ϩ
MeV 325). Bombardment was carried out for 1 to 2 min with a
to 2 µA beam of 16 MeV protons yielding 150–580 MBq of
72), 132 (M Ϫ C H , 5) and 41 (100). Addition of anhydrous
4 9
1
hydrogen chloride (1 M) in diethyl ether to a solution of 9c
in diethyl ether yielded quantitatively, after evaporation of
the solvent, 2-(2-methylpropyl)-1,2,3,4-tetrahydroisoquinoline
1
1
[
C]carbon dioxide. Radioactivity was measured with a Capin-
tec Radioisotope Calibrator (CRC-12). Identification of the
labelled compounds and determination of the radiochemical
purity were carried out by radio-TLC using a Berthold auto-
matic TLC-linear analyser and authentic stable isotope samples
as references.
26
hydrochloride as a white solid (mp 201–203 ЊC, lit., 205 ЊC).
2
7
2-(2,2-Dimethylpropyl)-1,2,3,4-tetrahydroisoquinoline 9d
Purification by column chromatography using dichloro-
methane–methanol (90:10) as eluent gave the pure title com-
pound 9d as a yellow oil, R 0.4 (dichloromethane–methanol,
Reductive amination of carboxylic acid 1: general procedure
f
Ϫ1
Method A. To a mixture of carboxylic acid 1 (4 mmol), amine
90:10); νmax (NaCl)/cm 2952, 2862, 1464 and 744; δ (CDCl )
H
3
2
–4 (4 mmol), salt 5–8 (12 mmol) in THF, dichloromethane or
0.90 (9H, s), 2.2 (2H, s), 2.6 (2H, t, J 5.8), 2.8 (2H, t, J 5.8), 3.65
(2H, s), 7.0–7.1 (4H, m); δ (CDCl ) 27.9, 29.6, 33.3, 53.7, 58.6,
3
toluene (15 cm ), NaBH (0.760 g, 20 mmol) was added at 50 ЊC
over a period of 15 min. After heating at 70 ЊC for 15 h, the
suspension was cooled to room temperature and hydrolysed
with sodium hydroxide (5%, 20 cm ). After extraction with
4
C
3
ϩ
ؒ
70.1, 125.5, 125.9, 126.6, 128.8, 134.8 and 137.0; m/z 203 (M
,
ϩ
1%) and 146 (M Ϫ C H , 100).
4
9
3
3
28
dichloromethane (3 × 20 cm ), the organic phase was dried over
2-Benzyl-1,2,3,4-tetrahydroisoquinoline 9e
magnesium sulfate, filtered and evaporated. The crude product
was purified by column chromatography to yield the desired
N-alkylated amines 9–11, the amine–borane complexes 15–17
or the starting amines 2–4 (Scheme 2, Table 1).
Purification by column chromatography using dichloro-
methane–methanol (90:10) as eluent gave the pure title com-
pound 9e as a white solid (mp 37 ЊC), R 0.5 (dichloromethane–
f
Ϫ1
methanol, 90:10); νmax (NaCl)/cm 3084, 3062, 3024, 2918,
2
800, 2756, 1496, 1454, 1094, 740 and 698; δH (CDCl ) 2.75
3
Method B. Carboxylic acid 1 (4 mmol) was added dropwise at
(
2H, t, J 5.7), 2.91 (2H, t, J 5.7), 3.64 (2H, s), 3.69 (2H, s), 6.7–
0
(
ЊC to a suspension of NaBH (0.760 g, 20 mmol) in a solvent
4
3
7
1
2
.4 (9H, m); δC (CDCl ) 29.3, 50.8, 56.3, 62.9, 125.7, 126.2,
3
15 cm ) (THF, diethyl ether, dioxane, dichloromethane, tolu-
26.7, 127.2, 128.4, 128.7, 129.2, 134.5, 135.1 and 138.5; m/z
23 (M , 8%), 146 (M Ϫ C H , 68), 132 (M Ϫ C H , 13)
ene, ethanol, N,N-dimethylformamide or dimethyl sulfoxide).
After stirring for 15 min, salt 5–8 (12 mmol) then amine 2–4
4 mmol) were added. The mixture was heated at 70 ЊC for 15 h,
ϩ
ؒ
ϩ
ؒ
ϩ
ؒ
6
5
7
7
and 41 (100). Addition of anhydrous hydrogen chloride (1 M)
in diethyl ether to a solution of 9e in diethyl ether yielded
quantitatively, after evaporation of the solvent, 2-benzyl-
(
cooled to room temperature and then hydrolysed with sodium
3
hydroxide (5%, 20 cm ). After extraction with dichloromethane
1
,2,3,4-tetrahydroisoquinoline hydrochloride as a white solid
3
(
3 × 20 cm ), the organic phase was dried over magnesium sul-
28
(
mp 203–204 ЊC, lit. 204 ЊC).
fate, filtered and evaporated. The crude product was purified to
yield the desired amines 9–11, the corresponding amides 12–14,
the amine–borane complexes 15–17 and the starting amines 2–4
2
9
2
-(2-Phenylethyl)-1,2,3,4-tetrahydroisoquinoline 9f
(
see Results and discussion, Scheme 2, Table 1).
Purification by column chromatography using dichloro-
methane–methanol (90:10) as eluent gave the pure title com-
11,25
2
-Ethyl-1,2,3,4-tetrahydroisoquinoline 9a
pound 9f as a yellow oil, R 0.67 (dichloromethane–methanol,
f
Ϫ1
9
2
0:10); νmax (NaCl)/cm 3024, 2928, 1672 and 740; δ (CDCl )
.7–2.8 (4H, m), 2.8–2.9 (4H, m), 3.72 (2H, s), 7.0–7.3 (9H, m);
H 3
Purification by column chromatography using dichloro-
methane–methanol (90:10) as eluent yielded 9a as a yellow oil,
R 0.4 (dichloromethane–methanol, 90:10); ν
2
δC (CDCl ) 29.2, 34.1, 51.1, 56.2, 60.5, 125.7, 126.2, 126.3,
Ϫ1
3
(NaCl)/cm
f
max
1
26.7, 127.2, 128.5, 132.3, 134.9, 134.8 and 140.5.
968, 2932, 2800, 2768, 1452 and 740; δH (CDCl ) 1.1 (3H, t,
3
J 7.2), 2.49 (2H, q, J 7.2), 2.65 (2H, t, J 5.9), 2.84 (2H, t, J 5.9),
1
2
1
-Ethylpiperidine 10a
3
5
.55 (2H, s), 6.92–7.03 (4H, m); δC (CDCl ) 12.4, 29.1, 50.7,
3
2.2, 55.8, 125.7, 126.7, 127.2, 128.7, 134.3 and 134.7; m/z 161
Purification by column chromatography using dichloro-
methane–cyclohexane–methanol–NH OH (68:15:15:2) as
eluent gave the pure title compound 10a as a yellow oil, R 0.5
ϩ
ؒ
ϩ
ϩ
(
(
M
, 1%), 146 (M Ϫ CH , 9), 132 (M Ϫ C H , 18) and 41
3
2
5
4
100).
f
(
dichloromethane–cyclohexane–methanol–NH OH,
68:15:
4
25
2
-Butyl-1,2,3,4-tetrahydroisoquinoline 9b
15:2); δH (CDCl ) 0.91 (3H, t, J 7.2), 1.4–1.6 (7H, m), 2.3 (5H,
3
m); δ (CDCl ) 24.8, 26.9, 29.5, 54.9 and 59.7.
C
3
Purification by column chromatography using light petroleum–
ethyl acetate (30:70) as eluent gave the pure title compound 9b
as a yellow oil, R 0.8 (light petroleum (bp 35–60 ЊC)–ethyl
3
0
1
-Butylpiperidine 10b
f
Ϫ1
acetate, 30:70); νmax (NaCl)/cm 2954, 2930, 1454 and 740;
Purification by column chromatography using dichloro-
δH (CDCl ) 0.9 (3H, t, J 7.4), 1.25–1.34 (2H, m), 1.45–1.58
methane–cyclohexane–methanol–NH OH (68:15:15:2) as
3
4
(
2H, m), 2.43 (2H, t, J 7.4), 2.65 (2H, t, J 5.9), 2.84 (2H, t,
eluent gave the pure title compound 10b as a yellow oil, R 0.5
f
J 5.9), 3.55 (2H, s), 6.92–7.03 (4H, m); δC (CDCl ) 14.2, 20.9,
(dichloromethane–cyclohexane–methanol–NH OH,
68:15:
3
4
2
9.2, 29.5, 51.1, 56.3, 58.4, 125.7, 126.2, 126.7, 128.7, 134.5
15:2); δH (CDCl ) 0.91 (3H, t, J 7.2), 1.3 (2H, sextet, J 7.2),
3
ϩ
ؒ
ϩ
and 134.9; m/z 189 (M , 5%), 146 (M Ϫ C H , 83), 132
1.5 (5H, m), 1.6 (4H, m), 2.3 (m, 5H); δC (CDCl ) 14.2, 21.2,
3
7
3
ϩ
(
M Ϫ C H , 8) and 41 (100).
24.6, 26.1, 29.2, 54.8 and 59.5.
4
9
26
2
-(2-Methylpropyl)-1,2,3,4-tetrahydroisoquinoline 9c
1-Benzyl-4-butylpiperazine 11b
Purification by column chromatography using dichloro-
methane–methanol (90: 10) as eluent gave the pure title com-
Purification by column chromatography using dichloro-
methane–methanol (90:10) as eluent gave the pure title com-
pound 9c as a yellow oil, R 0.8 (dichloromethane–methanol,
pound 11b as a yellow oil, R 0.66 (dichloromethane–methanol,
f
f
Ϫ1
ϩ
ؒ
9
0: 10); νmax (NaCl)/cm 2952, 2924, 1464 and 740; δ (CDCl )
90:10) (Found: M , 232.1922. C H N requires M,
H
3
15 24 2
0
.95 (6H, d, J 6.6), 1.90 (1H, m), 2.26 (2H, d, J 7.3), 2.68 (2H, t,
232.1934); δH (CDCl ) 0.83 (3H, t, J 7.3), 1.28–1.36 (2H, m),
3
J 5.8), 2.89 (2H, t, J 5.8), 3.58 (2H, s), 7.0–7.1 (4H, m); δC
1.4–1.6 (2H, m), 2.2–2.3 (2H, m), 2.5–2.6 (8H, m), 3.5 (2H, s),
(
1
CDCl ) 21.1, 25.8, 29.3, 47.5, 51.2, 56.8, 125.6, 126.1, 127.2,
7.2–7.3 (5H, m); δC (CDCl ) 14.1, 20.6, 29.3, 53.5, 53.9, 60.7,
63.3, 127.5, 128.3, 129.4 and 138.1.
3
3
ϩ
ؒ
ϩ
28.8, 134.8 and 135.4; m/z 189 (M , 2%), 146 (M Ϫ C H ,
3
7
3
14
J. Chem. Soc., Perkin Trans. 1, 2000, 311–316