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B. Nammalwar et al. / Tetrahedron 71 (2015) 9101e9111
J¼7.4 Hz, 3H), 6.28 (br s, 1H), 3.70 (q, J¼6.7 Hz, 2H), 2.92 (t, J¼7.0 Hz,
J¼8.3 Hz, 2H), 3.79 (m, 1H), 1.85 (m, 2H), 1.76 (m, 2H), 1.63 (d,
J¼12.7 Hz, 1H), 1.40e1.33 (m, 4H), 1.17 (m, 1H); 13C NMR (DMSO-d6)
2H); 13C NMR (CDCl3):
d 167.5, 138.9, 134.7, 131.4, 128.8, 128.7, 128.6,
126.8, 126.6, 41.2, 35.7. HRMS [ESI] calcd for C15H16NO [MþH]þ:
d 164.1, 149.3, 141.0, 129.2, 123.7, 49.2, 32.7, 25.7, 25.4. HRMS [ESI]
226.1232, found: 226.1242.
calcd for C13H17N2O3 [MþH]þ: 249.1239, found: 249.1234.
4.2.5. 5-Bromo-2-chloro-N-(4-methoxybenzyl)benzamide (3ba). Iso-
lated as an off-white solid, mp 183e185 ꢀC; IR: 3182, 2838,
4.2.13. N-(4-Fluorobenzyl)nicotinamide (3dh). Isolated as a pale
yellow solid, 73e74 ꢀC; IR: 3283, 1645 cmꢄ1 1H NMR (DMSO-d6):
;
1635 cmꢄ1; 1H NMR (DMSO-d6):
d
8.38 (br s, 1H), 7.45 (d, J¼2.0 Hz,
d
9.26 (br t, J¼6.0 Hz, 1H), 9.05 (s, 1H), 8.72 (d, J¼4.7 Hz, 1H), 8.23 (d,
1H), 7.38 (d, J¼8.4 Hz, 2H), 7.35 (dd, J¼8.5, 2.0 Hz, 1H), 7.24 (d,
J¼8.2 Hz, 1H), 7.52 (dd, J¼8.2, 4.7 Hz, 1H), 7.38 (m, 2H), 7.16 (t,
J¼8.4 Hz, 1H), 6.95 (d, J¼8.4 Hz, 2H), 3.94 (s, 2H), 3.75 (s, 3H); 13C
J¼8.7 Hz, 2H), 4.49 (d, J¼5.9 Hz, 2H); 13C NMR (DMSO-d6):
d 165.3,
NMR (DMSO-d6)
d
168.2, 159.7, 144.6, 131.8, 131.6, 131.0, 130.8, 129.2,
161.6 (d, J¼242.4 Hz) 152.4, 148.9, 135.9 (d, J¼3.0 Hz), 135.5, 130.2,
129.8 (d, J¼8.1 Hz), 123.9, 115.5 (d, J¼21.2 Hz), 42.4. HRMS [ESI]
calcd for C13H12FN2O [MþH]þ: 231.0934, found: 231.0943.
127.2, 119.7, 114.3, 55.6, 42.2. HRMS [ESI] calcd for C15H14BrClNO2
[MþH]þ: 353.9896, found: 353.9899.
4.2.6. N-Benzyl-5-bromo-2-chlorobenzamide (3be). Isolated as an
4.2.14. N-Phenylnicotinamide (3dk). Isolated as an off-whiteꢄs1olid,
off-white solid, mp 108e110 ꢀC; IR: 3205, 1637 cmꢄ1
;
1H NMR
mp 124e125 ꢀC (lit.37 mp 119e120 ꢀC); IR: 3340, 1653 cm
;
1H
(DMSO-d6):
d
8.42 (br s, 1H), 7.51e7.43 (m, 3H), 7.43e7.32 (m, 4H),
NMR (CDCl3):
d
9.06 (s, 1H), 8.72 (d, J¼4.7 Hz, 1H), 8.41 (br s, 1H),
7.26 (d, J¼8.5 Hz, 1H), 4.02 (s, 2H); 13C NMR (DMSO-d6)
d
167.7,
8.18 (d, J¼7.9 Hz, 1H), 7.63 (d, J¼7.9 Hz, 2H), 7.42e7.31 (m, 3H), 7.17
143.8, 134.8, 131.2, 131.1, 130.5, 128.6, 128.4, 128.0, 119.2, 42.1 (1
(t, J¼7.5 Hz, 1H); 13C NMR (CDCl3):
d 164.1, 152.4, 147.9, 137.5, 135.4,
aromatic
C
unresolved). HRMS [ESI] calcd for
C14H12BrClNO
130.9, 129.2, 125.1, 123.7, 120.6. HRMS [ESI] calcd for C12H11N2O
[MþH]þ: 323.9791, found: 323.9798.
[MþH]þ: 199.0871, found: 199.0876.
4.2.7. N-Allyl-5-bromo-2-chlorobenzamide (3bf). Isolated as an off-
white solid, mp 119e120 ꢀC; IR: 3265, 1645 cmꢄ1; 1H NMR (CDCl3):
4.2.15. N-(4-(Trifluoromethoxy)phenyl)nicotinamide (3ꢄd1l). Isolated
as a white solid, mp 136e137 ꢀC; IR: 3336, 1651 cm
;
1H NMR
d
7.80 (d, J¼2.4 Hz,1H), 7.48 (dd, J¼8.5, 2.5 Hz,1H), 7.29 (d, J¼8.5 Hz,
(CDCl3):
J¼7.9 Hz, 1H), 7.71 (d, J¼8.5 Hz, 2H), 7.39 (m, 1H), 7.20 (d, J¼8.5 Hz,
2H); 13C NMR (CDCl3):
164.2, 152.4, 148.0, 145.8, 136.3, 135.6,
d
9.10 (s, 1H), 8.83 (s, 1H), 8.71 (d, J¼4.2 Hz, 1H), 8.21 (d,
1H), 6.31 (s, 1H), 5.93 (ddt, J¼16.8, 10.6, 5.6 Hz, 1H), 5.30 (d,
J¼17.0 Hz, 1H), 5.21 (d, J¼10.4 Hz, 1H), 4.09 (t, J¼5.8 Hz, 2H); 13C
d
NMR (CDCl3)
d
164.8, 136.5, 134.3133.4, 133.0, 131.7, 129.6, 120.9,
130.5, 123.7, 121.9, 121.8, 120.5 (q, J¼258.5 Hz). HRMS [ESI] calcd for
117.1, 42.6. HRMS [ESI] calcd for C10H10BrClNO [MþH]þ: 273.9634,
C
13H10F3N2O2 [MþH]þ: 283.0694, found: 283.0699.
found: 273.9642.
4.2.16. N-Isobutylnicotinamide (3dm). Isolated as a broꢄw1n solid, mp
4.2.8. (5-Bromo-2-chlorophenyl) (morpholino)methanone (3bg). Iso-
lated as an off-white solid, mp 165e167 ꢀC; IR: 3396, 1590 cmꢄ1; 1H
50e51 ꢀC (lit.38 mp 49e52 ꢀC); IR: 3299, 1644 cm
;
1H NMR
(CDCl3):
d
8.98 (s, 1H), 8.69 (d, J¼5.0 Hz, 1H), 8.12 (d, J¼7.8 Hz, 1H),
NMR (DMSO-d6):
d
7.58 (d, J¼2.3 Hz, 1H), 7.43 (dd, J¼8.8, 2.3 Hz, 1H),
7.35 (dd, J¼7.8, 5.0 Hz,1H), 6.81 (br s,1H), 3.29 (t, J¼6.5 Hz, 2H), 1.93
7.31 (d, J¼8.8 Hz, 1H), 3.75 (br t, J¼5.3 Hz, 4H), 3.04 (br t, J¼5.2 Hz,
(nonet, J¼6.8 Hz, 1H), 0.97 (d, J¼6.7 Hz, 6H); 13C NMR (CDCl3):
4H); 13C NMR (DMSO-d6)
d
168.2, 142.8, 131.4, 131.3, 131.2, 128.9,
d 165.8, 152.0, 147.8, 135.1, 130.6, 123.5, 47.5, 28.6, 20.2. HRMS [ESI]
119.4, 63.7, 42.7; HRMS [ESI] calcd for C11H12BrClNO2 [MþH]þ:
calcd for C10H15N2O [MþH]þ: 179.1184, found: 179.1186.
303.9740, found: 303.9745.
4.3. Conversion of o-diacids to N-substituted phthalimides
4.2.9. N-Allyl-4-nitrobenzamide (3cf). Isolated as an off-white solid,
113e114 ꢀC; IR: 3318,1645,1638,1545,1344 cmꢄ1; 1H NMR (CDCl3):
These compounds were prepared using the same procedure as
reported above, but at 150 ꢀC for 18e26 h. Following workup, the
crude products were purified on 15 cmꢃ2.5 cm silica gel columns
eluted with 60e80% EtOAc in hexanes. The isolated yields are given
in Table 3. Note: Saturated NH4Cl was used for washing the pyridine
derivatives instead of 1 M HCl.
d
8.29 (d, J¼8.4 Hz, 2H), 7.96 (d, J¼8.4 Hz, 2H), 6.38 (br s, 1H), 5.94
(ddt, J¼16.9, 10.6, 5.8 Hz, 1H), 5.29 (d, J¼17.1 Hz, 1H), 5.23 (d,
J¼10.5 Hz, 1H), 4.12 (t, J¼5.8 Hz, 2H); 13C NMR (CDCl3):
d 165.3,
149.6, 140.0, 133.4, 128.2, 123.9, 117.4, 42.8. HRMS [ESI] calcd for
C
10H11N2O3 [MþH]þ: 207.0770, found: 207.0775.
4.2.10. N-(4-Fluorobenzyl)-4-nitrobenzamide (3ch). Isolated as
a white solid, mp 144e145 ꢀC; IR: 3266, 1643, 1548, 1347 cmꢄ1; 1H
4.3.1. 2-Benzylisoindoline-1,3-dione (5ae). Isolated as an off-white
solid, mp 111e113 ꢀC (lit.39 mp 114e116 ꢀC); IR: 1765, 1710 cmꢄ1
;
NMR (CDCl3):
(apparent s, 2H), 7.03 (apparent s, 2H), 6.71 (br s, 1H), 4.61 (s, 2H);
13C NMR (CDCl3):
d
8.26 (d. J¼7.9 Hz, 2H), 7.94 (d, J¼7.9 Hz, 2H), 7.31
1H NMR (CDCl3):
d
7.85 (m, 2H), 7.71 (m, 2H), 7.43 (d, J¼7.4 Hz, 2H),
7.32 (t, J¼7.3 Hz, 2H), 7.26 (t, J¼7.3 Hz, 1H), 4.85 (s, 2H); 13C NMR
d
165.4, 162.3 (d, J¼247.5 Hz), 149.7, 139.8, 133.3,
(CDCl3) d 168.0, 136.4, 134.0, 132.1, 128.7, 128.6, 127.8, 123.3, 41.6.
129.6 (d, J¼8.1 Hz), 128.2, 123.8, 115.7 (d, J¼22.2 Hz), 43.7. HRMS
HRMS [ESI] calcd for C15H12NO2 [MþH]þ: 238.0868, found: 238.0877.
[ESI] calcd for C14H12FN2O3 [MþH]þ: 275.0832, found: 275.0837.
4.3.2. 2-(4-Fluorobenzyl)isoindoline-1,3-dione (5ah). Isolated as an
4.2.11. N-(4-Methoxyphenyl)-4-nitrobenzamide (3ci). Isolated as
a yellow solid, mp 196e197 ꢀC; IR: 3295, 1644, 1533, 1347 cmꢄ1; 1H
off-white solid, mp 120e121 ꢀC; IR: 1766, 1710 cmꢄ1 1H NMR
;
(CDCl3):
d
7.84 (m, 2H), 7.72 (m, 2H), 7.42 (dd, J¼8.3, 5.4 Hz, 2H),
NMR (DMSO-d6):
d
10.5 (s, 1H), 8.37 (d, J¼8.4 Hz, 2H), 8.18 (d,
6.99 (t, J¼8.5 Hz, 2H), 4.81 (s, 2H); 13C NMR (CDCl3)
d 168.0,162.4 (d,
J¼8.4 Hz, 2H), 7.69 (d, J¼8.6 Hz, 2H), 6.96 (d, J¼8.6 Hz, 2H), 3.76 (s,
J¼247.5 Hz), 134.1, 132.2 (d, J¼3.0 Hz), 132.1, 130.6 (d, J¼9.1 Hz),
123.4, 115.6, 115.3 (d, J¼22.2 Hz), 40.9. HRMS [ESI] calcd for
3H); 13C NMR (DMSO-d6):
d 162.7, 155.3, 148.5, 140.1, 131.2, 128.5,
122.9, 121.5, 113.2, 54.6. HRMS [ESI] calcd for C14H13N2O4 [MþH]þ:
C
15H11FNO2 [MþH]þ: 256.0774, found: 256.0782.
273.0875, found: 273.0877.
4.3.3. 2-(3-Methoxyphenyl)isoindoline-1,3-dione (5an).ꢄI1solated as
4.2.12. N-Cyclohexyl-4-nitrobenzamide (3cj). Isolated as a yellow
a gray solid, mp 108e110 ꢀC; IR: 2836, 1772, 1721 cm
;
1H NMR
solid, mp 195e196 ꢀC; IR: 3318, 1634, 1544, 1349 cmꢄ1
;
1H NMR
(CDCl3):
d
7.96 (m, 2H), 7.80 (m, 2H), 7.41 (t, J¼8.1 Hz, 1H), 7.03 (d,
(DMSO-d6):
d
8.51 (d, J¼7.8 Hz, 1H), 8.28 (d, J¼8.3 Hz, 2H), 8.08 (d,
J¼8.0 Hz, 1H), 6.99 (br s, 1H), 6.96 (d, J¼8.3 Hz, 1H), 3.84 (s, 3H); 13
C