PAPER
Amidination of Amines under Microwave Conditions
465
1H NMR: d = 1.37–1.54 (m, 6 H, 3 CH2), 3.31 (t, J = 5.2 Hz, 4 H,
CH2NCH2), 4.3–5.2 (br, 3 H, NH guanidine).
13C NMR: d = 24.8, 49.9, 125.8, 127.1, 128.4, 143.7, 156.9.
LRMS (EI): m/z = 163 (M+).
13C NMR: d = 24.0, 25.1, 45.9, 158.8.
LRMS (EI): m/z = 127 (M+).
N-Furan-2-ylmethylguanidine (13)20
1H NMR: d = 4.40 (s, 2 H, CH2), 6.26 (d, J = 2.9 Hz, 1 H, 3-H), 6.39
(dd, J = 6.3, 2.7 Hz, 1 H, 4-H), 7.49 (s, 1 H, 5-H).
HRMS (ESI+): m/z calcd for C6H14N3 [M + H]+: 128.1182; found:
128.1183.
13C NMR d = 39.2, 108.9, 111.5, 145.7, 151.5, 159.0.
Amidination with Reagent 1b under Microwave Conditions;
L-Proline-N-carboxamidine (24); Typical Procedure
HRMS (ESI+): m/z calcd for C6H10N3O [M + H]+: 140.0818; found:
140.0820.
Reagent 1b (306 mg, 0.5 mmol), L-proline (30 mg, 0.25 mmol) and
Et3N (100 mL) in anhyd THF (4 mL) were heated in a microwave
tube at 300 W and 90 °C for 10 min. The mixture was filtered, the
resin was washed with MeOH (3 × 3 mL). The filtrate was evapo-
rated in vacuo, the residue was taken up in H2O (ca. 2 mL) and
passed through a column containing Amberlite IRA-400 (hydrox-
ide-form, 10 mL) eluting with H2O. Lyophilisation of the eluate af-
forded L-Proline-N-carboxamidine (24)14 as an amorphous white
solid; yield: 16 mg (33%).
N-(1-O-Methyl-2,3,6-trideoxy-b-L-lyxo-pyranoside-3-yl)guani-
dine (14)8
1H NMR: d = 1.13 (d, J = 6.5 Hz, 3 H, 6-CH3), 1.41 (m, 1 H, 2-
CHH), 1.64 (m, 1 H, 2-CHH), 3.27 (m, 1 H, 4-CH), 3.33 (s, 3 H,
OCH3), 3.44 (m, 1 H, 5-CH), 3.60 (m, 1 H, 3-CH), 4.29 (m, 1 H, 1-
CH), 4.3–4.6 (br, 5 H, 4 H guanidine and OH).
13C NMR: d = 17.0, 32.0, 50.2, 55.2, 67.9, 71.4, 101.1, 156.6.
LRMS (EI): m/z = 188 [(M – NH)+].
1H NMR: d = 3.96 (d, J = 7.7 Hz, 1 H, CH), 2.40 (ddd, J = 11.9, 9.2,
4.0 Hz, 1 H), 2.23 (m, 1 H) 1.83 (m, 4 H).
HRMS (ESI+): m/z calcd for C8H17N3O3 [M + H]+: 204.1348; found:
204.1345.
13C NMR: d = 23.7, 29.1, 47.2, 63.6, 156.2, 172.4.
HR-MS (ESI+): m/z calcd for C6H12N3O2 [M + H]+: 158.0924;
found: 158.0928.
N-(1-O-Allyl-2,3,6-trideoxy-a-L-arabino-pyranoside-3-
yl)guanidine (15)8
1H NMR: d = 1.10 (d, J = 6.2 Hz, 3 H, 6-CH3), 1.54 (m, 1 H, 2-
CHH), 1.81 (m, 1 H, 2-CHH), 2.77 (dd, J = 9.1, 9.1 Hz, 1 H, 4-CH),
3.40 (dq, J = 8.8, 6.3 Hz, 1 H, 5-CH), 3.60 (m, 1 H, 3-CH), 3.89 (m,
1 H, OCHH), 4.06 (m, 1 H, OCHH), 4.4-5.1 (br, 6 H, 1-CH, 5 H
guanidine and OH), 5.14 (dd, J = 10.4, 1.6 Hz, 1 H, =CHH), 5.27
(dd, J = 17.2, 1.8 Hz, 1 H, =CHH), 5.92 (m, 1 H, =CH).
N-Butylguanidine (6)15
1H NMR: d = 0.87 (t, J = 7.2 Hz, 3 H, CH3), 1.29 (m, 2 H, CH2),
1.38 (m, 2 H, CH2), 2.93 (t, J = 7.0 Hz, 2 H, CH2N), 4.83 (br, 4 H,
NH guanidine).
13C NMR: d = 13.8, 19.7, 31.7, 41.0, 157.4.
LRMS (EI): m/z = 115 (M+).
13C NMR: d = 17.8, 35.0, 50.0, 66.7, 68.4, 79.0, 95.1, 116.2, 134.9,
160.5.
N-Octylguanidine (7)
1H NMR: d = 0.9 (t, J = 7.0 Hz, 3 H, CH3), 1.55–1.32 (m, 12 H,
CH2), 3.16 (t, J = 7.0 Hz, 2 H, CH2N).
LRMS (EI): 230 [(M + H)+].
HRMS (ESI+): m/z calcd for C10H20N3O3 [M + H]+: 230.1505;
found: 230.1506.
13C NMR: d = 14.5, 23.7, 30.2, 30.3, 30.4, 30.5, 35.9, 42.6, 159.8.
N-(4-Methoxyphenyl)guanidine (16)12
1H NMR: d = 3.67 (s, 3 H, OCH3), 4.6–6.0 (br, 4 H, H guanidine),
6.68–6.78 (m, 4 Harom).
HRMS (ESI+): m/z calcd for C9H22N3 [M + H]+: 172.1814; found:
172.1809.
N-(2-Hydroxyethyl)guanidine (8)16
1H NMR: d = 3.05 (t, J = 5.2 Hz, 2 H, NCH2), 3.42 (t, J = 5.2 Hz, 2
H, OCH2), 4.99 (br, 5 H, 4 NH guanidine and OH).
13C NMR: d = 55.1, 114.2, 123.6, 143.2, 152.5, 153.5.
LRMS (EI): m/z = 165 (M+).
13C NMR: d = 44.6, 62.4, 159.1.
LRMS (EI): m/z = 103 (M+).
N1-Benzyl-N1-methylguanidine (17)21
1H NMR: d = 2.76 (s, 3 H, CH3), 4.46 (s, 2 H, CH2), 4.5–5.2 (br, 3
H, H guanidine), 7.17–7.35 (m, 5 H, C6H5).
N-(2-Mercaptoethyl)guanidine (9)17
1H NMR: d = 2.87 (t, J = 6.7 Hz, 2 H, CH2), 3.43 (t, J = 6.3 Hz, 2
H, CH2S), 4.70 (s, 1 H, SH).
13C NMR: d = 35.2, 52.3, 126.8, 127.2, 128.3, 138.4, 158.9.
LRMS (EI): m/z = 163 (M+).
13C NMR: d = 39.1, 42.1, 160.2.
L-Prolinamide-N-carboxamidine (19)22
1H NMR: d = 1.4–2.0 (m, 4 H, b-CH2 and g-CH2), 3.0–3.4 (m, 2 H,
d-CH2), 3.81 (t, J = 7.8 Hz, 1 H, a-CH), 4.3–5.1 (br, 5 H, 3 H ami-
dine and 2 H amide).
HRMS (ESI+): m/z calcd for C3H10N3S [M + H]+: 120.0590; found:
120.0589.
3-Guanidinopropionic Acid (10)18
1H NMR: d = 3.00–3.10 (m, 2 H, CH2), 3.27–3.35 (m, 2 H, CH2),
7.20 (br, 5 H, H guanidine).
13C NMR: d = 26.5, 27.1, 47.9, 67.0, 177.5, 189.0.
LRMS (EI): m/z =156 (M+).
13C NMR: d = 33.3, 36.7, 156.9, 172.5.
LRMS (EI): m/z = 131 (M + H+).
N-Ethyl-N-naphthalen-1-ylguanidine (20)
1H NMR: d = 1.39 (t, J = 7.0 Hz, 3 H, CH3), 3.20 (q, J = 7.0 Hz, 2
H, CH2), 7.71–8.10 (m, 7 Harom).
N-(1-Phenylethyl)guanidine (12)19
13C NMR: d = 9.2, 11.6, 121.4, 122.8, 126.2, 126.3, 127.1, 128.6,
128.7, 129.4, 130.4, 130.5, 131.6, 131.8, 136.0, 136.1, 157.5.
1H NMR: d = 1.37 (d, J = 6.8 Hz, 3 H, CH3), 4.69 (q, J = 6.3 Hz, 1
H, CHCH3), 7.25–7.35 (m, 5 H, C6H5), 7.6–8.3 (br, 4 H, NH guani-
dine).
HRMS (ESI+): m/z calcd for C13H16N3 [M + H]+: 214.1344; found:
214.1349.
Synthesis 2006, No. 3, 461–466 © Thieme Stuttgart · New York