H
J. Ban et al.
Paper
Synthesis
2,2′-Bis(acetamido)-5,5′-difluorobiphenyl (2e)
2,2′-Bis(acetamido)-4,4′,5,5′-tetramethoxybiphenyl (2j)65
White solid; yield: 0.21 g (70%); mp 186.0–186.5 °C; Rf = 0.13
Pale brown solid; yield: 0.24 g (62%); mp 204.0–204.5 °C; Rf = 0.08
(EtOAc/CH2Cl2 1:5).
(EtOAc/CH2Cl2 1:5).
IR (neat): 3180, 3005, 1659, 1535, 1428, 1371, 1294, 1257, 1235,
1H NMR (400 MHz, DMSO-d6): = 8.62 (br s, 2 H), 7.20 (s, 2 H), 6.71 (s,
2 H), 3.75 (s, 6 H), 3.73 (s, 6 H), 1.83 (s, 6 H).
1193, 1163, 873, 835, 819, 673, 596, 510, 501 cm–1
.
1H NMR (400 MHz, CDCl3): = 7.90 (dd, J = 9.0, 5.2 Hz, 2 H), 7.18–7.13
13C NMR (100 MHz, DMSO-d6): = 169.3, 148.2, 146.4, 129.3, 125.1,
(m, 2 H), 6.94–6.91 (m, 4 H), 1.98 (s, 6 H).
114.3, 110.2, 56.1, 56.0, 23.5.
13C NMR (100 MHz, DMSO-d6): = 169.2, 159.4 (d, J = 244.6 Hz),
134.2, 132.5, 128.1, 117.6 (d, J = 23.2 Hz), 115.4 (d, J = 18.0 Hz), 23.4.
2,2′-Bis(acetamido)-5,5′-bis(trifluoromethoxy)biphenyl (2k)
19F NMR (376 MHz, DMSO-d6): = –117.7.
HRMS (EI): m/z [M]+ calcd for C16H14F2N2O2: 304.1023; found:
White solid; yield: 0.34 g (77%); mp 200.0–200.5 °C; Rf = 0.25 (EtOAc/
CH2Cl2 1:5).
IR (neat): 3352, 1677, 1525, 1465, 1438, 1397, 1371, 1258, 1206,
304.1025.
1143, 1039, 1009, 835, 658, 593, 517 cm–1
.
1H NMR (400 MHz, DMSO-d6): = 9.12 (br s, 2 H), 7.70 (d, J = 8.8 Hz, 2
H), 7.40 (dd, J = 8.8, 2.0 Hz, 2 H), 7.16 (d, J = 2.0 Hz, 2 H), 1.85 (s, 6 H).
13C NMR (100 MHz, DMSO-d6): = 169.3, 145.4, 135.4, 133.4, 128.1,
123.5, 121.5, 120.5 (q, J = 254.7 Hz), 23.3.
2,2′-Bis(acetamido)-5,5′-dichlorobiphenyl (2f)63
White solid; yield: 0.22 g (66%); mp 252.0–252.5 °C; Rf = 0.20
(EtOAc/CH2Cl2 1:5).
1H NMR (400 MHz, DMSO-d6): = 8.90 (br s, 2 H), 7.62 (d, J = 8.8 Hz, 2
H), 7.43 (dd, J = 8.8, 2.4 Hz, 2 H), 7.26 (d, J = 2.4 Hz, 2 H), 1.80 (s, 6 H).
19F NMR (376 MHz, DMSO-d6): = –56.8.
13C NMR (100 MHz, DMSO-d6): = 169.1, 135.2, 133.3, 130.9, 129.2,
HRMS (EI): m/z [M]+ calcd for C18H14F6N2O4: 436.0858; found:
128.6, 127.5, 23.5.
436.0860.
2,2′-Bis(acetamido)-5,5′-diisopropylbiphenyl (2g)
2,2′-Bis(acetamido)-5,5′-bis(trifluoromethyl)biphenyl (2l)
Pale yellow solid; yield: 0.16 g (45%); mp 170.0–170.5 °C; Rf = 0.15
White solid; yield: 0.30 g (74%); mp 231.0–232.0 °C; Rf = 0.25
(EtOAc/CH2Cl2 1:5).
(EtOAc/CH2Cl2 1:5).
IR (neat): 3393, 3342, 2956, 2922, 2866, 1675, 1588, 1516, 1362,
IR (neat): 3362, 1685, 1592, 1523, 1471, 1399, 1375, 1309, 1260,
1303, 1250, 1035, 843, 643, 585, 530, 500, 470 cm–1
.
1229, 1118, 1076, 1031, 1006, 848, 681, 656, 639, 589, 504, 417 cm–1
.
1H NMR (400 MHz, CDCl3): = 7.92 (d, J = 8.4 Hz, 2 H), 7.28 (dd, J = 8.4,
1.7 Hz, 2 H), 7.06 (d, J = 1.2 Hz, 2 H), 7.00 (br s, 2 H), 2.92 (sept, J = 7.2
Hz, 2 H), 1.95 (s, 6 H), 1.26 (d, J = 7.2 Hz, 12 H).
13C NMR (100 MHz, CDCl3): = 169.1, 145.9, 132.9, 129.5, 128.3,
127.1, 123.5, 33.5, 24.0, 23.8.
1H NMR (400 MHz, DMSO-d6): = 9.18 (br s, 2 H), 7.90 (d, J = 8.0 Hz, 2
H), 7.76 (d, J = 8.0 Hz, 2 H), 7.58 (d, J = 8.0 Hz, 2 H), 1.86 (s, 6 H).
13C NMR (100 MHz, DMSO-d6): = 169.4, 139.9, 131.5, 128.6 (q, J = 3.6
Hz), 126.1, 125.8 (q, J = 3.7 Hz), 125.6 (q, J = 31.7 Hz), 124.7 (q, J =
270.2 Hz), 23.5.
HRMS (EI): m/z [M]+ calcd for C22H28N2O2: 352.2151; found:
19F NMR (376 MHz, DMSO-d6): = –60.4.
352.2153.
HRMS (EI): m/z [M]+ calcd for C18H14F6N2O2: 404.0959; found:
404.0960.
2,2′-Bis(acetamido)-5,5′-tert-butylbiphenyl (2h)
2,2′-Bis(acetamido)-4,4′-bis(trifluoromethyl)biphenyl (2m)66
Pale yellow solid; yield: 0.13 g (35%); mp 172.0–172.5 °C; Rf = 0.22
(EtOAc/CH2Cl2 1:5).
White solid; yield: 0.29 g (71%); mp 180.0–180.5 °C; Rf = 0.25
IR (neat): 3419, 3337, 2955, 2905, 2869, 1677, 1584, 1513, 1468,
(EtOAc/CH2Cl2 1:5).
1H NMR (400 MHz, DMSO-d6): = 9.19 (br s, 2 H), 8.05 (s, 2 H), 7.60
(d, J = 7.2 Hz, 2 H), 7.44 (d, J = 8.0 Hz, 2 H), 1.86 (s, 6 H).
13C NMR (100 MHz, DMSO-d6): = 169.5, 137.0, 135.7, 132.6, 129.3
(q, J = 31.6 Hz), 124.5 (q, J = 270.6 Hz), 122.1, 121.8, 23.6.
19F NMR (376 MHz, DMSO-d6): = –61.2.
1385, 1361, 1317, 1300, 1254, 831, 569, 516, 502 cm–1
.
1H NMR (400 MHz, CDCl3): = 8.00 (d, J = 8.4 Hz, 2 H), 7.46 (dd, J = 8.4,
2.0 Hz, 2 H), 7.21 (d, J = 2.0 Hz, 2 H), 6.89 (br s, 2 H), 1.95 (s, 6 H), 1.33
(s, 18 H).
13C NMR (100 MHz, CDCl3): = 169.0, 148.1, 132.7, 129.2, 127.3,
126.0, 123.2, 34.4, 31.2, 23.9.
HRMS (EI): m/z [M]+ calcd for C24H32N2O2: 380.2464; found:
380.2467.
Acid-Mediated Intramolecular Amination; General Procedure
In a 10-mL, round-bottom flask, 2,2′-bis(acetamido)biphenyl 2 (0.5
mmol, 1.0 equiv) was dissolved in diethylene glycol (10 mL), followed
by addition of phosphoric acid (0.49 g, 5 mmol, 10 equiv). The mix-
ture was stirred at 200 °C until completion and cooled to r.t. Organic
components were extracted into CH2Cl2 and the combined organic
extracts were washed with brine and dried (anhyd MgSO4). Solvents
were removed under reduced pressure to obtain the crude product,
which was purified by flash chromatography (EtOAc/n-hexane).
2,2′-Bis(acetamido)-4,4′-dimethoxybiphenyl (2i)64
White solid; yield: 0.18 g (54%); mp 181.5–182.0 °C; Rf = 0.10
(EtOAc/CH2Cl2 1:5).
1H NMR (400 MHz, DMSO-d6): = 8.58 (br s, 2 H), 7.29 (s, 2 H), 7.04
(d, J = 8.4 Hz, 2 H), 6.81 (d, J = 8.4 Hz, 2 H), 3.76 (s, 6 H), 1.83 (s, 6 H).
13C NMR (100 MHz, DMSO-d6): = 169.2, 159.1, 137.3, 132.2, 124.5,
111.1, 110.7, 55.6, 23.7.
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–K