4802 J . Org. Chem., Vol. 62, No. 14, 1997
Gibson et al.
5 -(B e n z y l o x y )-1 ,3 -p h e n y l e n e -m -p h e n y l e n e -3 2 -
cr ow n -10 (11a ). Using the procedure given for the synthesis
of 7a , except using K2CO3 instead of CsF, reaction of 6a and
1b24 gave 11a (48%), an oil. 1H NMR (CDCl3) δ (ppm): 3.70
(m, 16H), 3.83 (m, 8H), 4.03 (t, J ) 4.8 Hz, 4H), 4.06 (t, J )
4.8 Hz, 4H), 4.98 (s, 2H), 6.11 (t, J ) 2.2 Hz, 1H), 6.16 (d, J )
2.2 Hz, 2H), 6.49 (m, 3H), 7.12 (m, 1H), 7.37 (m, 5H). 13C NMR
(CDCl3) δ (ppm): 67.46, 67.42, 68.13, 69.58, 69.66, 69.99, 70.79,
94.33, 94.61, 101.62, 107.12, 127.50, 127.92, 128.52, 129.74,
136.84, 159.93, 160.46, 160.54 (19 peaks; theory 20).
(CdC), 1124 (CsOsC). 1H NMR (CDCl3) δ (ppm): 1.25 (br s,
2H), 3.7 (m, 18H), 3.83 (t, J ) 4.6 Hz, 8H), 4.06 (m, 8H), 6.36
(m, 1 H), 6.45-6.55 (m, 6H), 7.12 (t, J ) 8 Hz, 1H). MS (FAB)
m/ z (rel int): 566.4 [(M + H)+, 100%], 549.3 [(M - NH2)+,
14%]; HR FAB: calcd for C29H44NO10, (M + H)+: 566.2965,
found: 566.2958 (error 1.2 ppm).
m -P h en ylen e-p-p h en ylen e-33-cr ow n -10 (15). Using the
procedure given for the synthesis of 7a , reaction 6a and 5b
gave pure 15 (29%), an oil; lit.5f reported as an oil. 1H NMR
(CDCl3) δ (ppm): 3.69 (m, 16H), 3.82 (m, 8H), 4.03 (t, J ) 4.8
Hz, 8H), 6.45 (t, J ) 2.4 Hz, 1H), 6.50 (dd, J ) 8.4 and 2.4 Hz,
2H), 6.79 (s, 4H), 7.13 (t, J ) 8.4 Hz, 1H). 13C NMR (CDCl3)
δ (ppm): 67.44, 68.24, 69.66, 69.74, 70.79, 70.82, 101.49,
107.03, 115.68, 129.76, 153.04, 159.98 (12 peaks; theory 13).
MS (FAB) m/ z (rel int): 709.1 [(M + Na + NaI)+, 13%], 559.2
5 -( B e n z y l o x y ) -1 ,3 -p h e n y l e n e -p -p h e n y l e n e -3 3 -
cr ow n -10 (11b). Using the procedure given for the synthesis
of 7a , except using K2CO3 instead of CsF, reaction of 6b and
1b24 gave 11b (51%), an oil. 1H NMR (CDCl3) δ (ppm): 3.69
(m, 16H), 3.81 (m, 8H), 4.01 (m, 8H), 4.98 (s, 2H), 6.07 (t, J )
2.2 Hz, 1H), 6.17 (d, J ) 2.2 Hz, 2H), 6.79 (s, 4H), 7.40 (m,
5H). 13C NMR (CDCl3) δ (ppm): 67.49, 68.25, 69.60, 69.74,
70.00, 70.76, 70.80, 70.83, 94.21, 94.58, 115.68, 127.48, 127.92,
128.53, 136.84, 153.06, 160.48, 160.60 (18 peaks as required).
5-H yd r oxy-1,3-p h en ylen e-m -p h en ylen e-32-cr ow n -10
(12a ). A solution of 11a (4.20 g, 6.53 mmol) in 1:1 CHCl3/
MeOH (50 mL) was subjected to hydrogenolysis at 60 psi at
rt with 10% Pd/C (100 mg) for 48 h, filtered, and taken to
dryness under vacuum to give 12a (3.29 g, 92%), a white solid,
mp 103.1-105.0 °C. 1H NMR (CDCl3) δ (ppm): 3.69 (m, 16H),
3.77 (t, J ) 4.8 Hz, 4H), 3.84 (t, J ) 4.8 Hz, 4H), 4.02 (m, 8H),
6.02 (t, J ) 2.2 Hz, 1H), 6.10 (d, J ) 2.2 Hz, 2H), 6.46 (m,
3H), 7.10 (t, J ) 8.2 Hz, 1H). 13C NMR (CDCl3) δ (ppm): 67.22,
67.54, 69.63, 69.56, 70.60, 70.62, 70.67, 94.20, 95.57, 101.46,
107.08, 129.58, 157.99, 159.78, 160.48 (15 peaks as required).
MS (FAB) m/ z (rel int): 685.5 [(M - H + LiI)+, 71%], 553.5
[(M + H)+, 100%]. HRFAB: calcd for C28H41O11, [M + H]+:
553.2649, found 553.2663 (error 2.5 ppm). Anal. Calcd for
C28H40O11: C 60.84, H 7.30. Found: C 60.60, H 7.22.
5-H yd r oxy-1,3-p h e n yle n e -p -p h e n yle n e -33-cr ow n -10
(12b). Hydrogenolysis of 11b as above for 12a gave 12b (85%),
an oil. 1H NMR (DMSO) δ (ppm): 3.55 (m, 16H), 3.69 (m, 8H),
3.93 (t, J ) 4.4 Hz, 4H), 3.97 (t, J ) 4.4 Hz, 4H), 5.93 (s, 3H),
6.78 (s, 4H), 9.41 (s, 1H). 13C NMR (DMSO) δ (ppm): 67.01,
67.62, 68.91, 69.94, 69.99, 92.05, 94.56, 115.32, 152.46, 159.02,
160.32 (11 peaks; theory 13). MS (FAB) m/ z (rel int): 575.3
[(M + Na)+, 3%], 553.4 [(M + H)+, 100%], 460.3 [(M - C6H4O)+,
7%], 307.4 (87%), 133.0 (78%); MS (FAB, NaI) m/ z (rel int):
725.5 [(M + Na + NaI)+, 12%], 597.5 [(M - H + 2Na)+, 20%],
575.5 [(M + Na)+, 48%], 176.1 (100%); HRFAB: calcd for
C28H41O11, (M + H)+: 553.2649, found: 553.2665 (error 2.9
ppm).
5-(P h t h a lim id om et h yl)-1,3-p h en ylen e-m -p h en ylen e-
32-cr ow n -10 (13a ). A solution of 780 mg (1.2 mmol) of 10a ,
243 mg (1.31 mmol) of potassium phthalimide, and 3.5 mL of
DMF was held at 90 °C for 24 h, cooled, diluted with 50 mL of
H2O, and extracted with CHCl3. The extract was washed with
0.1 N NaOH and evaporated to give a crude oil, which was
passed through a short silica gel column with EtOAc to yield
790 mg (92%) of a colorless oil, 13a . IR (KBr) cm-1: 2778 (CH),
1769 and 1716 (CdO), 1596 (CdC), 1124 (CsOsC). 1H NMR
(CDCl3) δ (ppm): 3.69 (m, 16H), 3.81 (m, 8H), 4.04 (m, 8H),
4.73 (s, 2H), 6.3-6.6 (m, 6H), 7.09 (d of t, J ) 8, 2 Hz, 1H),
7.77 (A2B2 m, 4H). MS (FAB) m/ z (rel int): 868.2 [(M + Na
+ NaI)+, 25%], 718.3 [(M + Na)+, 68%], 550.7 [(M + H -
phthalimido)+, 6%], 325.9 (28%), 176 (100%); HR FAB: calcd
for C37H45NO12Na, (M + Na)+: 718.2839; found: 718.2850
(error 1.5 ppm).
[(M + Na)+, 100%], 132.9 (51%); HR FAB: calcd for C28H40O10
-
Na, (M + Na)+: 559.2519, found: 559.2511 (error 1.4 ppm).
5-(Hyd r oxym eth yl)-1,3-ph en ylen e-16-cr own -5 (17). Ap-
plication of the procedure described for 9a to 418,20 gave a solid
(90%), mp 82.3-83.4 °C. IR (KBr) cm-1: 3490 (OH), 2895
(CH), 1596 (CdC), 1171 (COC). 1H NMR (CDCl3) δ (ppm):
3.62 (A2B2 m, 8H), 3.78 (t, J ) 4.7 Hz, 4H), 4.28 (t, J ) 4.7
Hz, 4H), 4.57 (s, 2H), 6.54 (d, J ) 2.2 Hz, 2H), 7.02 (t, J ) 2.2
Hz, 1H). 13C NMR (CDCl3) δ (ppm): 64.79, 68.63, 70.23, 70.48,
70.61, 102.66, 108.28, 142.98, 160.22 (9 peaks; theory 9). MS
(EI) m/ z (rel int): 298.1 [(M)+, 8%], 211.1 [(M + H - 2CH2-
CH2O)+, 5%], 166.1[(M - 3CH2CH2O)+, 20%], 137.1 [(M + H
- CH2CH2O - CO)+, 30%], 140.0 [(C7H8O3)+, 41%], 69.1
(100%); HR EI, calcd for C15H22O6, (M)+: 298.1416; found:
298.1429 (error 2.4 ppm).
5-F or m yl-1,3-p h en ylen e-16-cr ow n -5 (18). To a solution
of 2.01 g (6.78 mmol) of 17 in 100 mL of DCM was added 1.72
g (7.98 mmol) of PCC, and the mixture was stirred at rt for 2
h and then filtered; the inorganic solid was washed with DCM,
and the organic phases were combined and evaporated to give
the crude product. Silica gel chromatography with EtOAc gave
a light yellow oil, which was recrystallized from acetone to
afford 1.70 g (85%) of pure 18, mp 75.8-76.5 °C. 1H NMR
(CDCl3) δ (ppm): 3.58 (m, 4H), 3.66 (m, 4H), 3.81 (t, J ) 4.4
Hz, 4H), 4.34 (t, J ) 4.4 Hz, 4H), 7.03 (d, J ) 2.0 Hz, 2H),
7.39 (t, J ) 2.0 Hz, 1H) and 9.88 (s, 1H). 13C NMR (CDCl3) δ
(ppm): 68.94, 70.31, 70.674, 110.30, 110.86, 137.95, 160.75 and
191.95 (8 peaks, theory 9). MS (FAB) m/ z (rel int): 429.2 [(M
- H + LiI)+, 8%], 297.3 [(M + H)+, 100%], 253.2 [(M + H -
CH2CH2O)+, 5%], 209.2 [(M + H - 2CH2CH2O)+, 9%], 165.1
[(M + H - 3 CH2CH2O)+, 19%], 137.1 [(M + H - CH2CH2O -
CO)+, 30%]; HR FAB, calcd for C15H21O6, (M + H)+: 297.1338;
found: 297.1336 (error 0.7 ppm).
5-(Br om om eth yl)-1,3-p h en ylen e-16-cr ow n -5 (19). Ap-
plication of the procedure described for 10a to 17 gave 19
(82%), mp 77.4-78.0 °C. IR (KBr) cm-1: 2944, 2877 (CH),
1596 (CdC), 1171 (COC), 686 (CsBr). 1H NMR (CDCl3) δ
(ppm): 3.63 (A2B2 m, 8H), 3.79 (t, J ) 4.7 Hz, 4H), 4.29 (t, J
) 4.7 Hz, 4H), 4.38 (s, 2H), 6.56 (d, J ) 2.2 Hz, 2H), 7.06 (t, J
) 2.2 Hz, 1H). 13C NMR (CDCl3) δ (ppm): 33.42, 68.83, 70.36,
70.65, 70.76, 103.64, 110.72, 139.16, 160.36 (9 peaks; theory
9). MS (HR EI) m/ z (rel int): calcd for C15H2181BrO5, (M)+:
362.0552; for C15H2179BrO5, (M)+: 360.0572; found: 362.0548
(13%, error 1.6 ppm), 360.0552 (14%, error 5.8 ppm), 281.1382
[(M - Br)+, 33%, error 2.5 ppm], 149 (28%), 121 (15%), 77
(34%), 45.0 (100%).
5-(P h th a lim id om eth yl)-1,3-p h en ylen e-16-cr ow n -5 (20).
Application of the procedure described for 13a to 19 afforded
pure 20 (95%), mp 130-131 °C. IR (KBr) cm-1: 2880 (CsH),
1769, 1769, 1709 (CdO), 1609 (CdC), 1131 (COC). 1H NMR
(CDCl3) δ (ppm): 3.61 (A2B2 m, 8H), 3.76 (t, J ) 4.7 Hz, 4H),
4.26 (t, J ) 4.7 Hz, 4H), 4.74 (s, 2H), 6.56 (d, J ) 2.2 Hz, 2H),
7.01 (t, J ) 2.2 Hz, 1H), 7.77 (A2B2 m, 4H). MS (FAB, NaI)
m/ z (rel int): 600.0 [(M + Na + NaI)+, 2%], 450.1 [(M + Na)+,
100%]; HR FAB: calcd for C23H25NO7Na, (M + Na)+: 450.1529;
found: 450.1515 (error 3.1 ppm).
5-(Azid om eth yl)-1,3-p h en ylen e-16-cr ow n -5 (21). A mix-
ture of 1.43 g (3.96 mmol) of 19, 310 mg (4.77 mmol) of NaN3,
and 20 mL of DMF was heated at 60 °C for 20 h, cooled, poured
into 75 mL of H2O, and extracted with DCM (3 × 50 mL). The
extract was washed with H2O (2 × 50 mL) and saturated NaCl,
dried (Na2SO4), and evaporated to give the crude product,
5-(Am in o m e t h y l)-1,3-p h e n y le n e -m -p h e n y le n e -32-
cr ow n -10 (14a ). A solution of 410 mg (0.59 mmol) of 13a ,
0.40 mL (8.2 mmol) of hydrazine monohydrate, and 3.0 mL of
MeOH was refluxed 18 h, cooled, concentrated by rotary
evaporation, and diluted with 4.0 mL of concd HCl. The
mixture was boiled for 6 h, cooled, diluted with H2O, and
filtered. The solid was washed with H2O (2 × 5 mL). The
filtrate was neutralized with 2 N NaOH and extracted with
DCM (3 × 20 mL). After drying (Na2SO4), DCM removal and
vacuum drying produced 330 mg (100%) of a nearly colorless
oil; IR (KBr) cm-1
: 3350, 3300 (b, NH2), 2900 (CH), 1596
(24) Nagvekar, D. S.; Gibson, H. W. Org. Prep. Proced. Int. 1997,
29, 240.