A. Herrmann et al.
FULL PAPER
(w), 1806 (w), 1747 (w), 1603 (w), 1584 (w), 1494 (m), 1452 (s),
1372 (w), 1361 (w), 1353 (w), 1341 (w), 1297 (w), 1197 (w), 1118
(m), 1094 (m), 1071 (m), 1050 (w), 1027 (m), 1001 (w), 966 (w),
912 (w), 853 (w), 823 (w), 807 (w), 730 (s), 695 (s), 620 (m) cm–1.
703 (m), 670 (w), 637 (w), 633 (w) cm–1. MS (HR-ESI-MS, pos.):
calcd. for C20H31N4 [M + H]+ 327.2548; found 327.2536.
+
N,NЈ-Bis[4-(dimethylamino)benzyl]propane-1,3-diamine (10): This
compound was produced as described above, from propane-1,3-
diamine (2.26 mL, 26.8 mmol), 4-(dimethylamino)benzaldehyde
(8.00 g, 53.6 mmol) and NaBH4 (2.00 g, 52.9 mmol) to give 9.02 g
+
MS (HR-ESI-MS, pos.): calcd. for C20H27N2 [M + H]+ 295.2174;
found 295.2158.
1
N,NЈ-Dibenzylcyclohexane-1,3-diamine (12): This compound was
produced as described above, from benzaldehyde (5.57 g,
52.5 mmol), cis/trans-cyclohexane-1,3-diamine (3.00 g, 26.3 mmol),
methanol (30 mL) and NaBH4 (2.38 g, 62.9 mmol) to give 6.83 g
(89%) of a yellow oil as a mixture of the cis/trans isomers in a ratio
of ca. 3:1. 1H NMR (400 MHz, [D6]DMSO, major isomer): δ =
7.34–7.24 (m, 8 H, Ph-H), 7.22–7.15 (m, 2 H, Ph-H), 3.70 (s, 4 H,
Ph-CH2-NH), 2.37–2.26 [m, 2 H, C(3)-H], 2.17–2.09 [m, 1 H, C(2)-
H], 1.90–1.70 [m, 4 H, C(4)-H and NH], 1.69–1.60 [m, 1 H, C(5)-
H], 1.10 [qt, J = 13.1, 3.3 Hz, 1 H, C(5)-H], 0.98–0.84 [m, 1 H,
C(4)-H], 0.84 [q, J = 11.4 Hz, 2 H, C(2)-H] ppm. 1H NMR
(400 MHz, [D6]DMSO, minor isomer): δ = 7.34–7.24 (m, 8 H, Ph-
(99%) of a yellow oil. H NMR (400 MHz, [D6]DMSO): δ = 7.09
(d, J = 8.7 Hz, 4 H, Ph-H), 6.64 (d, J = 8.7 Hz, 4 H, Ph-H), 3.53
(s, 4 H, Ph-CH2-NH), 2.84 [s, 12 H, N(CH3)2], 2.49 (t, J = 6.7 Hz,
4 H, NH-CH2-CH2), 1.59–1.50 (m, 2 H, NH-CH2-CH2) ppm. 13C
NMR (100.6 MHz, [D6]DMSO): δ = 149.24 [s, PhC(4Ј)], 128.54 [s,
PhC(1Ј)], 128.54 [d, PhC(2Ј)], 112.19 [d, PhC(3Ј)], 52.65 (t, Ph-
CH2-NH), 47.12 (t, NH-CH2-CH2), 40.25 [q, N(CH3)2], 29.59 (t,
NH-CH -CH ) ppm. IR (neat): ν = 3288 (w, br.), 3094 (w), 3071
˜
2
2
(w), 2918 (m), 2882 (m), 2843 (m), 2798 (m), 1879 (w), 1751 (w),
1613 (s), 1566 (w), 1519 (s), 1475 (m), 1442 (m), 1413 (w), 1341 (s),
1261 (w), 1222 (m), 1186 (m), 1161 (m), 1126 (m), 1058 (m), 1008
(w), 945 (m), 801 (s), 757 (m), 699 (w), 681 (w), 638 (w) cm–1. MS
H), 7.22–7.15 (m, 2 H, Ph-H), 3.65 (s, 4 H, Ph-CH2-NH), 3.34 (br. (HR-ESI-MS, pos): calcd. for C21H33N4 [M + H]+ 341.2705;
+
s, 2 H, NH), 2.85–2.76 [m, 2 H, C(3)-H], 1.60–1.45 [m, 6 H, C(2)- found 341.2691.
H, C(4)-H and C(5)-H], 1.37–1.23 [m, 2 H, C(4)-H] ppm. 13C NMR
Synthesis of (؎)-N-Benzyl-N-(2-piperidinylmethyl)amine (13): Benz-
(100.6 MHz, [D6]DMSO, major isomer): δ = 141.47 [s, PhC(1Ј)],
aldehyde (5.11 g, 48.1 mmol) was added to a solution of 2-(ami-
nomethyl)piperidine (5.00 g, 43.8 mmol) in methanol (50 mL). The
127.91 [d, PhC(3Ј)], 127.72 [d, PhC(2Ј)], 126.21 [d, PhC(4Ј)], 54.56
[d, C(3)], 49.92 (t, Ph-CH2-NH), 40.05 [t, C(2)], 32.71 [t, C(4)],
solution was heated to 60 °C and stirred for 12 h, after which
22.55 [t, C(5)] ppm. 13C NMR (100.6 MHz, [D6]DMSO, minor iso-
NaBH4 (2.00 g, 52.9 mmol) was added in small portions. Stirring
mer): δ = 141.53 [s, PhC(1Ј)], 127.91 [d, PhC(3Ј)], 127.78 [d,
PhC(2Ј)], 126.21 [d, PhC(4Ј)], 50.65 [d, C(3)], 50.18 (t, Ph-CH2-
NH), 37.08 [t, C(2)], 31.51 [t, C(4)], 19.29 [t, C(5)] ppm. IR (neat):
was continued at 60 °C for 1 h, and then more NaBH4 (2.00 g,
52.9 mmol) was added. After stirring at 60 °C for 1 h, the mixture
was left to cool to room temp. Evaporation of the solvent and
ν = 3308 (w, br.), 3084 (w), 3061 (w), 3025 (w), 3001 (w), 2924 (m),
˜
Kugelrohr distillation (0.09 mbar, 120 °C) yielded 6.02 g (61%) of
2851 (m), 2813 (w), 1950 (w), 1871 (w), 1809 (w), 1748 (w), 1602
(w), 1584 (w), 1540 (w), 1494 (m), 1451 (m), 1357 (m), 1302 (w),
1255 (w), 1198 (w), 1107 (m), 1073 (m), 1027 (m), 1001 (w), 966
(w), 936 (w), 906 (w), 873 (w), 825 (w), 805 (w), 785 (w), 729 (s),
695 (s), 631 (w), 618 (w) cm–1. MS (HR-ESI-MS, pos.): calcd. for
1
a slightly yellow oil. H NMR (400 MHz, CDCl3): δ = 7.36–7.28
(m, 4 H, Ph-H), 7.28–7.19 (m, 1 H, Ph-H), 3.77 (d, J = 2.6 Hz, 2
H, NH-CH2-Ph), 3.09–3.01 [m, 1 H, C(6)-H], 2.68–2.44 [m, 4 H,
C(2)-CH2-NH, C(2)-H, C(6)-H], 1.86–1.70 [m, 3 H, NH, C(4)-H],
1.63–1.51 [m, 2 H, C(3)-H and C(5)-H], 1.48–1.25 [m, 2 H, C(4)-
H and C(5)-H], 1.15–1.02 [m, 1 H, C(3)-H] ppm. 13C NMR
(100.6 MHz, CDCl3): δ = 140.62 [s, PhC(1Ј)], 128.34 [d, PhC(3Ј)],
128.04 [d, PhC(2Ј)], 126.85 [d, PhC(4Ј)], 56.64 [d, C(2)], 55.48 [t,
NH-CH2-C(2)], 54.19 (t, Ph-CH2-NH), 46.83 [t, C(6)], 30.94 [t,
+
C20H27N2 [M + H]+ 295.2174; found 295.2176.
General Method for the Preparation of the Diamines 7 and 10: The
primary diamine was added to a suspension of 4-(dimethylamino)
benzaldehyde and Na2SO4 (5.00 g) in dichloromethane (100 mL).
The reaction mixture was stirred at room temp. for 3 d. After evap-
oration of the solvent, the residue was filtered and taken up in
methanol (100 mL). NaBH4 was added in small portions, which
resulted in a rapid increase in temperature. After 24 h, the solvent
was evaporated, and the residue was taken up in dichloromethane
and washed with a satd. aq. solution of NaHCO3. The organic
layer was dried (Na2SO4) and concentrated.
C(3)], 26.69 [t, C(5)], 24.72 [t, C(4)] ppm. IR (neat): ν = 3310 (w,
˜
br.), 3084 (w), 3061 (w), 3026 (w), 2926 (m), 2849 (m), 2795 (m),
2703 (w), 1947 (w), 1869 (w), 1806 (w), 1668 (w), 1602 (w), 1585
(w), 1494 (w), 1451 (m), 1440 (m), 1360 (w), 1324 (m), 1263 (w),
1198 (w), 1150 (w), 1112 (m), 1075 (w), 1051 (w), 1027 (w), 993
(w), 964 (w), 921 (w), 895 (w), 835 (m), 815 (m), 731 (s), 696 (s),
+
607 (m) cm–1. MS (HR-ESI-MS, pos.): calcd. for C13H21N2 [M +
H]+ 205.1699; found 205.1676.
N,NЈ-Bis[4-(dimethylamino)benzyl]ethane-1,2-diamine (7): This
compound was produced as described above, from ethane-1,2-di-
amine (1.77 mL, 26.8 mmol), 4-(dimethylamino)benzaldehyde
(8.00 g, 53.6 mmol) and NaBH4 (2.00 g, 52.9 mmol) to give 7.80 g
Synthesis of N,NЈ-Bis{2-[2-(2-methoxyethoxy)ethoxy]ethyl}ethane-
1,2-diamine (14): [2-(2-Methoxyethoxy)ethoxy]acetaldehyde (15,[37]
10.0 g, 61.7 mmol) was added to a solution of ethane-1,2-diamine
(89%) of a yellow solid. M.p. 68 °C. 1H NMR (400 MHz, [D6]- (2.06 mL, 1.85 g, 30.8 mmol) in methanol (75 mL). The reaction
DMSO): δ = 7.10 (d, J = 8.7 Hz, 4 H, Ph-H), 6.65 (d, J = 8.7 Hz,
mixture was heated to 70 °C and stirred for 2 h, after which NaBH4
(2.0 g) was added. The reaction mixture was stirred for 4 h. After
4 H, Ph-H), 3.53 (s, 4 H, Ph-CH2-NH), 2.84 [s, 12 H, N(CH3)2],
2.54 (s, 4 H, NH-CH2) ppm. 13C NMR (100.6 MHz, [D6]DMSO): cooling to room temp., the solvent was evaporated, and the residue
δ = 149.26 [s, PhC(4Ј)], 128.58 [s, PhC(1Ј)], 128.54 [d, PhC(2Ј)],
112.20 [d, PhC(3Ј)], 52.50 (t, Ph-CH2-NH), 48.17 (t, NH-CH2),
was dissolved in water (100 mL). Ion exchange chromatography
[2ϫ, on Dowex® W50 H+ resin (200 g), eluted with water (1 L, pH
neutral) and then with HCl (10%, 500 mL)] gave 1.4 g (13%) of a
40.24 [q, N(CH ) ] ppm. IR (neat): ν = 3287 (m), 3096 (w), 3077
˜
3 2
(w), 3035 (w), 3004 (w), 2948 (w), 2905 (w), 2880 (m), 2864 (w), yellow oil and 4.1 g of a brown oil, containing the desired product
2814 (m), 2761 (w), 2618 (w), 2232 (w), 2048 (w), 1874 (w), 1759 still together with its monofunctionalised analogue and other im-
(w), 1614 (s), 1564 (m), 1519 (s), 1471 (m), 1454 (s), 1448 (w), 1441
purities. 1H NMR (400 MHz, D2O): δ = 3.74–3.67 (m, 12 H), 3.67–
(s), 1400 (m), 1371 (m), 1338 (s), 1267 (m), 1223 (m), 1209 (s), 1187 3.61 (m, 8 H), 3.39 (s, 6 H), 2.79 (t, J = 5.4 Hz, 4 H), 2.73 (s, 4 H)
(s), 1163 (s), 1129 (s), 1064 (m), 1051 (w), 1016 (w), 1009 (w), 984 ppm. 13C NMR (100.6 MHz, D2O): δ = 73.81 (t), 72.43 (t), 72.25
(m), 945 (s), 927 (w), 841 (w), 820 (m), 796 (s), 733 (w), 715 (m),
692
(t, 3 C), 72.19 (t), 60.88 (q), 50.33 (t) ppm. IR (neat): ν = 3504 (w),
˜
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Eur. J. Org. Chem. 2011, 681–695