446
JOURNAL OF CHEMICAL RESEARCH 2009
Preparation
[3.3]metacyclophane (4b):
2,4,6-trimethylbenzene 2b (4.34 g, 20 mmol) and
of 6-tert-butyl-9.14.16.18-tetramethyl-2.11-dithia
solution of 1,3-bis(chloromethyl)-
(4.77 g,
intermediate
A, from which inter-annular
bond formation
B.
A
at and 16-positions
8
occurs to form intermediate
3
The aromatisation transformed B to C and further protonation
might generate the intermediate D, from which the 1,2-methyl
shift leads to compound 9.
20 mmol) in benzene (100 mL) was added dropwise over a period of
12 h from a Hershberg funnel with stirring under nitrogen to a solution
of potassium hydroxide (4.0 g, 71 mmol) and sodium borohydride
(1 g) in ethanol (4 I). After the addition, the reaction mixture was
concentrated and the residue was extracted with CH2CI2 (200 mL
x 2). The CH2CI2 extract was concentrated to leave the residue.
The residue was chromatographed on silica gel (Wako C-300, 400 g)
with hexane-ethylacetate, I: I v/vand 1:5 as eluents) to give anti-4b
(4.3 g, 56%) and.syn-4b (0.54 g, 7%) as a colourless solid.
From the elemental analyses and parent ion peak in the mass
spectrum, the product was inferred to be isomeric with the
starting material. Detailed structure information was obtained
from the IH NMR spectrum and the 13C NMR spectrum.
Although the methylene protons exhibited a complex pattern
between Ii 1.6 and 2.8 ppm, the olefinic proton resonance at
I-position and the aromatic proton resonance at 7-position
showed a singlet at Ii 5.66 and 6.80 ppm, respectively. On the
basis of the IH NMR spectrum two isomeric structures 2-tert-
butyl-3a,6,8-trimethyl-3,3a,4,5,9,IO-hexahydropyrene
2-tert-butyl-3b,6,8-trimethyl-3a,3b,4,5,9, 10-hexahydropyrene
(intermediate in Scheme 6) are possible. As mentioned
above, the only one olefinic proton resonance was observed
at Ii 5.66 ppm. Thus isomer 9 might be a more favourable
anti-6-tert-Butyl-9. 14. 16. 18-tetramethyl-2. 11-dithia[3. 3]metacyclo-
phane (anti-4b): Colourless prisms (hexane), m.p. 171-172°C;
OH (CDCI3) 1.08 (3H, s, CH3), 1.33 (3H, s, CH3), 1.35 (9H, s, tBu),
2.40 (6H, s, CH3), 3.59 (2H, d, J 14.5 Hz, CH2), 3.62 (2H, d,
=
J
=
13.5 Hz, CH2), 3.69 (2H, d, J = 14.5 Hz, CH2), 3.80 (2H, d
9 and
J = 13.5 Hz, CH2), 6.78 (lH, s, ArH) and 7.38 (2H, s, ArH); m/z 384
(M+) (Found: C, 74.69; H, 8.62. C24H32S2(384.64) requires C, 74.94;
H,8.39%).
.syn-6-tert-Butyl- 9.14. 16. 18-tetramethyl-2. 11-dithia[3. 3]metacyclo-
phane (syn-4b): Colourless prisms (hexane), m.p. 171-172 °C;
OH (CDCI3) 1.18 (9H, s, tBu) , 2.19 (6H, s, CH3), 2.46 (3H, s, CH3),
C
structure
for the present isomerisation
product than the
2.47 (3H, s, CH3), 3.79 (2H, d, J 15.1 Hz, CH2), 3.88 (2H, d,
=
structure C having two kinds of olefinic protons at 1- and 3-
positions.13C NMR spectrum showed two quaternary carbons
at Ii 32.01 and 35.04 ppm for tert-butyl carbon and C-3a
carbon, respectively. From the DEPT NMR technique it was
found that four kinds of methyl carbons and five kinds of
methylene carbons do exist in the compound.
J
=
15.1 Hz, CH2), 3.94 (2H, d, J = 15.1 Hz, CH2), 4.09 (2H, d,
J = 15.1 Hz, CH2), 6.29 (lH, s, ArH) and 6.88 (2H, s, ArH); m/z 384
(M+) (Found: C, 74.85; H, 8.42. C24H32S2(384.64) requires C, 74.94;
H,8.39%).
Cyc1isation reactions of 2a and 3 was carried out using the same
procedure as described above to afford anti-4a in 73% yield.
anti-6-tert-Butyl-9.14.16-trimethyl-2.11-dithia[3.3 ]metacyclophane
(anti-4a): Colourless prisms, m.p.81-82°C; OH (CDCI3) 1.24 (9H, s,
tBu), 2.12 (3H, s, CH3), 2.17 (6H, s, CH3), 3.40 (2H, d, J= 15.0 Hz,
CH2), 3.63 (2H, d, J = 15.0 Hz, CH2), 3.80 (2H, d, J = 13.7 Hz, CH2),
Conclusions
5-tert-Butyl-8, 12, 14-trimethyl-
tetramethyl[2.2]MCP are prepared using the sulfur method.
Treatment of 5-tert-butyl-8,12,14,
AICI3-MeN02
afforded 8,12,14,16-tetramethyl[2.2]MCP
and 5-tert-butyl-8, 12, 14, 16-
3.98 (2H, d J = 13.7 Hz, CH2),
broad s, ArH) 6.67 (lH, s,
ArH) and 7.11 (2H, s, ArH); oe5(.C2D9 C(lIH3), 15.02, 18.76,31.19,32.83,
16-tetramethyl[2.2]MCP
in benzene led to trans-tert-butylation
with
which
34.07,35.47,126.75,128.96,131.41,133.48,133.91,
134.84, 134.88
and 148.10; m/z 370 (M+) (Found: C, 74.69; H, 8.62. C23H3oS2
(370.62) requires C, 74.54; H, 8.16%).
in good yield along
with tert-butylbenzene.
On the other hand the same treatment
Preparation of 9-methyl-2.11-dithia[3. 3]metacyclophane 2.2.11.11-
tetraoxides (5); typical procedure
of 5-tert-butyl-8,12,14-trimethyl[2.2]MCP
led to transannular
reaction to afford
cyclisation
reaction and isomerisation
To a solution of anti-4b (3.20 g, 8.3 mmol) in CHCI3 (150 mL) was
added m-chloroperbenzoic acid (3.96 g, 19.5 mmol, 85% purity) at
o°C while stirring with a magnetic stirrer. After the solution was
stirred for 24 h at room temperature, the solvent was evaporated in
vacuo to leave the residue which was washed with 10% NaHC03
(100 mL), water (50 mL) and ethanol to afford anti-6-tert-butyl-
the corresponding
strainless
2-tert-butyl-3a,6,8-trimethyl-
3,3a,4,5,9, IO-hexahydropyrene in good yield. The present study
indicates that the substituents effect at the 16-position of the
opposite benzene ring does exist in the reaction of [2.2]MCPs
with Lewis acids. Further studies on the mechanism for the
9,14,16, 18-tetramethyl-2, II-dithia[3.3]metacyc1ophane-2,2,
II,
cycloisomerisation
of anti-6a are in progress.
ll-tetraoxide (anti-5b) as colourless prisms (3.65 g, 98%), m.p.
>300°C; OH (CDCI3) 1.20 (3H, s, CH3), 1.27 (3H, s, CH3), 1.35 (9H,
s, tBu), 2.53 (6H, s, CH3), 4.16 (2H, d, J= 14.8 Hz, CH2), 4.45 (2H,
Experiment
d, J
= 14.8 Hz, CH2), 4.49 (2H, d J = 14.2 Hz, CH2), 4.61 (2H, d,
14.2 Hz, CH2), 7.02 (lH, s, ArH) and 7.78 (2H, s, ArH);
All melting points are uncorrected. IH 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-AQ20M
J
oe=(CDCI3) 14.43, 15.87,21.10,30.95,34.52,58.92,63.56,
123.88,
125.55, 125.88, 129.04, 131.36, 136.48, 140.70, 143.52 and 148.55;
m/z 320 (M+-2S02) (Found: C, 64.39; H, 7.26. C24H32S204(448.64)
requires C, 64.25; H, 7.19%).
spectrometer. Mass spectra were obtained on
a Nippon Denshi
JMS-HXllOA Ultrahigh performance mass spectrometer at 75 eV
using a direct-inlet system. Elemental analyses were performed by
Yanaco MT-5.
Oxidation of .syn-4b and anti-4a with m-CPBA was carried out
using the same procedure as described above to afford .syn-5b and
anti-Sa in 96 and 100% yields, respectively.
syn-6-tert-Butyl-9. 14. 16. 18-tetramethyl-2. 11-dithia[3. 3]meta-
Materials
cyclophane 2,2, 11,ll-tetraoxide
(.syn-5b): Colourless prisms.
Preparation of 4-tert-butyl-2,6-bis(sulfanylmethyl)toluene
as previously described.
321-23was
m.p. 2 17-220 °C (decomp.); OH (CDCI3) 1.14 (9H, s, tBu), 2.38 (6H, s,
CH3), 2.39 (3H, s, CH3), 2.43 (3H, s, CH3), 4.26 (2H, d, J = 14.4 Hz,
CH2), 4.32 (2H, d, J = 14.4 Hz, CH2), 4.65 (2H, d, J = 15.0 Hz, CH2),
4.65 (2H, d, J = 15.0 Hz, CH2), 6.64 (lH, s, ArH) and 7.57 (2H, s,
ArH; m/z 320 (M+-2S02) (Found: C, 64.27; H, 7.16. C24H32S204
(448.64) requires C, 64.25; H, 7.19%).
Preparation of 1.3-bis(chloromethyl}-2. 4.6-trimethylbenzene (2b)
To a solution of 1,3,5-trimethylbenzene Ib (60.0 g, 0.5 mol) and
chloromethyl methyl ether (150 mL) was added zinc chloride (40 g,
0.29 mol) at room temperature. After the reaction mixture was stirred
for 10 min, it was poured into ice-water (300 mL) and extracted with
CH2CI2 (200 mL x 3). The CH2CI2 extract was washed with water
(200 mL), saturated aqueous NaCI (100 mL x 2), and dried (Na2S04)
and evaporated in vacuo to leave a colourless solid. Recrystallisation
from hexane gave compound 2b as colourless prisms (82.5 g, 76%),
m.p. 102-104°C (lit.2s 102-103°C).
anti-6-tert-Butyl-9. 14. 16-trimethyl-2. 11-dithia[3.3 ]metacyclo-
phane 2,2,1l,1l-tetraoxide
(anti-Sa): Colourless prisms, m.p.
>250°C (decomp.); OH (CDCI3) 1.34 (9H, s, tBu), 2.11 (3H, s, CH3),
2.33 (6H, s, CH3), 4.15 (2H, d, J
=
15.2 Hz, CH2), 4.24 (2H, d,
J
=
15.2 Hz, CH2), 4.40 (2H, d, J = 14.4 Hz, CH2), 4.70 (2H, d,
J
=
14.4 Hz, CH 5.08 (lH, s, ArH), 6.91 (lH, s, ArH) and 7.60
Similarly, 1,5-bis(chloromethyl)-2,4-dimethylbenzene
(2a) was
(2H, s, ArH); oe 2()CDCI3) 16.46, 19.86,31.09,34.54,58.92,62.55,
prepared in 82% yield as colourless prisms (hexane), m.p. 99°C (lit. IS
99°C) by chloromethyation of m-xylene (la) under the same reaction
conditions as described above.
124.51,128.45,129.58,
133.12, 137.13, 139.98 and 150.89; m/z 306
(M+-2S02) (Found: C, 63.53; H, 6.85. C23H30S204(434.61) requires
C, 63.56; H, 6.96%).