The Journal of Organic Chemistry
Note
124.1, 123.3, 121.9, 120.6, 41.7; 19F NMR (CDCl3, 376 MHz) δ
−63.35 (s); HRMS (ESI) calcd for C17H13F3N3O4S [M + H]+
412.0573, found 412.0575.
Hz, 1H), 7.43 (dd, J = 8.3, 4.3 Hz, 1H), 7.32 (d, J = 8.8 Hz, 1H), 7.26
(d, J = 8.2 Hz, 2H), 6.99 (t, J = 6.3 Hz, 1H), 4.99 (d, J = 6.6 Hz, 2H);
13C NMR (CDCl3, 101 MHz) δ 150.1, 146.4, 143.7, 136.9, 134.8,
N-((6-Fluoroquinolin-8-yl)methyl)-4-(trifluoromethyl)-
133.8, 133.5, 133.1, 132.8, 130.3, 128.7, 128.0, 126.8, 126.8, 125.0(q),
124.4, 121.6, 121.4, 42.1; 19F NMR (CDCl3, 376 MHz) δ −63.4 (s);
HRMS (ESI) calcd for C17H13ClF3N2O2S [M + H]+ 401.0333, found
401.0336.
benzenesulfonamide (3ka): white solid (71 mg, 62%); mp 114−117
1
°C; H NMR (CDCl3, 400 MHz) δ 8.78 (dd, J = 4.2, 1.5 Hz, 1H),
8.00 (dd, J = 8.4, 1.4 Hz, 1H), 7.61 (d, J = 8.2 Hz, 2H), 7.42 (dd, J =
8.3, 4.2 Hz, 1H), 7.35 (d, J = 8.2 Hz, 2H), 7.27−7.24 (m, 1H), 7.22
(dd, J = 8.5, 2.7 Hz, 1H), 6.75 (t, J = 6.2 Hz, 1H), 4.72 (d, J = 6.6 Hz,
2H); 13C NMR (CDCl3, 101 MHz) δ 160.6, 158.1, 148.7, 143.9,
143.1, 136.2, 136.2, 136.1, 134.0, 133.7, 133.3, 133.0, 129.2, 129.1,
127.0, 125.2 (q), 124.4, 122.1, 121.7, 120.1, 119.8, 119.0, 110.8, 110.6,
46.0; 19F NMR (CDCl3, 376 MHz) δ −63.40 (s), −112.9 (s); HRMS
(ESI) calcd for C17H13F4N2O2S [M + H]+ 385.0628, found 385.0634.
N-((6-Chloroquinolin-8-yl)methyl)-4-(trifluoromethyl)-
benzenesulfonamide (3la): white solid (71 mg, 59%); mp 135−137
°C; 1H NMR (CDCl3, 400 MHz) δ 8.81 (d, J = 4.1 Hz, 1H), 7.96 (d, J
= 8.3 Hz, 1H), 7.59 (d, J = 8.5 Hz, 3H), 7.43 (dd, J = 8.2, 4.2 Hz, 1H),
7.39 (s, 1H), 7.34 (d, J = 7.9 Hz, 2H), 6.68 (t, J = 6.0 Hz, 1H), 4.71 (d,
J = 6.5 Hz, 2H); 13C NMR (CDCl3, 101 MHz) δ 149.6, 144.2, 143.8,
135.8, 134.9, 133.9, 133.6, 133.3, 132.9, 131.7, 130.4, 128.9, 127.0,
126.5, 125.1(q), 124.3, 122.2, 121.6, 45.8. 19F NMR (CDCl3, 376
MHz) δ −63.4 (s); HRMS (ESI) calcd for C17H13ClF3N2O2S [M +
H]+ 401.0333, found 401.0329.
N-((6-Bromoquinolin-8-yl)methyl)-4-(trifluoromethyl)-
benzenesulfonamide (3ma): white solid (75 mg, 56%); mp 160−164
°C; 1H NMR (CDCl3, 400 MHz) δ 8.83 (d, J = 4.2 Hz, 1H), 7.98 (d, J
= 8.2 Hz, 1H), 7.77 (s, 1H), 7.58 (d, J = 8.0 Hz, 2H), 7.53 (s, 1H),
7.45 (dd, J = 8.2, 4.3 Hz, 1H), 7.34 (d, J = 8.0 Hz, 2H), 6.69 (br s,
1H), 4.72 (d, J = 6.4 Hz, 2H); 13C NMR (CDCl3, 101 MHz) δ 149.7,
144.4, 143.8, 135.7, 134.9, 133.6, 133.3, 133.0, 130.0, 129.4, 126.9,
125.1(q), 124.3, 122.2, 121.6, 119.8, 45.8; 19F NMR (CDCl3, 376
MHz) δ −63.4 (s); HRMS (ESI) calcd for C17H13BrF3N2O2S [M +
H]+ 444.9828, found 444.9824.
N-((7-Bromoquinolin-8-yl)methyl)-4-(trifluoromethyl)-
benzenesulfonamide (3ra): white solid (87 mg, 65%); mp 150−153
1
°C; H NMR (CDCl3, 400 MHz) δ 8.82 (dd, J = 4.2, 1.7 Hz, 1H),
7.95 (dd, J = 8.3, 1.6 Hz, 1H), 7.75 (d, J = 2.1 Hz, 1H), 7.57 (d, J = 8.2
Hz, 2H), 7.51 (d, J = 2.0 Hz, 1H), 7.43 (dd, J = 8.3, 4.3 Hz, 1H), 7.33
(d, J = 8.3 Hz, 2H), 6.65 (t, J = 6.5 Hz, 1H), 4.71 (d, J = 6.7 Hz, 2H);
13C NMR (CDCl3, 101 MHz) δ 150.1, 146.4, 143.7, 136.9, 133.8,
133.5, 133.1, 132.8, 132.4, 130.9, 128.8, 127.3, 127.0, 126.8, 126.2(q),
125.5, 124.9(q, CF3), 124.4, 121.6, 121.6, 45.1; 19F NMR (CDCl3, 376
MHz) δ −63.4 (s); HRMS (ESI) calcd for C17H13BrF3N2O2S [M +
+
H] 444.9828, found 444.9822.
N-((7-Methylquinolin-8-yl)methyl)-4-(trifluoromethyl)-
benzenesulfonamide (3sa): white solid (78 mg, 68%); mp 126−130
°C; 1H NMR (CDCl3, 400 MHz) δ 8.77 (d, J = 3.0 Hz, 1H), 7.98 (d, J
= 7.3 Hz, 1H), 7.53 (d, J = 8.1 Hz, 2H), 7.48 (d, J = 8.4 Hz, 1H), 7.34
(dd, J = 7.1, 3.6 Hz, 1H), 7.27 (d, J = 6.4 Hz, 2H), 7.20 (d, J = 8.0 Hz,
1H), 6.92 (br s, 1H), 4.81 (d, J = 6.5 Hz, 2H), 2.56 (s, 3H); 13C NMR
(CDCl3, 101 MHz) δ 149.2, 146.2, 143.9, 137.8, 136.5, 133.5, 133.2,
132.9, 132.5, 129.9, 129.6, 127.4, 127.1, 126.6, 126.4, 124.8(q), 124.4,
121.7, 120.4, 41.6, 19.9; 19F NMR (CDCl3, 376 MHz) δ −63.4 (s);
+
HRMS (ESI) calcd for C18H16F3N2O2S [M + H] 381.0879, found
381.0881.
N-((5-Methyl-3-phenylquinolin-8-yl)methyl)-4-(trifluoromethyl)-
benzenesulfonamide (3ta): white solid (84 mg, 61%); mp 123−126
1
°C; H NMR (CDCl3, 400 MHz) δ 9.05 (s, 1H), 8.297 (s, 1H), 7.69
(d, J = 7.6 Hz, 2H), 7.57 (t, J = 7.5 Hz, 2H), 7.53−7.47 (3H, m), 7.32
(d, J = 6.2 Hz, 1H), 7.22 (d, J = 8.1 Hz, 2H), 7.16 (d, J = 6.7 Hz, 1H),
6.86 (br s, 1H), 4.74 (d, J = 6.5 Hz, 2H), 2.60 (s, 3H); 13C NMR
(CDCl3, 101 MHz) δ 148.2, 145.0, 143.9, 137.6, 135.5, 133.8, 133.0,
132.7, 130.8, 130.4, 129.4, 129.3, 128.4, 127.4, 127.3, 126.8, 126.6,
124.7(q), 124.5, 121.8, 46.7, 18.2; 19F NMR (CDCl3, 376 MHz) δ
−63.0 (s); HRMS (ESI) calcd for C24H20F3N2O2S [M + H]+
457.1192, found 457.1193.
N-((5-Nitroquinolin-8-yl)methyl)-4-nitrobenzenesulfonamide
(3cb): white solid (85 mg, 73%); mp 130−134 °C; 1H NMR (DMSO,
400 MHz) δ 9.00 (dd, J = 2.7, 1.4 Hz, 1H), 8.79 (t, J = 6.2 Hz, 1H),
8.75 (dd, J = 7.4, 1.4 Hz, 1H), 8.39 (d, J = 8.0 Hz, 1H), 8.25 (d, J = 8.8
Hz, 2H), 7.94 (d, J = 8.8 Hz, 2H), 7.90 (d, J = 8.0 Hz, 1H), 7.79 (dd, J
= 8.8, 4.7 Hz, 1H), 4.79 (d, J = 6.1 Hz, 2H); 13C NMR (DMSO, 101
MHz) δ 151.0, 149.3, 146.0, 144.4, 144.4, 142.5, 131.7, 127.9, 126.7,
124.3, 124.2, 119.7, 42.5; HRMS (ESI) calcd for C16H13N4O6S [M +
H]+ 389.0550, found 389.0540.
N-((5-Nitroquinolin-8-yl)methyl)-4-chlorobenzenesulfonamide
(3cc): white solid (79 mg, 70%); mp 134−136 °C; 1H NMR (CDCl3,
400 MHz) δ 9.00−8.96 (m, 2H), 8.23 (d, J = 7.9 Hz, 1H), 7.71−7.66
(m, 2H), 7.55 (d, J = 8.5 Hz, 2H), 7.20 (d, J = 8.5 Hz, 2H), 6.39 (br s,
1H), 4.76 (s, 2H); 13C NMR (CDCl3, 101 MHz) δ 150.6, 145.8,
145.3, 141.3, 138.8, 138.6, 132.7, 128.7, 128.1, 127.6, 124.0, 121.1,
45.7; HRMS (ESI) calcd for C16H13ClN3O4S [M + H]+ 378.0310,
found 378.0308.
N-((6-Methylquinolin-8-yl)methyl)-4-(trifluoromethyl)-
benzenesulfonamide (3na): white solid (70 mg, 61%); mp 130−132
1
°C; H NMR (CDCl3, 400 MHz) δ 8.74 (dd, J = 4.1, 1.2 Hz, 1H),
7.95 (d, J = 8.2 Hz, 1H), 7.37−7.34 (m, 2H), 7.28 (d, J = 8.3 Hz, 2H),
7.21 (br s, 1H), 7.45 (dd, J = 8.2, 4.3 Hz, 1H), 7.34 (d, J = 8.0 Hz,
2H), 6.88 (br s, 1H), 4.70 (d, J = 6.5 Hz, 2H), 2.40 (s, 3H); 13C NMR
(CDCl3, 101 MHz) δ 148.5, 144.6, 144.0, 136.0, 135.9, 133.7, 133.4,
133.0, 132.7, 132.4, 131.9, 128.4, 127.0, 126.8, 124.9(q), 124.4, 121.7,
121.3, 119.0, 46.5, 21.1; 19F NMR (CDCl3, 376 MHz) δ −63.4 (s);
HRMS (ESI) calcd for C18H16F3N2O2S [M + H]+ 381.0879, found
381.0880.
N-((7-(Trifluoromethyl)quinolin-8-yl)methyl)-4-(trifluoromethyl)-
benzenesulfonamide (3oa): white solid (84 mg, 64%); mp 140−142
1
°C; H NMR (CDCl3, 400 MHz) δ 8.94 (dd, J = 4.1, 1.6 Hz, 1H),
8.15 (dd, J = 8.3, 1.5 Hz, 1H), 7.76 (d, J = 8.7 Hz, 1H), 7.69−7.66 (m,
3H), 7.55 (dd, J = 8.3, 4.2 Hz, 1H), 7.38 (d, J = 8.3 Hz, 2H), 7.11 (br
s, 1H), 4.97 (br s, 2H); 13C NMR (CDCl3, 101 MHz) δ 150.6, 146.1,
143.7, 137.0, 129.6, 128.7, 127.1, 125.2(q), 125.0, 124.4, 123.0, 122.5,
122.5, 122.4, 122.4, 77.3, 77.0, 76.7, 41.5, 41.5; 19F NMR (CDCl3, 376
MHz) δ −57.2 (s), −63.3 (s); HRMS (ESI) calcd for C18H13F6N2O2S
[M + H]+ 435.0596, found 435.0591.
N-((7-Fluoroquinolin-8-yl)methyl)-4-(trifluoromethyl)-
benzenesulfonamide (3pa): white solid (69 mg, 60%); mp 146−149
°C; 1H NMR (CDCl3, 400 MHz) δ 8.86 (d, J = 4.2 Hz, 1H), 8.06 (d, J
= 8.2 Hz, 1H), 7.62 (d, J = 8.3 Hz, 2H), 7.59−7.57 (m, 1H), 7.40 (dd,
J = 8.3, 4.3 Hz, 1H), 7.29 (d, J = 8.3 Hz, 2H), 7.15 (t, J = 9.0 Hz, 1H),
6.92 (t, J = 6.1 Hz, 1H), 4.82 (d, J = 6.5 Hz, 2H); 13C NMR (CDCl3,
101 MHz) δ 160.8, 158.3, 150.4, 147.0, 146.9, 143.7, 136.7, 133.9,
133.5, 133.2, 132.9, 129.7, 129.6, 125.2, 125.0(q), 124.4, 121.7, 120.6,
120.6, 119.0, 117.4, 117.3, 116.8, 116.5, 37.8, 37.7; 19F NMR (CDCl3,
376 MHz) δ −63.4 (s), −111.6 (s); HRMS (ESI) calcd for
C17H13F4N2O2S [M + H]+ 385.0628, found 385.0626.
N-((5-Nitroquinolin-8-yl)methyl)-4-methylbenzenesulfonamide
(3cd): white solid (75 mg, 70%); mp 118−120 °C; 1H NMR (CDCl3,
400 MHz) δ 8.94 (d, J = 3.9 Hz, 1H), 8.89 (d, J = 8.8 Hz, 1H), 8.14
(d, J = 7.9 Hz, 1H), 7.65−7.61 (m, 2H), 7.44 (d, J = 8.0 Hz, 2H), 6.97
(d, J = 8.0 Hz, 2H), 6.35 (br s, 1H), 4.74 (s, 2H), 2.27 (s, 3H); 13C
NMR (CDCl3, 101 MHz) δ 150.5, 145.7, 145.1, 143.2, 141.6, 137.1,
132.6, 129.0, 127.6, 126.6, 124.0, 123.9, 121.0, 45.7, 21.3; HRMS
+
(ESI) calcd for C17H16N3O4S [M + H] 358.0856, found 358.0851.
N-((5-Nitroquinolin-8-yl)methyl)-4-methoxybenzenesulfonamide
(3ce): white solid (76 mg, 68%); mp 108−110 °C; 1H NMR (DMSO,
400 MHz) δ 8.84 (dd, J = 4.1, 1.6 Hz, 1H), 8.51 (t, J = 6.1 Hz, 1H),
8.37 (dd, J = 8.5, 1.6 Hz, 1H), 8.21 (d, J = 8.8 Hz, 2H), 7.89 (d, J = 8.8
Hz, 2H), 7.58 (d, J = 7.3 Hz, 1H), 7.54 (dd, J = 8.5, 4.2 Hz, 1H), 7.35
N-((7-Chloroquinolin-8-yl)methyl)-4-(trifluoromethyl)-
benzenesulfonamide (3qa): white solid (78 mg, 65%); mp 166−171
1
°C; H NMR (CDCl3, 400 MHz) δ 8.85 (dd, J = 4.3, 1.7 Hz, 1H),
8.04 (dd, J = 8.3, 1.5 Hz, 1H), 7.60 (d, J = 8.2 Hz, 2H), 7.51 (d, J = 8.0
E
dx.doi.org/10.1021/jo5008515 | J. Org. Chem. XXXX, XXX, XXX−XXX