1
H NMR spectroscopy showed that no reaction had taken
place.
diameter, eluant: 0.5% EtOH in CH Cl ) gave 6c (44 mg, 45%
yield) with melting point and spectroscopic properties as
2
2
described above and 6d (27 mg, 32% yield) with mp 119.5–120.5
17
1
Reactions with phenol and 4-methoxyphenol. 2b was reacted
ЊC (lit. 122 ЊC). The H NMR data were in accordance with
20 13
with phenol and 4-methoxyphenol at room temperature with
DMF as solvent. Both sodium metal and triethylamine were
those reported.
C NMR (100 MHz; CDCl ; Me Si) δ 14.5,
3 4
3
7.1, 105 (v. br.), 133.0 (br.), 135.8, 147.1, 161.1; IR (KBr):
1
Ϫ1
tried to generate phenoxide ions. H NMR spectroscopy
ν/cm 3347 (s), 3227 (m), 2981 (m), 2933 (w), 1604 (s), 1549
m), 1498 (m), 1474 (m), 1456 (w), 1424 (w), 1368 (w), 1323 (s),
286 (s), 1165 (w), 1138 (m), 1109 (s), 1060 (w), 994 (w), 938
showed that no reaction took place.
(
1
Substitution reactions with amines
(
(
(
w), 827 (m), 808 (w), 765 (m), 731 (w), 671 (m), 660 (w), 544
m), 501 (m), 425 (m); EIMS (250 ЊC, 70 eV) m/z (% rel. int.) 168
General procedure. A 25 volume% solution of the appropriate
amine in water (20 ml) was added to 2a (0.60 mmol) and stirred
at room temperature for 18 h. The reaction mixture was then
concentrated under reduced pressure, and to the residue was
added CH Cl (50 ml) and water (50 ml). The aqueous layer was
ϩ
M ϩ 1, 6), 167 (M , 54), 153 (7), 152 (100), 139 (34), 124 (6),
1
7
5
20 (14), 119 (9), 109 (7), 107 (7), 106 (92), 94 (9), 93 (12), 81 (6),
9 (13), 78 (37), 77 (5), 66 (24), 65 (10), 64 (8), 54 (7), 53 (6),
2 (15), 51 (20); UV-Vis(EtOH): λmax = 260 nm, ε = 13368,
2
2
λmax = 363 nm, ε = 16368.
For the two following compounds, the general procedure was
not used because the amines were not soluble in water.
extracted with CH Cl (3 × 25 ml). The combined organic layers
2
2
were washed with brine (2 × 50 ml) and dried (MgSO ). The
4
solvent was evaporated under reduced pressure, and the
obtained solid purified by flash chromatography.
2
-Amino-5-nitropyridine (6a). 6a was obtained with ammo-
2-Benzylamino-5-nitropyridine (6e). Benzylamine (0.32 g,
3.0 mmol) and 2a (0.60 mmol) were mixed in water (10 ml) and
stirred vigorously for 20 h. During this time the product precipi-
tated. Filtration and drying under reduced pressure gave 6e as
yellow crystals (106 mg, 77% yield) with mp 133.5–134.5 ЊC
nia as a yellow solid (77 mg, 92% yield) with mp 190.0–191.5 ЊC
11
(
lit. 188–189 ЊC). The flash chromatography system used was
0 ml silica, 1.5 cm column diameter, eluant: 2% EtOH
in CH Cl . The spectroscopic data were in accordance
2
2
2
11
18
with those reported. UV-Vis(EtOH): λmax = 220 nm, ε = 9761,
(lit. 130.1–131.1 ЊC). The spectroscopic data were in accord-
21 13
λmax = 345 nm, ε = 14283.
ance with those reported.
C NMR (100 MHz; CDCl ;
3
2
-n-Butylamino-5-nitropyridine (6b). 6b was obtained with
Me Si) δ 46.3, 106 (v. br.), 127.5, 127.9, 129.0, 133.1, 136.2, 137
4
Ϫ1
n-butylamine as a yellow solid (89 mg, 76% yield) with mp
(br.), 146.9, 161.0; IR (KBr): ν/cm 3221 (m), 1603 (s), 1546
(m), 1493 (s), 1455 (m), 1424 (s), 1334 (s), 1290 (s), 1165 (m),
1119 (s), 1033 (w), 1009 (m), 956 (w), 907 (m), 841 (m), 823 (m),
767 (s), 740 (s), 693 (m), 670 (w), 550 (s), 511 (m), 495 (m);
UV-Vis(EtOH): λmax = 361 nm, ε = 18698.
17
1
04.5–105.5 ЊC (lit. 102 ЊC). The flash chromatography system
used was 20 ml silica, 1.5 cm column diameter, eluant: 1.5%
1
EtOH in CH Cl . H NMR (300 MHz; CDCl ; Me Si) δ 0.97
2
2
3
4
(
3H, t, J = 7.3, CH ), 1.44 (2H, m, CH ), 1.64 (2H, m, CH ),
3
2
2
3
8
.39 (2H, m, br.), 5.30 (1H, s, br., NH), 6.34 (1H, d, J = 9.3),
13
.19 (1H, dd, J = 2.5, 9.3), 9.01 (1H, d, J = 2.5); C NMR (100
2-(R-1-Phenylethylamino)-5-nitropyridine (6f). R-1-Phenyl-
ethylamine (10 ml) and 2a (0.60 mmol) were mixed in water
(30 ml) and stirred vigorously for 20 h. To the reaction mixture
was added CH Cl (50 ml) and water (50 ml). The aqueous layer
MHz; CDCl ; Me Si) δ 13.8, 20.1, 31.3, 42.1, 105 (v. br.), 133.1
3
4
13
(
br.), 135.4, 147.1, 161.3; C NMR (75 MHz; D O–conc. HCl;
2
(
CH ) SiCD CD CO Na) δ 15.8, 22.3, 32.2, 45.6, 117 (br.),
3
3
2
2
2
2
2
Ϫ1
1
38.1 (br.), 138.5, 139.1, 157.0; IR (KBr): ν/cm 3233 (s), 3155
was extracted with CH Cl (3 × 25 ml). The combined organic
2 2
(
1
w), 3095 (m), 2995 (w), 2960 (s), 2930 (m), 2867 (s), 1606 (s),
548 (w), 1497 (m), 1459 (w), 1424 (m), 1330 (s), 1291 (s), 1165
layers were washed with brine (2 × 50 ml) and dried (MgSO ).
4
The solvent was evaporated under reduced pressure to give a
yellow liquid which contained 6f dissolved in R-1-phenyl-
ethylamine. These were separated by distillation to give 6f as a
yellow oil which was purified by flash chromatography (50 ml
silica, 2.0 cm column diameter, eluant: CH Cl –pentane =
(
(
m), 1114 (s), 1011 (m), 946 (w), 834 (m), 767 (m), 669 (m), 556
m); EIMS (250 ЊC, 70 eV) m/z (% rel. int.) 196 (M ϩ 1, 7),
ϩ
1
95 (M , 24), 179 (9), 166 (26), 153 (23), 152 (100), 139 (28), 136
(
(
5), 122 (21), 120 (11), 106 (52), 93 (7), 81 (5), 78 (16), 66 (12), 57
5), 41 (11), 29 (4); UV-Vis(EtOH): λmax = 227 nm, ε = 7950,
2
2
90 : 10). This gave 6f as yellow crystals (104 mg, 71% yield) with
22
1
λmax= 364 nm, ε = 15500.
-Diethylamino-5-nitropyridine (6c). 6c was obtained with
diethylamine as a yellow solid (73 mg, 62% yield) with mp 75.5–
mp. 79.5–81.0 ЊC (lit. 83 ЊC). H NMR (400 MHz; CDCl ;
3
2
Me Si) δ 1.62 (3H, d, J = 6.8, CH ), 4.6 (1H, m, br., CH), 5.3
4
3
(1H, s, br., NH), 6.22 (1H, d, J = 9.3), 7.3 (5H, m), 8.11 (1H, dd,
18
13
7
7.0 ЊC (lit. 75.2–76.2 ЊC). The flash chromatography system
J = 2.7, 9.3), 9.00 (1H, d, J = 2.7); C NMR (100 MHz; CDCl3;
used was 20 ml silica, 1.5 cm column diameter, eluant: 0.5%
EtOH in CH Cl . The spectroscopic data were in accordance
Me Si) δ 23.6, 52.1, 105.4 (br.), 125.5, 127.7, 129.0, 133.1, 136.1,
4
Ϫ1
2
2
142.8, 146.9, 160.4; IR (KBr): ν/cm 3405 (s), 3062 (w), 3029
19
Ϫ1
with those reported. IR (KBr): ν/cm 3102 (w), 2980 (m),
926 (m), 2602 (w), 2438 (w), 1596 (s), 1568 (s), 1527 (s), 1476
s), 1449 (m), 1431 (s), 1380 (m), 1327 (s), 1280 (s), 1187 (m),
(w), 2991 (w), 2968 (m), 2921 (w), 2864 (w), 2610 (w), 2534 (w),
2442 (w), 2360 (w), 1607 (s), 1575 (s), 1524 (s), 1492 (s), 1474 (s),
1448 (m), 1395 (w), 1374 (m), 1326 (s), 1286 (s), 1245 (s), 1204
(m), 1159 (m), 1110 (s), 1092 (m), 1026 (s), 1013 (m), 996 (m),
942 (m), 914 (w), 835 (s), 766 (s), 729 (m), 703 (s), 689 (m), 566
(m), 533 (s), 519 (m), 491 (m), 414 (m); EIMS (200 ЊC, 70 eV) m/z
2
(
1
7
4
114 (s), 1075 (m), 1016 (w), 993 (w), 939 (w), 829 (m), 796 (w),
82 (m), 764 (m), 739 (m), 605 (w), 560 (m), 534 (w), 499 (w),
20 (m); UV-Vis(EtOH): λmax = 231 nm, ε = 6250, λmax = 375 nm,
ϩ
ε = 20625.
(% rel. int.) 244 (M , 12), 243 (64), 229 (14), 228 (99), 182 (24),
1
9
66 (6), 139 (8), 120 (20), 106 (9), 105 (100), 104 (18), 103 (11),
1 (8), 79 (16), 78 (11), 77 (20), 51 (8); UV-Vis(EtOH):
Substitution reaction with diethylamine in refluxing DMF. A
mixture of 2a (0.50 mmol), diethylamine (10 ml) and DMF
λmax = 361 nm, ε = 18698.
(
10 ml) was heated with reflux under N for 20 h. The reaction
2
mixture was then concentrated under reduced pressure, and to
the residue was added CH Cl (30 ml) and water (30 ml). The
Reaction with aniline. 2b was reacted with aniline at room
temperature and at 100 ЊC with DMF as solvent. H NMR
spectroscopy showed that no reaction took place.
2
2
1
aqueous layer was extracted with CH Cl (3 × 15 ml). The com-
2
2
bined organic layers were washed with brine (2 × 20 ml) and
dried (MgSO ). The solvent was evaporated under reduced
4
Substitution reactions with halides and cyanide
pressure. This gave a yellow oil which contained 6c and 2-ethyl-
1
amino-5-nitropyridine (6d) (6c : 6d = 3 : 2 from H NMR).
2-Chloro-5-nitropyridine (3). A mixture of 2a (2.00 mmol)
Separation on a flash column (20 ml silica, 1.5 cm column
and PCl (4.17 g, 20.00 mmol) was heated to reflux for 0.5 h.
5
2
714
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 2 7 1 0 – 2 7 1 5