PAPER
New Ditopic and Tripodal 1,2,4-Triazole- and Tetrazole-Based Ligands
1509
Yield: 0.975 g (61%); mp 143–145 °C; Rf 0.4 (EtOAc–CH2Cl2,
Yield: 32.74 g (51%); mp 61–64 °C.
1:1).
IR (KBr): 3330 (s), 3108 (m), 2928 (m), 2874 (m), 1678 (vs), 1538
(s), 1462 (m), 1388 (m), 1188 (s), 1062 (s), 987 (w), 959 (w), 923
(w), 875 (w), 715 (w), 637 (m) cm–1.
1H NMR (200 MHz, CDCl3, 298 K): d = 1.99–2.09 (m, 2 H), 3.25
(br s, 1 H, OH), 3.65 (t, J = 5.9 Hz, 2 H), 4.25 (t, J = 6.7 Hz, 2 H),
8.24 (s, 2 H).
IR (KBr): 3457 (w), 3148 (w), 2951 (w), 2874 (w), 1767 (m), 1767
(m), 1708 (s), 1610 (w), 1485 (w), 1467 (m), 1441 (m), 1405 (s),
1374 (m), 1340 (m), 1237 (m), 1189 (m), 1165 (m), 1119 (m), 1098
(m), 1075 (m), 1047 (s), 963 (m), 917 (m), 859 (m), 728 (s), 660
(w), 620 (w), 552 (w), 533 (m) cm–1.
1H NMR (200 MHz, CDCl3, 298 K): d = 1.69–1.83 (m, 2 H), 1.94–
2.05 (m, 2 H), 3.76 (t, J = 6.7 Hz, 2 H), 4.53 (t, J = 7.2 Hz, 2 H),
7.72–7.82 (m, 2 H), 7.84–7.88 (m, 2 H), 8.65 (s, 1 H).
13C NMR (50 MHz, CDCl3, 298 K): d = 25.6, 27.2, 36.7, 47.6,
123.6, 132.2, 134.3, 142.6, 168.5.
MS: m/z calcd for C13H14N5O2 [M + H+]: 272.11; found: 272.1.
13C NMR (50 MHz, CDCl3, 298 K): d = 33.1, 42.2, 57.8, 143.3.
2-[3-(4H-1,2,4-Triazol-4-yl)propyl]isoindoline-1,3-dione (6)
PPh3 (3.12 g, 11.88 mmol, 1.5 equiv) in anhyd MeCN–THF (1:1, 20
mL) were cooled to 0 °C, DIAD (2.34 mL, 11.88 mmol, 1.5 equiv)
was added with stirring, and the mixture was stirred for 10 min.
Then a mixture of phthalimide (1.158 g, 7.87 mmol, 1 equiv) and 5
(1 g, 7.87 mmol, 1 equiv) in MeCN–THF (1:2, 20 mL) was added,
the mixture was allowed to warm to r.t., and then stirred overnight.
The white precipitate formed was removed by filtration and recrys-
tallized from H2O (10 mL) to afford pale-yellow sharp plates.
Anal. Calcd for C13H13N5O2 (271.28): C, 57.56; H, 4.83; N, 25.82.
Found C, 57.44; H, 4.82, N, 25.56.
4-(1H-Tetrazol-1-yl)butylamine (3)
Tetrazole 2 (60 mg, 0.22 mmol, 1 equiv) and NH2NH2·H2O (40 mL,
0.82 mmol, 3.7 equiv) in EtOH (10 mL) were heated to reflux for 2
h. After removal of the phthalhydrazide by filtration, the solvent
was removed under reduced pressure to give a pale-yellow solid. To
ensure that all phthalhydrazide was removed, MeCN (10 mL) was
added, the resulting solution was filtered, and concentrated; this
process was carried out three times to afford pure 3.
Yield: 1.513 g (75%); mp 176–178 °C.
IR (KBr): 3444 (w), 3137 (m), 3107 (m), 3041 (w), 2965 (w), 1760
(s), 1703 (s), 1521 (m), 1441 (m), 1399 (s), 1365 (m), 1346 (s), 1186
(s), 1118 (m), 1075 (m), 1030 (m), 969 (m), 810 (w), 726 (m), 531
(m), 631 (m) cm–1.
1H NMR (200 MHz, CDCl3, 298 K): d = 2.15–2.28 (m, 2 H), 3.76
(t, J = 6.3 Hz, 2 H), 4.10 (t, J = 7.0 Hz, 2 H), 7.77–7.81 (m, 2 H),
7.85–7.89 (m, 2 H), 8.34 (s, 2 H).
13C NMR (50 MHz, CDCl3, 298 K): d = 30.4, 34.8, 42.9, 123.6,
132, 134.5, 143, 168.5.
MS: m/z calcd for C13H13N4O2 [M + H+]: 257.1; found: 257.1.
Yield: 14 mg (45%).
IR (KBr): 3104 (m), 2944 (m), 2868 (m), 1639 (s), 1571 (s), 1482
(s), 1442 (s), 1368 (m), 1315 (m), 1170 (m), 109 (m), 1023 (w), 970
(m), 883 (w), 836 (w), 772 (w), 749 (w), 722 (w), 700 (w), 679 (w),
663 (w), 653 (w), 561 (w) cm–1.
1H NMR (200 MHz, DMSO, 298 K): d = 1.38–1.52 (m, 2 H), 1.84–
1.97 (m, 2 H), 2.71 (t, J = 7.0 Hz, 2 H), 4.57 (t, J = 7.1 Hz, 2 H), 9.2
(s, 1 H).
Anal. Calcd for C13H12N4O2 (256.26): C, 60.93; H, 4.72; N, 21.86,
O, 12.48. Found: C, 60.99; H, 4.92; N, 21.74; O, 12.48.
13C NMR (50 MHz, CDCl3, 298 K): d = 27.2, 29.9, 41.1, 48.2,
3-(4H-1,2,4-Triazol-4-yl)propylamine (7)
142.5.
Triazole 6 (5.40 g, 21.07 mmol, 1 equiv) and NH2NH2·H2O (2.20
mL, 22.26 mmol, 1.05 equiv) in EtOH (40 mL) were heated to re-
flux for 2 h. After removal of the phthalhydrazide by filtration at r.t.,
the solvent was removed under reduced pressure to give a pale-yel-
low solid. To ensure that all phthalhydrazide was removed, MeCN
(10 mL) was added, the resulting solution was filtered, and concen-
trated; this process was carried out three times to afford pure 7.
MS: m/z = 142 [M + H+].
HRMS: m/z calcd for C5H12N5 [M + H+]: 142.1092; found:
141.1091.
1-[4-(4H-1,2,4-Triazol-4-yl)butyl]-1H-tetrazole (4)
Freshly prepared anhyd formic hydrazide (25 mg, 0.42 mmol, 1
equiv) and HC(OEt)3 (0.2 mL, 1.20 mmol, 2.9 equiv) in MeOH (10
mL) were heated to reflux for 2 h, then 3 (60 mg, 0.42 mmol, 1
equiv) in anhyd MeOH (5 mL) was added dropwise, and the mixture
was kept at reflux for a further 4 h. After removal of the solvent un-
der reduced pressure, the resulting pink oil was dissolved in a small
amount of EtOH and purified by chromatography (EtOAc →
i-PrOH → EtOH) to afford 4 as a white solid.
Yield: 1.941 g (73%).
IR (NaCl): 3378 (s), 3120 (s), 2958 (s), 2358 (m), 2165 (w), 1646
(m), 1540 (s), 1488 (s), 1388 (m), 1321 (s), 1189 (s), 1079 (m), 993
(m), 636 (m) cm–1.
1H NMR (200 MHz, CD3OD, 298 K): d = 1.85–1.99 (m, 2 H), 2.59
(t, J = 7.0 Hz, 2 H), 4.16 (t, J = 7.2 Hz, 2 H), 8.52 (s, 2 H).
13C NMR (50 MHz, CD3OD, 298 K): d = 34.6, 39.6, 44.2, 144.8.
MS: m/z = 127.1 [M + H+].
HRMS: m/z calcd for C5H11N4 [M + H+]: 127.0983; found:
Yield: 7 mg (9%); Rf 0.25 (EtOH).
1H NMR (200 MHz, DMSO, 298 K): d = 1.61–1.85 (m, 4 H), 4.06
(t, J = 6.5 Hz, 2 H), 4.48 (t, J = 6.6 Hz, 2 H), 8.51 (s, 2 H), 9.40 (s,
1 H).
127.0985.
3-(4H-1,2,4-Triazol-4-yl)propan-1-ol (5)28
1-[3-(4H-1,2,4-Triazol-4-yl)propyl]-1H-tetrazole (8)
AcOH (40 mL) was added to a mixture of triazole amine 7 (2.65 g,
21.00 mmol, 1 equiv), NaN3 (1.37 g, 21.00 mmol, 1 equiv), and
HC(OEt)3 (4 mL, 24.05 mmol, 1.15 equiv). The reaction mixture
was heated to 105 °C and stirred for 20 h. AcOH was removed un-
der reduced pressure, the resulting yellow solid was dissolved in hot
MeCN, and the non soluble by-products were removed by filtration.
MeCN was subsequently removed under reduced pressure and the
yellow solid was dissolved in MeOH (30 mL). Upon addition of
Et2O (90 mL), the product precipitated as a white powder, which
was collected by filtration and dried under reduced pressure.
Freshly prepared anhyd formic hydrazide (30.81 g, 0.51 mol, 1
equiv) and HC(OEt)3 (102 mL, 0.61 mol, 1.2 equiv) in MeOH (650
mL) were heated to reflux for 2 h, then 3-aminopropan-1-ol (39.2
mL, 0.51 mol, 1 equiv) was added dropwise, and the mixture was
kept at reflux for a further 4 h. The solvent was subsequently re-
moved under reduced pressure to give a pink oil, which was left at
–18 °C overnight to afford white needles. The needles were re-
moved by filtration and washed with cold acetone. Finally, the
white compound was dried under reduced pressure.
Synthesis 2006, No. 9, 1504–1512 © Thieme Stuttgart · New York