was then added and the solution stirred at room temperature
for 2 h. Consecutive addition of benzylamine (36 µL, 0.33
mmol) and diisopropylethylamine (0.4 mL, 2.26 mmol) pro-
duced a light brown slurry which was stirred at room temper-
ature overnight. The polymer beads were collected on a filter
and washed with DCM (60 mL). The yellow filtrate was washed
with sodium hydrogen carbonate (3 × 50 mL, 5% aqueous
solution) and the combined DCM layers concentrated in vacuo.
Purification by flash chromatography (DCM) yielded N-benzyl-
N-(4-nitrobenzoyl)-4-nitrobenzamide as a pale yellow solid
(0.12 g, 90%). Mp 165–167 ЊC (Found: C, 62.23; H, 3.80; N,
10.21. Calc. for C21H15N3O6: C, 62.22; H, 3.73; N, 10.37%);
νmax(KBr)/cmϪ1 1350 (s, NO2), 1526 (s, NO2), 1603 (m, C(O)N),
1691 (s, C(O)N); δH (400 MHz, CDCl3) 5.23 (s, 2H, CH2),
7.2–7.4 (m, 5H, Ar–H), 7.57 (d, J = 9.0 Hz, 4H, Ar–H), 8.07 (d,
J = 9.0 Hz, 4H, Ar–H); δC (100 MHz, CDCl3) 50.6, 123.8, 128.3,
128.5, 128.9, 129.5, 136.0, 141.1, 149.5, 171.6; (ESMSϪ) m/z
405 (MHϪ, 10%), 255 (M Ϫ [C(O)C6H4NO2], 30%), 166
(NC(O)C6H4NO2, 100%).
GC/MS, which showed 2- and 3-menthenes: (1R,2S,5R)-(Ϫ)-
menthol : neomenthyl 4-nitrobenzoate = 79 : 16 : 5. The
1
identity of the products generated was confirmed by H NMR
spectroscopy.8
Representative example for the esterification of secondary
alcohols using the Hendrickson reagent 1 and DMAP:
synthesis of O-(4-nitrobenzoyl)-(؊)-menthol [(1R,2S,5R)-
5-methyl-2-(1-methylethyl)cyclohexyl 4-nitrobenzoate]
A solution of triphenylphosphine oxide (2 g, 7.2 mmol) in
DCM (10 mL) under nitrogen was cooled on ice. Triflic
anhydride (0.5 mL, 3 mmol) was added and the solution stirred
for 30 min. Addition of 4-nitrobenzoic acid (0.6 g, 3.6 mmol)
to the resulting white precipitate formed a clear solution after
stirring for 15 min at room temperature. DMAP (0.44 g, 3.6
mmol) was added and after 5 min, the solution treated with
(1R,2S,5R)-(Ϫ)-menthol (0.46 g, 3 mmol) and diisopropyl-
ethylamine (1.15 mL, 6.6 mmol). After stirring at room temper-
ature for 15 min, the solution was washed with sodium
hydrogen carbonate (3 × 20 mL, saturated aqueous solution)
and water (2 × 20 mL). The DCM layers were combined, dried
(anhydrous MgSO4) and concentrated in vacuo. The resulting
yellow residue was submitted to flash chromatography (DCM)
to afford O-(4-nitrobenzoyl)-(Ϫ)-menthol as a pale yellow solid
Synthesis of L,L-Z–Gly–Phe–Val–OMe using polymer-
supported triphenylphosphine ditriflate 4 and HOBT
Polymer-supported triphenylphosphine ditriflate 4 was pre-
pared as above from polymer-supported triphenylphosphine
oxide (0.15 g, 0.45 mmol, 3 mmol gϪ1) and triflic anhydride
(57.5 µL, 0.33 mmol). Diisopropylethylamine (0.32 mL, 1.82
mmol), 1-hydroxybenzotriazole (0.045 g, 0.33 mmol) and
Z–Gly–Phe–OH (0.118 g, 0.33 mmol) were then added and
the solution stirred at room temperature for 2 h. Addition of
H–Val–OMeؒHCl (0.0435 g, 0.33 mmol) produced a yellow
slurry which was stirred at room temperature overnight. The
polymer beads were collected on a filter and washed with
DCM (60 mL). The yellow filtrate was washed with sodium
hydrogen carbonate (3 × 50 mL, 5% aqueous solution) and
water (5 × 50 mL) and the combined DCM layers concentrated
in vacuo then dried under high vacuum to remove the remaining
traces of diisopropylethylamine. The single isomer of ,-Z–
Gly–Phe–Val–OMe was obtained as a light orange solid (0.1 g,
66%). Mp 95–97 ЊC, (lit.,17 98 ЊC).
1
(0.84 g, 92%). Mp 60–62 ЊC. The H NMR data obtained was
identical to that previously reported.18
Attempted preparation of O-(4-nitrobenzoyl)cyclohexanol using
polymer-supported triphenylphosphine ditriflate 4 and catalytic
DMAP
Polymer-supported triphenylphosphine ditriflate 4 was pre-
pared as above from polymer-supported triphenylphosphine
oxide (0.3 g, 0.9 mmol, 3 mmol gϪ1) and triflic anhydride (0.12
mL, 0.72 mmol). 4-Nitrobenzoic acid (0.11 g, 0.66 mmol) was
added and the solution stirred for 15 min at room temperature.
The slurry was then treated with DMAP (8 mg, 0.066 mmol)
and after 5 min, cyclohexanol (70 µL, 0.66 mmol) and diisopro-
pylethylamine (0.4 mL, 2.3 mmol) added. After stirring at room
temperature overnight, analysis of the reaction mixture by
GC/MS showed cyclohexene : O-(4-nitrobenzoyl)cyclohexanol :
cyclohexanol = 68 : 18 : 14. The identity of the products
generated was confirmed by 1H NMR spectroscopy.
Representative example for the use of polymer-supported
triphenylphosphine ditriflate 4 for general dehydrations:
synthesis of 4-nitrobenzyl 4-nitrobenzoate
Polymer-supported triphenylphosphine ditriflate 4 was pre-
pared as above from polymer-supported triphenylphosphine
oxide (0.3 g, 0.9 mmol, 3 mmol gϪ1) and triflic anhydride
(0.12 mL, 0.72 mmol). 4-Nitrobenzyl alcohol (0.1 g, 0.66
mmol), 4-nitrobenzoic acid (0.11 g, 0.66 mmol) and diisopro-
pylethylamine (0.4 mL, 2.3 mmol) were then added and
the reaction left to stir overnight at room temperature. The
polymer beads were removed by filtration, washed with DCM
(50 mL) and the filtrate washed with sodium hydrogen
carbonate (3 × 30 mL, saturated aqueous solution). The
organic phase was concentrated in vacuo and dried under high
vacuum to yield 4-nitrobenzyl 4-nitrobenzoate as a yellow solid
(0.19 g, 95%). Mp 165–167 ЊC, (lit.,20 168 ЊC).
Representative example for the esterification of secondary
alcohols using polymer-supported triphenylphosphine ditriflate
4 and DMAP: synthesis of O-(4-nitrobenzoyl)-(؊)-menthol
[(1R,2S,5R)-5-methyl-2-(1-methylethyl)cyclohexyl
4-nitrobenzoate]
Polymer-supported triphenylphosphine ditriflate 4 was pre-
pared as above from polymer-supported triphenylphosphine
oxide (0.3 g, 0.9 mmol, 3 mmol gϪ1) and triflic anhydride
(0.12 mL, 0.72 mmol). 4-Nitrobenzoic acid (0.13 g, 0.8 mmol)
was added and the solution stirred for 15 min at room temper-
ature. The slurry was then treated with DMAP (0.1 g, 0.8
mmol) and after 5 min (1R,2S,5R)-(Ϫ)-menthol (0.104 g, 0.66
mmol) and diisopropylethylamine (0.4 mL, 2.3 mmol) added.
After stirring at room temperature overnight, analysis of the
reaction mixture by GC/MS showed O-(4-nitrobenzoyl)-(Ϫ)-
menthol : 2- and 3-menthenes = 97 : 3. The polymer beads were
then collected on a filter and washed with DCM (60 mL). The
combined filtrates were extracted with sodium hydrogen
carbonate (3 × 50 mL, saturated aqueous solution) and water
(2 × 50 mL) and the DCM layers dried (anhydrous MgSO4) and
concentrated in vacuo. The resulting pale yellow oil was dried
under high vacuum to afford O-(4-nitrobenzoyl)-(Ϫ)-menthol
as a pale yellow oil which solidified upon standing (0.17 g,
84%). Mp 60–62 ЊC, identical to that obtained using the
Hendrickson reagent 1.
Attempted preparation of neomenthyl 4-nitrobenzoate
[(1S,2S,5R)-5-methyl-2-(1-methylethyl)cyclohexyl
4-nitrobenzoate] using polymer-supported triphenylphosphine
ditriflate 4
Polymer-supported triphenylphosphine ditriflate 4 was pre-
pared as above from polymer-supported triphenylphosphine
oxide (0.3 g, 0.9 mmol, 3 mmol gϪ1) and triflic anhydride
(0.12 mL, 0.72 mmol). (1R,2S,5R)-(Ϫ)-Menthol (0.103 g,
0.66 mmol), 4-nitrobenzoic acid (0.11 g, 0.66 mmol) and diiso-
propylethylamine (0.4 mL, 2.3 mmol) were then added and the
mixture heated to reflux overnight. The polymer beads were
separated by filtration and an aliquot of the filtrate analysed by
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 9 7 9 – 1 9 8 6
1985
Fairfull-Smith, Kathryn E.
