The Journal of Organic Chemistry
Article
(s, 3H); 13C NMR (100 MHz, TMS, CDCl3) δ 170.8, 162.2, 149.9,
148.0, 139.9, 137.6, 136.6, 130.2, 126.4, 125.3, 123.0, 122.9, 122.4,
64.3, 21.4, 20.8; HRMS (EI) calcd for C16H16N2O3 (M+) 284.1161,
found 284.1167; IR (neat, cm−1) ν 3442, 3351, 2958, 1747, 1683,
1527, 1217, 996, 753, 673.
(d, JCF = 244.7 Hz), 162.2, 149.4, 148.1, 138.4 (d, JCF = 16.9 Hz),
137.7, 131.2 (d, JCF = 10.5 Hz), 126.7, 122.5, 120.9 (d, JCF = 2.8 Hz),
110.9 (d, JCF = 22.0 Hz), 109.2 (d, JCF = 27.5 Hz), 63.8, 20.8; HRMS
(EI) calcd for C15H13FN2O3 (M+) 288.0910, found 288.0908; IR
(neat, cm−1) ν 3465, 3323, 2917, 1746, 1695, 1537, 1224, 1007, 750,
690.
2-Methyl-6-(picolinamido)benzyl acetate (2d): white solid (63
1
mg, 74% yield); mp 60−62 °C (uncorrected); H NMR (400 MHz,
4-Acetyl-2-(picolinamido)benzyl acetate (2l): white solid (58 mg,
1
TMS, CDCl3) δ 10.75 (s, 1H), 8.61 (d, J = 4.0 Hz, 1H), 8.30 (d, J =
8.0 Hz, 1H), 7.99 (d, J = 8.4 Hz, 1H), 7.90 (t, J = 7.6 Hz, 1H), 7.49−
7.46 (m, 1H), 7.32 (t, J = 7.6 Hz, 1H), 7.05 (d, J = 7.6 Hz, 1H), 5.26
(s, 2H), 2.46 (s, 3H), 2.17 (s, 3H); 13C NMR(100 MHz, TMS,
CDCl3) δ 171.2, 162.6, 150.0, 148.1, 138.4, 137.5, 137.1, 129.2, 127.0,
126.3, 125.2, 122.5, 121.4, 60.4, 20.8, 19.6; HRMS (EI) calcd for
C16H16N2O3 (M+) 284.1161, found 284.1164; IR (neat, cm−1) ν 3455,
3335, 2938, 1742, 1692, 1545, 1218, 1022, 729, 688.
62% yield); mp 127−129 °C (uncorrected); H NMR (400 MHz,
TMS, CDCl3) δ 10.69 (s, 1H), 8.91 (d, J = 1.2 Hz, 1H), 8.63 (d, J =
4.0 Hz, 1H), 8.33 (d, J = 8.0 Hz, 1H), 7.95 (dt, J = 8.0 Hz, J = 1.6 Hz,
1H), 7.79 (dd, J = 8.0 Hz, J = 1.6 Hz, 1H), 7.55−7.51 (m, 1H), 7.48
(d, J = 8.0 Hz, 1H), 5.24 (s, 2H), 2.67 (s, 3H), 2.22 (s, 3H); 13C NMR
(100 MHz, TMS, CDCl3) δ 197.6, 170.6, 162.6, 149.6, 148.2, 138.2,
137.8, 137.1, 130.6, 130.4, 126.8, 124.1, 122.7, 122.6, 63.9, 26.9, 20.8.
HRMS (EI) calcd for C17H16N2O4 (M+) 312.1110, found 312.1107;
IR (neat, cm−1) ν 3442, 3321, 2921, 1742, 1686, 1582, 1537, 1236,
1026, 749, 688.
(4-(Picolinamido)biphenyl-3-yl)methyl acetate (2f): white solid
1
(78 mg, 75% yield); mp 107−109 °C (uncorrected); H NMR (400
MHz, TMS, CDCl3) δ 10.67 (s, 1H), 8.62 (d, J = 3.6 Hz, 1H), 8.41 (d,
J = 8.4 Hz, 1H), 8.32 (d, J = 8.0 Hz, 1H), 7.92 (dt, J = 7.6 Hz, J = 1.6
Hz, 1H), 7.67 (dd, J = 8.4 Hz, J = 2.0 Hz, 1H), 7.61−7.59 (m, 3H),
7.51−7.42 (m, 3H), 7.36−7.32 (m, 1H), 5.27 (s, 3H), 2.22 (s, 3H);
13C NMR (100 MHz, TMS, CDCl3) δ 170.8, 162.4, 149.9, 148.1,
140.2, 137.7, 137.5, 136.1, 129.0, 128.7, 128.4, 127.4, 127.0, 126.6,
126.2, 122.8, 122.6, 64.7, 20.9; HRMS (EI) calcd for C21H18N2O3
(M+) 346.1317, found 346.1309; IR (neat, cm−1) ν 3458, 3344, 2983,
1743, 1688, 1519, 1495, 1220,1019, 771, 675.
Methyl 3-(acetoxymethyl)-4-(picolinamido)benzoate (2m): white
1
solid (63 mg, 65% yield); mp 145−147 °C (uncorrected); H NMR
(400 MHz, TMS, CDCl3) δ 10.84 (s, 1H), 8.62 (d, J = 4.0 Hz, 1H),
8.54 (d, J = 8.4 Hz, 1H), 8.32 (d, J = 4.0 Hz, 1H), 8.11 (dd, J = 8.8 Hz,
J = 2.0 Hz, 1H), 8.06 (m, 1H), 7.94 (dt, J = 7.6 Hz, J = 1.2 Hz, 1H),
7.53−7.51 (m, 1H), 5.26 (s, 2H), 3.92 (s, 3H), 2.22 (s, 3H); 13C NMR
(100 MHz, TMS, CDCl3) δ 170.6, 166.3, 162.4, 149.5, 148.2, 141.1,
137.8, 131.9, 131.4, 126.9, 125.7, 125.0, 122.7, 121.2, 64.2, 51.1, 20.8;
HRMS (EI) calcd for C17H16N2O5 (M+) 328.1059, found 328.1057;
IR (neat, cm−1) ν 3454, 3305, 2924, 1741, 1689, 1528, 1286, 961, 722,
690.
5-Iodo-2-(picolinamido)benzyl acetate (2g): white solid (84 mg,
1
71% yield); mp 128−130 °C (uncorrected); H NMR (400 MHz,
N-(2-Methyl-4-(methylsulfonyl)phenyl)picolinamide (2n): white
TMS, CDCl3) δ 10.61 (s, 1H), 8.61 (d, J = 4.4 Hz, 1H), 8.29 (d, J =
8.0 Hz, 1H), 8.11 (d, J = 8.8 Hz, 1H), 7.92 (t, J = 8.0 Hz, 1H), 7.73−
7.69 (m, 2H), 7.51 (t, J = 4.8 Hz, 1H), 5.14 (s, 2H), 2.21 (s, 3H); 13C
NMR(100 MHz, TMS, CDCl3) δ 170.5, 162.2, 149.5, 148.1, 138.7,
138.5, 137.7, 136.6, 127.8, 126.6, 123.9, 122.5, 87.8, 63.4, 20.8; HRMS
(EI) calcd for C15H13IN2O3 (M+) 395.9971, found 395.9968; IR (neat,
cm−1) ν 3451, 3324, 2973, 1735, 1690, 1522, 1261, 1021, 749, 688.
5-Bromo-2-(picolinamido)benzyl acetate (2h): white solid (75
mg, 72% yield); mp 131−133 °C (uncorrected); 1H NMR (400 MHz,
TMS, CDCl3) δ 10.60 (s, 1H), 8.61 (d, J = 3.6 Hz, 1H), 8.28 (d, J =
8.0 Hz, 1H), 8.22 (d, J = 8.8 Hz, 1H), 7.92 (t, J = 7.2 Hz, 1H), 7.54−
7.50 (m, 3H), 5.16 (s, 2H), 2.21 (s, 3H); 13C NMR (100 MHz, TMS,
CDCl3) δ 170.5, 162.2, 149.5, 148.1, 137.7, 135.8, 132.8, 132.5, 127.8,
126.6, 123.8, 122.5, 117.1, 63.5, 20.7; HRMS (EI) calcd for
C15H13BrN2O3 (M+) 348.0110, found 348.0111; IR (neat, cm−1) ν
3353, 3326, 2968, 1735, 1690, 1527, 1263, 1030, 748, 686.
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solid (61 mg, 59% yield); mp 152−154 °C (uncorrected); H NMR
(400 MHz, TMS, CDCl3) δ 10.92 (s, 1H), 8.69 (d, J = 8.4 Hz, 1H),
8.64 (s, 1H), 8.32 (t, J = 7.6 Hz, 1H), 8.01−7.95 (m, 3H), 7.57−7.54
(m, 1H), 5.27 (s, 2H), 3.08 (s, 3H), 2.23 (s, 3H); 13C NMR (100
MHz, TMS, CDCl3) δ 170.5, 162.7, 149.1, 148.2, 141.9, 138.0, 135.4,
129.5, 129.3, 127.2, 126.0, 122.8, 120.0, 63.7, 44.7, 20.8. HRMS (EI)
calcd for C16H16N2O5S (M+) 348.0780, found 348.0780; IR (neat,
cm−1) ν 3345, 3324, 2922, 1696, 1690, 1579, 1536, 1297, 1129, 976,
762, 679.
5-Nitro-2-(picolinamido)benzyl acetate (2o): white solid (40 mg,
1
49% yield); mp 183−185 °C (uncorrected); H NMR (400 MHz,
TMS, CDCl3) δ 10.80 (s, 1H), 9.28 (d, J = 1.6 Hz, 1H), 8.64(d, J = 4.8
Hz, 1H), 8.33 (d, J = 7.6 Hz, 1H), 8.01 (dd, J = 8.4 Hz, 2.0 Hz, 1H),
7.99−7.95 (m, 1H), 7.56−7.54 (m, 2H), 5.28 (s, 2H), 2.34 (s, 3H);
13C NMR (100 MHz, TMS, CDCl3) δ 170.4, 162.5, 149.9, 148.6,
148.1, 137.8, 137.7, 131.7, 130.6, 127.0, 122.7, 118.9, 116.9,63.3, 20.7;
HRMS (EI) calcd for C15H13N3O5 (M+) 315.0855, found 315.0861;
IR (neat, cm−1) ν 3481, 3329, 2918, 1752, 1693, 1536, 1236, 1010,
751, 689.
5-Chloro-2-(picolinamido)benzyl acetate (2i): white solid (69 mg,
1
76% yield); mp 127−129 °C (uncorrected); H NMR (400 MHz,
TMS, CDCl3) δ 10.79 (s, 1H), 8.61 (d, J = 3.6 Hz, 1H), 8.28 (t, J = 8.8
Hz, 2H), 7.92 (t, J = 7.2 Hz, 1H), 7.52−7.49 (m, 1H), 7.40−7.36 (m,
2H), 5.16 (s, 2H), 2.21 (s, 3H); 13C NMR (100 MHz, TMS, CDCl3) δ
170.5, 162.3, 149.5, 148.1, 137.7, 135.2, 129.9, 129.5, 127.6, 126.6,
123.6, 122.5, 63.6, 20.7; HRMS (EI) calcd for C15H13ClN2O3 (M+)
304.0615, found 304.0624; IR (neat, cm−1) ν 3446, 3343, 3060, 1742,
1686, 1526, 1244, 1029, 748, 676.
7-Methyl-8-(picolinamido)naphthalen-1-yl acetate (2p): white
1
solid (52 mg, 54% yield); mp 158−160 °C (uncorrected); H NMR
(400 MHz, TMS, CDCl3) δ 9.84 (s, 1H), 8.69 (d, J = 4.4 Hz, 1H),
8.33 (d, J = 7.6 Hz, 1H), 7.96−7.92 (m, 2H), 7.85 (d, J = 9.6 Hz, 1H),
7.55−7.46 (m, 3H), 7.23 (s, 1H), 2.45 (s, 6H); 13C NMR (100 MHz,
TMS, CDCl3) δ 169.5, 163.1, 149.6, 148.2, 145.6, 137.7, 133.4, 131.6,
128.0, 127.2, 126.7, 126.0, 125.8, 123.0, 122.8, 121.5, 120.9, 21.1, 18.9;
HRMS (EI) calcd for C19H16N2O3 (M+) 320.1161, found 320.1166;
IR (neat, cm−1) ν 3442, 3283, 2927, 1744, 1695, 1580, 1583, 1218,
1133, 958, 771.
5-Fluoro-2-(picolinamido)benzyl acetate (2j): white solid (42 mg,
1
49% yield); mp 114−116 °C (uncorrected); H NMR (400 MHz,
TMS, CDCl3) δ 10.49 (s, 1H), 8.61 (d, J = 4.4 Hz, 1H), 8.29 (d, J =
8.0 Hz, 1H), 8.19−8.15 (m, 1H), 7.92 (t, J = 8.0 Hz, 1H), 7.52−7.49
(m, 1H), 7.14−7.10 (m, 2H), 5.16 (s, 2H), 2.21 (s, 3H); 13C NMR
(100 MHz, TMS, CDCl3) δ 170.5, 162.4, 159.3 (d, JCF = 243.8 Hz),
149.6, 148.1, 137.6, 132.4 (d, JCF = 2.7 Hz), 128.6 (d, JCF = 8.1 Hz),
126.5, 124.6 (d, JCF = 7.0 Hz), 122.5, 116.7 (d, JCF = 22.5 Hz), 116.04
(d, JCF = 22.6 Hz), 63.5, 20.7; HRMS (EI) calcd for C15H13FN2O3
(M+) 288.0910, found 288.0909; IR (neat, cm−1) ν 3451, 3334, 2969,
1740, 1690, 1538, 1259, 1030, 749, 683.
2-(Quinoline-2-carboxamido)benzyl acetate (4a): white solid (62
mg, 65% yield); mp 143−145 °C (uncorrected); 1H NMR (400 MHz,
TMS, CDCl3) δ 10.80 (s, 1H), 8.42−8.36 (m, 3H), 8.13 (d, J = 8.4
Hz, 1H), 7.91 (t, J = 8.0 Hz, 1H), 7.81 (t, J = 7.2 Hz, 1H), 7.65 (t, J =
7.2 Hz,1H), 7.47(t, J = 7.6 Hz, 1H), 7.41 (d, J = 8.0 Hz, 1H), 7.19 (t, J
= 7.6 Hz,1H), 5.30 (s, 2H) 2.22 (s, 3H); 13C NMR (100 MHz, TMS,
CDCl3) δ 170.8, 162.4, 149.6, 146.3, 137.8, 136.9, 130.5, 130.3, 129.9,
129.6, 129.4, 128.2, 127.8,125.7, 124.5, 122.1, 118.7, 64.4, 21.0; HRMS
(EI) calcd for C19H16N2O3 (M+) 320.1161, found 320.1165; IR (neat,
cm−1) ν 3441, 3320, 2919, 1741, 1685, 1533, 1227, 1022, 760, 692.
4-Methyl-2-(quinoline-2-carboxamido)benzyl acetate (4b): white
4-Fluoro-2-(picolinamido)benzyl acetate (2k): white solid (68 mg,
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79% yield); mp 125−127 °C (uncorrected); H NMR (400 MHz,
TMS, CDCl3) δ 10.73 (s, 1H), 8.61 (d, J = 4.8 Hz, 1H), 8.30 (d, J =
8.4 Hz, 1H), 8.24−8.21 (m, 1H), 7.94 (t, J = 8.0 Hz, 1H), 7.53−7.50
(m, 1H), 7.34−7.31 (m, 1H), 6.85 (dt, J = 8.4 Hz, 2.4 Hz), 5.12 (s,
2H), 2.20 (s, 3H); 13C NMR (100 MHz, TMS, CDCl3) δ 170.7, 163.2
1
solid (67 mg, 67% yield); mp 105−107 °C (uncorrected); H NMR
I
dx.doi.org/10.1021/jo401830k | J. Org. Chem. XXXX, XXX, XXX−XXX