M. Eckert-Maksic´ et al.
FULL PAPER
(c = 1 moldm–3). The colorless crystals of 6a·HClO4 were grown 4.35 (s, 2 H, CH2) 7.23–7.28 (m, 3 H, C6H5), 7.31–7.33 (m, 2 H,
from the solution after 3 days by slow evaporation at room temp.;
C6H5) ppm. 13C NMR (150 MHz, D2O, 25 °C): δ = 21.1, 22.1, 43.5,
m.p. 128–129 °C. 1H NMR (600 MHz, [D6]DMSO, 25 °C): δ = 0.87 44.9, 126.6, 126.9, 128.2, 138.2, 154.8, 156.8, 179.8 ppm. HRMS-
3
3
(t, JH,H = 7.4 Hz, 3 H, CH3CH2CH2), 1.22 [d, JH,H = 6.6 Hz, 6
EI calcd. for C22H40N7 [M + H]+: 402.3345, found 402.3337.
3
H, (CH3)2CH], 1.25 [d, JH,H = 6.6 Hz, 6 H, (CH3)2CH], 1.49 [d,
N1-Benzyl-N2,N3-diisopropylguanidine (5c): 1H NMR (300 MHz,
3JH,H = 7.1 Hz, 6 H, (CH3)2CH], 1.50–1.54 (m, 2 H, CH3CH2CH2),
3.19–3.23 (m, 2 H, CH3CH2CH2), 4.30–4.38 [m, 2 H, (CH3)2CH],
3
[D6]DMSO, 25 °C): δ = 1.05 [d, JH,H = 6.3 Hz, 12 H, (CH3)2CH],
3.57–3.84 [m, 2 H, (CH3)2CH], 4.17 (s, 2 H, CH2), 4.40–4.80 (br.
s, 2 H, NH), 7.11–7.37 (m, 5 H, C6H5) ppm. 13C NMR (75 MHz,
[D6]DMSO, 25 °C): δ = 23.5, 42.5, 48.0, 125.6, 127.1, 127.7, 143.3,
3
4.54–4.61 [m, 1 H, (CH3)2CH], 6.98 (d, JH,H = 7.9 Hz, 1 H, NH),
3
3
7.19 (d, JH,H = 7.5 Hz, 1 H, NH), 8.25 (t, JH,H = 5.8 Hz, 1 H,
NH) ppm. 13C NMR (150 MHz, [D6]DMSO, 25 °C): δ = 11.3, 19.1,
21.3, 21.5, 22.1, 42.3, 44.1, 44.7, 48.7, 153.5, 154.1, 160.3 ppm. IR
150.4 ppm. HRMS-MALDI calcd. forC22H40N7 [M
234.1965, found 234.1968.
+
H]+:
(KBr): ν = 3349, 2974, 2935, 2876, 1599, 1560, 1464, 1142, 1119,
˜
1088, 1049, 785, 636, 625 cm–1.
4-Benzylamino-1-isopropyl-6-isopropylamino-2-isopropylimino-1,2-
dihydro-1,3,5-triazine Acetate (6c·AcOH): 1H NMR (600 MHz,
N1,N2,N6,N7-Tetraisopropyl-N4-(3-methoxypropyl)triguanide Acet-
ate (1b·AcOH): Two subsequent crystallizations from acetonitrile
afforded white crystals of cyanoguanidine 4 in a total of 0.3 g
(22%), while high vacuum distillation gave 0.4 g of the trisubsti-
tuted guanidine 5b (colorless oil, 17%). A 167 mg aliquot of the
residual crude product (3.0 g) was dissolved in 900 μL of methanol
(p.a.) and subjected to the semipreparative HPLC. Evaporation of
the collected fractions yielded the triguanide acetate 1b·AcOH as
colorless oil (157 mg, 63%) and the triazine acetate 6b·AcOH (col-
3
[D6]DMSO, 25 °C): δ = 1.12 [d, JH,H = 6.5 Hz, 6 H, (CH3)2CH],
3
1.18 [d, JH,H = 6.6 Hz, 6 H, (CH3)2CH], 1.45 [d, J = 7.0 Hz, 6 H,
(CH3)2CH], 1.79 (s, 3 H, CH3COO–), 4.21–4.27 [m, 1 H, (CH3)2-
3
CH], 4.27–4.34 [m, 1 H, (CH3)2CH], 4.40 (d, JH,H = 6.2 Hz, 2 H,
CH2), 4.66–4.73 [m, 1 H, (CH3)2CH], 7.20–7.32 (m, 5 H, C6H5),
8.20–8.34 (br. s, 1 H, NH) ppm. 13C NMR (150 MHz, [D6]DMSO,
25 °C): δ = 19.1, 21.9, 22.0, 22.7, 43.9, 44.0, 44.7, 47.7, 126.8, 127.5,
128.2, 139.6, 153.1, 153.6, 160.2, 173.2 ppm. HRMS-EI calcd. for
C19H31N6 [M + H]+: 343.2610, found 343.2604.
1
orless oil, 5 mg, 2%). H NMR (600 MHz, D2O, 25 °C): δ = 1.12
3
N1,N2,N6,N7-Tetraisopropyl-N4-(p-methoxybenzyl)triguanide Acet-
ate (1d·AcOH): Crystallization from acetonitrile afforded 0.3 g of
white crystals of cyanoguanidine 4 (20%), whereas high vacuum
distillation gave 0.6 g of the trisubstituted guanidine 5d (colorless
oil, 21%). A 200 mg aliquot of the residual reaction product (3.1 g)
was dissolved in 1000 μL of methanol (p.a.) and subjected to the
semipreparative HPLC. Evaporation of the appropriate fractions
yielded the triazine acetate 6d·AcOH as colorless oil (40 mg, 14%),
a 4:1 mixture of the triguanide acetate 1d·AcOH and the intermedi-
ate biguanide acetate 7d·AcOH (Scheme 2, R = p-MeOBn) as de-
termined by 1H NMR; (pale yellow oil,193 mg). 1H NMR
(600 MHz, D2O, 25 °C): δ = 0.67 [d, 3JH,H = 6.5 Hz, 24 H, (CH3)2-
CH], 1.49 (s, 3 H, CH3COO–), 3.22–3.29 [m, 4 H, (CH3)2CH], 3.33
[d, JH,H = 6.5 Hz, 24 H, (CH3)2CH], 1.72–1.79 (m, 2 H,
3
CH2CH2CH2OCH3), 1.85 (s, 3 H, CH3COO–), 3.23 (t, JH,H
=
6.8 Hz, 2 H, CH2CH2CH2OCH3), 3.26 (s, 3 H, OCH3), 3.45 (t,
3JH,H = 6.3 Hz, 2 H, CH2CH2CH2OCH3), 3.70–3.80 [m, 4 H,
(CH3)2CH] ppm. 13C NMR (150 MHz, D2O, 25 °C): δ = 21.2, 22.4,
28.0, 38.7, 43.7, 57.4, 69.5, 154.6 (br), 156.8, 180.1 ppm. HRMS-
EI calcd. for C19H42N7O [M + H]+: 384.3451, found 384.3433.
N1,N2-Diisopropyl-N3-(3-methoxypropyl)guanidine (5b): 1H NMR
3
(600 MHz,[D6]DMSO, 25 °C): δ = 1.01 [d, JH,H = 6.3 Hz, 12 H,
(CH3)2CH], 1.60–1.66 (m, 3JH,H
CH2CH2CH2OCH3), 2.94 (t, 3JH,H
CH2CH2CH2OCH3), 3.21 (s, 3 H, OCH3), 3.35 (t, JH,H = 6.4 Hz,
2 H, CH2CH2CH2OCH3), 3.54–3.62 [m, 2 H, (CH3)2CH], 4.2–4.6
(br. s, 2 H, NH) ppm. 13C NMR (75 MHz, [D6]DMSO, 25 °C): δ
= 23.7, 30.8, 40.7, 42.6, 57.8, 70.5, 150.0 ppm. HRMS-MALDI
calcd. for C19H42N7O [M + H]+: 216.2073, found 216.2083.
=
=
6.5 Hz,
2
2
H,
H,
6.7 Hz,
3
3
(s, 3 H, OCH3), 3.87 (s, 2 H, CH2), 6.51 (d, JH,H = 8.8 Hz, 2 H,
3
Ar-H), 6.81 (d, JH,H = 8.7 Hz, 2 H, Ar-H) ppm. 13C NMR
(150 MHz, D2O, 25 °C): δ = 21.0, 21.3, 44.1, 44.5, 54.92, 113.8,
127.9, 128.2, 129.9, 154.1 (br), 157.8, (one quaternary signal is not
observed) 178.5 ppm. HRMS-EI calcd. for C23H42N7O [M + H]+:
432.3451, found 432.3452.
1-Isopropyl-6-isopropylamino-2-isopropylimino-4-(3-methoxypropyl-
amino)-1,2-dihydro-1,3,5-triazine Acetate (6b·AcOH): 1H NMR
(600 MHz, [D6]DMSO, 25 °C): δ = 1.11–1.17 [12 H, (CH3)2CH,
N1,N2-Diisopropyl-N3-(p-methoxybenzyl)guanidine (5d): 1H NMR
3
overlapped iPr signals], 1.44 [d, JH,H = 7.0 Hz, 6 H, (CH3)2CH],
3
(300 MHz, [D6]DMSO, 25 °C): δ = 1.03 [d, JH,H = 6.4 Hz, 12 H,
1.68–1.73 (m, 2 H, CH2CH2CH2), 1.77 (s, 3 H, CH3COO), 3.21 (s,
3 H, OCH3, overlapped), 3.19–3.24 (m, 2 H, CH2CH2CH2OCH3,
3
(CH3)2CH], 3.62–3.76 [m, JH,H = 6.3 Hz, 2 H, (CH3)2CH, over-
3
lapped], 3.71 (s, 3 H, OCH3, overlapped), 4.11 (s, 2 H, CH2), 6.84
overlapped), 3.33 (t, JH,H = 6.3 Hz, 2 H, CH2CH2CH2OCH3),
3
3
(d, JH,H = 8.6 Hz, 2 H, Ar-H), 7.23 (d, JH,H = 8.6 Hz, 2 H, Ar-
H) ppm. 13C NMR (150 MHz, [D6]DMSO, 25 °C): δ = 23.9, 43.1,
47.3, 54.4, 113.8, 128.7, 135.1, 151.2, 158.0 ppm. HRMS-MALDI
calcd. forC15H25N3O [M + H]+: 264.2070, found 264.2074.
4.16–4.28 [m, 2 H, (CH3)2CH overlapped iPr signals], 4.68–4.76
[m, 1 H, (CH3)2CH], 7.08–7.35 (br. s, 1 H, NH) ppm. 13C NMR
(150 MHz, [D6]DMSO, 25 °C): δ = 19.3, 22.4, 22.6, 23.0, 29.2, 37.6,
43.5, 44.6, 46.7, 57.8, 69.7, 152.3, 153.4, 159.9, 172.9 ppm. HRMS-
EI calcd. for C16H33N6O [M + H]+: 325.2716, found 325.2720.
1-Isopropyl-6-isopropylamino-2-isopropylimino-4-[(p-methoxybenz-
N1,N2,N6,N7-Tetraisopropyl-N4-benzyltriguanide Acetate (1c·AcOH): yl)amino]-1,2-dihydro-1,3,5-triazine (6d·AcOH): 1H NMR
3
Crystallization from acetonitrile afforded 0.4 g of white crystals of
cyanoguanidine 4 (22%), while high vacuum distillation gave 0.6 g
of the trisubstituted guanidine 5c (colorless oil, 28%). A 200 mg
aliquot of the residual crude product (3.1 g) was dissolved in
1000 μL of methanol (p.a.) and subjected to the semipreparative
HPLC. Evaporation of the collected fractions yielded the triguan-
ide acetate 1c·AcOH as colorless oil (133 mg, 44%) and the triazine
(600 MHz, D2O, 25 °C): δ = 0.69 [d, JH,H = 6.6 Hz, 6 H, (CH3)2-
3
3
CH], 0.73 [d, JH,H = 6.6 Hz, 6 H, (CH3)2CH], 0.96 [d, JH,H
=
7.1 Hz, 6 H, (CH3)2CH], 1.48 (s, 3 H, CH3COO–), 3.24 (s, 3 H,
OCH3), 3.71–3.78 [m, 1 H, (CH3)2CH], 3.78–3.84 [m, 1 H, (CH3)2-
CH], 3.86 (s, 2 H, CH2), 4.00–4.06 [m, 1 H, (CH3)2CH], 6.36 (d,
3JH,H = 8.5 Hz, 2 H, Ar-H), 6.72 (d, JH,H = 8.4 Hz, 2 H, Ar-
3
H) ppm. 13C NMR (150 MHz, D2O, 25 °C): δ = 18.2, 20.46, 20.54,
acetate 6c·AcOH (colourless oil, 87 mg, 33%). 1H NMR 21.6, 43.4, 44.3, 44.6, 48.8, 54.8, 113.5, 128.5, 130.8, 153.6, 153.9,
3
(600 MHz, D2O, 25 °C): δ = 1.06 [d, JH,H = 6.5 Hz, 24 H, (CH3)
157.5, 160.5, 178.9 ppm. HRMS-EI calcd. for C20H33N6O [M +
2CH], 1.86 (s, 3 H, CH3COO–), 3.64–3.71 [m, 4 H, (CH3)2CH], H]+: 373.2716, found 373.2708.
6794
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Eur. J. Org. Chem. 2012, 6785–6797