4
Journal of Chemical Research 00(0)
[M+H]+ calcd for C17H25FN3O4: 354.1824; found: mmol scale). The crude residue was purified by column
354.1818; IR: 2998, 1716, 1494, 1305 cm−1.
chromatography (10% ethyl acetate in petroleum ether) to
give 4g as a colourless solid: Yield 1.05 g (89%); m.p. 115–
Synthesis of 1-[2,3-di(tert-butoxycarbonyl)guanidino]-4-methyl- 116°C; 1H NMR (CDCl3, 500 MHz): δ=11.66 (s, 1H), 10.20
benzene (4c). The general procedure was followed (3.22 (s, 1H), 7.50 (d, J=8.9 Hz, 2H), 6.88 (d, J=9.0 Hz, 2H), 3.81
mmol scale). The crude residue was purified by column (s, 3H), 1.55 (s, 9H), 1.51 (s, 9H); 13C NMR (CDCl3, 125
chromatography (10% ethyl acetate in petroleum ether) to MHz): δ=163.6, 156.8, 153.6, 153.3, 129.8, 123.8, 114.0,
give 4c as a colourless solid19: Yield 0.96 g (85%); m.p. 83.5, 79.4, 55.4, 28.2, 28.1; HRMS (ESI) m/z [M+H]+
120–122°C (lit. 120–122°C); 1H NMR (CDCl3, 500 MHz): calcd for C18H28N3O5: 366.2023; found: 366.2033; IR: 2982,
δ=11.68 (s, 1H), 10.28 (s, 1H), 7.48 (d, J=8.3 Hz, 2H), 1726, 1507, 1297, 764 cm−1.
7.14 (d, J=8.2 Hz, 2H), 2.33 (s, 3H), 1.56 (s, 9H), 1.52 (s,
9H); 13C NMR (CDCl3, 125 MHz): δ=163.4, 153.5, 153.3, Synthesis of 1-[2,3-di(tert-butoxycarbonyl)guanidino]-naphtha-
134.4, 134.1, 129.3, 122.2, 83.6, 79.5, 28.2, 28.1, 20.9; lene (4h). The general procedure was followed (3.22 mmol
HRMS (ESI) m/z [M+H]+ calcd for C18H28N3O4: scale). The crude residue was purified by column chroma-
350.2074; found: 350.2070.
tography (10% ethyl acetate in petroleum ether) to give 4h
as a colourless solid: Yield 1.06 g (85%); m.p. 146–148°C;
Synthesis of 1-[2,3-di(tert-butoxycarbonyl)guanidino]-2-methyl- 1H NMR (CDCl3, 500 MHz): δ=11.72 (s, 1H), 10.55 (s,
4-bromobenzene (4d). The general procedure was followed 1H), 8.20 (s, 1H), 7.79–7.84 (m, 3H), 7.67–7.70 (m, 1H),
(3.22 mmol scale). The crude residue was purified by col- 7.50–7.40 (m, 2H), 1.58 (s, 9H), 1.55 (s, 9H); 13C NMR
umn chromatography (10% ethyl acetate in petroleum (CDCl3, 125 MHz): δ=163.6, 153.6, 153.4, 134.3, 133.7,
ether) to give 4d as a colourless solid: Yield 0.94 g (68%); 130.9, 128.5, 127.8, 127.5, 126.2, 125.1, 121.9, 119.2,
m.p. 161–164°C; 1H NMR (CDCl3, 500 MHz): δ=11.69 (s, 83.8, 79.7, 28.2, 28.1; HRMS (ESI) m/z [M+H]+ calcd for
1H), 10.19 (s, 1H), 7.92 (d, J=7.9 Hz, 1H), 7.28–7.36 (m, C21H28N3O4: 386.2074; found: 386.2081; IR: 2972, 1716,
2H), 2.30 (s, 3H), 1.56 (s, 9H), 1.50 (s, 9H); 13C NMR 1507, 1371 cm−1.
(CDCl3, 125 MHz): δ=153.7, 153.4, 134.3, 132.9, 132.1,
129.5, 125.7, 118.0, 83.8, 79.8, 28.1, 28.0, 17.9; HRMS
General procedure for the synthesis of
guanidines
(ESI) m/z [M (79Br)]+ calcd for C18H27BrN3O4: 428.1179;
[M (81Br)]+: 430.1159; found: 428.1173; 430.1154; IR:
2983, 1708, 1487, 1305 cm−1.
Synthesis of 1-phenylguanidine trifluoroacetate (5a).
1-[2,3-Di(tert-butoxycarbonyl)guanidino]-4-benzene (4a)
Synthesis of 1-[2,3-di(tert-butoxycarbonyl)guanidino]-3-chloro- (0.95 g, 2.83 mmol) was dissolved in CF3COOH (3 mL)
benzene (4e). The general procedure was followed (3.22 and CHCl3 (3 mL). The resulting mixture was stirred for 5
mmol scale). The crude residue was purified by column h at 50°C and then evaporated to dryness. The crude resi-
chromatography (10% ethyl acetate in petroleum ether) to due was triturated with 50% ethyl acetate in petroleum
give 4e as a colourless solid: Yield 0.93 g (78%); m.p. 145– ether (3 mL) to give 5a as a colourless solid21: Yield 0.6 g
148°C; H NMR (CDCl3, 500 MHz): δ=11.64 (s, 1H), (85%); m.p. 160–163°C (lit. 175–177°C); 1H NMR
1
10.41 (s, 1H), 7.70 (s, 1H), 7.54 (d, J=8.1 Hz, 1H), 7.26 (d, (DMSO-d6, 500 MHz): δ=10.25 (s, 1H), 7.73 (s, 4H), 7.45
J=8.1 Hz, 1H), 7.13–7.08 (m, 1H), 1.56 (s, 9H), 1.53 (s, (t, J=7.8 Hz, 2H), 7.34–7.18 (m, 3H); 13C NMR (DMSO-
9H); 13C NMR (CDCl3, 125 MHz): δ=160.7, 158.8, 153.6, d6, 125 MHz): δ=160.3 (q, J=32.4 Hz), 156.4, 135.9,
153.3, 132.7, 124.0, 123.9, 115.6, 115.4, 83.8, 79.7, 28.1, 130.1, 126.7, 124.7, 117.3 (q, J=297.2 Hz); HRMS (ESI)
28.0; HRMS (ESI) m/z [M (35Cl)+H]+ calcd for m/z [M+H]+ calcd for C7H10N3: 136.0869; found:
C17H25ClN3O4: 370.1528; [M (37Cl)+H]+: 372.1499; 136.0868.
found: 370.1522; 372.1498; IR: 2893, 1708, 1487, 1297,
759 cm−1.
Synthesis of 1-(4-fluorophenyl)guanidine trifluoroacetate
(5b). The general procedure was followed (2.83 mmol
Synthesis of 1-[2,3-di(tert-butoxycarbonyl)guanidino]-4-chloro- scale). The crude residue was triturated with 50% ethyl ace-
benzene (4f). The general procedure was followed (3.22 tate in petroleum ether (3 mL) to give 5b as a colourless
mmol scale). The crude residue was purified by column solid: Yield 0.6 g (80%); m.p. 145–148°C. 1H NMR (DMSO-
chromatography (10% ethyl acetate in petroleum ether) to d6, 500 MHz): δ=10.11 (s, 1H), 7.66 (s, 4H), 7.29 (d, J=8.1
give 4f as a colourless solid20: Yield 1.04 g (87%); m.p. Hz, 4H); 13C NMR (DMSO-d6, 125 MHz): δ=160.9 (d,
141–144°C; 1H NMR (CDCl3, 500 MHz): δ=11.64 (s, 1H), J=241.9 Hz), 160.1 (q, J=32.0 Hz), 156.8, 132.0, 127.9 (d,
10.37 (s, 1H), 7.59 (d, J=8.8 Hz, 2H), 7.3–7.29 (m, 2H), J=8.8 Hz), 117.4 (q, J=296.0 Hz) 116.8 (d, J=22.6 Hz);
1.56 (s, 9H), 1.53 (s, 9H); 13C NMR (CDCl3, 125 MHz): HRMS (ESI) m/z [M+H]+ calcd for C7H9FN3: 154.0755;
δ=153.4, 153.3, 135.4, 129.8, 128.9, 123.3, 83.9, 79.9, found: 154.0785; IR: 3165, 1502, 1436, 1178 cm−1.
28.1, 28.0; HRMS (ESI) m/z [M (35Cl)+H]+ calcd for
C17H25ClN3O4: 370.1528; [M (37Cl)+H]+: 372.1499; Synthesis of 1-(p-tolyl)guanidine trifluoroacetate (5c). The
found: 370.1534; 372.1507.
general procedure was followed (2.83 mmol scale). The
crude residue was triturated with 50% ethyl acetate in
Synthesis of 1-[2,3-di(tert-butoxycarbonyl)guanidino]-4-methoxy- petroleum ether (3 mL) to give 5c as a colourless solid:
1
benzene (4g). The general procedure was followed (3.22 Yield 0.51 g (68%); m.p. 77–80°C; H NMR (DMSO-d6,