10.1002/ejoc.201601597
European Journal of Organic Chemistry
FULL PAPER
138.6, 123.6, 122.8, 48.9, 47.5, 41.1, 24.9, 22.8, 22.4 ppm; IR (ZnSn):
dicarboxamide 7b (1 g, 1.93 mmol) in CH2Cl2 (50 mL), aqueous NaOH
(6N, 40 mL) was added. The mixture was stirred 11 days at 40 °C. The
reaction was monitored by TLC (CH2Cl2/MeOH 9:1). The mixture was
extracted with CH2Cl2, dried over MgSO4, and concentrated in vacuo to
give a brown solid. After recrystallization (ethyl acetate/hexane), the
product was obtained as a white solid (0.7 g, 85% yield); mp: 204–
205 °C; [ꢀ]D = 112.1.65 (c = 1.08 in CH2Cl2); 1H NMR (400 MHz, CDCl3) δ
3305, 2954, 1722, 1650, 1566, 1465 cm–1
C24H33Cl2N4O2 (MH+) 479.1975, found 479.1987.
; HRMS: calcd for
N6,N6'-Bis((2S,3R)-1-chloro-3-methylpentan-2-yl)-2,2'-bipyridine-6,6'-
dicarboxamide (8d).[22] Yellow solid (0.5 g, 62% yield); mp: 148 °C; [ꢀ]D
1
3
= –35.7 (c = 0.66 in CH2Cl2); H NMR (400 MHz, CDCl3): δ 8.53 (d, J =
7.9 Hz, 2H), 8.35 (d, 3J = 9.8 Hz, 2H), 8.28 (d, 3J = 7.7 Hz, 2H), 8.06 (dd,
3J = 7.8, 7.8 Hz, 2H), 4.23–4.33 (m, 2H), 3.90 (dd, 2J = 11.5 Hz, 3J = 3.8
Hz, 2H), 3.83 (dd, 2J = 11.5 Hz, 3J = 3.8 Hz, 2H), 1.85–2.03 (m, 2H),
3
3
8.72 (dd, J = 7.9, 1.0 Hz, 2H), 8.22 (dd, J = 7.8, 1.0 Hz, 2H), 7.95 (dd,
3J = 7.8, 7.8 Hz, 2H), 7.34 – 7.41 (m, 8H), 7.28 – 7.34 (m, 2H), 5.50 (dd,
2J = 10.2 Hz, 3J = 8.5 Hz, 2H), 4.95 (dd, 2J = 10.3 Hz, 3J = 8.5 Hz, 2H),
4.43 (dd, 3J = 8.5, 8.5 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 163.9,
155.4, 146.1, 141.8, 137.7, 128.8, 127.7, 126.8, 124.7, 123.7, 75.4, 70.4;
IR (ZnSn): 1643, 1565, 1434, 1230, 1110, 1067, 945, 821, 791; HRMS:
calcd for C28H23N4O2 (MH+) 447.1816, found 447.1828.
3
1.56–1.71 (m, 2H), 1.18–1.35 (m, 2H), 1.05 (d, J = 6.7 Hz, 6H), 0.95 (t,
3J = 7.4 Hz, 6H) ppm; 13C NMR (125 MHz, CDCl3): δ 163.7, 153.7, 149.2,
138.6, 123.5, 122.8, 53.5, 47.1, 35.8, 25.2, 15.4, 11.1 ppm; IR (ZnSn):
3313, 2962, 2874, 1722, 1652, 1579, 1462 cm–1; HRMS: calcd for
C24H33Cl2N4O2 (MH+) 479.1975, found 479.1975.
N6,N6'-Bis((S)-1-chloro-3,3'-dimethylbutan-2-yl)-2,2'-bipyridine-6,6'-
dicarboxamide (8e). Yellow solid (0.5 g, 22% yield); mp: decomposition
155 °C; [ꢀ]D = 36.5 (c = 0.92 in CH2Cl2); 1H NMR (500 MHz, CDCl3) δ
6,6′-Bis(4-(S)-iso-butyloxazolin-2-y1)-2,2′-bipyridine (L3).[22] To
a
solution of the N6,N6'-bis((S)-1-chloro-4-methylpentan-2-yl)-2,2'-
bipyridine-6,6'-dicarboxamide 7c (0.5 g, 1.1 mmol) in THF (11 mL, 0.1 M),
NaH (0.1 g, 4.24 mmol) was added. The mixture was then stirred 7 days
at room temperature under argon atmosphere. The reaction was
monitored by TLC (CH2Cl2/MeOH 9:1). The mixture was extracted with
CH2Cl2, dried over MgSO4, and evaporated to afford a brownish solid.
After recrystallization (ethyl acetate/hexane), the product was obtained
as a white solid (0.35 g, 80% yield); mp: 134 °C; [ꢀ]D = –97.24 (c = 1.10
3
3
8.47 (dd, 3J = 7.9, 1.1 Hz, 2H), 8.31 (d, J = 10.5 Hz, 2H), 8.27 (dd, J =
7.7, 1.1 Hz, 2H), 8.03 (dd, 3J = 7.8, 7.8 Hz, 2H), 4.28 – 4.34 (m, 2H), 3.90
(dd, 2J = 11.6 Hz, 3J = 3.6 Hz, 2H), 3.69 (dd, 2J = 11.6 Hz, 3J = 8.3 Hz,
2H), 1.07 (s, 18H). 13C NMR (125 MHz, CDCl3) δ 164.0, 153.6, 149.2,
138.6, 123.4, 123.0, 58.0, 45.2, 35.4, 26.9; IR (ZnSn): 3312, 2963, 1651,
1517, 1434, 830, 761, 673; HRMS: calcd for C24H33Cl2N4O2 (MH+)
479.1975, found 479.1981.
1
3
in CH2Cl2); H NMR (400 MHz, CDCl3): δ 8.67 (d, J = 7.9 Hz, 2H), 8.10
3
N6,N6'-Bis((S)-1-chloro-3-phenylpropan-2-yl)-2,2'-bipyridine-6,6'-
dicarboxamide (8f).[22] Yellow solid (0.8 g, 79% yield); mp: 188–190 °C;
[ꢀ]D = –63.38 (c = 0.87 in CH2Cl2); 1H NMR (400 MHz, CDCl3): δ 8.49 (d,
3J = 7.8 Hz, 2H), 8.43 (d, 3J = 8.9 Hz, 2H), 8.28 (d, 3J = 7.6 Hz, 2H), 8.07
(dd, 3J = 7.7, 7.7 Hz, 2H), 7.34–7.39 (m, 8H), 7.26–7.33 (m, 2H), 4.66–
4.76 (m, 2H), 3.76 (dd, 2J = 11.1 Hz, 3J = 4.9 Hz, 2H), 3.69 (dd, 2J = 11.2
Hz, 3J = 3.5 Hz, 2H), 3.20 (dd, 2J = 13.8 Hz, 3J = 5.6 Hz, 2H), 3.09 (dd, 2J
= 13.8 Hz, 3J = 8.2 Hz, 2H) ppm; 13C NMR (125 MHz, CDCl3): δ 163.4,
153.5, 149.0, 138.6, 136.6, 129.5, 128.8, 127.0, 123.6, 122.8, 50.5, 46.2,
(dd, J = 7.8, 1.1 Hz, 2H), 7.92 (dd, 3J = 7.8, 7.8 Hz, 2H), 4.65 (dd, 3J =
9.5 Hz, 2J = 8.1 Hz, 2H), 4.41–4.48 (m, 2H), 4.14 (dd, 3J = 8.1 Hz, 2J =
8.1 Hz, 2H), 1.84–1.92 (m, 2H), 1.78–1.84 (m, 2H), 1.42–1.48 (m, 2H),
1.02 (d, J = 6.6 Hz, 6H), 1.00 (d, J = 6.5 Hz, 6H); 13C NMR (100 MHz,
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CDCl3): δ 162.0, 154.9, 146.0, 137.1, 124.0, 123.0, 73.2, 65.0, 45.1, 25.1,
22.8, 22.6 ppm; IR (ZnSn): 2953, 2924, 1632, 1577, 1380 1279 cm–1
HRMS: calcd for C24H31N4O2 (MH+) 407.2442, found 407.2450.
6,6′-Bis(4-(S)-sec-butyloxazolin-2-y1)-2,2′-bipyridine (L4).[22] To
;
a
solution of the N6,N6'-bis((2S,3R)-1-chloro-3-methylpentan-2-yl)-2,2'-
bipyridine-6,6'-dicarboxamide 7d (1.4 g, 2.9 mmol) in THF (30 mL, 0.1 M),
NaH (0.3 g, 11.9 mmol) was added. The mixture was stirred 7 days at
room temperature under argon atmosphere. The reaction was monitored
by TLC (CH2Cl2/MeOH 9:1). The mixture was extracted with CH2Cl2,
dried over MgSO4, and concentrated to give a brownish solid. After
recrystallization (ethyl acetate/hexane), the product was obtained as a
white solid (1.0 g, 85% yield). mp: 150–152 °C; [ꢀ]D = –76.41 (c = 1.10 in
CH2Cl2); 1H NMR (500 MHz, CDCl3): δ 8.66 (d, 3J = 7.9 Hz, 2H), 8.12 (dd,
3J = 7.7, 1.1 Hz, 2H), 7.91 (dd, 3J = 7.8, 7.8 Hz, 2H), 4.54 (dd, 3J = 9.3 Hz,
2J = 8.0 Hz, 2H), 4.30–4.36 (m, 2H), 4.28 (dd, 3J = 8.2 Hz, 2J = 8.0 Hz,
2H), 1.75–1.85 (m, 2H), 1.65–1.74 (m, 2H), 1.24–1.35 (m, 2H), 0.99 (t, 3J
= 7.5 Hz, 6H), 0.92 (d, 3J = 6.8 Hz, 6H) ppm; 13C NMR (100 MHz,
CDCl3): δ 162.3, 155.1, 146.2, 137.3, 124.2, 123.3, 71.3, 70.1, 38.9, 26.0,
37.3 ppm; IR (ZnSn): 3293, 3028, 1734, 1650. 1579, 1517, 1454 cm–1
HRMS: calcd for C30H29Cl2N4O2 (MH+) 547.1662, found 547.1670.
6,6′-Bis(4-(S)-iso-propyloxazolin-2-y1)-2,2′-bipyridine (L1).[20a, 22] To a
;
solution of the N6,N6'-bis((S)-1-chloro-3-methylbutan-2-yl)-2,2'-
bipyridine-6,6'-dicarboxamide 7a (2 g, 4.4 mmol) in MeOH (110 mL),
aqueous NaOH (6N, 35 mL) was added. The mixture was then stirred 2
days at 40 °C. The reaction was monitored by TLC (CH2Cl2/MeOH 9:1).
The mixture was extracted with CH2Cl2, dried over MgSO4, and
concentrated in vacuo to give a white solid. After recrystallization (ethyl
acetate/hexane), the product was obtained as a white solid (1.6 g, 96%
yield); mp: 184 °C (lit. 187 °C);[20a] [ꢀ]D = –87.65 (c = 1.07 in CH2Cl2); lit:
[ꢀ]D = –90.6 (c = 1.04 in CH2Cl2);[20a] 1H NMR (500 MHz, CDCl3) δ 8.66
3
(dd, J = 7.9, 1.1 Hz, 2H), 8.12 (dd, 3J = 7.8, 1.1 Hz, 2H), 7.91 (dd, 3J =
14.3, 11.4 ppm; IR (ZnSn): 2959, 2876, 1657, 1577, 1445, 1381 cm–1
HRMS: calcd for C24H31N4O2 (MH+) 407.2442, found 407.2440.
;
7.8 7.8 Hz, 2H), 4.55 (dd, 3J = 9.6 Hz, 2J = 8.2 Hz, 2H), 4.22 (dd, 3J = 8.2
Hz, 2J = 8.2 Hz, 2H), 4.16–4.22 (m, 2H), 1.88–1.96 (m, 2H), 1.09 (d, 3J =
6.8 Hz, 6H), 0.97 (d, 3J = 6.8 Hz, 6H) ppm; 13C NMR (125 MHz, CDCl3) δ
162.6, 155.3, 146.2, 137.5, 124.3, 123.5, 72.9, 70.7, 32.7, 19.1, 18.1
ppm; IR (ZnSn): 2953, 2864, 1636, 1577, 1474, 1445, 1263 cm–1; HRMS:
calcd for C22H27N4O2 (MH+) 379.2129, found 379.2133.
6,6′-Bis(4-(S)-tert-butyloxazolin-2-y1)-2,2′-bipyridine (L5). To
a
solution of the N6,N6'-bis((S)-1-chloro-3,3'-dimethylbutan-2-yl)-2,2'-
bipyridine-6,6'-dicarboxamide 7e (0.5 g, 0.97 mmol) in THF (10 mL, 0.1
M), NaH (0.093 g, 3.88 mmol) was added. The mixture was then stirred 7
days at room temperature under argon atmosphere. The reaction was
monitored by TLC (CH2Cl2/MeOH 9:1). The mixture was extracted with
6,6′-Bis(4-(S)-phenyloxazolin-2-y1)-2,2′-bipyridine (L2). To a solution
of the N6,N6'-bis((S)-1-chloro-2-phenylethan-2-yl)-2,2'-bipyridine-6,6'-
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