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DOI: 10.1055/s-0029-1217173
Improving the Efficiency of Forming ‘Unfavorable’ Products: Eight-Residue Macrocycles from Folded Aromatic Oligoamide Precursors
Publikationsverlauf
Publikationsdatum:
13. Mai 2009 (online)
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Abstract
Oligoamide macrocycles consisting of eight meta-linked benzene residues were synthesized based on the cyclization of aromatic oligoamide precursors having folded backbones rigidified by three-center hydrogen bonds. An alternative route based on the condensation of pentadimeric diamine and trimeric diacid provided the cyclic octamer in 75% yield using EDCI/HOBt as the coupling reagent.
Key words
macrocycles - synthesis - hydrogen bonds - folding oligoamides - cyclizations
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References and Notes
Selected Spectroscopic
Data of Compounds 4-8
Compound 4c: ¹H NMR (400 MHz,
95% CDCl3-5% CD3OD): δ = 10.00
(s, 4 H), 9.90 (s, 4 H), 9.40 (s, 2 H), 9.23 (s, 2 H), 9.00 (s,
2 H), 8.70 (s, 2 H), 6.80 (s, 2 H), 6.69 (s, 2 H), 6.50 (s, 4 H),
4.47 (s, 16 H), 3.99-3.43 (m), 3.28 (s, 24 H). MS (MALDI-TOF): m/z calcd for C120H168N8NaO48
[M + Na]:
2512.08; found: 2512.1. ESI-HRMS: m/z [M + Na] calcd
for C120H168N8NaO48:
2513.0882; found: 2513.0955.
Compound 6: ¹H
NMR (400 MHz, CDCl3): δ = 9.75 (s,
2 H), 9.37 (s, 1 H), 8.88 (s, 2 H), 6.63 (s, 2 H), 6.55 (s, 1 H),
4.40 (t, J = 4.8
Hz, 4 H), 4.25 (t, J = 4.8
Hz, 4 H), 4.00 (t, J = 4.8 Hz,
4 H), 3.94 (t, J = 4.8
Hz, 4 H), 3.92 (s, 6 H), 3.84 (s, 6 H), 3.80 (t, J = 4.8
Hz, 4 H), 3.68 (m, 12 H), 3.58 (m, 12 H), 3.47 (q, 4 H), 3.37 (s,
6 H), 3.32 (s, 6 H). ESI-HRMS: m/z [M + H] calcd
for C54H81N2O24: 1141.5179;
found: 1141.5125.
Compound 7: ¹H
NMR (400 MHz, CDCl3): δ = 9.57 (s,
2 H), 9.21 (s, 1 H), 8.96 (s, 2 H), 6.65 (s, 2 H), 6.41 (s, 1 H),
4.48 (t, J = 4.8
Hz, 4 H), 4.33 (t, J = 4.8
Hz, 4 H), 4.01 (t, J = 4.8 Hz,
4 H), 3.87 (s, 6 H), 3.84 (t, J = 4.8
Hz, 4 H), 3.71 (m, 8 H), 3.63 (m, 8 H), 3.57 (m, 12 H), 3.47 (m,
4 H), 3.37 (s, 6 H), 3.32 (s, 6 H).¹³C
NMR (100 MHz, CDCl3): δ = 164.8, 161.2,
160.9, 160.7, 145.6, 138.1, 120.1, 116.1, 111.4, 98.2, 94.4, 71.9,
71.8, 70.6, 70.5, 70.5, 70.4, 70.3, 69.4, 69.2, 69.0, 68.5, 58.9,
58.8, 55.8. ESI-HRMS: m/z [M - H] calcd
for C52H75N2O24: 1111.4710;
found: 1111.4769.
Compound 8a: ¹H
NMR (400 MHz, CDCl3): δ = 9.88 (s,
2 H), 9.65 (s, 2 H), 9.20 (s, 3 H), 8.98 (s, 2 H), 6.63 (s, 2 H), 6.56
(s, 1 H), 6.47 (s, 2 H), 4.49 (t, J = 4.8
Hz, 4 H), 4.36 (t, J = 4.8
Hz, 4 H), 4.07 (s, 6 H), 3.96 (t, J = 4.8
Hz, 4 H), 3.92 (d, 12 H), 3.76 (t, J = 4.8
Hz, 4 H), 3.70 (t, J = 4.8
Hz, 4 H), 3.64 (t, J = 4.8
Hz, 4 H), 3.56 (m, 12 H), 3.46 (m, 12 H), 3.31 (s, 12 H). ¹³C
NMR (100 MHz, CDCl3): δ = 161.6, 160.1, 160.0,
153.8, 151.0, 146.3, 137.0, 121.4, 120.6, 117.4, 115.3, 114.6, 97.7,
95.6, 95.2, 71.8, 70.7, 70.6, 70.6, 70.5, 70.4, 70.3, 69.4, 69.1,
69.0, 58.9, 56.7, 56.5, 56.1. ESI-HRMS: m/z [M + H] calcd
for C68H93N6O30: 1473.5936; found:
1473.5927.
Compound 8b: prepared
from hydrogenation of its dinitro compound 8a in
90% yield. ¹H NMR (400 MHz, DMSO-d
6): δ = 10.07
(s, 2 H), 10.02 (s, 2 H), 9.32 (s, 1 H), 8.91 (s, 2 H), 7.90 (s,
2 H), 7.10 (s, 2 H), 6.96 (s, 1 H), 6.75 (s, 2 H), 4.63 (s, 8 H),
4.03 (s, 6 H), 4.01-3.98 (m, 8 H), 3.91 (s, 6 H), 3.84 (s,
6 H), 3.65 (m, 8 H), 3.60-3.40 (m, 8 H), 3.36 (m, 8 H), 3.23
(s, 6 H), 3.21 (s, 6 H), 3.16-3.10 (m, 8 H).(15) Procedure For MacrocyclizationRoute
A
A mixture of 7 (23.7 mg,
0.021 mmol), EDCI (10.2 mg, 0.053 mmol), and HOBt (7.3 mg, 0.054
mmol) in CH2Cl2 (10 mL) was stirred at r.t.
for 50 min and then 8b (30.0 mg, 0.021
mmol) was added. The mixture was stirred at 28 ˚C overnight.
After washing with H2O, the residue was subjected to
chromatography (CHCl3-MeOH, 5:1) to afford the
product 4c as an off-white solid (37.5
mg, 75%).
Route B
The
diacid chloride (0.020 mmol), prepared from diacid 7 and
(COCl)2 in CH2Cl2, was added to
the diamine 1 (0.020 mmol) in the presence
of Et3N in 0.5 h. The mxiture was stirred 6 h. After
washing with 10% HCl, the residue was recrystallized several
times from acetone to provide 4c in 40% yield.