418 JOURNAL OF CHEMICAL RESEARCH 2010
Table 4 The effect of solvent on yields
temperature. The reaction mixture was irradiated for 9 min at 200 W
to give compound 4. The substituted thiosemicarbazide (0.5 mmol)
and dry pyridine 0.2 mL were added directly to the mixture, which
was then irradiated continually for 3–6 min at 240 W. The solvent
was removed and the residue was diluted with ethyl acetate 20 mL and
washed with 10% NaHCO3 (10 mL×3), brine (10 mL×3), and finally
dried over anhydrous Na2SO4. The crude product was purified by
column chromatography on silica gel H with dichloromethane/ethyl
acetate as eluant. The whole progress was monitored by TLC. The
physical and spectra data of the compounds 5a–l are as follows.
5a: White solid, yield 93%, m.p. 107–108 °C; [α]2D0 + 133.4 (c 0.15,
CH2Cl2); 1H NMR (CDCl3, 400 MHz, δ ppm): 8.85 (d, J = 8.8 Hz, 1H,
ArNHCS), 8.42 (s, 1H, NH), 8.16 (d, J = 6.8 Hz, 1H, ArH), 8.02–7.96
(m, 2H, ArH), 7.89 (d, J = 8.4 Hz, 1H, ArH), 7.63–7.46 (m, 5H, ArH),
7.13–7.10 (m, 2H, ArH), 6.86 (s, 1H, CONH), 5.11 (s, 1H, 12β-H),
5.07–5.03 (m, 1H, 3β-H), 3.64 (s, 3H, COOCH3), 0.96 (s, 3H,
19-CH3), 0.87 (d, J = 6.0 Hz, 3H, 21-CH3), 0.74 (s, 3H, 18-CH3); IR
(KBr, cm-1): 3336, 2934, 2859, 1711, 1594, 1524, 1470, 1246, 1018,
777; ESI–MS m/z (%): 788.4 [(M+1)+, 100]. Anal. Calcd for
C44H54ClN3O6S: C, 67.03; H, 6.90; N, 5.33. Found: C, 66.95; H, 6.85;
N, 5.29%.
Entry
Solvent
Yield/%
Volume of solvent/mL
1
2
3
THF
CH2Cl2
CHCl3
60
93
90
20
10
10
Table 5 Synthetic comparison of molecular tweezers 5a–5l
between microwave irradiation and conventional heating
a
b
Comp. Conventional method
Microwave method tC /tMW
t/min
Yield/%
t/min
Yield/%
5a
5b
5c
5d
5e
5f
5g
5h
5i
480
540
480
540
360
480
480
300
300
480
540
480
67
80
65
70
79
81
85
79
82
78
80
76
12.0
12.0
13.0
12.0
15.0
12.0
12.0
14.0
15.0
12.0
13.0
12.0
93
92
91
92
90
90
94
92
89
92
91
92
40
45
37
45
24
40
40
21
20
40
42
40
5b: Pale yellow crystal, yield 92%, m.p. 102–103 °C; [α]2D0 +122.7
(c 0.10, CH2Cl2); 1H NMR (CDCl3, 400 MHz, δ ppm): 8.87 (d, J = 9.2
Hz, 1H, ArNHCS), 8.18 (d, J = 7.6 Hz, 1H, ArH), 8.01 (d, J = 8.4 Hz,
2H, ArH+NH), 7.89 (d, J = 8.0 Hz, 1H, ArH), 7.62–7.47 (m, 4H,
ArH), 7.21 (s, 1H, ArH), 7.00 (s, 1H, ArH), 6.88 (s, 2H, ArH), 6.75 (d,
J = 6.8 Hz, 1H, CONH), 5.11 (s, 1H, 12β-H), 5.06 (s, 1H, 3β-H), 3.75
(s, 3H, COOCH3), 3.64 (s, 3H, COOCH3), 0.97 (s, 3H, 19-CH3), 0.89
(d, J = 6.0 Hz, 3H, 21-CH3), 0.75 (s, 3H, 18-CH3); IR (KBr, cm−1):
3320, 2942, 2859, 1715, 1603, 1453, 1246, 1006, 780; ESI–MS m/z
(%): 784.4 [(M+1)+, 100]. Anal. Calcd for C45H57N3O7S: C, 68.94;
H, 7.33; N, 5.36. Found: C, 68.91; H, 7.29; N, 5.39%.
5j
5k
5l
a
TC , time of conventional heating method; TMWb, time of micro-
wave irradiation method.
5c: White solid, yield 91%, m.p. 95–96 °C; [α]2D0 +114.9 (c 0.11,
CH2Cl2); 1H NMR (CDCl3, 400 MHz, δ ppm): 8.87 (d, J = 8.4 Hz, 1H,
ArNHCS), 8.21 (d, J = 7.2 Hz, 1H, ArH), 8.01 (d, J = 8.0 Hz, 2H,
ArH+NH), 7.89 (d, J = 8.4 Hz, 1H, ArH), 7.63–7.48 (m, 4H, ArH),
7.13–7.09 (m, 1H, ArH), 6.96–6.92 (m, 2H, ArH), 6.83–6.79 (m, 2H,
ArH+CONH), 5.12 (s, 1H, 12β-H), 5.08–5.03 (m, 1H, 3β-H), 3.78
(s, 3H, COOCH3), 3.64 (s, 3H, COOCH3), 0.97 (s, 3H, 19-CH3), 0.87
(d, J = 6.4 Hz, 3H, 21-CH3), 0.74 (s, 3H, 18-CH3); IR (KBr, cm−1):
3316, 2943, 2869, 1717, 1595, 1541, 1449, 1242, 1014, 790; ESI–MS
m/z (%): 784.5 [(M+1)+, 100]. Anal. Calcd for C45H57N3O7S: C, 68.94;
H, 7.33; N, 5.36. Found: C, 68.91; H, 7.29; N, 5.39%.
5d: White solid, yield 92%, m.p. 109–110 °C; [α]2D0 +78.4 (c 0.12,
CH2Cl2); 1H NMR (CDCl3, 400 MHz, δ ppm): 8.86 (d, J = 8.8 Hz, 1H,
ArNHCS), 8.17 (d, J = 6.8 Hz, 2H, ArH+NH), 8.01 (d, J = 8.0 Hz, 1H,
ArH), 7.89 (d, J = 8.0 Hz, 1H, ArH), 7.63–7.46 (m, 4H, ArH), 7.35–
7.26 (m, 4H, ArH), 7.19 (s, 1H, ArH), 6.87 (s, 1H, CONH), 5.11
(s, 1H, 12β-H), 5.08–5.05 (m, 1H, 3β-H), 3.64 (s, 3H, COOCH3), 0.97
(s, 3H, 19-CH3), 0.89 (d, J = 6.4 Hz, 3H, 21-CH3), 0.75 (s, 3H,
18-CH3); IR (KBr, cm-1): 3411, 2934, 2859, 1711, 1599, 1512, 1445,
1246, 1014, 786; ESI–MS m/z (%): 754.4 [(M+1)+, 100]. Anal. Calcd
for C44H54N3O6S: C, 70.09; H, 7.35; N, 5.57. Found: C, 69.95; H, 7.28;
N, 5.60%.
Fig. 1 Typical plot of 1/∆A vs the 1/[G0] for the inclusion
complexation of tweezer 5h with D -Tyr-OMe in CHCl3 at 25 °C.
reduced pressure, then mixed with the methyl 3α,12α-dihydroxy-7-
deoxy-5β-cholan-24-oate (1 mmol). The reaction mixture was irradi-
ated for 5 min at 460 W using solid K2CO3 as a support. The reaction
was monitored by TLC until it was completed. After cooling to room
temperature, the reaction mixture was extracted with ethyl acetate
(10 mL×3). The organic layer was washed successively with 10%
NaHCO3 (10 mL×3), brine (10 mL×3), and finally dried over anhy-
drous Na2SO4. The solvent was evaporated to give the crude product.
The crude product was purified by column chromatography on silica
gel H with dichloromethane/ethyl acetate as eluant. The physical and
spectra data of the compound 3 are as follows.
5e: Pale yellow crystal, yield 90%, m.p. 110–111 °C; [α]2D0 +136.3
(c 0.10, CH2Cl2); 1H NMR (CDCl3, 400 MHz, δ ppm): 8.83 (d, J = 8.4
Hz, 1H, ArNHCS), 8.12 (d, J = 7.2 Hz, 2H, ArH+NH), 7.99 (d, J = 8.0
Hz, 2H, ArH), 7.87–7.85 (m, 3H, ArH), 7.60–7.43 (m, 8H, ArH), 6.94
(s, 1H, CONH), 5.10 (s, 1H, 12β-H), 5.02 (s, 1H, 3β-H), 3.60 (s, 3H,
COOCH3), 0.96 (s, 3H, 19-CH3), 0.87 (d, J = 4.4 Hz, 3H, 21-CH3),
0.74 (s, 3H, 18-CH3); IR (KBr, cm-1): 3432, 2938, 2859, 1711, 1653,
1508, 1466, 1242, 1018, 777; ESI–MS m/z (%): 804.5 [(M+1)+, 100].
Anal. Calcd for C48H57N3O6S: C, 71.70; H, 7.15; N, 5.23. Found:
C, 71.66; H, 7.18; N, 5.20%.
3: White crystals, yield 89%, m.p. 42–43 °C; [α]2D0 +21.4 (c 0.15,
CH2Cl2); 1H NMR (CDCl3, 400 MHz, δ ppm): 8.87 (d, J = 8.4 Hz, 1H,
ArH), 8.20 (d, J = 7.2 Hz, 1H, ArH), 8.01 (d, J = 8.0 Hz, 1H, ArH),
7.88 (d, J = 8.0 Hz, 1H, ArH), 7.62–7.46 (m, 3H, ArH), 5.14–5.06
(m, 1H, 3β-H), 4.01 (s, 1H, 12β-H), 3.67 (s, 3H, COOCH3), 0.93 (d,
J = 6.8 Hz, 3H, 21-CH3), 0.89 (s, 3H, 19-CH3), 0.70 (s, 3H, 18-CH3);
IR (KBr, cm-1): 3549, 2978, 2871, 1717, 1515, 1472, 1131; ESI–MS
m/z (%): 561.4 [(M+1)+, 100]. Anal. Calcd for C36H48O5: C, 77.11;
H, 8.63; Found: C, 76.98; H, 8.57%.
5f: White solid, yield 90%, m.p. 118–119 °C; [α]2D0 + 93.7 (c 0.10,
CH2Cl2); 1H NMR (CDCl3, 400 MHz, δ ppm): 8.85 (d, J = 8.8 Hz, 1H,
ArNHCS), 8.37 (s, 1H, NH), 8.16 (d, J = 7.2 Hz, 1H, ArH), 8.01 (d,
J = 8.0 Hz, 1H, ArH), 7.89 (d, J = 8.0 Hz, 1H, ArH), 7.80 (s, 1H, ArH),
7.63–7.46 (m, 5H, ArH), 7.33–7.30 (m, 1H, ArH), 7.18–7.00 (m, 1H,
ArH), 6.79 (s, 1H, CONH), 5.11 (s, 1H, 12β-H), 5.07–5.02 (m, 1H,
3β-H), 3.64 (s, 3H, COOCH3), 0.96 (s, 3H, 19-CH3), 0.87 (d, J = 6.4
Hz, 3H, 21-CH3), 0.75 (s, 3H, 18-CH3); IR (KBr, cm-1): 3435, 2926,
2861, 1715, 1642, 1530, 1464, 1244, 1009, 781; ESI–MS m/z (%):
832.4 [(M+1)+, 100]. Anal. Calcd for C44H54BrN3O6S: C, 63.45;
H, 6.53; N, 5.05. Found: C, 63.41; H, 6.49; N, 5.01%.
Microwave method for preparation of 5a–l
Triphosgene (0.2 mmol) was added to a solution of compound 3
(0.5 mmol) in 10 mL dry CH2Cl2 and 0.1 mL dry pyridine at room