T. Hjelmgaard, S. Faure, D. Staerk, C. Taillefumier, J. Nielsen
FULL PAPER
NMR (300 MHz, CDCl3): δ = 7.96–7.90 (m, 2 H), 7.42–7.08 (br. 0.80ϫCH2, 2ϫ (t)-CONCH2Ar], 46.7 [br, 1.20ϫCH2, 2ϫ (c)-
m, 10 H), 4.87–4.62 [br. s, 2.32 H, 2ϫ (c)-CONCH2Ar], 4.62–4.39 CONCH2Ar], 43.3 (CH2, HNCH2CH3), 43.0 [br, 1.20ϫCH2, 2ϫ
[br. s, 1.68 H, 2ϫ (t)-CONCH2Ar], 3.75 (s, 2 H, HNCH2Ar), 3.56– (c)-CONCH2CH3], 39.6 [br, 0.80ϫCH2, 2ϫ (t)-CONCH2CH3],
3.32 [br. m, 1.68 H, 2ϫ (t)-CONCH2CH3], 3.32–3.05 [br. m, 2.32 28.0 (3ϫCH3), 15.1 (CH3), 13.6 [br, 1.20ϫCH3, 2ϫ (c)-
H, 2ϫ (c)-CONCH2CH3], 2.62 (q, J = 7.0 Hz, 2 H, HNCH2CH3), CONCH2CH3], 12.1 [br, 0.80ϫCH3, 2ϫ (t)-CONCH2CH3] ppm.
1.54 (s, 9 H), 1.42–1.37 (br. s, 1 H), 1.21–0.95 (br. m, 9 H) ppm.
HRMS (TOF MS ES+): calcd. for C34H44N3O4 [M + H]+ 558.3326;
13C NMR (75 MHz, CDCl3): δ = 171.7 (Cq), 171.4 (Cq), 165.2 (Cq), found 558.3317. HPLC purity: 98.8%.
142.0, 139.0 (3ϫCq), 135.4 (Cq), 134.8 (Cq), 131.1 (Cq), 129.7
tert-Butyl 4-[(Methylamino)methyl]benzoate (p-2c): Treatment of p-
(2ϫCH), 128.0, 127.5, 126.7, 126.4 (10ϫCH), 80.9 (Cq), 53.3
(CH2, HNCH2Ar), 51.8 [br, 0.84ϫCH2, 2ϫ (t)-CONCH2Ar], 46.8
[br, 1.16ϫCH2, 2ϫ (c)-CONCH2Ar], 43.5 (CH2, HNCH2CH3),
43.0 [br, 1.16ϫCH2, 2ϫ (c)-CONCH2CH3], 39.8 [br, 0.84ϫCH2,
2ϫ (t)-CONCH2CH3], 28.0 (3ϫCH3), 15.1 (CH3), 13.6 [br,
1.16ϫCH3, 2ϫ (c)-CONCH2CH3], 12.1 [br, 0.84ϫCH3, 2ϫ (t)-
CONCH2CH3] ppm. HRMS (TOF MS ES+): calcd. for
C34H44N3O4 [M + H]+ 558.3326; found 558.3333. HPLC purity:
98.9%.
1 (543 mg, 2.00 mmol) by Method A with methylamine (2 m) in
THF yielded p-2c (387 mg, 87%) as a colorless gel. Rf (EtOAc/
MeOH 80:20) = 0.12. H NMR (300 MHz, CDCl3): δ = 7.96–7.92
(m, 2 H), 7.38–7.33 (m, 2 H), 3.79 (s, 2 H), 2.44 (s, 3 H), 1.66–1.63
(br. s, 1 H), 1.58 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
165.7 (Cq), 144.8 (Cq), 130.8 (Cq), 129.5 (2ϫCH), 127.8 (2ϫCH),
80.8 (Cq), 55.6 (CH2), 35.9 (CH3), 28.2 (3ϫCH3) ppm. HRMS
(TOF MS ES+): calcd. for C13H20NO2 [M + H]+ 222.1489; found
222.1491. HPLC purity: 99.9%.
1
tert-Butyl 3-[(Ethylamino)methyl]benzoate (m-2b): Treatment of m-
1 (814 mg, 3.00 mmol) by Method A with ethylamine (2 m) in THF
yielded m-2b (649 mg, 87%) as a pale yellowish oil. Rf (EtOAc/
Arylopeptoid Dimer p-3c: Treatment of p-2c (354 mg, 1.60 mmol)
by Method B with methylamine (2 m) in THF and flash column
chromatography in EtOAc/MeOH 80:20 to 70:30 yielded p-3c
(513 mg, 87%) as a pale yellowish solid. Rf (EtOAc/MeOH 70:30)
= 0.05; m.p. 64–66 °C. 1H NMR (300 MHz, CDCl3): δ = 7.97–7.91
(m, 2 H), 7.41–7.24 (br. m, 4.90 H), 7.24–7.11 (br. m, 1.10 H), 4.84–
4.65 [br. s, 1.10 H, (c)-CONCH2Ar], 4.64–4.41 [br. s, 0.90 H, (t)-
CONCH2Ar], 3.71 (s, 2 H, HNCH2Ar), 3.06–2.90 [br. s, 1.35 H,
(t)-CONCH3], 2.90–2.74 [br. s, 1.65 H, (c)-CONCH3], 2.38 (s, 3 H,
HNCH3), 1.74–1.65 (br. s, 1 H), 1.54 (s, 9 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 172.1, 171.4 (Cq), 165.2 (Cq), 141.9 (Cq),
141.6 (0.55ϫCq), 141.3 (0.45ϫCq), 134.4 (Cq), 131.2 (Cq), 129.7
(2ϫCH), 128.0 (2ϫCH), 127.7, 126.9, 126.8, 126.2 (4ϫCq), 80.9
(Cq), 55.4 (CH2, HNCH2Ar), 54.8 [br, 0.45ϫCH2, (t)-CON-
CH2Ar], 50.5 [br, 0.55ϫCH2, (c)-CONCH2Ar], 37.0 [br,
0.55ϫCH3, (c)-CONCH3], 35.8 (CH3, HNCH3), 33.2 [br,
0.45ϫCH3, (t)-CONCH3], 28.0 (3ϫCH3) ppm. HRMS (TOF MS
ES+): calcd. for C22H29N2O3 [M + H]+ 369.2173; found 369.2180.
HPLC purity: 98.6%.
1
MeOH 90:10) = 0.10. H NMR (300 MHz, CDCl3): δ = 7.93–7.90
(m, 1 H), 7.89–7.84 (m, J = 7.6 Hz, 1 H), 7.52–7.47 (m, J = 7.6 Hz,
1 H), 7.36 (t, J = 7.6 Hz, 1 H), 3.83 (s, 2 H), 2.67 (q, J = 7.1 Hz,
2 H), 1.59 (s, 9 H), 1.51–1.45 (br. s, 1 H), 1.13 (t, J = 7.1 Hz, 3
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 165.8 (Cq), 140.6 (Cq),
132.2 (CH), 132.1 (Cq), 129.0 (CH), 128.2 (CH), 128.0 (CH), 80.9
(Cq), 53.6 (CH2), 43.6 (CH2), 28.2 (3ϫCH3), 15.2 (CH3) ppm.
HRMS (TOF MS ES+): calcd. for C13H20NO2 [M + H]+ 236.1645;
found 236.1642. HPLC purity: 99.9%.
Arylopeptoid Dimer m-3b: Treatment of m-2b (565 mg, 2.40 mmol)
by Method B with ethylamine (2 m) in THF yielded m-3b (794 mg,
1
83%) as a pale yellowish oil. Rf (EtOAc/MeOH 80:20) = 0.10. H
NMR (300 MHz, CDCl3): δ = 7.94–7.70 (br. m, 2 H), 7.56–7.21
(br. m, 6 H), 4.88–4.62 [br. s, 1.16 H, (c)-CONCH2Ar], 4.62–4.38
[br. s, 0.84 H, (t)-CONCH2Ar], 3.76 (s, 2 H, HNCH2Ar), 3.58–3.33
[br. m, 0.84 H, (t)-CONCH2CH3], 3.33–3.05 [br. m, 1.16 H, (c)-
CONCH2CH3], 2.70–2.50 (m, 2 H, HNCH2CH3), 1.84–1.75 (br. s,
1 H), 1.55 (s, 9 H), 1.23–0.96 (br. m, 6 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 171.8 (Cq), 165.3 (Cq), 140.7 (Cq), 137.5
(Cq), 136.5 (Cq), 132.2 (Cq), 131.8 (CH), 130.5 (CH), 129.1 (CH),
128.5 (CH), 128.3 (CH), 127.8 (CH), 126.0 (CH), 124.7 (CH), 81.0
(Cq), 53.3 (CH2, HNCH2Ar), 51.8 [br, 0.42ϫCH2, (t)-CON-
CH2Ar], 46.7 [br, 0.58ϫCH2, (c)-CONCH2Ar], 43.4 (CH2,
HNCH2CH3), 43.0 [br, 0.58ϫCH2, (c)-CONCH2CH3], 39.6 [br,
0.42ϫCH2, (t)-CONCH2CH3], 28.0 (3ϫCH3), 14.9 (CH3), 13.6
[br, 0.58ϫCH3, (c)-CONCH2CH3], 12.1 [br, 0.42ϫCH3, (t)-
CONCH2CH3] ppm. HRMS (TOF MS ES): calcd. for
C24H33N2O3 [M + H]+ 397.2486; found 397.2486. HPLC purity:
99.9%.
Arylopeptoid Trimer p-4c: Treatment of p-3c (442 mg, 1.20 mmol)
by Method B with methylamine (2 m) in THF yielded p-4c (490 mg,
79%) as a colorless, amorphous solid. Rf (EtOAc/MeOH 70:30) =
1
0.05. H NMR (300 MHz, CDCl3): δ = 7.97–7.92 (m, 2 H), 7.44–
7.06 (br. m, 10 H), 4.83–4.62 [br. s, 2.20 H, 2ϫ (c)-CONCH2Ar],
4.62–4.39 [br. s, 1.80 H, 2ϫ (t)-CONCH2Ar], 3.71 (s, 2 H,
HNCH2Ar), 3.08–2.90 [br. m, 2.70 H, 2ϫ (t)-CONCH3], 2.90–2.74
[br. m, 3.30 H, 2ϫ (c)-CONCH3], 2.38 (s, 3 H, HNCH3), 1.73–1.64
(br. s, 1 H), 1.55 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
172.0, 171.4, 171.1 (2ϫCq), 165.2 (Cq), 141.9, 141.5, 141.0, 138.7,
138.4 (3ϫCq), 135.0 (Cq), 134.4 (Cq), 131.2 (Cq), 129.7 (2ϫCH),
128.0, 127.7, 127.3, 127.0, 126.2 (10ϫCH), 80.9 (Cq), 55.4 (CH2,
HNCH2Ar), 54.8 [br, 0.90ϫCH2, 2ϫ (t)-CONCH2Ar], 50.4 [br,
1.10ϫCH2, 2ϫ (c)-CONCH2Ar], 37.0 [br, 1.10ϫCH3, 2ϫ (c)-
CONCH3], 35.8 (CH3, HNCH3), 33.2 [br, 0.90ϫCH3, 2ϫ (t)-
CONCH3], 28.0 (3ϫCH3) ppm. HRMS (TOF MS ES+): calcd. for
C31H38N3O4 [M + H]+ 516.2857; found 516.2853. HPLC purity:
97.5%.
Arylopeptoid Trimer m-4b: Treatment of m-3b (635 mg, 1.60 mmol)
by Method B with ethylamine (2 m) in THF yielded m-4b (781 mg,
1
87%) as a thick colorless oil. Rf (EtOAc/MeOH 70:30) = 0.11. H
NMR (300 MHz, CDCl3): δ = 7.96–7.69 (br. m, 2 H), 7.56–7.12
(br. m, 10 H), 4.88–4.60 [br. s, 2.40 H, 2ϫ (c)-CONCH2Ar], 4.60–
4.32 [br. s, 1.60 H, 2ϫ (t)-CONCH2Ar], 3.76 (s, 2 H, HNCH2Ar), tert-Butyl 3-[(Methylamino)methyl]benzoate (m-2c): Treatment of
3.58–3.32 [br. m, 1.60 H, 2ϫ (t)-CONCH2CH3], 3.33–3.02 [br. m, m-1 (543 mg, 2.00 mmol) by Method A with methylamine (2 m) in
2.40 H, 2ϫ (c)-CONCH2CH3], 2.70–2.51 (m, 2 H, HNCH2CH3), THF yielded m-2c (312 mg, 70%) as a pale yellowish oil. Rf
1.55 (s, 9 H), 1.39–1.28 (br. s, 1 H), 1.25–0.92 (br. m, 9 H) ppm.
(EtOAc/MeOH 80:20) = 0.13. 1H NMR (300 MHz, CDCl3): δ =
13C NMR (75 MHz, CDCl3): δ = 171.8 (Cq), 171.5 (Cq), 165.3 (Cq), 7.92–7.89 (m, 1 H), 7.89–7.84 (m, J = 7.6 Hz, 1 H), 7.52–7.46 (m,
141.0 (Cq), 137.9 (Cq), 137.5 (Cq), 136.9 (Cq), 136.4 (Cq), 132.2 J = 7.6 Hz, 1 H), 7.36 (t, J = 7.6 Hz, 1 H), 3.78 (s, 2 H), 2.44 (s, 3
(Cq), 131.8, 129.0, 128.8, 128.6, 128.4, 128.3, 127.7, 126.9, 125.3, H), 2.05–2.00 (br. s, 1 H), 1.58 (s, 9 H) ppm. 13C NMR (75 MHz,
124.6 (12ϫCH), 81.0 (Cq), 53.4 (CH2, HNCH2Ar), 51.7 [br,
CDCl3): δ = 165.7 (Cq), 140.0 (Cq), 132.3 (CH), 132.1 (Cq), 129.1
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Eur. J. Org. Chem. 2011, 4121–4132