L. Racané, et al.
BioorganicChemistry95(2020)103537
4.1.1.8. 6-Amidinium-2-(2-hydroxyphenyl)benzothiazole
4.1.1.12. 2-(2-Methoxyphenyl)-6-nitrobenzothiazole (6b). According to
Method D, bis(2-amino-5-nitrophenyl) disulfide (3b) (0.170 g,
0.5 mmol) and 2-methoxybenzaldehide (4b) (0.136 g, 1.0 mmol)
were used and heated at 170–175 °C for 30 min, giving 0.223 g
(77.9%) of beige solid; mp = 193–195 °C. UPLC (254 nm): 98.7 area %;
MS (ESI) m/z: 287.1 (M+H+). 1H NMR (300 MHz, DMSO‑d6) (δ ppm):
9.19 (d, 1H, J = 2.3 Hz, Ar-H), 8.49 (dd, 1H, J = 7.8 Hz, J = 1.6 Hz,
Ar-H), 8.35 (dd, 1H, J = 9.0 Hz, J = 2.4 Hz, Ar-H), 8.21 (d, 1H,
J = 8.9 Hz, Ar-H), 7.65 (m, 1H, Ar-H), 7.37 (d, 1H, J = 8.2 Hz, Ar-H),
7.21 (m, 1H, Ar-H), 4.11 (s, 3H, eOCH3). 13C NMR (75 MHz, DMSO‑d6)
(δ ppm): 168.3 (s), 157.4 (s), 156.1 (s), 143.8 (s), 135.7 (s), 133.3 (d),
128.6 (d), 122.4 (d), 121.5 (d), 120.0 (d), 120.5 (s), 118.6 (d), 112.6
(d), 56.0 (q). Analysis calcd for C14H10N2O3S (286.31): C, 58.73; H,
3.52; N, 9.78. Found: C, 58.90; H, 3.34; N, 9.74.
methanesulfonate (5d). According to Method E, 2-amino-5-
amidiniumbenzenethiolate (2d) (0.167 g, 1.0 mmol) and 2-
hydroxybenzaldehyde (4a) (0.122 g, 1.0 mmol) were used giving
0.240 g (65.8%) of pale yellow solid; mp = 287–289 °C. UPLC
(254 nm): 99.4 area %; MS (ESI) m/z: 270.2 [(M+H+) calcd for free
base C14H11N3OS (269.06)]. 1H NMR (600 MHz, DMSO‑d6) (δ ppm):
11.57 (bs, 1H, eOH), 9.39 (s, 2H, eC(NH2)2+), 9.06 (s, 2H,
eC(NH2)2+), 8.65 (s, 1H, Ar-H), 8.34 (d, 1H, J = 7.0 Hz, Ar-H), 8.24
(d, 1H, J = 7.8 Hz, Ar-H), 7.80 (d, 1H, J = 8.6 Hz, Ar-H), 7.47 (m, 1H,
Ar-H), 7.13 (d, 1H, J = 8.6 Hz, Ar-H), 7.05 (m, 1H, Ar-H), 2.36 (s, 3H,
CH3SO3−). 13C NMR (75 MHz, DMSO‑d6) (δ ppm): 168.0 (s), 165.5 (s),
156.6 (s), 154.7 (s), 135.2 (s), 133.2 (d), 128.6 (d), 126.0 (d), 124.2 (s),
123.0 (d), 122.3 (d), 119.8 (d), 118.6 (s), 116.9 (d), 39.8. Analysis calcd
for C15H15N3O4S2 (365.43): C, 49.30; H, 4.14; N, 11.50. Found: C,
49.28; H, 4.18; N, 11.47.
4.1.1.13. 6-Cyano-2-(2-methoxyphenyl)benzothiazole (6c). According to
Method D, bis(2-amino-5-cyanophenyl) disulfide (3c) (0.150 g,
0.5 mmol) and 2-methoxybenzaldehide (4b) (0.136 g, 1.0 mmol)
were used and heated at 160–165 °C for 60 min, giving 0.210 g
(78.8%) of pale yellow solid; mp = 177–179 °C. UPLC (230 nm): 98.4
area %; MS (ESI) m/z: 267.2 (M+H+). 1H NMR (300 MHz, DMSO‑d6)
(δ ppm): 8.75 (d, 1H, J = 1.7 Hz, Ar-H), 8.47 (dd, 1H, J = 8.0 Hz,
J = 1.6 Hz, Ar-H), 8.19 (d, 1H, J = 8.5 Hz, Ar-H), 7.92 (dd, 1H,
J = 8.5 Hz, J = 1.7 Hz, Ar-H), 7.63 (m, 1H, Ar-H), 7.36 (d, 1H,
J = 8.2 Hz, Ar-H), 7.21 (dd, 1H, J = 8.0 Hz, J = 7.4 Hz, Ar-H), 4.10 (s,
3H, eOCH3). 13C NMR (75 MHz, DMSO‑d6) (δ ppm): 166.6 (s), 157.4
(s), 153.9 (s), 135.8 (s), 133.4 (d), 129.3 (d), 128.8 (d), 127.3 (d), 123.1
(d), 121.2 (d), 120.4 (s), 119.0 (s), 112.7 (d), 106.7 (s), 56.2 (q).
Analysis calcd for C15H10N2OS (266.32): C, 67.65; H, 3.78; N, 10.52.
Found: C, 67.49; H, 3.84; N, 10.51.
4.1.1.9. 6-(4,5-Dihydro-1H-imidazol-3-ium-2-yl)-2-(2-hydroxyphenyl)
benzothiazole methanesulfonate (5e). According to Method E, 2-amino-
5-(4,5-dihydro-1H-imidazol-3-ium-2-yl)benzenethiolate hydrate (2e)
(0.211 g, 1.0 mmol) and 2-hydroxybenzaldehyde (4a) (0.122 g,
1.0 mmol) were used giving 0.245 g (62.7%) of colourless solid;
mp = 279–282 °C. UPLC (254 nm): 100 area %; MS (ESI) m/z: 296.2
[(M+H+
)
calcd for free base C16H13N3OS (295.08)]. 1H NMR
(300 MHz, DMSO‑d6) (δ ppm): 11.60 (bs, 1H, eOH), 10.57 (bs, 2H,
eC(NHe)2+), 8.75 (d, 1H, J = 1.5 Hz, Ar-H), 8.35 (dd, 1H, J = 7.8 Hz,
J = 1.5 Hz, Ar-H), 8.28 (d, 1H, J = 8.4 Hz, Ar-H), 8.02 (dd, 1H,
J = 8.6 Hz, J = 1.8 Hz, Ar-H), 7.48 (m, 1H, Ar-H), 7.14 (d, 1H,
J = 8.0 Hz, Ar-H), 7.06 (m, 1H, Ar-H), 4.06 (s, 4H, eCH2CH2e), 2.35
(s, 3H, CH3SO3−). 13C NMR (75 MHz, DMSO‑d6) (δ ppm): 168.4 (s),
164.9 (s), 156.6 (s), 155.0 (s), 135.5 (s), 133.3 (d), 128.6 (d), 126.0 (d),
123.3 (d), 122.6 (d), 119.8 (d), 118.6 (s), 118.0 (s), 116.9 (d), 44.5 (t,
2C), 39.7 (q). Analysis calcd for C17H17N3O4S2 (391.46): C, 52.16; H,
4.38; N, 10.73. Found: C, 52.32; H, 4.49; N, 10.57.
4.1.1.14. 6-Amidinium-(2-methoxyphenyl)benzothiazole methanesulfonate
(6d). According to Method E, 2-amino-5-amidiniumbenzenethiolate
(2d) (0.167 g, 1.0 mmol) and 2-methoxybenzaldehide (4b) (0.136 g,
1.0 mmol) were used giving 0.282 g (74.5%) of colorless solid;
mp = 265–267 °C. UPLC (254 nm): 99.3 area %; MS (ESI) m/z:
284.2 [(M+H+) calcd for free base C15H13N3OS (283.08)]. 1H NMR
(300 MHz, DMSO‑d6) (δ ppm): 9.26 (bs, 4H, eC(NH2)2+), 8.65 (s, 1H,
Ar-H), 8.49 (d, 1H, J = 7.7 Hz, Ar-H), 8.25 (d, 1H, J = 8.9 Hz, Ar-H),
7.91 (d, 1H, J = 8.9 Hz, Ar-H), 7.64 (m, 1H, Ar-H), 7.37 (d, 1H,
J = 8.2 Hz, Ar-H), 7.22 (m, 1H, Ar-H), 4.11 (s, 3H, eOCH3), 2.37 (s,
3H, CH3SO3−). 13C NMR (150 MHz, DMSO‑d6) (δ ppm): 166.3 (s),
165.5 (s), 157.3 (s), 154.5 (s), 135.5 (s), 133.3 (d), 128.7 (d), 125.8 (d),
124.3 (s), 122.8 (d), 122.4 (d), 121.2 (d), 120.5 (s), 112.7 (d), 56.2 (q),
39.7 (q). Analysis calcd for C16H17N3O4S2 (379.45): C, 50.64; H, 4.52;
N, 11.07. Found: C, 50.39; H, 4.71; N, 11.21.
4.1.1.10. 2-(2-Hydroxyphenyl)benzothiazole-6-ammonium
methanesulfonate (5f). According to Method F, 2-(2-hydroxyphenyl)-6-
nitrobenzothiazole (5b) (0.272 g, 1.0 mmol) was used and heated to
reflux for 30 min. Afterwards, the obtained crude amine was suspended
in 2-propanol (10 ml), methanesulfonic acid (0.065 ml, 1.0 mmol) was
added and stirred at room temperature for 2 h. After cooling overnight,
the resulting precipitate was filtered, washed with diethyl-ether and
dried at 75 °C giving 0.302
g (89.3%) of colorless solid;
mp = 287–290 °C (dec.). UPLC (230 nm): 100 area %; MS (ESI) m/z:
243.1 [(M+H+) calcd for free amine C13H10N2OS, 242.05]. 1H NMR
(600 MHz, DMSO‑d6) (δ ppm): 11.53 (bs, 1H, eOH), 8.15 (dd, 1H,
J = 8.0 Hz, J = 1.4 Hz, Ar-H), 8.03 (d, 1H, J = 8.5 Hz, Ar-H), 7.87 (s,
1H, Ar-H), 7.41 (m, 1H, Ar-H), 7.31 (dd, 1H, J = 8.5 Hz, J = 1.8 Hz,
Ar-H), 7.09 (d, 1H, J = 8.0 Hz, Ar-H), 7.02 (m, 1H, Ar-H), 2.35 (s, 3H,
CH3SO3−). 13C NMR (75 MHz, DMSO‑d6) (δ ppm): 165.1 (s), 156.2 (s),
149.8 (s), 135.7 (s), 132.5 (d), 131.0 (s), 128.4 (d), 123.0 (d), 120.9 (d),
119.8 (d), 118.5 (s), 116.9 (d), 115.0 (d), 39.8 (q). Analysis calcd for
4.1.1.15. 6-(4,5-Dihydro-1H-imidazol-3-ium-2-yl)-2-(2-methoxyphenyl)
benzothiazole methanesulfonate (6e). According to Method E, 2-amino-
5-(4,5-dihydro-1H-imidazol-3-ium-2-yl)benzenethiolate hydrate (2e)
(0.211 g, 1.0 mmol) and 2-methoxybenzaldehide (4b) (0.136 g,
1.0 mmol) were used giving 0.336 g (83.0%) of colorless solid;
mp = 285–289 °C. UPLC (254 nm): 99.3 area %; MS (ESI) m/z:
310.2 [(M+H+) calcd for free base C17H15N3OS (309.39)]. 1H NMR
(300 MHz, DMSO‑d6) (δ ppm): 10.57 (s, 2H, eC(NHe)2+), 8.74 (d, 1H,
J = 1.2 Hz, Ar-H), 8.49 (dd, 1H, J = 8.0 Hz, J = 1.2 Hz, Ar-H), 8.30 (d,
1H, J = 8.6 Hz, Ar-H), 8.03 (dd, 1H, J = 8.6 Hz, J = 1.4 Hz, Ar-H),
7.65 (m, 1H, Ar-H), 7.37 (d, 1H, J = 8.4 Hz, Ar-H), 7.22 (m, 1H, Ar-H),
4.12 (s, 3H, eOCH3), 4.07 (s, 4H, eCH2CH2e), 2.32 (s, 3H, CH3SO3−).
13C NMR (150 MHz, DMSO‑d6) (δ ppm): 166.9 (s), 164.9 (s), 157.5 (s),
154.9 (s), 135.8 (s), 133.6 (d), 128.8 (d), 126.0 (d), 123.2 (d), 122.9
(d), 121.2 (d), 120.4 (s), 118.1 (s), 112.8 (d), 56.2 (q), 44.5 (t, 2C), 39.7
(q). Analysis calcd for C18H19N3O4S2 (405.49): C, 53.32; H, 4.72; N,
10.36. Found: C, 53.33; H, 4.81; N, 10.29.
C
14H14N2O4S2 (338.40): C, 49.69; H, 4.17; N, 8.28. Found: C, 49.91; H,
4.03; N, 8.11.
4.1.1.11. 2-(2-Methoxyphenyl)benzothiazole
(6a). According
to
Method D, bis(2-aminophenyl) disulfide (3a) (0.125 g, 0.5 mmol)
and 2-methoxybenzaldehide (4b) (0.136 g, 1.0 mmol) were used and
heated at 160–165 °C for 60 min, giving 0.169 g (70.4%) of colorless
solid; mp = 105–107 °C (lit [48] mp = 103–105 °C). UPLC (230 nm):
100 area %; MS (ESI) m/z: 242.1 (M+H+). 1H NMR (300 MHz,
DMSO‑d6) (δ ppm): 8.45 (dd, 1H, J = 7.9 Hz, J = 1.7 Hz, Ar-H),
8.13 (bd, 1H, J = 7.4 Hz, Ar-H), 8.06 (d, 1H, J = 8.0 Hz, Ar-H),
7.60–7.51 (m, 2H, Ar-H), 7.44 (ddd, 1H, J = 8.0 Hz, J = 7.4 Hz,
J = 1.0 Hz, Ar-H), 7.32 (bd, 1H, J = 8.0 Hz, Ar-H), 7.18 (ddd, 1H,
J = 7.9 Hz, J = 7.4 Hz, J = 0.8 Hz, Ar-H), 4.07 (s, 3H, eOCH3).
7