1606
M. Fischer, R. Troschütz
PAPER
Synthesis of Alkyl 2-(Phenoxysulfonyl)ethanimidoates Hydro-
chlorides (7·HCl); General Procedure
Phenyl 2-Amino-6-(4-methoxyphenyl)pyridine-3-sulfonate (3b)
Method A; colorless crystals; yield: 470 mg (67%); mp 148 °C.
Dry HCl was passed through a stirred solution of phenyl cya-
nomethanesulfonate (5) (1.97 g, 10 mmol) and alcohol (12 mmol)
in anhyd Et2O (30 mL) at 0 °C over 2 h. After addition of Et2O (30
mL) the product crystallized completely on standing overnight at 4
°C. Filtration of the mixture gave the salt.
IR (KBr): 3461, 3312, 3081, 2965, 1605, 1571, 1358, 1145 cm–1.
1H NMR (DMSO-d6): = 3.83 (s, 3 H, OCH3), 6.89 (br s, 2 H,
NH2), 7.01–7.09 (m, 2 H, 3 -H, 5 -H), 7.10–7.16 (m, 2 H, 2 -H, 6 -
H), 7.19 (d, J = 8 Hz, 1 H, 5-H), 7.26–7.46 (m, 3 H, 3 -H, 4 -H, 5 -
H), 7.71 (d, J = 8 Hz, 1 H, 4-H), 8.02–8.11 (m, 2 H, 2 -H, 6 -H).
MS (EI, 70 eV): m/z (%) = 356 (38) [M+], 263 (63), 215 (79), 199
(100).
Methyl 2-(Phenoxysulfonyl)ethanimidoate Hydrochloride
(7a·HCl)
Colorless needles; yield: 2.40 g (90%); mp 95 °C.
IR (KBr): 3391, 3050, 3014, 2975, 2904, 1662, 1387, 1142 cm–1.
Anal. Calcd for C18H16N2O4S (356.40): C, 60.7; H, 4.53; N, 7.86.
Found: C, 60.8; H, 4.16; N, 7.79.
1H NMR (DMSO-d6): = 3.76 (s, 3 H, OCH3), 4.88 (s, 2 H, CH2),
7.33–7.55 (m, 5 H, Ph), 7.80 (s, 2 H, NH2).
MS (EI, 70 eV): m/z (%) = 230 (27) [M+ – Cl], 94 (100).
Phenyl 2-Amino-6-(4-fluorophenyl)pyridine-3-sulfonate (3c)
Method A; colorless needles; yield: 591 mg (86%); mp 112 °C.
IR (KBr): 3460, 3307, 1639, 1569, 1369, 1145, 1163 cm–1.
1H NMR (DMSO-d6): = 6.97 (br s, 2 H, NH2), 7.09–7.17 (m, 2 H,
2 -H, 6 -H), 7.24 (d, J = 8 Hz, 1 H, 5-H), 7.28–7.46 (m, 5 H, 3 -H,
5 -H, 3 -H, 4 -H, 5 -H), 7.77 (d, J = 8 Hz, 1 H, 4-H), 8.10–8.20 (m,
2 H, 2 -H, 6 -H).
Anal. Calcd for C9H12ClNO4S (265.72): C, 40.7; H 4.55; N, 5.27.
Found: C, 40.7; H, 4.24, N, 5.67.
Ethyl 2-(Phenoxysulfonyl)ethanimidoate Hydrochloride
(7b·HCl)
Colorless needles; yield: 2.69 g (96%); mp 105–106 °C.
MS (EI, 70 eV): m/z (%) = 344 (45) [M+], 251 (81), 203 (34), 187
IR (KBr): 3369, 2995, 2946, 1381, 1143 cm–1.
(100).
1H NMR (DMSO-d6): = 1.23 (t, J = 7 Hz, 3 H, OCH2CH3), 4.22
(q, J = 7 Hz, 2 H, OCH2CH3), 4.85 (s, 2 H, CH2), 7.10 (s, 2 H, NH2),
7.36–7.55 (m, 5 H, Ph).
Anal. Calcd for C17H13FN2O3S (344.37): C, 59.3; H, 3.81; N, 8.13.
Found: C, 58.9, H, 3.74; N, 8.42.
Phenyl 2-Amino-6-(4-chlorophenyl)pyridine-3-sulfonate (3d)
Method A; colorless crystals; yield: 511 mg (71%); mp 134 °C.
MS (EI, 70 eV): m/z (%) = 244 (24) [M+ – Cl], 94 (100).
Anal. Calcd for C10H14ClNO4S (279.74): C, 42.9; H, 5.04; N, 5.01.
Found: C, 43.0; H, 5.26; N, 4.65.
IR (KBr): 3452, 3306, 1639, 1572, 1365, 1148, 1091 cm–1.
1H NMR (DMSO-d6): = 6.99 (br s, 2 H, NH2), 7.09–7.17 (m, 2 H,
2 -H, 6 -H), 7.26 (d, J = 8 Hz, 1 H, 5-H), 7.28–7.46 (m, 3 H, 3 -
H, 4 -H, 5 -H), 7.54–7.62 (m, 2 H, 3 -H, 5 -H), 7.79 (d, J = 8 Hz, 1
H, 4-H), 8.07–8.15 (m, 2 H, 2 -H, 6 -H).
MS (EI, 70 eV): m/z (%) = 362/360 (34/95) [M+], 269/267 (35/97),
221/219 (10/30), 205/203 (30/100), 168 (100).
Synthesis of Phenyl 2-Aminopyridine-3-sulfonates 3; General
Procedure
Method A
7b·HCl (560 mg, 2 mmol), ammonium acetate (2 g) and 8a–g (2
mmol), 9 (2 mmol), or 10 (2 mmol) were refluxed in EtOH (20 mL)
for 4 h. Cooling at 4 ° C overnight yielded the product as a crystal-
line solid.
Anal. Calcd for C17H13ClN2O3S (360.82): C, 56.6; H, 3.63; N, 7.76.
Found: C, 56.9; H, 3.52; N, 7.78.
Method B
Phenyl 2-Amino-6-(4-bromophenyl)pyridine-3-sulfonate (3e)
Method A; colorless needles; yield: 600 mg (74%); mp 136–137 °C.
IR (KBr): 3453, 3306, 1639, 1572, 1364, 1147, 1070 cm–1.
1H NMR (DMSO-d6): = 7.00 (br s, 2 H, NH2), 7.09–7.18 (m, 2 H,
2 -H, 6 -H), 7.26 (d, J = 8 Hz, 1 H, 5-H), 7.28–7.46 (m, 3 H, 3 -H,
4 -H, 5 -H), 7.68–7.75 (m, 2 H, 3 -H, 5 -H), 7.79 (d, J = 8 Hz, 1 H,
4-H), 8.00–8.08 (m, 2 H, 2 -H, 6 -H).
MS (EI, 70 eV): m/z (%) = 406/404 (22/21) [M+], 313/311 (39/38),
249/247 (15/15), 168 (100).
( )-Phenyl 2-[1-(phenylethyl)amino]pyridine-3-sulfonates 16a–c
(0.5 mmol) were heated with polyphosphoric acid (PPA) (4 g) for 2
h at 60 °C. After cooling to r.t. the mixture was hydrolyzed with ice-
water (15 mL) and neutralized with concd NH3. The thus formed
precipitate was filtered and crystallized from EtOH.
Phenyl 2-Amino-6-phenylpyridine-3-sulfonate (3a)
Colorless needles; yield: 495 mg (76%, method A), 75 mg (46%,
method B); mp 127–129 °C.
IR (KBr): 3400, 3066, 1608, 1573, 1560, 1357, 1144 cm–1.
1H NMR (DMSO-d6): = 6.97 (br s, 2 H, NH2), 7.10–7.18 (m, 2 H,
2 -H, 6 -H), 7.26 (d, J = 8 Hz, 1 H, 5-H), 7.28–7.46 (m, 3 H, 3 -H,
4 -H, 5 -H), 7.47–7.55 (m, 3 H, 3 -H, 4 -H, 5 -H), 7.78 (d, J = 8 Hz,
1 H, 4-H), 8.08–8.14 (m, 2 H, 2 -H, 6 -H).
Anal. Calcd for C17H13BrN2O3S (405.28): C, 50.9; H, 3.27, N, 6.98.
Found: C, 51.0; H, 3.29; N, 7.04.
Phenyl 2-Aminopyridine-3-sulfonate (3f)
Method A; colorless needles; yield: 140 mg (28%); mp 103–104 °C.
13C NMR (DMSO-d6): = 108.7, 109.6 (C-3, C-5), 122.5 (C-2 , C-
6 ), 127.9, 129.6, 131.5 (C-2 , C-3 , C-4 , C-5 , C-6 ), 128.4 (C-4 ),
130.8 (C-3 , C-5 ), 137.3 (C-1 ), 141.7 (C-4), 149.4 (C-1 ), 155.9,
160.0 (C-2, C-6).
MS (EI, 70 eV): m/z (%) = 326 (32) [M+], 233 (52), 185 (19), 169
(100).
IR (KBr): v = 3465, 3449, 3084, 1656, 1636, 1364, 1174 cm–1.
1H NMR (DMSO-d6): = 6.65 (dd, J1 = 8 Hz, J2 = 4.5 Hz, 1 H, 5-
H), 6.89 (br s, 2 H, NH2), 7.05–7.13 (m, 2 H, 2 -H, 6 -H), 7.27–7.45
(m, 3 H, 3 -H, 4 -H, 5 -H), 7.70 (dd, J1 = 8 Hz, J3 = 2 Hz, 1 H, 4-H),
8.31 (dd, J2 = 4.5 Hz, J3 = 2 Hz, 1 H, 6-H).
MS (EI, 70 eV): m/z (%) = 250 (15) [M+], 157 (33), 93 (100).
Anal. Calcd for C17H14N2O3S (326.38): C, 62.6; H, 4.32; N, 8.58.
Found: C, 62.6; H, 4.66; N, 8.53.
Anal. Calcd for C11H10N2O3S (250.28): C, 52.8; H, 4.02; N, 11.19.
Found: C, 53.0; H, 4.12; N, 11.19.
Synthesis 2003, No. 10, 1603–1609 © Thieme Stuttgart · New York