dimethyl[2.2.MCP having
the isobenzofuran group at the 13-position in which benzene
ring cause one of the methyl protons to the upper field shift at
d –0.26 ppm due to the ring current effect.
5-Acetyl-13-tert-butyl-8,16-dimethyl[2.2]metacyclophane
(5a):
Colourless prisms (hexane), m.p. 157–161°C; nmax/cm-1 (KBr) 1665
(C=O); dH (CDCl3) 0.50 (3H, s, Me), 0.63 (3H, s, Me), 1.30 (9H, s,
tBu), 2.55 (3H, s, Me), 2.73–3.04 (8H, m, CH2), 7.13 (2H, s, ArH) and
7.73 (2H, s, ArH); m/z 334 (M+) (Found: C, 86.65; H, 8.98. C24H30O
(334.51) requires C, 86.18; H, 9.04%).
2,7-Di-tert-butyl-trans-10b,10c-dimethyl-10b,10c-dihydropyrene
(7): Deep green prisms (hexane), m.p. 203–204°C (lit.20 m.p. 203–
204°C).
Compound 5b was obtained by the acylation of 1 with benzoic
anhydride in the same manner described above. The yields are
compiled in Table 1.
We conclude that the ipso-acylation reactions of 1 lead
to the first-reported direct introduction of one acyl group.
The selective ipso-acylation of 1 is attributed to the highly
activated character of the aryl ring and the increased
stabilisation of s-complex intermediate.Also we have deduced
that a first s-complex intermediate, (b-phenylethyl)arenium
ion is stabilised by the through-space electronic interaction
with the other benzene ring in acylation like the electrophilic
aromatic substitution of MCPs. Further studies on ipso-
acylation and Friedel–Crafts intramolecular cyclisation of
10c and 10d to prepare 8,16-dimethyl[2.2]benzonapthaleno-
and benzoanthracenoMCPs are currently in progress in our
laboratory.
5-Benzoyl-13-tert-butyl-8,16-dimethyl[2.2]metacyclophane (5b):
Colourless prisms (hexane), m.p. 179–182°C; nmax/cm-1 (KBr) 1648
(C=O); dH (CDCl3) 0.58 (3H, s, Me), 0.67 (3H, s, Me), 1.30 (9H, s,
tBu), 2.74–3.03 (8H, m, CH2), 7.14 (2H, s, ArH), 7.45–7.78 (5H, m,
ArH) and 7.65 (2H, s, ArH); m/z 396 (M+) (Found: C, 87.74; H, 8.22.
C29H32O (396.58) requires C, 87.83; H, 8.13%).
Acylation of 1 with acid anhydrides in the presence of AlCl3-MeNO2;
typical procedure
To a solution of 1 (1.0 g, 2.87 mmol) and succinic anhydride (432 mg,
4.31 mmol) in CH2Cl2 (17 mL) was added a solution of aluminum
chloride (1.73 g, 12.9 mmol) in nitromethane (3 mL) at 0°C.
After the reaction mixture was stirred at room temperature for 2 h,
it was poured into a large amount of water. The organic layer was
extracted with diethyl ether (20 mL ¥ 3). The extract was washed
with 10% hydrochloric acid (10 mL ¥ 2) and water (10 mL ¥ 2), dried
with Na2SO4, and evaporated in vacuo. The residue was recrystallised
from benzene to afford 13-tert-butyl-5-(3-carboxylpropionyl)-8,16-
dimethyl[2.2]metacyclophane (5c) (821 mg, 73%) as colourless
prisms, m.p. 176–178°C; nmax/cm-1 (KBr) 1712, 1676 (C=O);
Experiment
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. IR spectra were
measured as KBr pellets on a Nippon Denshi JIR-AQ2OM spectrometer.
Mass spectra were obtained on a Nippon Denshi JMS-HX110Aultrahigh
performance mass spectrometer at 75 eV using a direct-inlet system.
Elemental analyses were performed by Yanaco MT-5.
d
H (CDCl3) 0.50 (3H, s, Me), 0.63 (3H, s, Me), 1.30 (9 H, s, tBu),
2.69–2.86 (6H, m, CH2), 2.90–3.07 (4H, m, CH2), 3.27–3.33 (2H, m,
CH2), 7.13 (2H, s, ArH) and 7.69 (2H, s, ArH); m/z 392 (M+) (Found:
C, 79.89; H, 8.13. C26H32O3 (392.56) requires C, 79.56; H, 8.22%).