PAPER
Synthesis of Amino-Bridged 6,6 -Disubstituted-2,2 -Bipyridines
2717
1H NMR (CDCl3): = 0.83 (t, 3 H, 3J = 7.3 Hz), 1.33 (m, 2 H), 1.44
(t, 6 H, 3J = 7.2 Hz), 1.60 (m, 2 H), 2.61 (t, 2 H, 3J = 7.2 Hz), 3.92
Tris[(6 -carboethoxy-2,2 -bipyridine-6-yl)methyl]butylammo-
nium Bromide (7)
3
3
(s, 4 H), 4.46 (q, 4 H, J = 7.2 Hz), 7.60 (dd, 2 H, J = 7.7 Hz,
A solution of 6 (121 mg, 135 mol) and Pd(PPh3)2Cl2 (12 mg, 0.017
mmol) in a mixture of EtOH (10 mL) and Et3N (10 mL) was heated
at 70 °C for 20 h under a CO atmosphere. After the solution had
cooled to r.t., the solvents were removed under vacuum and the re-
sulting solid was dissolved in CH2Cl2 (30 mL), and the CH2Cl2 layer
was washed with aq NaOH (pH 10, 10 mL). The aqueous layer was
extracted with CH2Cl2 (15 mL) and the combined organic layers
were dried (MgSO4), filtered and evaporated to dryness. The resi-
due was dissolved in a minimum amount of CH2Cl2, and Et2O was
added until a white precipitate forms. The solid was filtered off and
the mother liquor was evaporated to dryness and the residue was
dried under vacuum to give 7; yield: 112 mg (95%, using CO of
99.995% purity); 12 mg (10% using standard CO of 99% purity) as
an orange oil.
3
3
4J = 0.9 Hz), 7.80 (t, 2 H, J = 7.7 Hz), 7.90 (t, 2 H, J = 7.8 Hz),
8.10 (dd, 2 H, 3J = 7.5 Hz, 4J = 1.1 Hz), 8.40 (dd, 2 H, 3J = 7.7 Hz,
4J = 0.8 Hz), 8.60 (dd, 2 H, 3J = 7.9 Hz, 4J = 1.1 Hz).
13C{1H} NMR (CDCl3): = 13.9, 14.2, 20.4, 29.5, 54.2, 60.4, 61.6,
119.6, 123.2, 124.0, 124.6, 137.1, 137.5, 147.7, 154.2, 156.5, 159.6,
165.2.
MS (FAB+): m/z (%) = 480.2 ([M – CO2Et], 10), 554.2 ([M + H]+,
100).
Anal. Calcd for C32H35N5O4: C, 69.42; H, 6.37; N, 12.65. Found: C,
69.17; H, 6.14; N, 12.44.
Bis[(6 -carboxy-2,2 -bipyridine-6-yl)methyl]butylamine (5)
Compound 4 (136 mg, 250 mol) was dissolved in a mixture of
EtOH (25 mL) and H2O (18 mL) containing NaOH (40 mg, 1.0
mmol) and the solution was refluxed overnight. After cooling to r.t.,
dil. HCl was slowly added until the mixture reached pH 3–4, result-
ing in the precipitation of a white solid. The solid was isolated by
centrifugation, washed with H2O (5 mL), isolated by centrifugation,
and dried under vacuum to give compound 5; yield: 103 mg (79%);
white solid.
IR (CH2Cl2): 3063 (w), 2959 (m), 2925 (s), 2854 (m), 1739 (s),
1721 (s), 1581 (s), 1465 (m), 1441 (s), 1082 (m), 1024 cm–1 (m).
1H NMR (CDCl3): = 0.75 (t, 3 H, 3J = 7.5 Hz), 1.20 (m, 2 H), 1.45
3
(t, 9 H, J = 7.0 Hz), 1.92 (m, 2 H), 4.02 (m, 2 H), 4.48 (q, 6 H,
3
3J = 7.0 Hz), 5.61 (s, 6 H), 7.83 (t, 3 H, J = 8.0 Hz), 7.93 (t, 3 H,
3J = 8.0 Hz), 8.11 (d, 3 H, 3J = 7.5 Hz), 8.19 (d, 3 H, 3J = 7.5 Hz),
8.31 (d, 3 H, 3J = 7.5 Hz), 8.58 (d, 3 H, 3J = 7.5 Hz).
13C{1H} NMR (CDCl3): = 13.5, 13.6, 20.0, 25.5, 31.0, 62.1, 64.0,
122.8, 123.7, 125.4, 128.8, 138.0, 138.9, 148.3, 149.7, 155.3, 155.6,
165.0.
IR (KBr): 3446 (s), 2966 (w), 2926 (w), 1716 (s), 1541 cm–1 (s).
1H NMR (CD3OD): = 0.97 (t, 3 H, 3J = 7.7 Hz), 1.45 (m, 2 H),
1.97 (m, 2 H), 3.51 (t, 2 H, 3J = 8.4 Hz), 4.8 (s, 4 H), 7.5 (d, 2 H,
3J = 7.7 Hz), 7.7 (t, 2 H, 3J = 7.8 Hz), 8.0 (t, 2 H, 3J = 7.8 Hz), 8.1
(d, 2 H, 3J = 7.7 Hz), 8.5 (d, 2 H, 3J = 8.0 Hz), 8.6 (d, 2 H, 3J = 8.0
Hz).
13C{1H} NMR (CD3OD): = 13.9, 21.0, 27.1, 57.1, 58.9, 123.1,
125.2, 125.3, 126.2, 139.4, 140.2, 150.5, 151.6, 156.2, 156.5, 168.7.
MS (FAB+): m/z (%) = 704.2 ([M – C4H10O2], <5),749.2 ([M –
C2H5O], 20), 794.3 ([M – Br]+, 100).
Anal. Calcd for C46H48BrN7O6: C, 63.16; H, 5.53; N, 11.21. Found:
C, 62.83; H, 5.20; N, 10.88.
Tris[(6 -carboxy-2,2 -bipyridine-6-yl)methyl]butylammonium
Chloride (8)
MS (FAB+): m/z = 498.2 ([M + H]+, 100%).
Compound 7 (112 mg, 128 mol) was suspended in a mixture of
conc. HCl (0.5 mL) and H2O (3.5 mL) and the solution was heated
at 70 °C overnight. After the mixture had cooled to r.t., the solvents
were evaporated under reduced pressure. Recrystallisation from
MeOH–Et2O gave compound 8; yield: 44 mg (38%); white solid.
Anal. Calcd for C28H27N5O4·HCl·2H2O: C, 59.00; H, 5.66; N, 12.29.
Found: C, 58.91; H, 5.39; N, 12.09.
Tris[(6 -bromo-2,2 -bipyridine-6-yl)methyl]butylammonium
Bromide (6)
Compound 2 (600 mg, 1.83 mmol) was added to a stirred solution
containing freshly distilled n-butylamine (46 L, 0.46 mmol) and
K2CO3 (345 mg, 2.5 mmol) in anhyd MeCN (35 mL) in a Schlenk
tube under argon. The mixture was heated at 85 °C during 44 h. The
MeCN was distilled under reduced pressure resulting in the isola-
tion of an orange solid. The solid was partitioned between H2O (20
mL) and CH2Cl2 (40 mL), and the aqueous layer was extracted with
CH2Cl2 (3 × 15 mL). The combined organic layers were dried
(MgSO4), filtered, evaporated to dryness, and the resulting solid
was purified by column chromatography (Al2O3 previously deacti-
vated with H2O; CH2Cl2–hexane, 20:80) to give compound 6 [Rf
0.32 (Al2O3), CH2Cl2–MeOH, 95:5]; yield: 150 mg (36%); white
solid.
IR (CH2Cl2): 3421 (s), 3098 (w), 1717 (s), 1633 (m), 1618 (m),
1580 cm–1 (m).
1H NMR (CD3OD): = 0.93 (t, 3 H, 3J = 7.0 Hz), 1.3–1.4 (m, 2 H),
2.3–2.4 (m, 2 H), 3.6–3.7 (m, 2 H), 5.5 (s, 6 H), 7.7–7.8 (br s, 3 H),
7.8–8.0 (m, 6 H), 8.0–8.1 (m, 3 H), 8.31 (t, 3 H, 3J = 7.0 Hz), 8.55
(d, 3 H, 3J = 8.0 Hz).
13C{1H} NMR (CD3OD): = 13.9, 27.1, 53.4, 57.4, 60.2, 109.4,
123.0, 125.0, 125.9, 127.9, 140.7, 147.2, 147.6, 148.6, 159.1, 166.5.
MS (FAB+): m/z = 710.2 ([M – Cl ]+, 100%).
Anal. Calcd for C40H36ClN7O6·3HCl·2H2O: C, 53.88; H, 4.86; N,
11.00. Found: C, 53.73; H, 4.52; N, 10.88.
IR (CH2Cl2): 2906 (w), 1653 (s), 1541 (s), 1123 (m), 785 cm–1 (w).
N-(3-Aminopropyl)-4-nitrobenzamide (9)18
IR (KBr): 2976 (m), 2921 (m), 1638 (s), 1597 (s), 1548 (s), 1516 (s),
1352 cm–1 (s).
1H NMR (DMSO-d6): = 1.60 (q, 2 H, 3J = 7.0 Hz), 2.60 (t, 2 H,
3J = 7.0 Hz), 3.34 (br t, 2 H, 3J = 7.0 Hz), 8.02–8.09 (m, 2 H), 8.29–
8.33 (m, 2 H), 8.88 (br t, 1 H).
1H NMR (CDCl3): = 0.78 (t, 3 H, 3J = 7.5 Hz), 1.19 (m, 2 H), 2.04
(m, 2 H), 4.01 (t, 2 H, 3J = 7.5 Hz), 5.50 (s, 6 H), 7.38–7.52 (m, 6
H), 7.75 (t, 3 H, 3J = 8.0 Hz), 8.0 (t, 6 H, 3J = 7.5 Hz), 8.25 (d, 3 H,
3J = 8.0 Hz).
13C{1H} NMR (CDCl3): = 13.5, 14.9, 25.3, 61.7, 63.9, 119.3,
122.3, 128.5, 128.6, 138.6, 139.0, 142.0, 149.6, 154.5, 155.9.
13C{1H} NMR (CD3OD): = 28.7, 37.3, 51.2, 123.4, 128.5, 140.1,
148.8, 164.5.
MS (FAB+): m/z (%) = 814.2 ([M – Br]+, 95), 816.2 ([M – Br]+,
100).
MS (FAB+): m/z = 224.1 ([M + H]+, 100%).
Anal. Calcd for C37H33Br4N7: C, 49.64; H, 3.72; N, 10.95. Found:
C, 50.14; H, 3.95; N, 11.36.
Anal. Calcd for C10H13N3O3: C, 53.81; H, 5.87; N, 18.82. Found: C,
53.72; H, 5.75; N, 18.69.
Synthesis 2003, No. 17, 2713–2719 © Thieme Stuttgart · New York