Pardin et al.
of EtOAc. The combined organic phase was dried, filtered, and
evaporated to a residue that was purified by chromatography on
silica gel with EtOAc as eluant.
Hz), 7.58 (t, 1H, J ) 6.9 Hz), 7.46 (t, 1H, J ) 8.2 Hz), 6.78 (d,
1H, J ) 16.1 Hz). Anal. Calcd for C15H10N4O4: C, 58.07; H, 3.25;
N, 18.06. Found: C, 59.23; H, 3.35; N, 19.16. The structure of the
trifluoroacetate salt of 14a, which was crystallized in TFA, was
solved at the Universite´ de Montre´al X-ray facility using direct
methods (SHELXS 97) and refined with SHELXL 97:
C15H10N4O4.C2HF3O2; Mr ) 424.30; triclinic, colorless crystal;
space group P1; unit cell dimensions a ) 7.7137(2) Å, b )
9.7911(2) Å, c ) 12.1711(2) Å, R ) 96.2560(10)°, ꢀ )
107.4280(10)°, γ ) 96.4560(10)°; volume of unit cell 861.55(3)
Å3; Z ) 2.
General Procedure E: Synthesis of Amides and Esters of
p-Nitrocinnamic Acid. p-Nitrocinnamoyl p-nitrophenyl ester (46;
0.16 mmol) was dissolved in 2 mL of CH2Cl2, and this solution
was treated with the specified alcohol or amine (0.18 mmol) using
Et3N (0.48 mmol) as base. After the mixture was stirred overnight
at room temperature, the volatiles were removed and the resulting
mixture was diluted with 30 mL of EtOAc. The organic phase was
washed with 3 × 6 mL of 0.1 N HCl, 8 × 6 mL of 1 N NaOH,
and 2 × 5 mL of brine, dried with MgSO4, filtered, and evaporated
to a residue that was triturated with diethyl ether to give a solid.
m-Nitrocinnamic Acid (13b). Acid 13b was prepared from
m-nitrobenzaldehyde using general procedure B and isolated as a
p-Nitrocinnamoyl Benzotriazolyl Amide (15a). Amide 15a was
prepared from p-nitrocinnamic acid using general procedure A and
1
isolated as a pale yellow solid (70% yield). Mp: 213-215 °C. H
NMR (d6-DMSO): δ 8.27 (m, 8H), 7.81 (t, 1H, J ) 7.2 Hz), 7.64
(t, 1H, J ) 7.2 Hz). 13C NMR (d6-DMSO): δ 168.1, 149.0, 142.4,
141.8, 139.7, 131.3, 130.4, 130.2, 126.4, 125.2, 125.0, 124.7, 115.9.
HRMS (ESI): m/z calcd for C15H11N4O3 ([M + H]+) 295.0826,
found 295.0816.
1
pale yellow solid (74% yield). Mp: 200-202 °C. H NMR (d6-
DMSO): δ 8.50 (s, 1H), 8.21 (dd, 1H, J ) 8.2, 1.7 Hz), 8.17 (d,
1H, J ) 8.0 Hz), 7.69 (m, 2H), 6.73 (d, 1H, J ) 15.8 Hz). 13C
NMR (d6-DMSO): δ 158.0, 140.6, 134.4, 129.4, 127.5, 124.1, 118.6,
117.2, 116.7. HRMS (ESI): m/z: m/z calcd for C9H6NO4 ([M -
H]-) 192.0302, found 192.0310.
p-Nitrocinnamoyl p-Nitrophenyl Ester (17a). Ester 17a was
prepared by treating p-nitrocinnamic acid (1 mmol) in acetonitrile
(6 mL) with Et3N (1 mmol) and DMAP (0.1 mmol) at room
temperature for 5 min, followed by addition of p-nitrophenyl
chloroformate (1.1 mmol) and stirring for 1 h. The precipitate was
filtered and washed with 5 mL of acetonitrile, which gave a pale
yellow solid (94% yield). Mp: 181-183 °C. 1H NMR (CDCl3): δ
8.32 (d, 2H, J ) 9.1 Hz), 8.27 (d, 2H, J ) 8.8 Hz), 8.10 (d, 2H,
J ) 8.9 Hz), 8.02 (d, 1H, J ) 16.1 Hz), 7.54 (d, 2H, J ) 9.1 Hz),
7.13 (d, 1H, J ) 16.1 Hz). 13C NMR (d6-DMSO): δ 164.7, 156.2,
149.3, 146.1, 145.5, 141.0, 130.8, 126.3, 125.0, 124.2, 121.8. HRMS
(ESI): m/z calcd for C15H10N2O6Ag ([M + Ag]+) 420.9584, found
420.9589.
p-Aminocinnamic Acid (13r). Acid 13r was prepared using
general procedure D from the ester 20a to give a product that was
diluted in a minimum of CH2Cl2 and treated with TFA (3 mL) at
0 °C for 4 h. The volatiles were removed under vacuum, and the
product was triturated with diethyl ether to give an orange solid
(64% yield). Mp: 265-267 °C dec. 1H NMR (CD3OD): δ 7.73 (d,
2H, J ) 8.5 Hz), 7.67 (d, 1H, J ) 16.1 Hz), 7.40 (d, 2H, J ) 8.5
Hz), 6.52 (d, 1H, J ) 16.0 Hz). 13C NMR (CD3OD): δ 161.1, 137.5,
130.5, 127.6, 125.1, 119.6, 116.5. HRMS (ESI): m/z calcd for
C9H9NO2 ([M + H]+) 164.0706, found 164.0709.
p-((tert-Butoxycarbonyl)amino)cinnamic Acid (13n). Acid 13n
(0.5 mmol) was dissolved in 5 mL of a dioxane/H2O (1:1) solution,
and this solution was treated with di-tert-butyl dicarbonate
((BOC)2O) (0.6 mmol) and solid NaHCO3 (5 mmol), stirred
overnight at room temperature, and evaporated to a residue that
was diluted with 40 mL of 1 N NaOH. The aqueous phase was
washed with 3 × 10 mL of CH2Cl2 and neutralized with 1 N HCl.
The acid was extracted with 3 × 10 mL of EtOAc. The combined
organic phase was dried with MgSO4 and filtered. The volatiles
were removed, and the product was obtained without further
purification as a white solid (45% yield). Mp: 195-197 °C dec.
1H NMR (CD3OD): δ 7.61 (d, 1H, J ) 16.0 Hz), 7.47 (d, 4H, J )
5.4 Hz), 6.35 (d, 1H, J ) 15.9 Hz), 1.51 (s, 9H). 13C NMR
(CD3OD): δ 171.6, 155.7, 147.0, 143.7, 130.9, 130.7, 120.3, 117.8,
82.0, 29.5. HRMS (ESI): m/z calcd for C14H17NO4Na ([M + Na]+)
286.1050, found 286.1045.
p-Nitrocinnamoyl Imidazolyl Amide (18a). Amide 18a was
prepared using general procedure E, from imidazole in acetone, to
1
give a white solid (68% yield). Mp: 178-179 °C dec. H NMR
(d6-DMSO): δ 8.82 (s, 1H), 8.32 (d, 2H, J ) 8.9 Hz), 8.20 (d, 2H,
J ) 8.9 Hz), 8.09 (d, 1H, J ) 15.6 Hz), 7.96 (t, 1H, J ) 1.31 Hz),
7.85 (d, 1H, J ) 15.5 Hz), 7.17 (t, 1H, J ) 0.9 Hz). 13C NMR
(d6-DMSO): δ 158.0, 140.3, 134.1, 133.7, 128.5, 124.0, 123.1,
118.3, 118.2, 118.1. HRMS (ESI): m/z calcd for C12H10N3O3 ([M
+ H]+) 244.0717, found 244.0727.
p-Nitrocinnamoyl tert-Butyl Ester (20a). ((tert-Butoxycarbon-
yl)methyl)triphenylphosphonium bromide (0.33 mmol) and KH-
MDS (0.297 mmol) were dissolved in 3 mL of THF. p-Nitroben-
zaldehyde (0.165 mmol) was dissolved in 1 mL of THF and added
dropwise to the ylide suspension. The mixture was stirred for 1 h.
The organic phase was then treated twice with 2 mL of saturated
NH4Cl and dried with MgSO4, and the volatiles were removed by
rotary evaporation. The product was purified by chromatography
with EtOAc/hexane (20:80) as eluant to give a pale yellow solid
p-(((9-Fluorenylmethoxy)carbonyl)amino)cinnamic Acid (13p).
Acid 13r (0.5 mmol) was dissolved in 5 mL of a dioxane/H2O
(1:1) solution, and this solution was treated with (9-fluorenyl-
methoxy)carbonyl chloride (Fmoc-Cl; 0.6 mmol) using NaHCO3
(5 mmol) as base. The mixture was stirred overnight at room
temperature. Then the solvent was reduced and the residue was
diluted in 40 mL of water. The aqueous phase was acidified with
6 N HCl. The acid was extracted with 3 × 10 mL of EtOAc. The
organic phase was dried with MgSO4 and filtered. The solvent was
removed and the product obtained after trituration with diethyl ether
1
(75% yield). Mp: 146-148 °C. H NMR (CDCl3): δ 8.21 (d, 2H,
J ) 8.9 Hz), 7.63 (d, 2H, J ) 8.9 Hz), 7.60 (d, 1H, J ) 16.1 Hz),
6.47 (d, 1H, J ) 16.0 Hz), 1.52 (s, 9H). 13C NMR (CDCl3): δ
165.6, 148.6, 141.1, 140.9, 128.8, 124.8, 124.4, 81.6, 28.4. HRMS
(ESI): m/z calcd for C13H15NO4Na ([M + Na]+) 272.0893, found
272.0895.
3-((E)-3-(4-Nitrophenyl)acryloyl)-2H-chromen-2-one (28a). Cou-
marin 36 (1 mmol) was dissolved in 10 mL of toluene, and this
solution was treated dropwise with p-nitrobenzaldehyde (0.67
mmol) in 5 mL of toluene and stirred overnight at room temperature.
At this point a precipitate formed, which was filtered and washed
with toluene to give a yellow solid (36% yield). Mp: 272-274 °C.
1H NMR (d6-DMSO): δ 8.73 (s, 1H), 8.30 (d, 2H, J ) 8.8 Hz),
8.03 (d, 2H, J ) 8.7 Hz), 7.97 (d, 1H, J ) 6.7 Hz), 7.84 (s, 2H),
7.78 (t, 1H, J ) 8.4 Hz), 7.51 (d, 1H, J ) 8.4 Hz), 7.45 (t, 1H, J
) 7.5 Hz). HRMS (ESI): m/z calcd for C18H12NO5 ([M + H]+)
322.0710, found 322.0716.
1
as an orange solid (37% yield). Mp: 270-272 °C dec. H NMR
(d6-DMSO): δ 9.92 (s, 1H), 7.90 (d, 2H, J ) 7.3 Hz), 7.73 (d, 2H,
J ) 7.4 Hz), 7.45 (m, 9H), 6.37 (d, 1H, J ) 16.0 Hz), 4.50 (d, 2H,
J ) 6.4 Hz), 4.30 (t, 1H, J ) 6.4 Hz). 13C NMR (d6-DMSO): δ
158.6, 145.2, 136.4, 136.4, 133.9, 133.8, 123.0, 122.3, 121.7, 121.2,
119.3, 114.8, 112.9, 111.9, 64.6, 47.0. HRMS (ESI): m/z calcd for
C24H20NO4 ([M + H]+) 386.1387, found 386.1383.
p-Nitrocinnamoyl Oxybenzotriazolyl Amide (14a). Amide 14a
was prepared from p-nitrocinnamic acid using general procedure
A and isolated as a pale yellow solid (55% yield). Mp: 212-214
°C dec. 1H NMR (d6-DMSO): δ 8.28 (d, 2H, J ) 8.8 Hz), 8.02 (d,
3H, J ) 8.6 Hz), 7.75 (d, 1H, J ) 8.3 Hz), 7.68 (d, 1H, J ) 16.1
(E)-3-(4-Nitrophenyl)-1-(pyridin-3-yl)prop-2-en-1-one (30a). Ke-
tone 30a was prepared using general procedure C from p-
5774 J. Org. Chem. Vol. 73, No. 15, 2008