C- vs. O-Alkylation Using Aryl Grignard Reagents
Bis(1,3-benzothiazol-2-yl)(2-methoxyphenyl)methanol (5e): White
solid, 1.27 g (90% from 10e); m.p. 199–200 °C. 1H NMR
136.1, 129.7, 126.6, 126.3, 125.6, 123.5, 121.8, 79.8, 61.0, 14.3 ppm.
MS (70 eV, EI): m/z (%) = 446 (100) [M]+, 429 (5), 401 (11), 312
(400 MHz, CDCl3, 25 °C): δ = 8.08–8.01 (m, 2 H), 7.92–7.85 (m, 2 (55), 297 (30), 269 (46), 135 (17). C24H18N2O3S2 (446.54): calcd. C
H), 7.50–7.43 (m, 2 H), 7.42–7.34 (m, 3 H), 7.28–7.21 (m, 1 H), 64.50, H 4.06, N 6.26; found C 64.53, H 4.07, N 6.28.
7.01–6.90 (m, 2 H), 6.22 (s, 1 H, OH, exch. with D2O), 3.66 (s, 3
2,2Ј-(Phenoxymethylene)bis(1,3-benzothiazole) (6a): 1H NMR
H, OCH3) ppm. 13C NMR (100.56 MHz, CDCl3, 25 °C): δ = 174.3,
(300 MHz, CDCl3, 25 °C): δ = 8.00 (d, J = 8.0 Hz, 2 H), 7.79 (d,
157.0, 152.9, 135.9, 130.49, 130.46, 128.7, 125.8, 125.1, 123.7,
J = 7.7 Hz, 2 H), 7.42–7.37 (m, 2 H), 7.33–7.29 (m, 2 H), 7.24–
121.6, 121.2, 112.1, 80.7, 55.8 ppm. MS (70 eV, EI): m/z (%) = 404
7.19 (m, 2 H), 7.15–7.08 (m, 2 H), 7.02 (s, 1 H, CHO), 6.97–6.92
(1) [M]+, 238 (35), 149 (12), 135 (100), 92 (14). MS (ESI+): m/z =
(m, 2 H) ppm. 13C NMR (75.46 MHz, CDCl3, 25 °C): δ = 168.2,
427 [M + Na]+. C22H16N2O2S2 (404.50): calcd. C 65.32, H 3.99, N
156.8, 153.0, 135.3, 129.8, 126.2, 125.6, 124.0, 122.8, 121.8, 116.1,
6.93; found C 65.29, H 4.00, N 6.91.
78.5 ppm. MS (70 eV, EI): m/z (%) = 374 (2) [M]+, 281 (100), 248
Bis(1,3-benzothiazol-2-yl)(3-methoxyphenyl)methanol (5f): White
solid, 1.21 g (85% from 10f); m.p. 126–127 °C. 1H NMR
(300 MHz, CDCl3, 25 °C): δ = 8.09–7.99 (m, 2 H), 7.91–7.81 (m, 2
H), 7.62–7.42 (m, 2 H), 7.42–7.32 (m, 4 H), 7.32 (m, 1 H), 6.90–
6.81 (m, 1 H), 6.19 (s, 1 H, OH, exch. with D2O), 3.76 (s, 3 H,
OCH3) ppm. 13C NMR (75.46 MHz, CDCl3, 25 °C): δ = 174.5,
159.6, 152.2, 143.8, 136.1, 129.5, 126.1, 125.4, 123.4, 121.7, 119.0,
114.0, 112.5, 79.9, 55.2 ppm. MS (70 eV, EI): m/z (%) = 404 (1)
[M]+, 269 (46), 241 (28), 135 (100), 107 (29), 91 (21). C22H16N2O2S2
(404.50): calcd. C 65.32, H 3.99, N 6.93; found C 65.30, H 4.00, N
6.90.
(9), 146 (11), 134 (6). HRMS: calcd. for C21H14N2OS2 374.0548;
found 374.0545.
2,2Ј-[(2-Methylphenoxy)methylene]bis(1,3-benzothiazole) (6b): 1H
NMR (400 MHz, CDCl3, 25 °C): δ = 8.09 (d, J = 8.4 Hz, 2 H),
7.87 (d, J = 8.0 Hz, 2 H), 7.53–7.43 (m, 2 H), 7.42–7.32 (m, 2 H),
7.26–7.17 (m, 1 H), 7.11 (s, 1 H, CHO), 7.12–7.00 (m, 2 H), 6.96–
6.87 (m, 1 H), 2.49 (s, 3 H, CH3) ppm. 13C NMR (100.57 MHz,
CDCl3, 25 °C): δ = 168.6, 154.8, 153.0, 135.2, 131.2, 127.5, 127.0,
126.2, 125.6, 123.9, 122.4, 121.8, 112.8, 78.1, 23.8 ppm. MS (70 eV,
EI): m/z (%) = 388 (3) [M]+, 281 (54), 268 (100), 162 (55), 134 (76).
HRMS: calcd. for C22H16N2OS2 388.0704; found 388.0709.
Bis(1,3-benzothiazol-2-yl)(4-methoxyphenyl)methanol (5g): White
solid, 1.39 g (98% from 10g); m.p. 182–183 °C. 1H NMR
(300 MHz, CDCl3, 25 °C): δ = 8.08–8.02 (m, 2 H), 7.91–7.85 (m, 2
H), 7.65 (d, J = 9.0 Hz, 2 H), 7.52–7.44 (m, 2 H), 7.43–7.35 (m, 2
H), 6.92–6.84 (m, 2 H), 6.03 (s, 1 H, OH, exch. with D2O), 3.78 (s,
3 H, OCH3) ppm. 13C NMR (75.46 MHz, CDCl3, 25 °C): δ =
174.9, 159.8, 152.3, 136.2, 134.6, 128.1, 126.1, 125.4, 123.4, 121.8,
113.8, 79.8, 55.3 ppm. MS (70 eV, EI): m/z (%) = 404 (1) [M]+, 269
(30), 241 (19), 135 (100), 91 (12). C22H16N2O2S2 (404.50): calcd. C
65.32, H 3.99, N 6.93; found C 65.28, H 4.00, N 6.91.
2,2Ј-[(3-Methylphenoxy)methylene]bis(1,3-benzothiazole) (6c): 1H
NMR (300 MHz, CDCl3, 25 °C): δ = 8.11–8.05 (m, 2 H), 7.90–7.84
(m, 2 H), 7.51–7.41 (m, 2 H), 7.41–7.33 (m, 2 H), 7.20–7.12 (m, 1
H), 7.08 (s, 1 H, CHO), 7.04–6.93 (m, 2 H), 6.88–6.78 (m, 1 H),
2.31 (s, 3 H, CH3) ppm. 13C NMR (100.57 MHz, CDCl3, 25 °C): δ
= 168.4, 156.7, 152.9, 140.0, 135.3, 129.4, 126.2, 125.6, 123.8, 123.7,
121.8, 117.0, 112.7, 78.3, 21.4 ppm. MS (70 eV, EI): m/z (%) = 388
(5) [M]+, 281 (51), 268 (100), 135 (71). HRMS: calcd. for
C22H16N2OS2 388.0704; found 388.0708.
2,2Ј-[(4-Methylphenoxy)methylene]bis(1,3-benzothiazole) (6d): 1H
NMR (400 MHz, CDCl3, 25 °C): δ = 8.12–8.06 (m, 2 H), 7.89–7.83
(m, 2 H), 7.49–7.43 (m, 2 H), 7.40–7.15 (m, 2 H), 7.08–7.07 (m, 4
H), 7.04 (s, 1 H, CHO), 2.25 (s, 3 H, CH3) ppm. 13C NMR
(100.56 MHz, CDCl3, 25 °C): δ = 168.4, 154.7, 152.9, 135.3, 132.2,
130.2, 126.2, 125.6, 123.8, 121.8, 115.9, 78.6, 20.5 ppm. MS (70 eV,
EI): m/z (%) = 388 (7) [M]+, 281 (56), 268 (100), 135 (73). HRMS:
calcd. for C22H16N2OS2 388.0704; found 388.0700.
2,2Ј-[(3-Methoxyphenoxy)methylene]bis(1,3-benzothiazole) (6f): 1H
NMR (400 MHz, CDCl3, 25 °C): δ = 8.11–8.04 (m, 2 H), 7.91–7.84
(m, 2 H), 7.51–7.43 (m, 2 H), 7.43–7.34 (m, 2 H), 7.21–7.10 (m, 1
H), 7.08 (s, 1 H, CHO), 6.79–6.71 (m, 2 H), 6.61–6.54 (m, 1 H),
6.50–6.39 (m, 1 H), 3.77 (s, 3 H, OCH3) ppm. 13C NMR
(100.57 MHz, CDCl3, 25 °C): δ = 168.1, 160.9, 157.9, 152.9, 135.3,
130.2, 126.3, 125.7, 123.9, 121.8, 108.7, 107.8, 102.6, 78.4,
55.3 ppm. MS (70 eV, EI): m/z (%) = 404 (41) [M]+, 388 (45), 372
(30), 282 (10), 268 (100), 162 (65), 135 (59). HRMS: calcd. for
C22H16N2O2S2 404.0653; found 404.0655.
2,2Ј-[(4-Methoxyphenoxy)methylene]bis(1,3-benzothiazole) (6g): 1H
NMR (300 MHz, CDCl3, 25 °C): δ = 8.12–8.06 (m, 2 H), 7.94–7.83
(m, 2 H), 7.54–7.43 (m, 2 H), 7.43–7.35 (m, 2 H), 7.11 (d, J =
9.2 Hz, 2 H), 6.98 (s, 1 H, CHO), 6.81 (d, J = 9.2 Hz, 2 H), 3.73
(s, 3 H, OCH3) ppm. 13C NMR (100.57 MHz, CDCl3, 25 °C): δ =
168.5, 155.3, 153.0, 150.9, 135.3, 126.2, 125.6, 123.8, 121.8, 117.4,
114.8, 79.4, 55.6 ppm. MS (70 eV, EI): m/z (%) = 404 (47) [M]+,
388 (39), 372 (22), 282 (18), 268 (100), 162 (78), 135 (64). HRMS:
calcd. for C22H16N2O2S2 404.0653; found 404.0650.
Bis(1,3-benzothiazol-2-yl)(4-methoxy-2-methylphenyl)methanol (5h):
Pale-yellow solid, m.p. 136–138 °C. 1H NMR (300 MHz, CDCl3,
25 °C): δ = 8.06–8.00 (m, 2 H), 7.90–7.83 (m, 2 H), 7.55–7.43 (m,
2 H), 7.43–7.33 (m, 2 H), 6.93 (d, J = 9.1 Hz, 1 H), 6.76 (d, J =
2.8 Hz, 1 H), 6.59 (dd, J = 9.1, 2.8 Hz, 1 H), 5.89 (s, 1 H, OH,
exch. with D2O), 3.77 (s, 3 H, OCH3), 2.18 (s, 3 H, CH3) ppm. 13C
NMR (75.46 MHz, CDCl3, 25 °C): δ = 175.8, 159.9, 152.3, 140.2,
133.3, 132.7, 129.7, 126.2, 125.5, 123.5, 121.8, 118.4, 109.9, 81.3,
51.1, 21.4 ppm. MS (70 eV, EI): m/z (%) = 418 (1) [M]+, 283 (35),
266 (43), 254 (63), 149 (100), 121 (22), 91 (36). MS (ESI+): m/z =
441 [M + Na]+. C23H18N2O2S2 (418.53): calcd. C 66.00, H 4.33, N
6.69; found C 65.95, H 4.35, N 6.67.
Ethyl 3-[Bis(1,3-benzothiazol-2-yl)(hydroxy)methyl]benzoate (5i):
1
Greasy yellow solid. H NMR (300 MHz, CDCl3, 25 °C): δ = 8.54
(dd, J = 1.6, 1.6 Hz, 1 H), 8.10–8.03 (m, 3 H), 8.03–7.98 (m, 1 H),
7.90–7.86 (m, 2 H), 7.53–7.37 (m, 5 H), 6.18 (s, 1 H, OH, exch.
with D2O), 4.35 (q, J = 7.2 Hz, 2 H, CH2), 1.36 (t, J = 7.2 Hz, 3
H, CH3) ppm. 13C NMR (100.57 MHz, CDCl3, 25 °C): δ = 174.2,
166.4, 152.2, 142.6, 136.0, 131.2, 129.8, 129.0, 128.6, 127.7, 126.2,
125.6, 123.4, 121.8, 79.6, 61.1, 14.3 ppm. MS (70 eV, EI): m/z (%)
= 446 (100) [M]+, 429 (9), 401 (13), 312 (58), 297 (25), 269 (40),
134 (13). C24H18N2O3S2 (446.54): calcd. C 64.47, H 4.07, N 6.27;
found C 64.59, H 4.05, N 6.25.
Ethyl 4-[Bis(1,3-benzothiazol-2-yl)(hydroxy)methyl]benzoate (5j):
White solid, m.p. 133–135 °C. 1H NMR (600 MHz, CDCl3, 25 °C):
δ = 8.06 (d, J = 8.2 Hz, 2 H), 8.04 (d, J = 8.7 Hz, 2 H), 7.92 (d, J
= 8.7 Hz, 2 H), 7.88 (d, J = 7.9 Hz, 2 H), 7.51–7.47 (m, 2 H), 7.42–
7.38 (m, 2 H), 6.16 (s, 1 H, OH, exch. with D2O), 4.35 (q, J = 2,2Ј-[(4-Methoxy-2-methylphenoxy)methylene]bis(1,3-benzothiazole)
7.2 Hz, 2 H, CH2), 1.36 (t, J = 7.2 Hz, 3 H, CH3) ppm. 13C NMR (6h): H NMR (400 MHz, CDCl3, 25 °C): δ = 8.10–8.05 (m, 2 H),
1
(75.46 MHz, CDCl3, 25 °C): δ = 173.8, 166.1, 160.5, 152.2, 146.5,
7.90–7.84 (m, 2 H), 7.51–7.43 (m, 2 H), 7.42–7.34 (m, 2 H), 6.98
Eur. J. Org. Chem. 2010, 5659–5665
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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