Clayden et al.
under reduced pressure, and precipitation from CH2Cl2/petroleum
ether and filtration gave a white powder (1.09 g). The white powder
was dried under vacuum and dissolved in dry THF (30 mL).
Carbonyl diimidazole (CDI) (330 mg, 2.02 mmol, 0.5 equiv) was
added. The reaction mixture was stirred at 70 °C for 18 h and
evaporated under reduced pressure. CH2Cl2 was added, and the solid
was collected by filtration. The white powder was dried under
vacuum and suspended in THF (30 mL). 60% NaH in mineral oil
(646 mg, 16.2 mmol, 8 equiv) and methyl iodide (1.01 mL,
16.2 mmol, 8 equiv) were added successively, and the mixture was
stirred overnight before adding H2O (2 mL). The aqueous phase
was extracted with CH2Cl2, and the combined organic phases were
dried (MgSO4) and concentrated under reduced pressure. Flash
chromatography on silica gel (CH2Cl2/MeOH: 95:5) afforded
766 mg (55%) of urea 23 as a white powder. mp: 164 °C. IR νmax
146.5, 160.2, 161.6. MS (APCI+): 811 (MH+). HRMS for
C48H59N8O4 (MH+): calcd: 811.4667; found: 811.4654. Elem.
Anal. for C48H58N8O4: calcd: C, 71.08%; H, 7.21%; N, 13.82%;
found: C, 71.02%; H, 7.14%; N, 13.79%.
N,N′,N′′,N′′′,N′′′′,N′′′′′,N′′′′′′,N′′′′′′′,N′′′′′′′′,N′′′′′′′′′,N′′′′′′′′′′,N′′′′′′′′′′′,N′′′′′′′′′′′,
N′′′′′′′′′′′′′-Tetradecamethyl-1,3-bis[3-(3-(3-(2-isopropylphenyl-
ureyl)phenylureyl)phenylureyl)phenyl]urea 25. By the method
used for compound 10a, 3-nitrophenylisocyanate (1.05 g, 6.41
mmol, 1 equiv) and 2-isopropylaniline (1.09 mL, 7.69 mmol, 1.2
equiv) gave an intermediate aniline. Carbonyldiimidazole (151 mg,
0.930 mmol, 0.5 equiv) was used instead of phenylisocyanate,
heating the mixture for 5 h in THF at 70 °C. Methylation in THF
(30 mL) with NaH 60% in mineral oil (744 g, 18.6 mmol, 20 equiv)
and methyl iodide (1.16 mL, 18.6 mmol, 10 equiv) gave crude
material that was purified by flash chromatography on silica gel
(CH2Cl2/MeOH: 90:10) to yield urea 25 (640 mg, 15%) as a white
powder. mp: 192 °C. IR νmax cm-1: 3003, 2968, 1659, 1650, 1597,
1431, 1356, 874. 1H NMR (300 MHz, CDCl3) δ (ppm): 1.08 (12H,
d, J ) 6.9 Hz), 2.77 (2H, m), 2.78 (6H, s), 2.84 (6H, s), 2.85
(6H, s), 2.86 (12H, s), 2.89 (6H, s), 3.04 (6H, s), 5.90 (2H, t, J )
1.8 Hz), 6.00 (4H, m), 6.25-6.38 (14H, m), 6.65 (6H, m), 6.71
(2H, t, J ) 8.0 Hz), 6.93 (2H, t, J ) 7.5 Hz), 7.06 (2H, d, J )
7.8 Hz). 13C NMR (75 MHz, CDCl3) δ (ppm): 22.7, 25.2, 27.2,
39.1 (10C), 39.7, 39.9, 122.0, 122.5, 122.8, 123.1, 125.8, 126.3,
126.7, 128.3, 128.4, 128.6, 141.8, 145.4, 145.5, 145.60, 145.61,
145.7, 145.8, 146.5, 160.1, 160.2, 161.6. MS (APCI+): 1298
(MH+). Elem. Anal. for C75H88N14O7: calcd: C, 69.42%; H, 6.84%;
N, 15.11%; found: C, 69.30%; H, 6.82%; N, 15.13%.
1
cm-1: 2995, 2965, 1659, 1651, 1597, 1428, 1355, 872. H NMR
(300 MHz, CDCl3) δ(ppm): 1.10 (12H, d, J ) 6.8 Hz), 2.77
(2H, m), 2.82 (6H, s), 2.92 (6H, s), 3.07 (6H, s), 5.94 (2H, t, J )
1.9 Hz), 6.27 (2H, dd, J ) 1.3, 7.9 Hz), 6.35 (2H, dd, J ) 1.0, 7.9
Hz), 6.42 (2H, dd, J ) 1.1, 8.0 Hz), 6.65 (2H, dt, J ) 1.5, 7.5 Hz),
6.75 (2H, t, J ) 8.0 Hz), 6.95 (2H, t, J ) 7.3 Hz), 7.08 (2H, dd,
J ) 1.5, 7.8 Hz). 13C NMR (75 MHz, CDCl3) δ (ppm): 22.7, 25.2,
27.2, 39.1, 39.7, 40.0, 122.6, 122.7, 123.3, 125.8, 126.3, 126.8,
128.5, 128.6, 141.9, 145.8, 145.9, 146.5, 160.4, 161.7. MS
(APCI+): 649 (MH+). HRMS for C39H49N6O3 (MH+): calcd:
649.3861; found: 649.3871. Elem. Anal. for C39H48N6O3: calcd:
C, 72.19%; H, 7.46%; N, 12.95%; found: C, 71.96%; H, 7.40%;
N, 12.78%.
N,N′,N′′,N′′′,N′′′′,N′′′′,N′′′′′′,N′′′′′′′′-Octamethyl-1,3-bis[3-(2-iso-
propylphenylureyl)phenylureyl]benzene 24. Under nitrogen at-
mosphere, 3-nitrophenylisocyanate (700 mg, 4.27 mmol, 1 equiv)
was dissolved in dry THF (10 mL), and 2-isopropylaniline
(725 µL, 5.12 mmol, 1.2 equiv) was added. The mixture was stirred
at r.t. for 3 h and evaporated under reduced pressure. CH2Cl2/
petroleum was added, and the solid was collected by filtration. The
white powder was dried under vacuum and dissolved in MeOH
(30 mL). Pd/C 10% (100 mg) was added, and the reaction mixture
was stirred overnight, at r.t., under hydrogen atmosphere. After
removal of the Pd/C by filtration on celite, the solvent was
evaporated under reduced pressure, and the product was precipitated
in CH2Cl2/petroleum ether and collected by filtration (1.09 g). The
white powder was dried under vacuum and dissolved in dry THF
(30 mL). 1,3-Phenylene diisocyanate (326 mg, 2.02 mmol,
0.5 equiv) was added. The mixture was stirred at r.t. for 3.5 h and
evaporated under reduced pressure. CH2Cl2 was added, and the solid
was collected by filtration. The white powder was dried under
vacuum and suspended in THF (20 mL). 60% NaH in mineral oil
(808 mg, 20.2 mmol, 10 equiv) and methyl iodide (1.26 mL,
20.2 mmol, 10 equiv) were added successively, and the reaction
mixture was stirred overnight before adding H2O (2 mL). The
aqueous phase was extracted with CH2Cl2, and the combined
organic phases were dried (MgSO4) and concentrated under reduced
pressure. Flash chromatography on silica gel (CH2Cl2/MeOH: 95:
5) afforded 785 mg (45%) of urea 24 as a white powder. mp:
152 °C. IR νmax cm-1: 3005, 2968, 1659, 1650, 1597, 1431, 1357.
1H NMR (300 MHz, CDCl3) δ (ppm): 1.08 (12H, d, J ) 6.8 Hz),
2.78 (2H, m), 2.80 (6H, s), 2.88 (6H, s), 3.05 (6H, s), 5.91 (2H, t,
J ) 2.0 Hz), 6.02 (1H, t, J ) 2.0 Hz), 6.26 (2H, dd, J ) 1.2,
7.9 Hz), 6.30 (2H, dd, J ) 2.1, 8.0 Hz), 6.33 (2H, d, J ) 7.9 Hz),
6.38 (2H, d, J ) 8.0 Hz), 6.63 (3H, m), 6.68 (1H, d, J ) 8.0 Hz),
6.74 (1H, d, J ) 8.0 Hz), 6.93 (2H, dt, J ) 1.2, 7.5 Hz), 7.07 (2H,
dd, J ) 1.4, 7.9 Hz). 13C NMR (75 MHz, CDCl3) δ (ppm): 22.7,
25.2, 27.2, 39.0, 39.1, 39.7, 40.0, 122.0, 122.4, 122.5, 122.9, 123.2,
125.8, 126.3, 126.8, 128.3, 128.4, 128.6, 141.8, 145.6, 145.7, 145.8,
N,N′,N′′,N′′′,N′′′′,N′′′′′,N′′′′′′,N′′′′′′′,N′′′′′′′′,N′′′′′′′′′,N′′′′′′′′′′,N′′′′′′′′′′′,N′′′′′′′′′′′′,
N′′′′′′′′′′′′,N′′′′′′′′′′′′′′,N′′′′′′′′′′′′′′′-Hexadecamethyl-1,3-bis[3-(3-(3-
(2-isopropylphenylureyl)phenylureyl)phenylureyl)phenylureyl]-
benzene 26. By the method used for compound 10a, 3-nitrophe-
nylisocyanate (525 mg, 3.20 mmol, 1 equiv) and 2-isopropylaniline
(545 µL, 3.85 mmol, 1.2 equiv) gave an intermediate aniline. 1,3-
Phenyldiisocyanate (74.5 mg, 0.465 mmol, 0.5 equiv) was used
instead of phenyl isocyanate. After methylation in THF (20 mL)
with NaH 60% in mineral oil (372 g, 9.3 mmol, 20 equiv) and
methyl iodide (580 µL, 9.3 mmol, 10 equiv), a crude product was
obtained that was purified by flash chromatography on silica gel
(CH2Cl2/MeOH: 90:10) to yield octa-urea 26 (415 mg, 18%) was
isolated by as a white powder. mp: 196 °C. IR νmax cm-1: 3005,
2968, 2932, 1659, 1650, 1597, 1431, 1356, 875. 1H NMR
(500 MHz, CDCl3) δ (ppm): 1.08 (12H, d, J ) 6.5 Hz), 2.77
(2H, m), 2.79 (6H, s), 2.85 (18H, s), 2.86 (12H, s), 2.89 (6H, s),
3.05 (6H, s), 5.91 (2H, t, J ) 2.0 Hz), 6.00 (5H, m), 6.25-6.31
(12H, m), 6.33 (2H, d, J ) 8.0 Hz), 6.37 (2H, d, J ) 6.0 Hz),
6.61-6.67 (7H, m), 6.72 (2H, t, J ) 8.0 Hz), 6.93 (2H, t, J )
7.5 Hz), 7.07 (2H, dd, J ) 1.2, 7.8 Hz). 13C NMR (75 MHz, CDCl3)
δ (ppm): 22.7, 25.3, 27.2, 39.1 (12C), 39.7, 40.0, 122.0, 122.5,
122.8, 122.9, 123.2, 125.8, 126.3, 126.8, 128.4, 128.5, 128.6, 141.8,
145.50 (4C), 145.55, 145.58, 145.63, 145.7, 145.8, 146.5, 160.0,
160.1, 160.2, 161.6. MS (APCI+): 1461 (MH+). Elem. Anal. for
C84H98N16O8: calcd: C, 69.11%; H, 6.77%; N, 15.35%; found:
C, 68.84%; H, 6.81%; N, 15.11%.
Acknowledgment. We are grateful to the Leverhulme Trust
and the EPSRC for support of this work.
Supporting Information Available: Experimental procedures
and data for 9b-d, 10b,c, 11b,e, 16, and 17b-g. X-ray crystal-
lographic data (CIF) for 9a, 10a, 17a, 17b, 17e, 17f, and 17g. This
materialisavailablefreeofchargeviatheInternetathttp://pubs.acs.org.
JO061989W
2308 J. Org. Chem., Vol. 72, No. 7, 2007