SUPRAMOLECULAR CHEMISTRY
3
s), 3.91 (3H, s), 7.05 (1H, t, J = 7.5 Hz), 7.34 (1H, dd, J1 = 7.5
Hz, J2 = 1.6 Hz), 7.63 (1H, dd, J1 = 7.5 Hz, J2 = 1.6 Hz).
13C NMR (CDCl3) δ (ppm): 16.2, 52.3, 61.6, 123.7, 124.7,
129.3, 132.9, 135.3, 158.5, 167.1.
eluent (obtained 6.9 g, yield 74%). MS m/z (ESI): 311.1 (M
1
+ H+); H NMR: (400 MHz, CDCl3) δ (ppm): 2.41 (6H, s),
3.91 (6H, s), 7.18 (2H, t, J= 7.6 Hz), 7.40 (2H, dd, J1= 7.6 Hz,
J2= 1.2 Hz), 7.91 (2H, dd, J1= 7.6 Hz, J2= 1.2 Hz). 13C NMR
(CDCl3) δ (ppm): 16.1, 61.2, 118.0, 124.3, 128.0, 133.1,
134.7, 157.2, 163.2.
2-Methoxy-3-methylbenzhydrazide (3)
Hydrazine monohydrate (9.06 g, 181 mmol) was carefully
added to a solution of ester 2 (10.0 g, 55.5 mmol) in
100 cm3 of methanol and refluxed for 24 h under nitro-
gen. Subsequently, the mixture was cooled to room
temperature then concentrated under reduced pressure
to one-third of the initial volume, then poured under
stirring into cold water (500 cm3). The resulting white
precipitate was filtered off, washed with cold water and
dried under reduced pressure affording 3 as a white
solid (8.9 g, 89%). MS m/z (ESI): 181.1 (M + H+);
1H NMR: (400 MHz, CDCl3) δ (ppm): 2.33 (3H, s), 3.77
(3H, s), 7.13 (1H, t, J = 7.6 Hz); 7.31 (1H, dd, J1 = 7.6 Hz,
J2 = 1.5 Hz), 7.89 (1H, dd, J1 = 7.6 Hz, J2 = 1.5 Hz).
2,5-bis(3-bromomethyl-2-methoxypnenyl)-
1,3,4-oxadiazole (7)
Compound 6 (2.0 g, 6.4 mmol), N-bromosuccinimide (2.4
g 13.4 mmol), and 2,2ʹ-azobis(2-methylpropionitrile) (0.1
g, 0.6 mmol) were dissolved in 100 cm3 of CCl4 under
nitrogen. The reaction was stirred under reflux for 24
h and then cooled and filtered and the solvent removed
under reduced pressure. The crude product was washed
with methanol (5 x 25 cm3) and dried, giving 7 as a yellow
solid (1.9 g, 63%). MS m/z (ESI): 467.0 (M + H+); H NMR:
1
(400 MHz, CDCl3) δ (ppm): 4.05 (6H, s), 4.67 (4H, s), 7.30
(2H, t, J = 7.6 Hz), 7.64 (2H, dd, J1 = 7.6 Hz, J2 = 1.6 Hz), 8.06
(2H, dd, J1 = 7.6 Hz, J2 = 1.6 Hz). 13C NMR (CDCl3) δ (ppm):
26.9, 62.7, 118.3, 125.0, 130.9, 133.5, 135.0, 157.2, 163.2.
2-Methoxy-3-methylbenzoic acid (4)
15% w/w aqueous NaOH (50 cm3) was carefully added to
a refluxing solution of ester 2 (10.0 g, 55.5 mmol) in
100 cm3 of methanol. Subsequently, the mixture was
cooled to room temperature then concentrated under
reduced pressure to one-third of the initial volume,
adjusted to pH = 7 by carefull addition of 10 M HCl then
poured under stirring into cold water (500 cm3). The
resulting white precipitate was filtered off, washed with
cold water and dried under reduced pressure affording 4
as a white solid (8.3 g, yield 90%). MS m/z (ESI): 167.1 (M +
H+); 1H NMR: (400 MHz, CDCl3) δ (ppm): 2.83 (3H, s), 3.93
(3H, s), 7.18 (1H, t, J = 7.7 Hz), 7.43 (1H, br d, J= 7.7 Hz), 7.96
(1H, dd, J1= 7.7, J2 = 1.8 Hz). 13C NMR (CDCl3) δ (ppm): 16.1,
62.3, 122.1, 125.2, 130.9, 131.7, 137.1, 157.9, 166.4.
28,29-dimethoxy-8,11,14,17-tetrakis
(4-methylbenzensulfonyl)-27-oxa-8,11,14,17,25,26-
hexaazatetracyclo[22.2.1.1(2,6).1(19.23)]nonacosa-
2,4,6(28),19,21,23(29),24,26(1)-octaene (9)
Over a period of 6 h, a solution of 8 (2.7 g, 3.6 mmol) in
150 cm3 of anhydrous DMF was added to a suspension of 7
(1.7 g, 3.6 mmol) and K2CO3 (5.0 g. 36 mmol) in 250 cm3 of
anhydrous DMF, at 90°C under nitrogen. The reaction mix-
ture was maintained at 90°C for further 12 h. Subsequently,
the mixture was cooled to room temperature then concen-
trated under reduced pressure to one-third of the initial
volume, then poured under stirring into cold water (1 dm3).
The resulting white precipitate was filtered off, washed with
cold water, dried under vacuum and purified by flash-
chromatography (silica gel, chloroform) obtaining 9
as white solid (1.7 g, 44%). MS m/z (ESI): 1069.3 (M + H+);
1H NMR: (400 MHz, CDCl3) δ (ppm): 2.40 (6H, s), 2.46 (6H, s),
3.08 (4H, br t, J = 7.5 Hz), 3.26 (4H, s), 3.35 (4H, br t, J = 7.5 Hz),
3.61 (6H, s), 4.49 (4H, s) 7.19 (4H, d, J = 8.4 Hz), 7.28 (2H, t, J =
7.6 Hz), 7.36 (4H, d, J = 8.0 Hz), 7.48 (4H, d, J = 8.0 Hz), 7.60
(2H, dd, J1 = 7.6 Hz, J2 = 1.6 Hz), 7.77 (4H, d, J = 8.4 Hz), 8.05
(2H, dd, J1 = 7.6 Hz, J2 = 1.6 Hz). 13C NMR (CDCl3) δ (ppm):
21.5, 21.6, 45.7, 46.1, 47.5, 48.4, 63.2, 117.8, 125.3, 127.2,
127.3, 129.7, 129.9, 131.0, 131.7, 135.0, 136.0, 137.0, 143.6,
157.2, 164.0.
2,5-bis(2-methoxy-3-methylphenyl)-1,3,4-oxadiazole
(6)
A suspension of 4 (5 g, 30 mmol) in 150 cm3 of phos-
porus oxychloride (POCl3) was refluxed under nitrogen
until complete dissolution (about 3 h) forming the inter-
mediate acyl-chloride 5. The solution containing 5 was
freshly used without purification cooling it at 0-5°C in an
ice bath, then 3 (5.4 g, 30 mmol) was slowly added. The
resulting solution was warmed to room temperature and
stirred for 2 h, then refluxed overnight. After cooling the
yellow solution was poured in 2 dm3 of an ice/water
mixture and carefully neutralised adding solid sodium
carbonate (Na2CO3) in a small portion until the crude
product 6 precipitates. The solid sample was filtered off,
washed with cold water, collected and dried under
vacuum at 60°C. Pure product 6 was obtained by flash-
chromatografy on silica gel using chloroform (CHCl3) as
28,29-dimethoxy-27-oxa-8,11,14,17,25,26-
hexaazatetracyclo[22.2.1.1(2,6).1(19.23)]nonacosa-
2,4,6(28),19,21,23(29),24,26(1)-octaene (L)
Macrocycle 9 (1.7 g, 1.6 mmol) and phenol (3.6 g, 38.3
mmol) were dissolved in HBr/CH3COOH (33%, 40 ml). The