282 J . Org. Chem., Vol. 65, No. 2, 2000
Sasaki et al.
Diamine 19 was prepared by the same procedure as
described for the preparation of 8 in 31% yield (for the two
steps) from the above chloride. 1,3-Di-tert-butyl-4,6-bis(phthal-
imidomethyl)benzene: mp 260-262 °C; IR (KBr) 1715, 872,
753, 714 cm-1; 1H NMR (270 MHz, CDCl3) δ 1.50 (s, 18H), 4.98
(s, 4H), 6.64 (s, 1H), 7.44 (s, 1H), 7.59-7.68 (m, 8H); MS (EI)
m/z (rel intensity) 508 (M+, 12), 451 (100). Anal. Calcd for
8H), 4.54 (br s, 8H), 4.72 (br s, 8H), 6.93 (s, 4H), 7.20 (s, 2H),
7.40 (s, 2H), 7.47 (br s, 4H), 7.57 (br s, 4H); MS (FAB) m/z
1225 (M+). Anal. Calcd for C68H104N8O4S4: C, 66.63; H, 8.55;
N, 9.14. Found: C, 66.33; H, 8.60; N, 8.86.
Cyclic Recep tor 4. A solution of 1,5-diaminopentane (123
mg, 1.2 mmol) in 200 mL of CHCl3 and a solution of diisothio-
cyanate 20 (400 mg, 1.2 mmol) in 200 mL of CHCl3 were added
dropwise simultaneously to 20 mL of CHCl3 at 60 °C. The
mixture was refluxed for 4.5 h and cooled to room temperature.
The resulting solid was filtered and washed with CHCl3 to give
257 mg of pure 4 as a white solid. The filtrate was concentrated
and purified by column chromatography (silica gel, CHCl3-
MeOH 97:3) to afford 133 mg of 4 (total 390 mg, 75%): mp
268-270 °C; IR (KBr) 3247, 1559, 887, 850, 668 cm-1; 1H NMR
(300 MHz, DMSO-d6, 60 °C) δ 1.39 (s, 18H), 1.48-1.57 (m,
6H), 3.46 (br s, 4H), 4.91 (d, J ) 5.2 Hz, 4H), 7.20 (s, 1H), 7.27
(br s, 2H), 7.31 (s, 1H), 7.54 (br s, 2H); MS (FAB) m/z 435
(M+ + 1). Anal. Calcd for C23H38N4S2: C, 63.55; H, 8.81; N,
12.89. Found: C, 63.28; H, 8.81; N, 12.77.
C
32H32N2O4: C, 75.57; H, 6.34; N, 5.51. Found: C, 75.35; H,
6.44; N, 5.62. Diamine 19: mp 78-79 °C; IR (KBr) 3257, 3189,
925 cm-1; 1H NMR (400 MHz, CDCl3) δ 1.42 (s, 18H), 1.45 (s,
4H), 4.05 (s, 4H), 7.38 (s, 1H), 7.42 (s, 1H); MS (EI) m/z (rel
intensity) 248 (M+, 7), 57 (100). Hydrochloride salt of 19: mp
250 °C (dec); IR (KBr) 3435, 912 cm-1. Anal. Calcd for
C
16H28N2‚2HCl: C, 59.81; H, 9.41; N, 8.72. Found: C, 59.66;
H, 9.62; N, 8.71.
1,3-Di-ter t-b u t yl-4,6-b is(isot h iocya n a t om e t h yl)b e n -
zen e (20). Diisothiocyanate 20 was prepared by the same
procedure as described for the preparation of 9 in 93% yield
from diamine 19: mp 118-120 °C; IR (KBr) 2179, 2091, 893,
773, 668 cm-1; 1H NMR (300 MHz, CDCl3) δ 1.41 (s, 18H), 4.93
(s, 4H), 7.38 (s, 1H), 7.47 (s, 1H); MS (EI) m/z (rel intensity)
332 (M+, 20), 274 (100). Anal. Calcd for C18H24N2S2: C, 65.02;
H, 7.27; N, 8.42. Found: C, 64.89; H, 7.34; N, 8.50.
3,5-Di-ter t-bu tylp h en yl Isoth iocya n a te (23). Isothiocy-
anate 23 was prepared by the same procedure as described
for the preparation of 9 in 89% yield from 3,5-di-tert-butyl-
aniline (22): mp 78-80 °C; IR (KBr) 2151, 867, 737, 698 cm-1
;
1H NMR (300 MHz, CDCl3) δ 1.30 (s, 18H), 7.05 (d, J ) 1.6
Hz, 2H), 7.32 (t, J ) 1.6 Hz, 1H); MS (EI) m/z (rel intensity)
247 (M+, 52), 232 (100).
Or th o-Meta Typ e Recep tor 1. A solution of 19 (248 mg,
1.0 mmol) in 200 mL of CHCl3 and a solution of 9 (365 mg,
1.0 mmol) in 200 mL of CHCl3 were added dropwise simulta-
neously to 100 mL of CHCl3 at 60 °C. The mixture was refluxed
for 30 min and then the solvent was removed to dryness. The
crude product was dissolved in 100 mL of CHCl3 and passed
through a column of silica gel (CHCl3-EtOAc 9:1), and con-
centrated to leave a white solid. To this solid was added 10
mL of CHCl3 and the mixture was stirred at room temperature.
The insoluble material was filtered off and washed with a 3
mL portion of CHCl3, and the solvent was removed in vacuo
to give pure 1 (485 mg, 79%) as a white solid: mp 268-270
2-(N′-(3,5-Di-ter t-b u t ylp h en yl)t h iou r eid o)et h yl-b is(2-
isoth iocya n a toeth yl)a m in e (24). To a solution of tris(2-
aminoethyl)amine (517 mg, 3.5 mmol) in 10 mL of THF was
added dropwise a solution of isothiocyanate 23 (874 mg, 3.5
mmol) in 25 mL of THF. After stirring for 2 h, 1.82 g (8.8 mmol)
of DCC and 0.56 mL (0.35 mol) of CS2 were added, the mixture
was stirred for 26 h at room temperature, and then the solvent
was removed to dryness. The product was purified by column
chromatography (silica gel, 8:2 hexanes-EtOAc) to afford 409
mg (24%) of 24 as a white solid: mp 109-110 °C; IR (KBr)
1
°C (dec); IR (KBr) 3318, 1557, 884, 720 cm-1; H NMR (400
MHz, DMSO-d6, 60 °C) δ 0.94 (t, J ) 7.4 Hz, 6H), 1.38 (s, 18H),
1.41-1.49 (m, 4H), 1.66-1.73 (m, 4H), 4.00 (t, J ) 6.5 Hz, 4H),
4.48 (br s, 4H), 4.93 (br s, 4H), 7.04 (s+s, 3H), 7.23 (br s, 2H),
7.30 (s, 1H), 7.39 (br s, 2H); MS (FAB) m/z 613 (M+). Anal.
Calcd for C34H52N4O2S2: C, 66.63; H, 8.55; N, 9.14. Found: C,
66.69; H, 8.61; N, 9.17.
3356, 3165, 2079, 1545, 871, 709 cm-1 1H NMR (300 MHz,
;
CDCl3) δ 1.32 (s, 18H), 2.87 (t, J ) 6.0 Hz, 6H), 3.49 (t, J )
6.0 Hz, 4H), 3.69 (dt, J ) 6.0, 6.0 Hz, 2H), 6.38 (t, J ) 6.0 Hz,
1H), 7.06 (d, J ) 1.6 Hz, 2H), 7.38 (t, J ) 1.6 Hz, 1H), 7.58 (br
s, 1H); MS (CI) m/z 478 (M+ + 1). Anal. Calcd for C23H35N5S3:
C, 57.82; H, 7.38; N, 14.66. Found: C, 57.60; H, 7.30; N, 14.53.
Th e La r ia t-Typ e Recep tor 5. Cyclization reaction be-
tween diamine 19 (213 mg, 0.86 mmol) and diisothiocyanate
24 (409 mg, 0.86 mmol) was carried out as described for the
preparation of 1. The crude product was purified by column
chromatography (silica gel, CHCl3) followed by recrystalliza-
tion from hexane-CH2Cl2 to afford 340 mg (55%) of 5 as a
white solid: mp 228-230 °C; IR (KBr) 3275, 1560, 872, 709
Meta -Meta Typ e Recep tor 2. Cyclization reaction be-
tween diamine 19 (50 mg, 0.20 mmol) and diisothiocyanate
13 (73 mg, 0.20 mmol) was carried out as described for the
preparation of 1. The crude product was passed through a
column of silica gel (CHCl3-MeOH 98:2) to afford 102 mg of
a white solid. The sample (72 mg) was purified by preparative
HPLC to give 61 mg (70%) of 2 as a white solid: mp 194-196
°C; IR (KBr) 3302, 1559, 887 cm-1; 1H NMR (400 MHz, DMSO-
d6, 120 °C) δ 0.96 (t, J ) 7.4 Hz, 6H), 1.41 (s, 18H), 1.44-1.51
(m, 4H), 1.70-1.76 (m, 4H), 4.01 (t, J ) 6.3 Hz, 4H), 4.69 (br
s, 4H), 4.99 (br s, 4H), 6.56 (s, 1H), 7.02 (s, 1H), 7.32 (s, 1H),
7.35 (s, 1H), 7.49 (t, J ) 6.0 Hz, 2H), 7.57 (t, J ) 5.2 Hz, 2H);
MS (FAB) m/z 613 (M+ + 1). Anal. Calcd for C34H52N4O2S2:
C, 66.63; H, 8.55; N, 9.14. Found: C, 66.33; H, 8.51; N, 9.17.
Meta -P a r a Typ e Recep tor 3. Cyclization reaction be-
tween diamine 19 (450 mg, 1.23 mmol) and diisothiocyanate
13 (306 mg, 1.23 mmol) was carried out as described for the
preparation of 1. The product was purified by column chro-
matography (silica gel, CHCl3-AcOEt 9:1) followed by pre-
parative HPLC to afford 230 mg (31%) of 3 and 130 mg (17%)
of 21 both as white solids. 3: mp 243-245 °C; IR (KBr) 3384,
1
cm-1; H NMR (400 MHz, CDCl3, 50 °C) δ 1.15 (s, 18H), 1.37
(s, 18H), 2.69 (br s, 4H), 2.78 (br s, 2H), 3.66 (br s, 4H), 3.94
(br s, 2H), 4.90 (br s, 4H), 6.76 (br s, 5H), 7.06 (s, 1H), 7.15 (s,
1H), 7.31 (s, 2H), 7.33 (s, 1H), 8.57 (br s, 1H); MS (FAB) m/z
726 (M++1). Anal. Calcd for C39H63N7S3: C, 64.51; H, 8.74; N,
13.50. Found: C, 64.21; H, 8.81; N, 13.41.
X-r a y Cr ysta llogr a p h y. Data collection was carried out
at 20 °C on a Rigaku AFC7R diffractometer with graphite-
monochromated Mo KR radiation (λ ) 0.71069 Å). The
structure was solved by direct method (SHELXS-9726) and
refined by full-matrix least-squares techniques. The non-
hydrogen atoms were refined anisotropically. Hydrogen atoms
were included but not refined.
Cr ysta l Da ta for 3. Single crystals were obtained from a
DMSO solution. A colorless crystal with dimensions of 0.45 ×
0.30 × 0.30 mm was used for data collection. C34H52N4O2S2‚
3DMSO, fw ) 847.30, triclinic, space group P1h, a ) 14.408(1),
b ) 17.467(1), c ) 10.089(7) Å, R ) 93.08(6), â ) 108.44(5),
γ ) 92.71(6)°, V ) 2400(3) Å3, Z ) 2, Dc ) 1.173 g cm-3, µ(Mo
KR) ) 2.84 cm-1. Unique reflections (11005) were obtained,
and 5546 observed reflections (I > 2σ(I)) were used for
refinement to give R ) 0.073 and Rw ) 0.210.
1
3237, 1548, 890, 749 cm-1; H NMR (400 MHz, DMSO-d6, 30
°C) δ 0.88 (t, J ) 7.3 Hz, 6H), 1.2-1.3 (m, 4H), 1.37 (s, 18H),
1.4-1.6 (m, 4H), 3.2-3.4 (-OCH2- signals overlap with the
H2O signal), 3.71 (dt, J ) 8.7, 6.8 Hz, 2H), 4.05 (dd, J ) 15.6,
6.6 Hz, 2H), 4.36 (dd, J ) 15.6, 5.2 Hz, 2H), 4.43 (d, J ) 13.2
Hz, 2H), 4.75 (dd, J ) 13.2, 4.4 Hz, 2H), 6.31 (br s, 2H), 6.39
(s, 1H), 6.88 (s, 2H), 7.34 (s, 1H), 8.20 (br s, 2H); MS (FAB)
m/z 612 (M+). Anal. Calcd for C34H52N4O2S2: C, 66.63; H, 8.55;
N, 9.14. Found: C, 66.53; H, 8.65; N, 8.78. 21: mp 210 °C (dec);
IR (KBr) 3332, 3234, 1578, 884, 755, 729 cm-1; 1H NMR (300
MHz, DMSO-d6, 30 °C) δ 0.89 (t, J ) 7.3 Hz, 12H), 1.38 (s,
36H), 1.4-1.5 (m, 8H), 1.6-1.7 (m, 8H), 3.86 (t, J ) 6.3 Hz,
(26) Sheldrick, G. M. SHELXS-97, Program for the Refinement of
Crystal Structures, University of Go¨ttingen, Germany, 1997.