2516 J . Org. Chem., Vol. 61, No. 7, 1996
Kanamathareddy and Gutsche
140.2, 133.8, 133.0, 127.9, 123.6, 107.1, 102.0, 78.4, 75.8, 74.2,
60.1, 55.9, 34.2, 33.9, 31.6, 31.4, 31.1, 29.8. Anal. Calcd for
C108H120O12: C, 80.56; H, 7.51. Found: C, 80.43; H, 7.62.
5,11,17,23-Tetr a-ter t-bu tyl-25,27-bis[[3-(2-pr opyn yloxy)]-
ben zyl]oxy]ca lix[4]a r en e-26,28-d iol (30). The 1,3-diether
was prepared from p-tert-butylcalix[4]arene 1a and aryl
bromide 23 follwing the procedure described below for 31 and
doublets, 4), 4.79 (s, 4), 4.52 (d, 4, J ) 13.1 Hz), 3.41 (d, 4, J
) 13.1 Hz), 1.35 (s, 18), 0.88 (s, 18); 13C NMR (CDCl3) δ 163.1,
157.5, 150.7, 150.6, 146.5, 141.1, 138.6, 131.8, 127.8, 125.5,
125.0, 109.5, 78.5, 74.1, 71.1, 55.3, 33.9, 33.8, 31.7, 31.5, 30.9;
MS(FAB)14 M+ 1041.9 (calcd 1041.3). Anal. Calcd for C70
-
H72O8‚1/2CHCl3: C, 76.91; H, 6.64. Found: C, 77.37; H, 6.65.
5,11,17,23,29,35-H e x a -t er t -b u t y l-39,42-b i s [[3-(2-
p r o p y n y lo x y )b e n zy l]o x y ]c a lix [6]a r e n e -37,38,40,41-
tetr ol (34). A sample of 0.97 g (1 mmol) of 1b was dissolved
in a mixture of 40 mL of THF and 10 mL of DMF. To this
was added 0.77 g (6 mmol) of Me3SiOK at ice-bath tempera-
ture, stirring was continued for 5 min, and a solution of 0.5 g
(2.2 mmol) of 3-(2-propynyloxy)benzyl bromide (23) in 2 mL
of THF was introduced. The reaction mixture was stirred at
rt for 8 h, THF was removed under vacuum, cold water was
added, and the mixture was acidified with dilute HCl. The
precipitate was collected by suction filtration, dried, and
triturated with MeOH to give 1.0 g (76%) of 34 as a white
powder. Recrystallization from CHCl3-MeOH yielded an
1
was obtained in 90% yield: mp 147-48 °C; H NMR (CDCl3)
δ 7.36 (s, 2, D2O exchange), 7.29-7.22 (m, 6), 7.04 (s, 4), 6.95
(bd, 2), 6.79 (s, 4), 5.04 (s, 4), 4.53 (d, 4, J ) 2.4 Hz), 4.27 (d,
4, J ) 13.1 Hz), 3.26 (d, 4, J ) 13.1 Hz), 2.42 (t, 2, J ) 2.4
Hz), 1.28 (s, 18), 0.95 (s, 18); 13C NMR (CDCl3) δ 157.8, 150.7,
149.6, 147.0, 141.4, 138.6, 132.6, 129.6, 127.7, 125.5, 124.9,
120.3, 115.1, 113.1, 78.7, 77.8, 75.3, 55.6, 33.9, 33.8, 31.7, 31.6,
30.9. Anal. Calcd for C64H72O6: C, 82.02; H, 7.74. Found:
C, 82.27; H, 7.90.
5 ,1 1 ,1 7 ,2 3 -T e t r a -t e r t -b u t y l -2 5 ,2 7 -b i s [[3 ,5 -b i s (2 -
p r op yn yloxy)ben zyl]oxy]ca lix[4]a r en e-26,28-d iol (31). A
mixture of 1.3 g (2 mmol) of p-tert-butylcalix[4]arene (1a ), 1.1
g (8 mmol) of K2CO3, and 1.4 g (4.5 mmol) of arylmethyl
bromide 25 in 30 mL of acetone was stirred at 70 °C for 6 h.
Acetone was removed under vacuum, cold water (100 mL) was
added to the reaction flask, and the contents were acidified
with dilute HCl. The product was extracted into CH2Cl2 (3 ×
25 mL), and the combined organic layer was washed with
water and brine and dried over Na2SO4. The solvent was
removed under vacuum, and the residue was crystallized from
hexane-CH2Cl2 to give 1.88 g (90%) of 1,3-diether 31 in the
cone conformation as a white powder: mp 174-75 °C; 1H NMR
(CDCl3) δ 7.33 (s, 2, exchanged with D2O), 7.05 (s, 4), 6.98 (d,
4, J ) 2.2 Hz), 6.81 (s, 4), 6.58 (t, 2, J ) 2.2 Hz), 5.01 (s, 4),
4.50 (d, 8, J ) 2.3 Hz), 4.28 (d, 4, J ) 13.0 Hz), 3.29 (d, 4, 13.0
Hz), 2.44 (t, 4, J ) 2.3 Hz), 1.28 (s, 18), 0.95 (s, 18); 13C NMR-
(CDCl3) δ 158.9, 150.7, 149.4, 147.2, 141.6, 139.4, 132.6, 127.8,
125.6, 125.0, 106.2, 102.3, 78.6, 77.8, 75.4, 55.8, 33.9, 33.8, 31.7,
31.6, 31.0. Anal. Calcd for C70H76O8: C, 80.43; H, 7.33.
Found: C, 80.68; H, 7.21.
1
analytical sample: mp 216-217 °C; H NMR (CDCl3) δ 7.87
and 7.84 (s, 2), 7.32-6.74 (m), 5.07 and 4.94 (s, 2), 4.65 and
4.47 (d, 2, J ) 2.1 Hz), 4.28, 3.84, 3.62 and 3.52 (d, 4, J ) 15.0
Hz), 4.05 (d, J ) 15.0 Hz), 3.74 (s), 3.68 (d, J ) 15.0 Hz), 2.47
and 2.18 (t, 2, J ) 2.1 Hz), 1.24, 1.23, 1.17 and 1.00 (4s); 13C
NMR (CDCl3) δ 157.7 and 157.5 (2s), 150.2-112.9 (30 lines),
78.5 and 78.2 (2 lines), 75.7 and 75.6 (2 lines), 55.9 and 55.7
(2 lines), 34.3-31.1 (11 lines). Anal. Calcd for C86H100O8: C,
81.87; H, 7.99. Found: C, 81.99; H, 8.05.
5,11,17,23,29,35-H e x a -t er t -b u t y l-39,42-b i s [[4-(2-
p r o p y n y lo x y )b e n zy l]o x y ]c a lix [6]a r e n e -37,38,40,41-
t et r ol (35) was prepared using 24 following the procedure
described above for 34 and was obtained as a white powder in
70% yield: mp 214-215 °C; 1H NMR (CDCl3) δ 7.95 (s, 4, OH),
7.42 (d, 4, J ) 8.6 Hz), 7.07 (d, 4, J ) 2.3 Hz), 7.05 (d, 4, J )
2.3 Hz), 6.97 (d, 4, J ) 8.6 Hz), 6.86 (s, 4), 5.04 (s, 4), 4.65 (d,
4, J ) 2.4 Hz), 4.25 (d, 4, J ) 14.6 Hz), 3.80 (d, 2, J ) 14.2
Hz), 3.66 (d, 2, J ) 14.2 Hz), 3.52 (d, 4, J ) 14.6 Hz), 2.50 (t,
2, J ) 2.4 Hz), 1.24 (s, 36), 1.01 (s, 18); 13C NMR (CDCl3) δ
157.6, 150.2, 149.7, 147.4, 142.3, 132.2, 129.7, 129.3, 126.7,
126.1, 125.8, 125.6, 125.4, 115.0, 78.5, 75.5, 55.8, 34.1, 33.8,
32.0, 31.5, 31.1. Anal. Calcd for C86H100O8: C, 81.87; H, 7.99.
Found: C, 81.23; H, 8.01.
Br id ged com p ou n d 32 was prepared by the oxidative
coupling of 30 following the procedure described below for 33
and was obtained in 75% yield as a white powder. In this
experiment the product was isolated soon after the addition
1
was completed: mp > 260 °C dec; H NMR (CDCl3) δ 7.30-
7.24 (m, 4), 7.09 (m, 2), 7.05 (s, 4), 6.96 (bd, 2), 6.69 (s, 4), 6.62
(s, 2, exchanged with D2O), 4.93 (s, 4), 4.79 (s, 4), 4.27 (d, 4, J
) 13.2 Hz), 3.22 (d, 4, J ) 13.2 Hz), 1.31 (s, 18), 0.88 (s, 18);
13C NMR (CDCl3) δ 157.5, 150.6, 150.3, 146.6, 141.2, 138.3,
132.2, 129.3, 127.9, 125.4, 124.9, 122.7, 116.3, 115.79, 78.6,
75.25, 71.9, 56.6, 33.8, 31.7, 31.6, 30.9; MS (FAB)14 M+ 935.6
(calcd 935.3). Anal. Calcd for C64H70O6: C, 82.19; H, 7.54.
Found: C, 82.11; H, 7.57.
Br id ged Com p ou n d 36. Oxygen was bubbled through a
mixture of 125 mL of acetone and 25 mL of pyridine in a 1 L
3-necked flask for 10 min. To this was added 1.44 g (8 mmol)
of Cu(OAc)2, and the contents were heated to 65 °C (bath
temperature) with stirring. A solution of 0.50 g (0.4 mmol) of
34 in 100 mL of acetone was then added over a period of 4 h.
After the addition was completed the reaction mixture was
left at 65 °C for another 2 h while stirring continued. The
solvents were removed under vacuum, cold water (150 mL)
was added, and the contents were acidified with dilute HCl.
The pale white precipitate was removed by filtration, dried,
and chromatographed over silica gel (70-230 mesh) using CH2-
Cl2-hexane (60/40 v/v). The fractions containing the product
(as indicated by TLC) were collected and recrystallized from
Br id ged Com p ou n d 33. Oxygen was bubbled through a
mixture of 125 mL of acetone and 25 mL of pyridine in a 1 L
3-necked flask for 10 min. To this solvent mixture was added
1.44 g (8 mmol) of Cu(OAc)2, and the contents were heated to
65 °C (bath temperature) with stirring. A solution of 0.52 g
(0.5 mmol) of 31 in 100 mL of acetone was added over a period
of 4 h. After the addition was completed the reaction mixture
was maintained at 65 °C for another 12 h with continued
stirring. The solvent was removed under vacuum, cold water
(150 mL) was added, and the contents were acidified with
dilute HCl. The product was extracted into CH2Cl2 (3 × 25
mL), and the combined organic layer was washed with water
and brine and dried over Na2SO4. Removal of the solvent
under vacuum gave a dark brown residue which was chro-
matographed over silica gel (70-230 mesh) using CH2Cl2-
hexane (60/40 v/v). The fractions containing the product were
collected and recrystallized from CHCl3-MeOH to give 0.29 g
(55%) of 33 as a pale yellow powder: mp > 290 °C dec; 1H
NMR (CDCl3) δ 7.12 (s, 4), 6.82 (bs, 4), 6.71 (s, 4), 6.50 (bs, 2),
6.45 (s, 2, D2O exchange), 4.81 (q or an overlapping doublet of
1
CHCl3-MeOH to give 20-25% of 36: mp > 250 °C; H NMR
(CDCl3) δ 7.90 (s, 4, OH), 7.45 (bs, 2), 7.32 (m, 2), 7.11 (d, 4, J
) 2.5 Hz), 7.05 (d, 4, J ) 2.5 Hz), 6.99-6.90 (m, 4), 6.83 (s, 4),
5.16 (s, 4), 4.87 (s, 4), 4.30 (d, 4, J ) 15.1 Hz), 4.05 (d, 2, J )
4.30 Hz), 3.58 (d, 4, J ) 15.5 Hz), 3.54 (d, 2, J ) 14.5 Hz),
1.24 (s, 36), 0.95 (s, 18); 13C NMR (CDCl3) δ 157.8, 150.1, 149.5,
147.6, 142.4, 137.7, 132.2, 129.6, 126.6, 125.9, 125.8, 125.4,
125.2, 119.9, 116.6, 112.2, 75.6, 74.9, 71.8, 56.5, 34.1, 33.9, 31.6,
30.9; MS(FAB)14 M+ 1259.4 (calcd 1259.7). Anal. Calcd for
C86H98O8: C, 82.00; H, 7.84. Found: C, 82.09; H, 7.87.
Ack n ow led gm en t. We are indebted to the National
Science Foundation and the Robert A. Welch Founda-
tion for generous support of this research.
(14) Mass sectrum provided by the Washington University Mass
Spectrometry Resource, an NIH Research Resource (Grant P41RR0954).
J O952054A