8866 J. Am. Chem. Soc., Vol. 122, No. 37, 2000
Bisson et al.
to yield the desired product as a white solid (0.32 g; 85%); mp >270
°C. δH in 5% CD3OD in CDCl3 (v/v) (ppm): 8.60(s, 1H, NH); 8.49(s,
1H, I Ar-CH);8.40(s, 1H, NH); 8.06(m, 2H, I Ar-CH); 7.51(t, 1H, I
Ar-CH); 7.36(t, 1H, A Ar-CH);7.23(d, 2H, A Ar-CH); 7.03(s, 2H,
B Ar-CH); 6.85(s, 2H, B Ar-CH); 3.15(sept, 2H, A CHMe2); 2.23-
(m, 10H, B Me, B c-hexyl); 2.15(s, 6H, B Me); 1.65-1.55(m, 6H, B
c-hexyl); 1.20(d, 12H, A CHMe2). δC in CDCl3 (ppm): 166.0; 165.0;
148.8; 146.4; 140.1; 135.2; 135.0; 134.7; 130.8; 130.6; 130.3; 129.4;
128.7; 127.1; 126.0; 123.6; 121.5; 44.9; 37.2; 28.9; 26.5; 23.7; 23.0;
18.9; 18.1. FAB[+ve] m/z ) 630, C42H51N3O2 requires 629. IR in KBr
disk (cm-1): 3429; 2961; 2934; 2863; 1648; 1510; 1471; 1383; 1362.
37.2; 26.5; 23.0; 18.7; 18.1. FAB[+ve] m/z ) 775, C52H62N4O2 requires
774. IR in KBr disk (cm-1): 3431; 2933; 2858; 1654; 1492.
H2N-BIBIB-NH2: mp 243 °C. δH in d6-DMSO (ppm): 9.80(s,
4H, NH); 8.50(s, 2H, I Ar-CH); 8.15(d, 4H, I Ar-CH); 7.65(t, 2H, I
Ar-CH); 7.10(s, 2H, B Ar-CH); 7.00(s, 2H, B Ar-CH); 6.80(s, 2H,
B Ar-CH); 4.35(s, 4H, NH2); 2.25(m, 8H, B c-hexyl); 2.20(s, 12H, B
Me); 2.16(s, 12H, B Me); 2.07(s, 12H, B Me); 1.65-1.55(m, 12H, B
c-hexyl). δC in CDCl3 (ppm): 165.6; 165.5; 148.6; 147.3; 140.0; 137.8;
135.6; 135.0; 133.7; 131.8; 131.1; 127.1; 121.7; 44.8; 18.7; 18.0. FAB-
[+ve] m/z ) 1228, C82H94N6O4 requires 1226. IR in KBr disk (cm-1):
3425; 2934; 2858; 1654; 1493.
Synthesis of AIBT. The AIB-NH2 (1.89 × 10-4 mol; 119 mg)
and Et3N (2.84 × 10-4 mol; 40 µl) were dissolved in dry CH2Cl2 (10
mL). tert-Butyl benzoyl chloride (2.84 × 10-4 mol; 53 µl) was then
added and the reaction allowed to stir for 5 h. The reaction was then
washed with 1 M HCl (2 × 20 mL) and 1 M NaOH (2 × 20 mL)
before the organic phase was dried over Na2SO4 (anhydrous). The Na2-
SO4 was removed by filtration and the organic solution reduced to
dryness on the rotary evaporator, to yield a yellow solid. The products
were separated by preparative TLC mixture eluting with 2% EtOH/
CH2Cl2 to yield the desired product as the lowest band. The product
was recrystallized from CH2Cl2/pet ether(40-60) to give a white solid
(115 mg; 77%); mp 214-215 °C. δH in d6-DMSO (ppm): 9.90(s, 1H,
NH); 9.85(s, 1H, NH); 9.55(s, 1H, NH); 8.55(s, 1H, I Ar-CH); 8.20-
(m, 2H, I Ar-CH); 7.92(d, 2H, T Ar-CH); 7.70(t, 1H, I Ar-CH);
7.53(d, 2H, T Ar-CH); 7.37(t, 1H, A Ar-CH); 7.23(d, 2H, A Ar-
CH); 7.10(s, 4H, B Ar-CH); 3.15(sept, 2H, A CHMe2); 2.30(m, 4H,
B c-hexyl); 2.22(s, 6H, B Me); 2.15(s, 6H, B Me); 1.65-1.55(m, 6H,
B c-hexyl); 1.35(s, 9H, T CMe3); 1.20(2d,12H, A CHMe2). δC in d6-
DMSO (ppm): 166.2; 165.2; 165.1; 154.7; 147.2; 146.9; 146.6; 135.6;
135.5; 135.4; 135.3; 133.2; 133.1; 132.9; 132.1; 130.6; 129.2; 128.2;
127.8; 127.6; 126.6; 125.7; 123.4; 45.2; 36.7; 31.4; 28.7; 26.3; 24.0;
23.8; 23.2; 19.0. FAB[+ve] m/z ) 791, C53H63N3O3 requires 789. IR
in C2H2Cl4 solution (cm-1): 3422; 2992; 2980; 2969; 2937; 2867; 1668;
1609; 1490; 1470; 1383.
Synthesis of TBIB-NH2. Et3N (2.89 mmol; 0.4 mL) and H2N-
B-NH2 (2.89 mmol; 2.23 g) were dissolved in dry CH2Cl2 (50 mL),
and to this solution was added dropwise over 2 h tert-butyl benzoyl
chloride (0.41 mmol; 77 µl) in dry CH2Cl2 (100 mL). The reaction
was then allowed to stir for 8 h. The reaction mixture was then made
up to 500 mL by adding CH2Cl2 and extracted with 1 M HCl (2 × 500
mL). The aqueous phase was made basic with NaOH pellets and
extracted with CH2Cl2 (3 × 300 mL). The organic solvent was then
removed on a rotary evaporator. Flash column chromatography on silica,
eluting with 50% ethyl acetate/pet ether (40-60), yielded the desired
product as the first band. The product was recrystallized from CH2-
Cl2/pet ether (196 mg; 51%) to give a white solid; mp 210-211 °C.
δH in CDCl3 (ppm): 8.45(s, 1H, I Ar-CH); 7.95(m, 2H, I Ar-CH);
7.80(m, 3H, NH, T Ar-CH); 7.70(s, 1H, NH); 7.45(m, 3H, NH, T
Ar-CH); 7.23(t, 1H, I Ar-CH); 7.05(s, 2H, B Ar-CH); 7.03(s, 2H,
B Ar-CH); 7.00(s, 2H, B Ar-CH); 6.85(s, 2H, B Ar-CH); 3.45(bs,
2H, NH2); 2.20(m, 14H, B Me, B c-hexyl); 2.17(s, 6H, B Me); 2.10(s,
6H, B Me); 1.65-1.55(m, 12H, B c-hexyl); 1.35(s, 9H, T CMe3). δC
in CDCl3 (ppm): 166.1; 165.5; 165.4; 155.2; 148.6; 147.3; 140.1; 137.7;
135.3; 134.9; 134.3; 134.1; 131.6; 131.4; 131.3; 131.1; 130.5; 128.8;
127.2; 127.1; 126.9; 126.0; 125.5; 121.5; 45.0; 44.9; 37.3; 36.9; 34.9;
26.5; 23.0; 18.8; 18.7; 18.1. FAB[+ve] m/z ) 936, C63H74N4O3 requires
934. IR in KBr disk (cm-1): 3431; 2935; 2859; 1654; 1493; 1376.
Synthesis of TBIBT. Et3N (6.38 × 10-4 mol; 0.1 mL) and H2N-
BIB-NH2 (3.19 × 10-4 mol; 247 mg) were dissolved in dry CH2Cl2
(75 mL). tert-Butyl benzoyl chloride (6.38 × 10-4 mol; 0.12 mL) was
then added and the reaction allowed to stir for 4 h. The reaction was
then washed with 1 M HCl (2 × 50 mL) and 1 M NaOH (2 × 50 mL)
before being dried over Na2SO4 (anhydrous). The Na2SO4 was removed
by filtration and the solvent removed under reduced pressure. Flash
column chromatography on silica, eluting with 2% EtOH/CH2Cl2, gave
the desired product as the second band. The first band was impurity.
The product was recrystallized form CH2Cl2/pet ether (40-60) to give
a white solid (302 mg; 86%); mp 239-240 °C. δH in d6-DMSO
(ppm): 9.80(s, 2H, NH); 9.55(s, 2H, NH); 8.53(s, 1H, I Ar-CH); 8.15-
(d, 2H, I Ar-CH); 7.92(d, 4H, T Ar-CH); 7.68(t, 1H, I Ar-CH);
7.55(d, 4H, T Ar-CH); 7.15(s, 8H, B Ar-CH); 2.35-2.25(m, 8H, B
c-hexyl); 2.2(s, 12H, B Me); 2.17(s, 12H, B Me) 1.60-1.55(m, 12H,
B c-hexyl); 1.35(s, 18H, T CMe3). δC in CDCl3 (ppm): 165.9; 155.0;
147.5; 147.1; 135.1; 131.6; 131.4; 127.2; 126.9; 125.4; 45.0; 36.8; 34.9;
31.2; 26.3; 22.9; 18.7;18.6. FAB[+ve] m/z ) 1096, C74H85N4O4 requires
1094 IR in C2H2Cl4 solution (cm-1): 3422; 2982; 2970; 2939; 2863;
1670; 1609; 1491.
Synthesis of TBIBIA. TBIB-NH2 (1.07 × 10-4 mol; 100 mg) and
Et3N (2.68 × 10-4 mol; 37 µl) were dissolved in dry CH2Cl2 (10 mL),
and the AI-COCl (2.14 × 10-4 mol; 73 mg) in dry CH2Cl2 (10 mL)
was added dropwise over 20 min. The reaction was then allowed to
stir for 4 h. The solvent was then removed under reduced pressure on
the rotary evaporator. The desired product was separated by preparative
TLC eluting with 2% EtOH/CH2Cl2 to yield the product as the lowest
band. Recrystallization from CH2Cl2/MeOH/Pet ether (40-60) gave a
white solid (122 mg; 92%); mp 252-253 °C. δH in d6-DMSO (ppm):
9.92(s, 1H, NH); 9.80(m, 3H, NH); 9.55(s, 1H, NH); 8.52(s, 1H, I
Ar-CH); 8.50(s, 1H, I Ar-CH); 8.25-8.10(m, 4H, I Ar-CH); 7.90-
(d, 2H, T Ar-CH); 7.75-7.62(m, 2H, I Ar-CH); 7.52(d, 2H, T Ar-
CH); 7.32(t, 1H, A Ar-CH); 7.21(d, 2H, A Ar-CH); 7.15-7.07(m,
8H, B Ar-CH); 3.14(sept, 2H, A CHMe2); 2.35-2.25(m, 8H, B
c-hexyl); 2.23-2.12(m, 24H, B Me); 1.60-1.45(m, 12H, B c-hexyl);
1.39(s, 9H, T CMe3); 1.22-1.10(2d, 12H, A CHMe2). δC in 5% CD3-
OD in CDCl3 (v/v) (ppm): 165.8; 147.3; 146.6; 135.6; 134.5; 134.3;
Synthesis of AIBIA. AI-COCl (3.30 mmol; 1.13 g) was dissolved
in dry CH2Cl2 (15 mL), and to this solution was added over 20 min a
solution of H2N-B-NH2 (1.32 mmol; 425 mg) and Et3N (3.95 mmol;
0.55 mL) in dry CH2Cl2 (30 mL). The reaction was allowed to stir for
2 h and then washed with 1 M HCl (2 × 200 mL), 1 M NaOH (2 ×
200 mL), and water (2 × 200 mL). The organic phase was then dried
over Na2SO4 (anhydrous). The Na2SO4 was removed by filtration and
the organic solution reduced to dryness on the rotary evaporator. Flash
column chromatography on silica, eluting with 1% EtOH/CH2Cl2, gave
the desired product as the third band. The product was recrystallized
from CH2Cl2/MeOH/pet ether (40-60) to give a white solid (876 mg;
71%); mp >270 °C. δH in 5% CD3OD in CDCl3 (v/v) (ppm): 8.52(s,
2H, I Ar-CH); 8.15(m, 4H, I Ar-CH); 7.57(t, 2H, I Ar-CH); 7.35(t,
2H, A Ar-CH); 7.22(d, 2H, A Ar-CH); 7.13(s, 4H, B Ar-CH); 3.15-
(sept, 2H, A CHMe2); 2.25(m, 16H, B Me, B c-hexyl); 1.65-1.45(m,
6H, B c-hexyl); 1.22(d, 12H, A CHMe2). δC in d6-DMSO (ppm): 166.2;
165.2; 147.2; 146.6; 135.5; 135.4; 135.2; 133.1; 133.0; 130.6; 129.2;
128.2; 127.5; 126.6; 123.5; 45.2; 36.7; 28.7; 23.8; 23.5; 23.2; 19.0.
FAB[+ve] m/z ) 937, C62H72O4N4 requires 936. IR in C2H2Cl4 solution
(cm-1): 3414; 3295; 2994; 2933; 2866; 1646; 1584; 1517; 1496; 1469.
Synthesis of H2N-BIB-NH2, H2N-BIBIB-NH2. H2N-B-NH2
(33.67 mmol; 10.857 g) and Et3N (10.36 mmol; 1.44 mL) were
dissolved in dry CH2Cl2 (50 mL). To this solution was added dropwise
over 2 h a solution of isophthaloyl dichloride (5.179 mmol; 1.05 g) in
dry CH2Cl2 (100 mL). The reaction was then left to stir for 8 h. Flash
column chromatography on silica, eluting with 100% CHCl3 and finally
2.0% EtOH/CHCl3, yielded H2N-BIB-NH2 as the second band (white
solid 2.94 g; 73%) and H2N-BIBIB-NH2 as the third band (white
solid 671 mg; 11%). The first band was unreacted H2N-B-NH2.
H2N-BIB-NH2: mp 179-180 °C. δH in CDCl3 (ppm): 8.45(s,
1H, I Ar-CH); 8.00(d, 2H, I Ar-CH); 7.50(m, 3H, NH, I Ar-CH);
7.20(s, 2H, B Ar-CH); 6.85(s, 2H, B Ar-CH); 3.45(s, 4H, NH2); 2.25-
(m, 20H, B Me, B c-hexyl); 2.10(s, 12H, B Me); 1.65-1.55(m, 12H,
B c-hexyl). δC in CDCl3 (ppm): 165.3; 148.7; 140.1; 137.7; 134.8;
134.7; 131.0; 130.3; 129.1; 127.2; 127.1; 126.9; 126.0; 121.6; 44.9;