6654 J . Org. Chem., Vol. 61, No. 19, 1996
Larsen and J ørgensen
1
(180 mL), and evaporation in vacuo to half the volumn.
5
6 in 88% yield as white needles: mp 196-197 °C; H NMR δ
crystallizes as a white microcrystalline compound in 83%
6.60 (s, 8 H), 4.45 (d, 4H, J ) 13.3 Hz), 3.84 (t, 8H, J ) 7.4
Hz), 3.14 (d, 4H, J ) 13.3 Hz), 1.90 (m, 8H), 0.99 (t, 12H, J )
7.4 Hz); 13C NMR δ 157.29, 135.82, 128.69, 122.26 (t), 77.36,
31.70, 23.94, 11.02. Anal. Calcd for C40H44D4O4: C, 80.50;
H, 7.43. Found: C, 80.51; H, 6.28.
5,11,17,23-Tetr a ca r boxy-25,26,27,28-tetr a p r op oxyca lix-
[4]a r en e (7). Hydrochloric acid (10 mL, 6 M) was added to
the reaction mixture. The white suspension was evaporated
to dryness in vacuo. The crude product was boiled with 96%
EtOH (230 mL) and filtered from insoluble material. Water
(80 mL) was added, and the solution was evaporated to half
the volumn. Cooling on ice and filtration gave 7 as a very fine
white crystalline product. Drying in vacuo at 70 °C for 5 h
1
yield: mp > 300 °C dec; H NMR δ 7.31 (s, 4H), 6.83 (s, 4H),
4.37 (d, 4H, J ) 13.8 Hz), 3.96 (t, 4H, J ) 8.0 Hz), 3.64 (t, 4H,
J ) 6.7 Hz), 3.12 (d, 4H, J ) 13.8 Hz), 2.0-1.85 (m, 8H), 1.08
(t, 6H, J ) 7.4 Hz), 0.84 (t, 6H, J ) 7.4 Hz); 13C NMR δ 171.66,
159.81, 156.84, 138.47, 133.12, 131.88, 129.80, 123.71, 115.03,
77.46, 76.96, 31.23, 23.84, 23.12, 11.14, 10.06. Anal. Calcd
for C42H46Br2O8: C, 60.15; H, 5.53; Br, 19.06. Found: C, 60.32;
H, 5.57; Br, 18.91.
5,17-D ic a r b o x y -25,26,27,28-t e t r a p r o p o x y c a lix [4]-
a r en e (10) fr om 4. The crude product was titruated with
hot 96% EtOH (50 mL) and cooled to -10 °C before filtration
to give 10 in 76% yield as a white powder. Recrystallization
from 1,4-dioxane gave an analytical sample: mp > 280 °C dec;
1H NMR δ 12.87 (s, 2H), 7.17 (d, 4H, J ) 7 Hz), 7.03 (t, 2H, J
) 7 Hz), 6.77 (s, 4H), 4.42 (d, 4H, J ) 14.0 Hz), 4.00 (t, 4H, J
) 9.0 Hz), 3.66 (t, 4H, J ) 6.0 Hz), 3.14 (d, 4H, J ) 14.0 Hz),
1.90 (m, 8H), 1.10 (t, 6H, J ) 7.0 Hz), 0.86 (t, 6H, J ) 7.0 Hz);
13C NMR δ 172.42, 160.13, 157.98, 136.95, 134.06, 130.11,
129.79, 123.58, 123.20, 77.29, 76.92, 31.31, 23.88, 23.33, 11.16,
10.15. Anal. Calcd for C44H52O9 (10 + 1/2dioxane): C, 72.90;
H, 7.23. Found: C, 72.89; H, 7.40.
5,17-Difor m yl-25,26,27,28-t et r a p r op oxyca lix[4]a r en e
(11) fr om 4. Recrystallization from MeOH gave 11 in 75%
yield as white flakes: mp 216-218 °C; 1H NMR δ 9.50 (s, 2H),
7.03 (s, 4H), 6.81-6.67 (A2B system, 6H), 4.50 (d, 4H, J ) 13.6
Hz), 3.92 (t, 4H, J ) 7.2 Hz), 3.91 (t, 4H, J ) 7.4 Hz), 3.26 (d,
4H, J ) 13.6 Hz), 2.0-1.75 (m, 8H), 1.06 (t, 6H, J ) 7.4 Hz),
1.00 (t, 6H, J ) 7.4 Hz); 13C NMR δ 192.34, 162.62, 157.25,
136.62, 135.46, 131.72, 130.52, 129.46, 123.34, 77.40, 77.19,
31.62, 24.06, 23.83, 11.05, 10.84. Anal. Calcd for C42H48O6:
C, 77.75; H, 7.46. Found: C, 77.64; H, 7.60.
25,26,27,28-Tet r a p r op oxyca lix[4]a r en e-5,17-d ib or on -
ic a cid (12) fr om 4. The crude boronic acid was suspended
in benzene (130 mL), and 1,3-propanediol (1.5 mL, 20 mmol)
was added. The mixture was refluxed until all the water had
been azeotropically removed. The slightly yellow solution was
diluted with CHCl3 (100 mL), washed with water (2 × 100 mL),
dried (Na2SO4), evaporated to dryness on a rotary evaporator,
and recrystallized from n-heptane. The white crystalline ester
was dried in vacuum at 50 °C for 3 h and gave 60% yield: mp
248-250 °C dec; 1H NMR δ 7.55 (s, 4H), 6.2-6.0 (AB2 system,
6H), 4.42 (d, 4H, J ) 13.4 Hz), 4.19 (t, 8H, J ) 5.40 Hz), 4.05
(t, 4H, J ) 8.0 Hz), 3.65 (t, 4H, J ) 6.8 Hz), 3.18 (d, 4H, J )
13.4 Hz), 2.08 (m, 4H, J ) 5.4 Hz), 2.0-1.7 (m, 8H), 1.09 (t,
6H, J ) 7.4 Hz), 0.86 (t, 6H, J ) 7.4 Hz); 13C NMR δ 161.10,
155.40, 136.78, 135.05, 133.52, 127.87, 122.40, 77.01, 76.52,
62.40, 31.34, 27.94, 23.96, 23.42, 11.24, 10.26. Anal. Calcd
for C46H58B2O8: C, 72.64; H, 7.69. Found: C, 72.75; H, 7.79.
The ester (1.80 g, 2.37 mmol) was hydrolyzed in THF/H2O
(110 mL, 80/30, 0.1 M hydrochloric acid was added until the
pH was 4) at reflux for 1 h. The mixture was cooled on ice,
and the crude boronic acid was isolated by filtration. Recrys-
tallization from acetone yielded 12 in 71% yield as white
flakes: mp 249-251 °C dec; 1H NMR δ (DMSO-d6) 7.83 (s,
4H), 7.56 (s, 4H), 6.3-6.1 (AB2 system, 6H), 4.36 (d, 4H, J )
13.1 Hz), 4.01 (t, 4H, J ) 7.7 Hz), 3.63 (t, 4H, J ) 6.5 Hz),
3.13 (d, 4H, J ) 13.1 Hz), 2.1-1.7 (m, 8H), 1.09 (t, 6H, J )
7.4 Hz), 0.89 (t, 6H, J ) 7.4 Hz); 13C NMR (DMSO-d6) δ 159.14,
154.65, 135.07, 135.02, 132.72, 127.11, 121.52, 76.64, 75.77,
30.30, 23.01, 22.54, 10.62, 9.70. Anal. Calcd for C40H50B2O8:
C, 70.60; H, 7.41. Found: C, 70.42; H, 7.50.
Gen er a l P r oced u r e for th e Syn th esis of Tetr a lith io-
tetr a p r op oxyca lix[4]a r en e a n d Its Rea ction s w ith Elec-
tr op h iles 6-8. To a stirred solution of 1 (1.00 g, 1.10 mmol)
in dry THF (50 mL) at -78 °C was added t-BuLi/pentane (7.0
mL 1.47 M, 10 mmol). The yellow solution was stirred at -78
°C for 30 min and quenched with D2O (10 equiv), CO2(g) (large
excess), or CH3SSCH3 (10 equiv). The reaction mixture was
stirred for 30 min. The workup procedure is given below.
5,11,17,23-Tetr adeu ter io-25,26,27,28-tetr apr opoxycalix-
[4]a r en e (6). The reaction mixture was poured into water
(200 mL), extracted with ether (2 × 50 mL), washed with water
(50 mL), and dried (Na2SO4), and the solvent was removed on
a rotary evaporator. Recrystallization from 96% EtOH gave
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afforded a 70.6% yield: mp > 300 °C dec; H NMR (DMSO-
d6) δ 7.32 (s, 8H), 4.37 (d, 4H, J ) 13.3 Hz), 3.90 (t, 8H, J )
7.2 Hz), 3.39 (d, 4H, J ) 13.3 Hz), 1.90 (m, 8H), 0.99 (t, 12H,
J ) 7.3 Hz); 13C NMR (DMSO-d6) δ 166.74, 159.77, 134.19,
129.58, 124.69, 76.51, 30.04, 22.72, 10.04. Anal. Calcd for C44-
H48O12: C, 68.73; H, 6.29. Found: C, 68.49; H, 6.45.
5,11,17,23-Tet r a k is(m et h ylt h io)-25,26,27,28-t et r a p r o-
p oxyca lix[4]a r en e (8). Excess CH3SSCH3 was destroyed by
adding NaBH4 (1 g, 27 mmol) and stirring at 20 °C for 30 min.
The mixture was poured into NaOH(aq) (100 mL, 1 M). The
organic phase was separated, and the water phase was
extracted with Et2O (2 × 100 mL). The combined organic
phases were washed with NaOH (100 mL 1 M), dried (Na2-
SO4), and evaporated to a yellow oil in vacuo. The oil was
titruated with MeOH (20 mL), and the crude product was
filtrated and washed with MeOH (50 mL). Recrystallization
from MeCN gave 8 in 85% yield as white crystals: mp 178-
179 °C; 1H NMR δ 6.67 (s, 8H, ArH), 4.41 (d, 4H, J ) 13.2
Hz), 3.84 (t, 8H, J ) 7.5 Hz), 3.11 (d, 4H, J ) 13.2 Hz,), 2.30
(s, 12H), 1.93 (m, 8H, J ) 7.5 Hz), 1.00 (t, 12H, J ) 7.5 Hz);
13C NMR δ 155.52, 135.95, 131.16, 128.67, 77.60, 31.61, 23.84,
18.29, 10.96. Anal. Calcd for C44H56O4S4: C, 68.00; H, 7.26.
Found: C, 68.01; H, 7.32.
Gen er a l P r oced u r e for th e Bor a n e Red u ction of th e
Ca r boxylic Acid s (13-15). The carboxylic acid (2, 5, 9) (3.78
mmol) was dissolved in dry THF (50 mL). NaBH4 (1 g, 26
mmol) was added, and the suspension was stirred at 10 °C
for 10 min. BF3‚OEt2 (5 mL, 36 mmol) was added over 5 min,
and the mixture was stirred at 10 °C for 2 h. MeOH (15 mL)
was then carefully added to destroy excess diborane. The
reaction mixture was poured into NaHCO3 (100 mL, 5%) and
extracted with CHCl3 (2 × 50 mL). The organic phase was
washed with water (50 mL) and dried (Na2SO4) and the solvent
removed on a rotary evaporator.
5,11,17-Tr ibr om o-23-(h ydr oxym eth yl)-25,26,27,28-tetr a-
p r op oxyca lix[4]a r en e (13). Recrystallization from 96%
EtOH gave 13 in 93% yield as white microcrystals: mp 224-
1
226 °C; H NMR δ 6.99 (d, 2H, J ) 2.3 Hz), 6.95 (d, 2H, J )
2.3 Hz), 6.56 (s, 2H), 6.49 (s, 2H), 4.39 (d, 2H, J ) 13.6 Hz),
4.37 (s, 2H), 4.34 (d, 2H, J ) 13.6 Hz), 3.95-3.80 (m, 4H),
3.80-3.65 (m, 4H), 3.12 (d, 2H, J ) 13.6 Hz), 3.06 (d, 2H, J )
13.6 Hz), 2.0-1.8 (m, 8H), 0.95 (t, 6H, J ) 7.4Hz), 0.93 (t, 6H,
J ) 7.4Hz); 13C NMR δ 156.80, 156.20, 155.97, 138.56, 137.69,
136.76, 135.97, 134.30, 132.11, 131.57, 131.30, 127.39, 115.51,
115.29, 77.51, 77.43, 77.23, 65.72, 31.59, 31.41, 23.96, 23.86,
23.65, 11.12, 11.05, 10.69. Anal. Calcd for C41H47Br3O5: C,
57.29; H, 5.51. Found: C, 57.41; H, 5.67.
5,17-Dib r om o-11,23-b is(h yd r oxym et h yl)-25,26,27,28-
tetr a p r op oxyca lix[4]a r en e (14). Recrystallization from
96% EtOH gave 14 in 83% yield as white crystals: mp 235-
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237 °C; H NMR δ 6.98 (s, 4H), 6.47 (s, 4H), 4.40 (d, 4H, J )
13.4 Hz), 4.28 (s, 4H), 3.92 (t, 4H, J ) 7.3 Hz), 3.73 (t, 4H, J
) 7.3 Hz), 3.11 (d, 4H, J ) 13.4 Hz), 2.0-1.7 (m, 8H), 1.03 (t,
6H, J ) 7.4 Hz), 0.94 (t, 6H, J ) 7.4 Hz); 13C NMR δ 156.55,
156.10, 138.15, 135.24, 134.11, 131.49, 127.06, 115.06, 77.52,
77.19, 65.18, 31.33, 23.70, 23.39, 10.87, 10.45. Anal. Calcd
for C42H50Br2O6: C, 62.23; H, 6.22; Br, 19.71. Found: C, 62.11;
H, 6.45; Br, 19.93.
5-Br om o-17-(h ydr oxym eth yl)-25,26,27,28-tetr apr opoxy-
ca lix[4]a r en e (15). Recrystallization from n-hexane gave 15
1
in 56% yield as white crystals: mp 205-207 °C; H NMR δ