220
A. Ghinet et al. / Tetrahedron 66 (2010) 215–221
50 MHz)
d
23.1 (CH2), 30.3 (CH2), 52.4 (CH3), 101.3 (CH2), 105.2 (CH),
6/4 to generate pure product 21 as a white powder in 73% yield; TLC
108.0 (CH), 116.0 (CH), 131.9 (C), 145.6 (C), 147.9 (C), 172.1 (C), 174.2
Rf (EtOAc/n-heptane 6/4)¼0.28; 1H NMR (CDCl3, 200 MHz)
d (ppm)
(C). IR:
n
cmꢁ1: 1740, 1695, 1509, 1489, 1433, 1390, 1201. Anal. Calcd
2.20–2.36 (m, 1H, CH2CH2CH), 2.44–2.88 (m, 3H, CH2CH2CH), 3.72
(s, 3H, CO2CH3), 4.71 (dd, J¼9.2, 3.0 Hz, 1H, CH2CH2CH), 6.73–7.21
for C13H13O5N: C 59.31, H 4.98, N 5.32; found: C 59.31, H 4.95, N,
5.53. This product has been reported in a patent written in
Japanese.39
(m, 7H, ArH). IR:
n
cmꢁ1: 1746, 1691, 1456, 1392, 1321, 1290. Anal.
Calcd for C16H15O3N: C 71.36, H 5.61, N 5.20; found: C 71.22, H 5.46,
N, 5.09.
4.1.7. Methyl N-(4-fluorophenyl)pyroglutamate (18)37,40. The gen-
eral procedure was followed using DL-methyl pyroglutamate (2.0 g,
14 mmol), 4-fluorobromobenzene (2.9 g, 17 mmol), cesium car-
bonate (9.1 g, 28 mmol), copper (I) iodide (1.3 g, 7 mmol), and
DMEDA (1.5 mL, 14 mmol) in dioxane (30 mL). The mixture was
stirred under nitrogen atmosphere at 60 ꢀC for 8 h. The residue was
separated by chromatography on silica gel, eluting EtOAc/n-hep-
tane 5/5 to generate pure product 18 as a white powder in 81%
yield; TLC Rf (EtOAc/n-heptane 5/5)¼0.18; 1H NMR (CDCl3,
4.1.11. N-(a-Naphthyl)pyroglutamic acid (6). A stirred mixture of
ester 21 (Scheme 4) (3.2 g, 12 mmol) and sodium hydroxide (0.7 g,
17.5 mmol) in distilled water (9.0 mL) was refluxed for 2 h (till
complete solubilisation of starting ester which is equivalent to so-
dium carboxylate formation). After cooling at room temperature,
the solution was stirred by using a magnetic bar, and then acidified
to pH¼5–6 by adding slowly concentrated HCl. The solid obtained
by filtration was washed with distilled water and dried to give acid
200 MHz)
d
(ppm) 2.11–2.29 (m, 1H, CH2CH2CH), 2.40–2.87 (m, 3H,
6
as white solid in quantitative yield; mp 185 ꢀC; TLC Rf
CH2CH2CH), 3.73 (s, 3H, CO2CH3), 4.69 (dd, J¼9.1, 3.2 Hz, 1H,
(dichloromethane/methanol 95/5)¼0.29; 1H NMR (CDCl3,
CH2CH2CH), 7.01–7.10 (m, 2H, ArH), 7.37–7.46 (m, 2H, ArH). 13C NMR
200 MHz) d (ppm) 2.20–2.36 (m, 1H, CH2CH2CH), 2.44–2.88 (m, 3H,
(CDCl3, 50 MHz)
(CH), 116.0 (CH), 123.9 (CH), 124.1 (CH), 157.8 (C), 162.7 (C), 172.1 (C),
174.1 (C). IR:
cmꢁ1: 1746, 1685, 1518, 1380, 537. Anal. Calcd for
d
23.1 (CH2), 30.4 (CH2), 52.5 (CH3), 61.8 (CH), 115.5
CH2CH2CH), 4.63 (m, 1H, CH2CH2CH), 7.40–7.67 (m, 4H, ArH), 7.80–
7.91 (m, 3H, ArH). 13C NMR (CDCl3, 50 MHz)
24.1 (CH2), 29.7 (CH2),
63.2 (CH), 125.5 (CH), 126.3 (2CH), 126.8 (CH), 128.5 (C), 128.6 (C),
128.9 (2CH), 129.5 (C), 134.4 (C), 171.2 (C), 174.6 (C). IR:
cmꢁ1
d
n
C12H12O3NF: C 60.76, H 5.10, N 5.90; found: C 60.79, H 5.21, N, 6.02.
n
:
3070, 1733, 1636, 1510, 1412, 1250, 1143. Anal. Calcd for C15H13O3N:
C 70.58, H 5.13, N 5.49; found: C 70.34, H 5.28, N, 5.65.
4.1.8. Methyl N-(3-trifluoromethylphenyl)pyroglutamate (19)37,41. The
general procedure was followed using DL-methyl pyroglutamate
(3.0 g, 21 mmol), 3-trifluoromethylphenyl-bromobenzene (3.2 mL,
23 mmol), cesium carbonate (13.7 g, 42 mmol), copper (I) iodide
(2.0 g, 10 mmol), and DMEDA (2.3 mL, 21 mmol) in dioxane (40 mL).
The mixture was stirred under nitrogen atmosphere at 60 ꢀC for 16 h.
The residue was separated by chromatography on silica gel, eluting
EtOAc/n-heptane 5/5 to generate pure product 19 as a white powder
in 91% yield; TLC Rf (EtOAc/n-heptane 5/5)¼0.34; 1H NMR (CDCl3,
4.1.12. N-(a-Naphthyl)-5-oxoprolyl chloride (22). A mixture of acid
6 (Scheme 4) (2.2 g, 8.6 mmol) and thionyl chloride (1.9 mL,
25.8 mmol) in dichloromethane (15 mL) was refluxed for 3 h. The
pale yellow solution was concentrated in vacuo to give the crude
acid chloride 22 (Scheme 4) as a yellow pale solid in a quantitative
yield. 1H NMR (CDCl3, 200 MHz)
d (ppm) 2.52–2.68 (m, 1H,
CH2CH2CH), 2.71–3.00 (m, 3H, CH2CH2CH), 4.92–5.07 (m, 1H,
CH2CH2CH), 7.47–7.61 (m, 4H, ArH), 7.75–7.96 (m, 3H, ArH).
200 MHz)
d (ppm) 2.13–2.32 (m, 1H, CH2CH2CH), 2.42–2.93 (m, 3H,
CH2CH2CH), 3.75 (s, 3H, CO2CH3), 4.78 (dd, J¼8.7, 2.6 Hz, 1H,
CH2CH2CH), 7.47 (dd, J¼15.7, 7.8 Hz, 2H, ArH), 7.68 (d, J¼7.5 Hz, 1H,
4.1.13. 8,9-Dihydro-7H-benzo[de]pyrrolo[1,2-a]quinoline-7,10(7aH)-
dione (2). The above acid chloride 22 (2.3 g, 8.4 mmol) was dis-
solved in 15 mL dichloromethane. Aluminium trichloride (3.4 g,
25.5 mmol) was then added as a catalyst. The resulting mixture was
stirred at room temperature for 12 h. After hydrolysis, extraction,
and evaporation, the residue was recrystallized from acetone to
give ketone 2 as brown solid in 76% yield; TLC Rf (dichloromethane/
ArH), 7.79 (s, 1H, ArH). 13C NMR (CDCl3, 50 MHz)
d 23.0 (CH2), 30.6
(CH2), 52.6 (CH3), 61.1 (CH), 117.9 (q, J¼8.1, 4.2 Hz, CH), 121.8 (q, J¼7.8,
3.8 Hz, CH), 124.2 (q, J¼3.2, 1.7 Hz, CH), 124.3 (C), 129.4 (CH), 131.2 (q,
J¼65.2, 33.0 Hz, C), 138.6 (C), 171.7 (C), 174.2 (C). IR:
n
cmꢁ1: 1743,
1698, 1455, 1394, 1333, 1299, 690, 550, 497. Anal. Calcd for
C13H12O3NF3: C 54.36, H 4.21, N 4.88; found: C 54.21, H 4.38, N, 5.12.
methanol 95/5)¼0.21; 1H NMR (CDCl3, 200 MHz)
d (ppm) 2.47–2.64
4.1.9. Methyl N-(pyridin-2-yl)pyroglutamate (20). The general pro-
cedure was followed using DL-methyl pyroglutamate (2.0 g,
14 mmol), 2-bromopyridine (1.6 mL, 17 mmol), cesium carbonate
(9.1 g, 28 mmol), copper (I) iodide (1.3 g, 7 mmol), and DMEDA
(1.5 mL, 14 mmol) in dioxane (20 mL). The mixture was stirred
under nitrogen atmosphere at 60 ꢀC for 16 h. The residue was
separated by chromatography on silica gel, eluting EtOAc to gen-
erate pure product 20 as a brown oil in 73% yield; TLC Rf
(m, 2H, CH2CH2CH), 2.68–2.89 (m, 2H, CH2CH2CH), 4.71 (t, J¼8.1 Hz,
1H, CH2CH2CH), 7.62 (t, J¼7.3 Hz, 1H, ArH), 7.67 (t, J¼7.3 Hz, 1H,
ArH), 7.76 (dd, J¼8.3, 1.3 Hz, 1H, ArH), 8.17 (dd, J¼8.2, 1.4 Hz, 1H,
ArH), 8.29 (dd, J¼7.3, 1.4 Hz, 1H, ArH), 8.55 (dd, J¼7.7, 1.3 Hz,
1H, ArH). 13C NMR (CDCl3, 50 MHz)
d 20.1 (CH2), 31.3 (CH2), 63.3
(CH), 118.2 (CH), 124.2 (CH), 124.6 (C), 125.5 (CH), 125.9 (CH), 126.1
(C), 126.9 (CH), 131.3 (C), 133.2 (C), 134.9 (CH), 173.7 (C), 192.8 (C).
IR:
n
cmꢁ1: 1696, 1653, 1508, 1464, 1405, 1375, 1351, 1335, 1267,
(EtOAc)¼0.22; 1H NMR (CDCl3, 200 MHz)
d
(ppm) 2.09–2.20 (m, 1H,
1148. Anal. Calcd for C15H11O2N: C 75.94, H 4.67, N 5.90; found: C
75.58, H 4.88, N, 5.80.
CH2CH2CH), 2.31–2.98 (m, 3H, CH2CH2CH), 3.71 (s, 3H, CO2CH3),
4.68 (dd, J¼8.7, 2.4 Hz, 1H, CH2CH2CH), 7.40–8.32 (m, 4H, ArH). 13
C
NMR (CDCl3, 50 MHz)
d
23.0 (CH2), 31.3 (CH2), 53.2 (CH3), 60.1 (CH),
4.1.14. 10H-Benzo[de]pyrrolo[1,2-a]quinolin-10-one (4). A stirred
mixture of ketone 2 (Scheme 4) (0.15 g, 0.632 mmol) in poly-
phosphoric acid (8 mL) was heated at 140 ꢀC for 6 h. The hot mix-
ture was decanted over crushed ice. The aqueous solution was
extracted with dichloromethane. The organic phase was washed
with distilled water, dried (magnesium sulfate), filtered, and con-
centrated in vacuo to give a brown oil which was treated at room
temperature overnight in dichloromethane with activated carbon
and filtered to give ethylenic compound 4 (Scheme 5) as brown
113.1 (CH), 144.2 (CH), 150.6 (CH), 171.7 (C), 174.6 (C). IR:
n :
cmꢁ1
1720, 1698, 1455, 1394, 1333, 1299. Anal. Calcd for C11H12O3N2: C
59.99, H 5.49, N 12.72; found: C 59.47, H 5.60, N, 12.83.
4.1.10. Methyl N-(
cedure was followed using DL-methyl pyroglutamate (7.0 g,
49 mmol), -bromonaphthalene (6.1 mL, 49 mmol), cesium car-
a-naphthyl)pyroglutamate (21). The general pro-
a
bonate (31.9 g, 98 mmol), copper (I) iodide (4.7 g, 24.5 mmol), and
DMEDA (5.3 mL, 49 mmol) in dioxane (70 mL). The mixture was
stirred under nitrogen atmosphere at 60 ꢀC for 12 h. The residue was
separated by chromatography on silica gel, eluting EtOAc/n-heptane
solid in 32% yield; 1H NMR (CDCl3, 200 MHz)
CH), 6.41 (d, J¼5.6 Hz, 1H, CH]CH), 7.25 (d, J¼5.6 Hz, 1H, CH]CH),
7.76–8.60 (m, 6H, ArH).13C NMR (CDCl3, 50 MHz)
105.1 (CH), 127.4
d (ppm) 6.31 (s, 1H,
d