The Journal of Organic Chemistry
Article
2-(Hexyl(phenyl)amino)-N-methoxybenzamide (1o): yield for
four steps 31%, 1.01 g; light yellow oil; 1H NMR (600 MHz,
CDCl3) δ 10.44 (br s, 1H), 8.16 (d, J = 7.8 Hz, 1H), 7.49 (dt, J = 1.8,
7.2 Hz, 1H), 7.38 (t, J = 7.2 Hz, 1H), 7.24 (t, J = 7.8 Hz, 2H), 7.12 (d,
J = 7.8 Hz, 1H), 6.89 (t, J = 7.8 Hz, 1H), 6.74 (t, J = 8.4 Hz, 2H), 3.71
(s, 3H), 3.52 (t, J = 7.8 Hz, 2H), 1.59−1.64 (m, 2H), 1.27−1.31 (m,
6H), 0.86 (t, J = 6.6 Hz, 3H); 13C NMR (150 MHz, CDCl3) δ 164.8,
148.3, 146.0, 133.0, 131.6, 130.5, 129.5, 129.1, 127.0, 120.1, 116.3,
64.3, 53.1, 31.5, 26.8, 26.5, 22.6, 14.0; HRMS (ESI) calcd for
CDCl3) δ 163.5, 158.6 (d, JC−F = 243.1 Hz), 158.5, 148.9, 148.9, 147.8,
127.7, 126.2, 122.5, 119.3 (d, JC−F = 22.7 Hz), 118.3 (d, JC−F = 7.7
Hz), 118.0 (d, JC−F = 24.3 Hz), 109.1, 104.6, 62.0, 55.6, 37.7; HRMS
+
(ESI) calcd for C16H15FN2NaO3 [M + Na+] 325.0959, found
325.0959.
7,8,10-Trimethoxy-5-methyl-5H-dibenzo[b,e][1,4]diazepin-11-
(10H)-one (2e): yield 60%, 188 mg; yellow solid; decomposed when
heated to 60 °C; 1H NMR (600 MHz, CDCl3) δ 7.88 (dd, J = 1.2, 7.8
Hz, 1H), 7.39 (dt, J = 1.2, 7.8 Hz, 1H), 7.02 (s, 1H), 7.04−7.08 (m,
2H), 6.65 (s, 1H), 3.88 (s, 3H), 3.87 (s, 3H), 3.85 (s, 3H), 3.33 (s,
3H); 13C NMR (150 MHz, CDCl3) δ 165.0, 153.7, 147.6, 146.2,
139.1, 132.5, 132.1, 126.2, 125.9, 123.0, 116.4, 104.8, 102.2, 62.1, 56.3,
+
C20H26N2NaO2 [M + Na+] 349.1886, found 349.1889.
2-(Methyl(phenyl)amino)-N-phenylbenzamide (1p): yield for four
steps 52%, 1.57 g; yellow oil; 1H NMR (600 MHz, CDCl3) δ 10.65 (s,
1H), 8.38 (dd, J = 1.8, 7.8 Hz, 1H), 7.51 (dt, J = 1.8, 7.8 Hz, 1H),
7.42−7.45 (m, 3H), 7.26−7.30 (m, 4H), 7.16 (d, J = 7.8 Hz, 1H), 7.06
(t, J = 7.8 Hz, 1H), 6.95 (t, J = 7.8 Hz, 1H), 6.86 (d, J = 7.8 Hz, 2H),
3.26 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 163.4, 148.9, 148.1,
138.3, 133.2, 131.9, 130.9, 129.5, 129.0, 128.1, 127.2, 124.1, 120.7,
120.1, 116.3, 41.0; HRMS (ESI) calcd for C20H18N2NaO+ [M + Na+]
325.1311, found 325.1314.
+
56.3, 37.5; HRMS (ESI) calcd for C17H18N2NaO4 [M + Na+]
337.1159, found 337.1161.
3-Chloro-7,8,10-trimethoxy-5-methyl-5H-dibenzo[b,e][1,4]-
diazepin-11(10H)-one (2f): yield 72%, 251 mg; yellow solid;
1
decomposed when heated to 80 °C; H NMR (600 MHz, CDCl3) δ
7.82 (d, J = 8.4 Hz, 1H), 7.03−7.04 (m, 2H), 7.01 (s, 1H), 6.65 (s,
1H), 3.89 (s, 3H), 3.86 (s, 3H), 3.85 (s, 3H), 3.33 (s, 3H); 13C NMR
(150 MHz, CDCl3) δ 164.3, 154.4, 147.7, 146.5, 138.8, 138.0, 133.3,
126.2, 124.1, 123.1, 116.9, 104.6, 102.3, 62.2, 56.3, 56.3, 37.6; HRMS
N-Methoxy-2-(methyl(4-nitrophenyl)amino)benzamide (1q):
1
yield for four steps 20%, 0.60 g; yellow solid; mp 117−123 °C; H
+
(ESI) calcd for C17H1735ClN2NaO4 [M + Na+] 371.0769, found
NMR (600 MHz, CDCl3) δ 9.15 (br s, 1H), 8.04 (d, J = 9.0 Hz, 2H),
7.77 (d, J = 7.2 Hz, 1H), 7.59 (t, J = 7.8 Hz, 1H), 7.44 (t, J = 7.8 Hz,
1H), 7.26 (d, J = 7.8 Hz, 1H), 6.58 (d, J = 9.0 Hz, 2H), 3.58 (s, 3H),
3.37 (s, 3H); 13C NMR (150 MHz, CDCl3) δ 164.7, 153.7, 144.4,
138.7, 133.2, 131.6, 130.4, 129.1, 128.1, 125.8, 112.6, 64.1, 40.9;
371.0773.
3-Chloro-10-methoxy-5,8-dimethyl-5H-dibenzo[b,e][1,4]-
diazepin-11(10H)-one (2g): yield 81%, 245 mg; white solid; mp 172−
178 °C; 1H NMR (600 MHz, CDCl3) δ 7.83 (d, J = 9.0 Hz, 1H), 7.30
(s, 1H), 6.99−7.03 (m, 4H), 3.86 (s, 3H), 3.31 (s, 3H), 2.32 (s, 3H);
13C NMR (150 MHz, CDCl3) δ 164.3, 154.0, 142.4, 138.9, 134.8,
+
HRMS (ESI) calcd for C15H15N3NaO4 [M + Na+] 324.0955, found
324.0957.
133.5, 133.4, 127.3, 123.9, 123.1, 121.3, 118.4, 117.0, 62.4, 37.8, 20.8;
General Procedure for the Preparation of Product 2. To a
solution of substrate 1 (1 mmol) in acetonitrile (20 mL) was added
PIDA (386 mg, 1.2 mmol) portionwise under an ice bath within 15
min. Then the reaction mixture as stirred at room temperature for
additional 30 min. The reaction mixture was treated with water (10
mL) and stirred for 5 min before saturated aqueous NaHCO3 (10 mL)
was added. The mixture was extracted with EtOAc (10 mL × 4). The
combined organic layer was dried over anhydrous Na2SO4. The
solvent was removed under vacuum, and the crude product was
purified by flash column chromatography on silica gel using EA/PE as
eluent to give the desired product.
+
HRMS (ESI) calcd for C16H1535ClN2NaO2 [M + Na+] 325.0714,
found 325.0716.
10-Methoxy-2,5,8-trimethyl-5H-dibenzo[b,e][1,4]diazepin-11-
(10H)-one (2h): yield 84%, 237 mg; white solid; mp 125−127 °C; 1H
NMR (600 MHz, CDCl3) δ 7.67 (d, J = 1.8, 1H), 7.29 (s, 1H), 7.19
(dd, J = 1.8, 8.4 Hz, 1H), 6.96−7.00 (m, 2H), 6.93 (d, J = 8.4 Hz, 1H),
3.86 (s, 3H), 3.29 (s, 3H), 2.31 (s, 3H), 2.27 (s, 3H); 13C NMR (150
MHz, CDCl3) δ 165.2, 151.0, 143.8, 134.0, 133.4, 132.5, 132.0, 127.1,
125.4, 121.4, 117.9, 116.3, 62.3, 37.5, 20.8, 20.4; HRMS (ESI) calcd
+
for C17H18N2NaO2 [M + Na+] 305.1260, found 305.1261.
8-Chloro-2-fluoro-10-methoxy-5-methyl-5H-dibenzo[b,e][1,4]-
diazepin-11(10H)-one (2i): yield 83%, 254 mg; yellow solid; mp 157−
160 °C; 1H NMR (600 MHz, CDCl3) δ 7.59 (d, J = 8.4, 1H), 7.49 (s,
1H), 7.13−7.17 (m, 2H), 7.06 (d, J = 8.4, 1H), 7.02 (dd, J = 4.8, 8.4,
1H), 3.89 (s, 3H), 3.31 (s, 3H); 13C NMR (150 MHz, CDCl3) δ
163.7, 158.5 (d, JC−F = 243.6 Hz), 148.6, 144.1, 134.8, 129.9, 136.8,
126.5, 120.9, 119.8 (d, JC−F = 22.7 Hz), 119.5, 118.2 (q, JC−F = 8.2
10-Methoxy-5-methyl-5H-dibenzo[b,e][1,4]diazepin-11(10H)-one
1
(2a): yield 82%, 208 mg; yellow solid; mp 126−128 °C; H NMR
(600 MHz, CDCl3) δ 7.90 (dd, J = 1.2, 7.8 Hz, 1H), 7.50 (dd, J = 1.8,
8.4 Hz, 1H), 7.41 (dt, J = 1.2, 7.8 Hz, 1H), 7.18 (dt, J = 1.8, 7.2 Hz,
1H), 7.12−7.15 (m, 2H), 7.07 (t, J = 8.4 Hz, 2H), 3.87 (s, 3H), 3.36
(s, 3H); 13C NMR (150 MHz, CDCl3) δ 165.0, 153.0, 145.8, 133.8,
132.8, 132.1, 126.5, 125.6, 124.4, 123.1, 121.0, 118.5, 116.7, 62.3, 37.7;
+
Hz), 62.7, 38.0; HRMS (ESI) calcd for C15H1235Cl19FN2NaO2 [M +
+
HRMS (ESI) calcd for C15H14N2NaO2 [M + Na+] 277.0947, found
Na+] 329.0464, found 329.0463.
277.0949.
8-Chloro-2,10-dimethoxy-5-methyl-5H-dibenzo[b,e][1,4]-
diazepin-11(10H)-one (2j): yield 78%, 248 mg; yellow solid; mp 117−
123 °C; 1H NMR (600 MHz, CDCl3) δ 7.47 (d, J = 2.4, 1H), 7.39 (s,
1H), 7.13 (dd, J = 2.4, 9.0 Hz, 1H), 7.03 (d, J = 9.0 Hz, 1H), 6.99 (d, J
= 1.2 Hz, 2H), 3.88 (s, 3H), 3.79 (s, 3H), 3.29 (s, 3H); 13C NMR
(150 MHz, CDCl3) δ 164.6, 155.6, 146.0, 144.8, 134.9, 129.4, 126.3,
126.1, 120.9, 120.1, 119.1, 118.0, 115.0, 62.6, 55.7, 37.8; HRMS (ESI)
8,10-Dimethoxy-5-methyl-5H-dibenzo[b,e][1,4]diazepin-11-
(10H)-one (2b): yield 90%, 256 mg; white solid; mp 125−127 °C; 1H
NMR (600 MHz, CDCl3) δ 7.90 (dd, J = 1.2, 7.8 Hz, 1H), 7.40 (dt, J
= 1.2, 7.8 Hz, 1H), 7.04−7.06 (m, 3H), 7.03 (s, 1H), 6.73 (dd, J = 2.4,
8.4 Hz, 1H), 3.89 (s, 3H), 3.77 (s, 3H), 3.31 (s, 3H); 13C NMR (150
MHz, CDCl3) δ 165.2, 156.6, 153.4, 138.8, 134.9, 132.8, 132.2, 125.4,
122.8, 119.2, 116.3, 112.2, 105.9, 100.0, 62.4, 55.7, 37.7; HRMS (ESI)
+
calcd for C16H1535ClN2NaO3 [M + Na+] 341.0663, found 341.0662.
+
calcd for C16H16N2NaO3 [M + Na+] 307.1053, found 307.1054.
8-Bromo-10-methoxy-2,5-dimethyl-5H-dibenzo[b,e][1,4]-
diazepin-11(10H)-one (2k): yield 71%, 246 mg; white solid; mp 90−
95 °C; 1H NMR (600 MHz, CDCl3) δ 7.68 (d, J = 1.8 Hz, 1H), 7.61
(d, J = 2.4 Hz, 1H), 7.27 (dd, J = 2.4, 9.0 Hz, 1H), 7.22 (dd, J = 1.8,
8.4 Hz, 1H), 6.97 (d, J = 8.4 Hz, 1H), 6.94 (d, J = 7.8 Hz, 1H), 3.88 (s,
3H), 3.30 (s, 3H), 2.29 (s, 3H); 13C NMR (150 MHz, CDCl3) δ
165.0, 150.2, 145.0, 135.2, 133.7, 133.0, 132.2, 129.1, 124.9, 123.7,
119.6, 116.8, 116.6, 62.6, 37.7, 20.4; HRMS (ESI) calcd for
7,10-Dimethoxy-5-methyl-5H-dibenzo[b,e][1,4]diazepin-11-
(10H)-one (2c): yield 76%, 216 mg; yellow solid; mp 125−130 °C; 1H
NMR (600 MHz, CDCl3) δ 7.87 (dd, J = 1.8, 7.8 Hz, 1H), 7.38−7.40
(m, 2H), 7.07 (t, J = 7.8 Hz, 1H), 7.04 (d, J = 8.4 Hz, 1H), 6.66−6.69
(m, 2H), 3.83 (s, 3H), 3.79 (s, 3H), 3.32 (s, 3H); 13C NMR (150
MHz, CDCl3) δ 164.6, 158.4, 152.8, 147.7, 132.5, 131.9, 126.6, 126.0,
123.2, 122.3, 116.8, 109.0, 104.7, 62.0, 55.6, 37.5; HRMS (ESI) calcd
+
for C16H16N2NaO3 [M + Na+] 307.1053, found 307.1055.
+
C16H1579BrN2NaO2 [M + Na+] 369.0209, found 369.0211.
2-Fluoro-7,10-dimethoxy-5-methyl-5H-dibenzo[b,e][1,4]-
diazepin-11(10H)-one (2d): yield 73%, 220 mg; yellow solid; mp
154−158 °C; 1H NMR (600 MHz, CDCl3) δ 7.56 (dd, J = 3.0, 9.0 Hz,
1H), 7.40 (d, J = 9.0 Hz, 1H), 7.10 (dt, J = 3.0, 7.8 Hz, 1H), 7.01 (dd,
J = 4.2, 7.8 Hz, 1H), 6.70 (dd, J = 2.4, 8.4 Hz, 1H), 6.66 (d, J = 1.8 Hz,
1H), 3.83 (s, 3H), 3.81 (s, 3H), 3.30 (s, 3H); 13C NMR (150 MHz,
7-Bromo-2,10-dimethoxy-5-methyl-5H-dibenzo[b,e][1,4]-
diazepin-11(10H)-one (2l): yield 51%, 185 mg; yellow solid; mp 133−
135 °C; 1H NMR (600 MHz, CDCl3) δ 7.38 (d, J = 3.0 Hz, 1H), 7.34
(t, J = 4.8 Hz, 1H), 7.22−7.24 (m, 2H), 6.97−7.00 (m, 2H), 3.85 (s,
3H), 3.78 (s, 3H), 3.29 (s, 3H); 13C NMR (150 MHz, CDCl3) δ
164.4, 155.7, 147.5, 145.7, 132.9, 127.1, 126.3, 122.3, 121.4, 119.9,
F
dx.doi.org/10.1021/jo402413g | J. Org. Chem. XXXX, XXX, XXX−XXX