7
768 J . Org. Chem., Vol. 65, No. 23, 2000
Potluri and Maitra
1H NMR (300 MHz, CDCl
) δ 4.354 (m, 1 H), 3.934 (s, 1
H),3.613 (s, 3 H), 2.38-1.97 (m, 2 H), 1.83-0.99 (m), 0.928 (d,
UV (λmax, log ꢀ) (5% CHCl
/CH
CN v/v) 383 (4.11), 350 (4.48),
3
3
3
300 (4.56), 282 (4.65), 243 (4.86); fluorescence (5% CHCl
CH
2951, 2868, 1736, 1700, 1597 cm ; H NMR (300 MHz, CDCl
3
/
1
3
J ) 5.7 Hz, 3 H), 0.87 (s, 1 H), 0.632 (s, 1 H); C NMR (300
MHz, CDCl ) δ 174.53, 170.53, 74.15, 72.86, 51.34, 48.09, 47.11,
6.35, 41.72, 35.85, 34.97, 34.55, 33.98, 33.47, 32.01, 30.90,
3
CN v/v) λex 355 nm, λem 390 and 408 nm; FT-IR (neat):
-1 1
3
3
4
3
1
) δ 9.154 (d, J ) 9.6 Hz, 1 H), 8.588 (d, J ) 8.1 Hz, 1 H), 8.249
(d, J ) 9.0.0 Hz, 1 H), 8.15-8.19 (m, 2 H), 8.089 (d, J ) 8.1
Hz, 1 H), 8.048 (d, J ) 9.0 Hz, 1 H), 7.987 (d, J ) 7.2 Hz, 1 H),
0.77, 28.61, 27.32, 26.83, 26.33, 25.89, 23.48, 22.98, 21.30,
7.16, 12.59.
7
1
.902 (t, J ) 7.8 Hz, 1 H), 7.815 (d, J , ) 9.3 Hz, 1 H), 7.66, (s,
H), 7.273 (dd, J ) 1.5 Hz, 10.5 Hz, 1 H), 6.695 (d, J ) 10.8
Meth yl 3r-Acetoxy-12r-(1-p yr en oyloxy)-5â-ch ola n -24-
oa te (7). To a solution of 6 (0.312 g, 0.696 mmol) in toluene
Hz, 1 H), 5.620 (s, 1 H), 4.972 (m, 1 H), 3.569 (s, 3 H), 3.097
(2 mL) were added calcium hydride (0.40 g, 9.52 mmol) and
(
h, J ) 6.9 Hz, 1 H), 2.574 (s, 3 H), 2.340 (s, 3 H), 2.31-1.12
benzyltriethylammonium chloride (0.01 g, 0.04 mmol), and the
mixture was refluxed for 5 min. To the refluxing solution was
added a solution of freshly prepared 1-pyrenoyl chloride (0.264
g, 0.10 mmol) in toluene (1 mL) and refluxed for 18 h. The
reaction mixture was filtered through a pad of Celite, and the
solvent removed in vacuo. The crude product was chromato-
graphed on silica gel (100-200 mesh, 2 cm × 20 cm) with 10%
ethyl acetate/hexanes to give the pure product in 75% yield
(
m), 1.363 (d, J ) 6.9 Hz, 6 H), 1.035 (s, 3 H), 0.976 (d, J ) 6.6
1
3
Hz, 3 H), 0.88 (s, 3 H); C NMR (75 MHz, CDCl ) δ: 174.51,
3
1
1
1
1
4
67.74, 167.04, 146.82, 142.88, 139.89, 139.78, 135.46, 135.30,
34.14, 133.93, 130.94, 130.63, 130.39, 129.86, 129.40, 129.19,
27.71, 127.10, 126.18, 126.08, 125.98, 125.14, 124.81, 124.69,
24.43, 124.23, 123.75, 117.69, 73.95, 51.39, 50.00, 47.87,
5.50, 41.90, 37.90, 35.82, 35.03, 34.99, 34.78, 34.27, 32.47,
2
4
30.99, 30.78, 27.43, 27.35, 26.91, 26.69, 26.17, 25.91, 24.60,
(
ꢀ
2
λ
355 mg): mp 112 °C; [R]
) (5% CHCl /CH CN v/v) 383 (3.85), 350 (4.46), 280 (4.47),
44 (4.74); fluorescence (5% CHCl /CH CN v/v): λex 355 nm,
em 388 and 408 nm; FT-IR (neat) 2947, 2869, 1735, 1705, 1596
D
+89 (c 1.0, CHCl
3
); UV (λmax, log
+
2
1
3.56, 23.07, 17.68, 12.63, 12.61.; FAB MS (m/z): 859 (M
, 100). Anal. Calcd for C58 : C: 81.08, H: 7.74. Found:
+
3
3
66 6
H O
3
3
C: 80.96, H: 7.78.
Extr a ction Meth od for Deter m in in g Ka Va lu es. A
solution of picric acid (2 mL, ≈5.0 mM, absorbance ) A after
diluting n fold with buffer) in 0.11 M HCl was stirred with a
solution of the host in CCl ) in a
-
1 1
cm ; H NMR (300 MHz, CDCl
3
) δ 9.198 (d, J ) 9.6 Hz, 1 H),
8
)
1
.615 (d, J ) 8.1 Hz, 1 H), 8.223-8.285 (m, 4 H), 8.189 (d, J
0
8.7 Hz, 1 H), 8.107 (d, J ) 9.0 Hz, 1 H), 8.061 (t, J ) 7.8 Hz,
H), 5.592 (s, 1 H), 4.361 (s, 1 H), 3.576 (s, 3 H), 2.33-1.03
4
(2 mL, ≈5.0 mM, H
0
1
3
thermostated bath at 26 °C. After 20 min an aliquot of the
aqueous layer was diluted n fold with phosphate buffer (pH
(
(
m), 1.759 (s, 1 H), 0.96-0.98 (m, 6 H), 0.870 (s, 3 H); C NMR
75 MHz, CDCl
3
) δ 174.49, 170.44, 167.58, 134.05, 131.04,
8
.2), and the absorbance (A) was measured at 380 nm. Another
run was made in which the solution of the host was replaced
by CCl alone and the absorbance A was measured. K
distribution coefficient) was calculated as A /(A - A ) (the
1
1
4
3
2
30.77, 130.43, 129.52, 129.36, 127.83, 127.11, 126.33, 126.23,
26.03, 124.96, 124.87, 124.82, 124.28, 124.26, 73.92, 51.38,
9.99, 47.91, 45.50, 41.74, 35.79, 34.94, 34.78, 34.14, 32.20,
0.97, 30.78, 27.35, 26.84, 26.47, 26.10, 25.81, 23.55, 23.02,
4
d
d
(
d
o
d
+
dissociation of picric acid in the aqueous solution and its
possible association in the organic solvent were ignored in the
1.22, 17.64, 12.60. LRMS: m/z M 676 (30), 246 (100).
Meth yl 3r-Hyd r oxy-12r-(1-p yr en oyloxy)-5â-ch ola n -24-
oa te (8). To a solution of 7 (0.355 g, 0.525 mmol) in MeOH/
THF (1:1, 4 mL) was added K CO (0.138 g, 0.530 mL) and
2 3
stirred for 3 h at room temperature. The reaction mixture was
quenched with acetic acid (1.5 mL), suspended in water and
extracted with ethyl acetate. The organic layer was dried over
d
determination of K ). Considering a 1:1 stoichiometry, together
with the knowledge of the ꢀ at 380 (11700) of picrate, the K
values were calculated using eq 1.
a
H + G h HG
2 4
anhyd Na SO , and volatiles were removed. The crude product
was chromatographed on silica gel (100-200 mesh) with 20%
ethyl acetate/hexanes to yield the pure product in 285 mg
Concentration of uncomplexed guest in organic layer is given
by
2
4
(
84%): mp 180-181 °C; [R]
log ꢀ) (5% CHCl /CH CN v/v): 383 (3.91), 350 (4.53), 280 (4.54),
44 (4.92). Fluorescence (5% CHCl /CH CN, v/v) λex 355 nm,
em 388 and 408 nm; FT-IR (neat) 3600-3100, 2934, 1734, 1704
D
+72° (c 1.53, CHCl
3
); UV: (λmax,
[G] ) nA/Kdꢀ
3
3
2
λ
3
3
Concentration of host-guest complex [HG] in organic layer
is given by
-
1 1
cm ; H NMR (300 MHz, CDCl
3
) δ 9.221 (d, J ) 9.6 Hz, 1 H),
8
9
1
.612 (d, J ) 8.1 Hz, 1 H), 8.29-8.23 (m, 4 H), 8.187 (d, J )
HG ) [(A - A)n/ꢀ] - [An/K ꢀ] ) n(A - A - A/K )/ꢀ
.0 Hz, 1 H), 8.107 (d, J ) 8.7 Hz, 1 H), 8.060 (t, J ) 7.8 Hz,
H), 5.574 (s, 1 H), 3.568 (s, 3 H), 3.52 (m, 1 H), 2.32-1.01
o
d
o
d
(
m), 0.973 (s, 3 H), 0.951 (d, J ) 6.6 Hz, 3 H), 0.869 (s, 3 H);
where the first term represents the total concentration of guest
in organic layer, and the second term represents the concen-
tration of free guest in organic layer.
Concentration of uncomplexed host in organic layer is given
by
1
3
C NMR (75 MHz. CDCl3) δ 174.52, 167.49, 134.16, 131.05,
1
1
4
3
2
30.95, 130.43, 129.53, 129.41, 127.80, 127.18, 126.30, 126.24,
26.13, 124.93, 124.76, 124.65, 124.39, 124.28, 71.61, 51.38,
9.98, 47.94, 45.53, 41.97, 36.30, 35.90, 35.08, 35.01, 34.78,
4.15, 30.96, 30.79, 30.64, 27.38, 27.06, 26.18, 25.87, 23.59,
3.14, 17.61, 12.62.; LRMS: m/z M+ 634 (50). HRMS: calcd
[H] ) H - [HG] ) H - n(A - A - A/K )/ꢀ
o
o
o
d
for C42
50 5
H O 634.366, found 634.365.
Meth yl 3r-(1-Gu a ia zu loyloxy)-12r-(1-p yr en oyloxy)-5â-
ch ola n -24-oa te (3). To a solution of guaiazulene (0.180 g,
a
and association constant K is defined as
0
(
.909 mmol) in toluene (0.5 mL) was added oxalyl bromide
0.300 g, 1.4 mmol) and stirred for 5 h. Excess oxalyl bromide
was pumped off, and the acid bromide dissolved in CHCl (3
mL) was added to compound 8 (0.24 g, 0.380 mmol). Pyridine
0.5 mL, 6.33 mmol)) was added, and the mixture was stirred
for 12 h. The reaction mixture was diluted with CHCl and
washed with 10% HCl. The organic layer was dried over anhyd
Na SO , and volatiles were removed. The crude product was
K ) [HG]/[H][G]
a
3
Therefore
(
K ) (A - A - A/K )/[H - n(A - A - A/K )/ꢀ]A/K (1)
a
o
d
o
o
d
d
3
1H NMR Titr a tion . For compound 1, K
determined by keeping the concentration of guest constant and
incrementing the concentration of the host. For compounds 2
a
and 3, K values were determined by keeping the concentration
of the host constant and varying the concentration of guest.
Guest at 9 mM was titrated with the host at 2.5-12.5 mM,
and the upfield shift of 1H NMR signal of the guest was
followed. The binding constant was determined from these
a
values were
2
4
chromatographed on silica gel (100-200 mesh, 2 cm × 20 cm)
with 1% ethyl acetate/hexanes to yield the pure product in 90%
2
4
yield (295 mg): mp 84-86 °C; [R]
D
3
: +124° (c 2.5, CHCl );
(34) Ksenija, K.; J ulijan, K.; Vera, C.-N.; Dusan, M. Collect. Czech.
Chem. Commun. 1996, 61, 1073.