Jul-Aug 2004
Substituted 2,3,4,5-Tetrahydro-1H-1-benzazepine-5-carboxylic Esters
567
Methyl (±)-(2S * , 5S *)-2-Methyl-2,3,4,5-tetrahydro-1 H- 1 - b e n-
zazepine-5-carboxylate (11).
13
J = 7.4);
C nmr: δ 173.8, 148.6, 130.9, 130.5, 127.9, 121.2,
120.8, 59.7, 51.8, 50.2, 32.7, 30.1, 28.0, 10.8; hrms: m/z Calcd.
for C H NO : 233.1416; Found: 233.1414.
Anal. Calcd. for C H NO : C, 72.10; H, 8.15; N, 6.01.
14 19
2
This compound (70 mg, 9%) was isolated as a light yellow oil
that crystallized on standing at 0˚. The crystals were triturated at
0˚ with 1% ether in petroleum ether to give a white solid, mp 45-
14 19
2
Found: C, 72.27; H, 8.23; N, 5.91.
-1
1
47˚; ir: 3353, 1735 cm ; H nmr: δ 7.07 (td, 1H, J = 7.5, 1.4),
6.94 (dd, 1H, J = 7.6, 1.4), 6.85 (td, 1H, J = 7.5, 1.2), 6.73 (dd,
1H, J = 7.6, 1.2), 3.84 (dd, 1H, J = 8.5, 2.0), 3.75 (s, 3H), 3.33 (br
Reductive Cyclization of 7.
To a solution of 510 mg (1.56 mmole) of 7 in 200 mL of
methanol was added 125 mg of 5% palladium-on-carbon and the
mixture was hydrogenated as described for the preparation of 9.
The crude product was purified by preparative thin layer chro-
matography eluted with 25-50% ether in hexanes to give three
major bands. Band 1 (fastest moving) gave 15; band 2 gave 14;
band 3 gave 16.
s, 1H), 3.05 (m, 1H), 2.15 (m, 1H), 1.88 (m, 2H), 1.51 (m, 1H),
13
1.20 (d, 3H, J = 6.4);
C nmr: δ 175.3, 148.3, 129.7, 128.8,
127.4, 121.0, 120.3, 52.5, 51.8, 48.9, 36.2, 27.5, 23.3; hrms: m/z
Calcd. for C H NO : 219.1259; Found: 219.1257.
Anal. Calcd. for C H NO : C, 71.23; H, 7.76; N, 6.39.
13 17
2
13 17
2
Found: C, 71.42; H, 7.82; N, 6.31.
Methyl (±)-(2R*,5S*)-2-Phenyl-2,3,4,5-tetrahydro-1 H- 1 - b e n-
zazepine-5-carboxylate (15).
Methyl (±)-(2R*,5S *)-2-Methyl-2,3,4,5-tetrahydro-1H-1-ben-
zazepine-5-carboxylate (10).
This compound (14 mg, 3%) was isolated as a white solid, mp
This compound (740 mg, 90%) was isolated as a white solid,
1
-1
1
-1
mp 102-104˚ (ether-petroleum ether); ir: 3359, 1737 cm ;
68-70˚ (ether-petroleum ether); ir: 3349, 1733 cm ; H nmr: δ
7.38-7.25 (complex, 5H), 7.12 (m, 2H), 6.92 (td, 1H, J = 7.3, 1.2),
6.74 (d, 1H, J = 7.6), 3.94 (dd, 1H, J = 5.8, 3.3), 3.85 (dd, 1H, J =
11.2, 1.7), 3.70 (s, 3H), 3.59 (br s, 1H), 2.52 (m, 1H), 2.16 (m,
H
nmr: δ 7.10 (td, 1H, J = 7.5, 1.6), 7.03 (dd, 1H, J = 7.4, 1.6), 6.87
(td, 1H, J = 7.4, 1.3), 6.74 (dd, 1H, J = 7.5, 1.3), 3.84 (dd, 1H, J =
6.0, 2.3), 3.65 (s, 3H), 3.27 (br s, 1H), 2.91 (m, 1H), 2.42 (m,
13
13
1H), 1.97-1.72 (complex, 2H); C nmr: δ 173.5, 148.4, 145.7,
131.3, 130.4, 128.7, 128.1, 127.5, 126.4, 121.6, 121.0, 63.4, 51.9,
1H), 1.69 (m, 3H), 1.21 (d, 3H, J = 6.5); C nmr: δ 173.7, 148.6,
131.2, 130.3, 127.9, 121.2, 120.8, 53.6, 51.8, 50.3, 34.9, 28.1,
50.1, 35.2, 28.1; hrms: m/z Calcd. for C H NO : 281.1416;
18 19
24.0; hrms: m/z Calcd. for C
219.1258.
H
13 17
NO : 219.1259; Found:
2
2
Found: 281.1415.
Anal. Calcd. for C H NO : C, 76.87; H, 6.76; N, 4.98.
Found: C, 77.04; H, 6.83; N, 4.89.
Anal. Calcd. for C H NO : C, 71.23; H, 7.76; N, 6.39.
18 19
2
13 17
Found: C, 71.45; H, 7.84; N, 6.29.
2
Methyl (±)-(2S* , 5S* )-2-Phenyl-2,3,4,5-tetrahydro-1H-1-ben-
zazepine-5-carboxylate (14).
Reductive Cyclization of 6.
To a solution of 1.00 g (3.58 mmole) of 6 in 200 mL of
methanol was added 200 mg of 5% palladium-on-carbon and the
mixture was hydrogenated as described for the preparation of 9.
The crude product was purified by preparative thin layer chro-
matography eluted with 25-50% ether in hexanes to give two
major bands. Band 1 (fastest moving) gave 13; band 2 gave 12.
This compound (73 mg, 17%) was isolated as a white solid, mp
-1
1
82-84˚ (ether-petroleum ether); ir: 3343, 1732 cm ; H nmr: δ
7.42-7.27 (complex, 5H), 7.10 (td, 1H, J = 7.2, 1.7), 6.99 (dd, 1H,
J = 7.6, 1.7), 6.92 (td, 1H, J = 7.2, 1.3), 6.76 (dd, 1H, J = 7.6, 1.3),
3.96 (m, 2H), 3.79 (s, 3H), 3.63 (br s, 1H), 2.22 (m, 1H), 1.95
13
(overlapping m, 3H);
C nmr: δ 175.5, 148.1, 145.5, 134.2,
Methyl (±)-(2S*, 5S*)-2-Ethyl-2, 3, 4, 5-tetrahydro-1 H-1-ben -
zazepine-5-carboxylate (13).
130.6, 128.8, 128.1, 127.6, 126.4, 121.7, 120.8, 62.4, 51.9, 48.6,
36.9, 27.8; hrms: m/z Calcd. for C H NO : 281.1416; Found:
18 19
2
281.1414.
Anal. Calcd. for C H NO : C, 76.87; H, 6.76; N, 4.98.
Found: C, 76.99; H, 6.84; N, 4.88.
This compound (67 mg, 8%) was isolated as a light yellow oil
that crystallized on standing at 0˚. The crystals were triturated at
0˚ with 1% ether in petroleum ether to give a white solid, mp 46-
18 19
2
-1
1
48˚; ir: 3365, 1735 cm ; H nmr: δ 7.05 (td, 1H, J = 7.4, 1.5),
6.95 (dd, 1H, J = 7.6, 1.5), 6.85 (td, 1H, J = 7.4, 1.2), 6.73 (dd,
1H, J = 7.6, 1.2), 3.85 (dd, 1H, J = 8.3, 2.3), 3.74 (s, 3H), 3.42 (br
s, 1H), 2.81 (m, 1H), 2.16 (m, 1H), 1.92 (m, 2H), 1.58-1.42 (com-
(±)-3-(3-Phenylpropyl)-2-indolinone (16).
This compound (125 mg, 32%) was isolated as a white pow-
der, mp 82-83˚ (ether-petroleum ether); lit mp 84-85˚ [18]; ir:
-1
1
3217, 1708 cm ; H nmr: δ 8.70 (br s, 1H), 7.28-7.10 (complex,
13
plex, 3H), 0.98 (t, 3H, J = 7.4); C nmr: δ 175.2, 148.2, 129.5,
129.1, 127.4, 120.8, 120.3, 58.3, 51.8, 49.0, 33.5, 29.5, 26.9,
7H), 7.01 (t, 1H, J = 7.5), 6.88 (d, 1H, J = 7.5), 3.48 (t, 1H, J =
5.9), 2.61 (overlapping m, 2H), 2.00 (m, 2H), 1.78-1.60 (com-
10.7; hrms: m/z Calcd. for C H NO : 233.1416; Found:
14 19 2
233.1413.
13
plex, 2H);
127.8, 125.8, 124.1, 122.3, 109.7, 45.9, 35.8, 30.1, 27.5; hrms:
C nmr: δ 180.4, 141.8, 141.5, 129.6, 128.3 (2),
Anal. Calcd. for C H NO : C, 72.07; H, 8.21; N, 6.00.
14 19
Found: C, 72.16; H, 8.25; N, 5.89.
2
m/z Calcd. for C H NO: 251.1310; Found: 251.1307.
17 17
Anal. Calcd. for C H NO: C, 81.27; H, 6.77; N, 5.58.
17 17
Found: C, 80.96; H, 6.87; N, 5.54.
Methyl (±)-(2R*,5S*)-2-Ethyl-2, 3, 4, 5-tetrahydro-1H-1-ben-
zazepine-5-carboxylate (12).
Dimethyl (±)-2-(2-Aminophenyl)pentanedioate (17).
This compound (566 mg, 68%) was isolated as a white solid,
-1
1
To a solution of 750 mg (2.66 mmole) of 8 in 200 mL of
methanol was added 180 mg of 5% palladium-on-carbon and the
mixture was hydrogenated as described for the preparation of 9.
The crude product was purified by preparative thin layer chro-
matography eluted with 25-50% ether in hexanes to give 650 mg
mp 74-76˚ (ether-petroleum ether); ir: 3360, 1728 cm ; H nmr:
δ 7.11 (td, 1H, J = 7.4, 1.6), 7.03 (dd, 1H, J = 7.7, 1.6), 6.88 (td,
1H, J = 7.4, 1.2), 6.76 (dd, 1H, J = 7.7, 1.2), 3.85 (dd, 1H, J = 6.3,
2.2), 3.66 (s, 3H), 3.39 (br s, 1H), 2.65 (m, 1H), 2.42 (m, 1H),
1.79-1.63 (complex, 3H), 1.52 (quintet, 2H, J = 7.4), 0.99 (t, 3H,