S. Cesarini et al. / Tetrahedron 62 (2006) 10223–10236
10231
2a–e (1.5 equiv). The slurries were agitated for 18 h at rt,
then washed successively with alternating washes of 3ꢃ
(a) CH2Cl2, (b) dioxane; 3ꢃ (a) CH2Cl2, (b) EtOEt then
with 3ꢃEtOEt. The resins were dried in vacuo and analyzed
by IR and NMR.
thienyl), 8.06, 7.93 (1H, linker), 7.17 (1H, H4, thienyl),
6.55–6.73 (2H, linker), 4.39 (2H, –NH–CH2– spacer), 4.12
(2H, –CH2–O– spacer), 3.84 (3H, Me, linker), 2.49 (2H,
–COCH2– spacer), 2.13 (2H, –CH2– spacer); determination
of loading by elemental analysis: N: 3.74%, 0.89 mmol/g, S:
2.31%, 0.79 mmol/g.
Note: The elemental analysis of resins is not very exact, due
to residual solvent. It is an approximation of the loading. All
following NMR experiments revealed quantitative conver-
sion.
5.3. Reduction of resin-bound hydrazones 3a–e
to hydrazides 4a–e
Hydrazone resins 3a–e (1000 mg, loading 0.86 mmol/g)
were suspended in 10 mL of (CH2Cl2–HOAc–pyridine$BH3
(85:10:5, v/v/v) and agitated for 8 h at rt. The reaction mix-
tures were washed successively with alternating washes of
3ꢃ (a) DMF, (b) CH2Cl2; 3ꢃ (a) MeOH, (b) CH2Cl2; 3ꢃ
(a) CH2Cl2, (b) EtOEt and 3ꢃEtOEt. The resins were dried
in vacuo and analyzed by IR and NMR. All following NMR
experiments revealed quantitative conversion.
5.2.1. Resin 3a. IR (powder): 3025, 2972, 2920, 2850, 1645,
1601, 1546, 1503, 1492, 1451, 1420, 1352, 1308, 1272,
1200, 1163, 1115, 1074, 1028, 976, 909, 873, 834, 795,
757, 696 cmꢁ1
;
1H MAS NMR (500 MHz, DMF-d7)
d 11.86 (1H, NH, hydrazone), 8.90 (1H, CH]N, hydra-
zone), 8.09 (2H, benzoyl), 7.96 (1H, linker), 7.41–7.57
(3H, benzoyl), 6.67, 6.62 (2H, linker), 4.38 (2H, –NH–
CH2– spacer), 4.10 (2H, –CH2–O– spacer), 3.83 (3H, Me,
linker), 2.49 (2H, –COCH2– spacer), 2.11 (2H, –CH2–
spacer); determination of loading by elemental analysis:
N: 3.86%, 0.91 mmol/g.
5.3.1. Resin 4a. IR (powder): 1651, 1611, 1506, 1493, 1419,
1284, 1263, 1198, 1160, 1131, 1028, 970, 901, 821, 757,
1
697 cmꢁ1; H MAS NMR (500 MHz, DMF-d7) d 9.97–
10.27 (1H, –CO–NH–NH–), 7.85–8.03 (2H, o-CH, benzoyl),
7.32–7.58 (1H, p-CH, benzoyl), 7.03–7.29m (1H, linker),
7.03–7.28 (2H, m-CH, benzoyl), 6.54–6.65 (1H, linker),
6.42–6.51 (1H, linker), 4.23–4.53 (2H, –N–CH2– spacer),
3.9–4.12 (4H, –CH2–O–, –CH2–NH–NH– linker), 2.36–
2.55 (2H, –COCH2– spacer), 2.03–2.07 (2H, –CH2– spacer).
5.2.2. Resin 3b. IR (powder): 3058, 3025, 2924, 1651, 1601,
1549, 1493, 1452, 1420, 1372, 1309, 1272, 1199, 1163,
1
1113, 1029, 974, 905, 833, 755, 697 cmꢁ1; H MAS NMR
(500 MHz, DMF-d7) d 11.53, 11.12 (1H, NH, hydrazone),
8.47, 8.62 (1H, CH]N, hydrazone), 7.90, 7.84 (1H, linker),
7.16–7.45 (5H, phenyl), 6.67–6.70 (2H, linker), 4.39 (2H,
NH–CH2– spacer), 4.10 (2H, –CH2–O– spacer), 4.06, 3.63
(2H, CH2), 3.81 (3H, Me, linker), 2.49 (2H, CO–CH2–O–
spacer), 2.12 (2H, –CH2– spacer); determination of loading
by elemental analysis: N: 3.83%, 0.91 mmol/g.
5.3.2. Resin 4b. IR (powder): 1662, 1647, 1613, 1506, 1493,
1451, 1419, 1286, 1262, 1197, 1160, 1132, 1031, 971, 829,
756, 679 cmꢁ1; 1H MAS NMR (500 MHz, DMF-d7) d 9.44–
9.86 (1H, –CO–NH–NH–), 6.82–7.52 (6H, 5H: phenyl, 1H:
linker), 6.53–6.60 (1H, 1H, linker), 6.43–6.49 (1H, linker),
4.22–4.50 (2H, –N–CH2– spacer), 3.45–3.49 (2H, CH2, ben-
zyl), 3.98–4.13 (4H, –CH2–O–), 3.83–3.93 (2H, –N–CH2–
spacer), 3.68–3.81 (5H, Me linker, –CH2–NH–NH– linker),
2.41–2.59 (2H, –COCH2– spacer), 2.06–2.18 (2H, –CH2–
spacer).
5.2.3. Resin 3c. IR (powder): 305, 2972, 2925, 2851, 1647,
1600, 1586, 1549, 1503, 1493, 1452, 1420, 1359, 1310,
1270, 1200, 1163, 1114, 1029, 961, 907, 817, 799, 748,
1
697 cmꢁ1; H MAS NMR (500 MHz, DMF-d7) d 12.41,
11.88 (1H, NH, hydrazone), 9.14, 8.88 (1H, CH]N, hydra-
zone), 7.94, 7.87, 7.55, 7.37 (5H, 4H: 3-fluoro benzoyl, 1H:
linker), 6.69, 6.63 (2H, linker), 4.39 (2H, –NH–CH2–
spacer), 4.10 (2H, –CH2–O– spacer), 3.84 (3H, Me, linker),
2.49 (2H, –COCH2– spacer), 2.11 (2H, –CH2– spacer); de-
termination of loading by elemental analysis: N: 3.67%,
0.89 mmol/g; F: 2.03%, 1.07 mmol/g.
5.3.3. Resin 4c. IR (powder): 2920, 1647, 1612, 1585, 1493,
1451, 1420, 1286, 1269, 1199, 1160, 1130, 1030, 972, 942,
1
888, 820, 795, 754, 697 cmꢁ1; H MAS NMR (500 MHz,
DMF-d7) d 9.92–10.52 (1H, –CO–NH–NH–), 7.76–7.85
(1H, 3-fluorophenyl), 7.68–7.76 (1H, 3-fluorophenyl),
7.16–7.34 (2H, 1H: 3-fluorophenyl, 1H: linker), 6.52–6.64
(1H, linker), 6.41–6.50 (1H, linker), 4.22–4.53 (2H,
–N–CH2– spacer), (2H, –CH2–NH–NH– linker, –CH2–
NH–NH– linker), 3.91–4.16 (4H, –CH2–O–, N–CH2–
spacer), 3.61–3.96 (3H, Me, linker), 2.29–2.61 (2H,
–COCH2– spacer), 1.99–2.22 (2H, –CH2– spacer).
5.2.4. Resin 3d. IR (powder): 3057, 3025, 2923, 1645, 1599,
1544, 1491, 1451, 1420, 1357, 1273, 1199, 1163, 1114,
1
1030, 973, 908, 972, 804, 747, 697 cmꢁ1; H MAS NMR
(500 MHz, DMF-d7) d 12.38, 11.82 (1H, NH, hydrazone),
9.06, 8.88 (1H, CH]N, hydrazone), 7.94 (1H, linker),
7.66, 7.41, 7.12 (4H, 3-methoxybenzoyl), 6.58–6.69 (2H,
linker), 4.38 (2H, –NH–CH2– spacer), 4.10 (2H, –CH2–O–
spacer), 3.82 (6H, 3H: Me, linker, 3H: Me, 3-methoxy-
benzoyl), 2.49 (2H, –COCH2– spacer), 2.11 (2H, –CH2–
spacer).
5.3.4. Resin 4d. IR (powder): 1653, 1607, 1582, 1539, 1506,
1492, 1451, 1421, 1284, 1198, 1160, 1132, 1119, 1033, 972,
835, 793, 756, 697 cmꢁ1 1H MAS NMR (500 MHz,
;
DMF-d7) d 9.92–10.33 (1H, –CO–NH–NH–), 7.48–7.59
(2H, 3-methoxybenzoyl), 7.29–7.41 (1H, 1H: 3-methoxy-
benzoyl), 7.21–7.27 (1H, linker), 7.00–7.13 (1H, 3-methoxy-
benzoyl), 6.53–6.63 (1H, linker), 6.41–6.52 (1H, linker),
4.15–4.52 (2H, –N–CH2– spacer), 3.92–4.07 (2H, –CH2–
O–), 3.90–4.09 (2H, –CO–NH–NH–CH2–), 3.67–3.85 (6H,
3H: Me methoxybenzoyl, 3H: Me, linker), 2.41–2.53 (2H,
–COCH2– spacer), 2.04–2.17 (2H, –CH2– spacer).
5.2.5. Resin 3e. IR (powder): 3034, 2922, 1641, 1600, 1550,
1505, 1551, 1493, 1451, 1417, 1377, 1309, 1272, 1223,
1200, 1163, 1113, 1030, 975, 908, 826, 756, 732,
1
697 cmꢁ1; H MAS NMR (500 MHz, DMF-d7) d 11.88,
11.56 (1H, NH, hydrazone), 8.82, 8.60 (1H, CH]N, hydra-
zone), 8.17, 7.85 (1H, H3, thienyl), 8.06, 7.80 (1H, 1H: H5,