Katritzky et al.
N-(Furan-2-ylmethyl)-2-hydroxybenzamide112 (7a): white
needles from diethyl ether (83%); mp 109-110 °C; IR (neat) ν )
117.8, 113.5, 45.2, 34.8, 27.0, 17.1, 15.8, 11.2. Anal. Calcd for
C13H19NO2: C, 70.56; H, 8.65; N, 6.33. Found: C, 70.77; H, 8.97;
N, 6.63.
1
3364, 1645, 1592, 1546, 1496 cm-1; H NMR δ 12.20 (s, 1H),
7.42-7.34 (m, 3 H), 6.90 (dd, J ) 8.24, 1.0 Hz, 1H), 6.84 (dt, J
) 7.14, 1 Hz, 1H), 6.60 (br s, 1H), 6.35 (dd, J ) 3.3, 1.8 Hz, 1H),
6.32 (d, J ) 3.3 Hz, 1H), 4.63 (d, J ) 5.94 Hz, 2H); 13C NMR δ
169.7, 161.6, 150.4, 142.6, 142.5, 134.4, 125.4, 118.7, 114.0, 110.6,
108.1, 36.5. Anal. Calcd for C12H11NO3: C, 66.35; H, 5.10; N,
6.45. Found: C, 65.97; H, 5.18; N, 6.49.
2-Hydroxy-N-phenyl-1-naphthamide (10a): white microcrys-
tals from chloroform (95%); mp171.0-172.0 °C; IR (neat) ν )
1
3283 (br w), 1627, 1597, 1532, 1443 cm-1; H NMR δ 11.1 (s,
1Η), 8.19 (d, J ) 8.5 Hz, 1H), 7.97 (br s, 1H), 7.85 (t, J ) 8.2 Hz,
2H), 7.62 (d, J ) 7.8 Hz, 2H), 7.58 (t, J ) 7.1 Hz, 1H) 7.45-7.38
(m, 3H), 7.26-7.19 (m, 2H); 13C NMR δ 168.4, 159.8, 136.9, 134.4,
130.5, 129.7, 129.3, 128.8, 128.5, 125.3, 123.7, 122.3, 120.7, 119.4,
109.9. Anal. Calcd for C17H13NO2: C, 77.55; H, 4.98; N, 5.32.
Found: C, 77.17; H, 4.94; N, 5.31.
(2-Hydroxyphenyl)piperidin-1-ylmethanone53 (7b): white
needles from methanol (94%); mp 142-143 °C; IR (neat) ν ) 3153,
1
2939, 2856, 1591, 1475 cm-1; H NMR δ 9.67 (s, 1H), 7.31 (t, J
) 7.7 Hz, 1H), 7.22 (d, J ) 7.8 Hz, 1H), 6.97 (d, J ) 8.2 Hz, 1H),
6.82 (t, J ) 7.3 Hz, 1H), 3.65-3.61 (m, 4H), 1.70-1.62 (m, 6H);
13C NMR δ 170.6, 158.7, 132.2, 128.1, 118.4, 117.8, 117.5, 46.7,
26.0, 24.4.
(2-Hydroxynaphthalen-1-yl)piperidin-1-ylmethanone (10b):
white needles from methanol (90%); mp 242-243 °C; IR (KBr) ν
1
) 3175, 1606, 1514 cm-1; H NMR (DMSO-d6) δ 9.93 (s, 1H),
7.83-7.77 (m, 2H), 7.51-7.41 (m, 2H), 7.33-7.28 (m, 1H), 7.19
(d, J ) 8.9 Hz, 1H), 3.90 (br s, 1H), 3.56 (br s, 1H), 3.09 (s, 2H),
1.59 (s, 4H), 1.44 (br s, 1H), 1.24 (br s, 1H); 13C NMR δ 165.9,
150.7, 131.2, 129.6, 128.2, 127.7, 126.9, 123.6, 123.1, 118.2, 117.1,
47.0, 24.3. Anal. Calcd for C16H17NO2: C, 75.27; H, 6.71; N, 5.49.
Found: C, 75.34; H, 6.93; N, 5.15.
5-Bromo-2-hydroxy-N-pentylbenzamide (7c): pale yellow
microcrystals from diethyl ether (84%); mp 54-55 °C; IR (neat) ν
1
) 3374, 2930, 2859, 1635, 1591, 1543, 1475 cm-1; H NMR δ
12.36 (s, 1H), 7.46-7.43 (m, 2H), 6.88 (d, J ) 9.3 Hz, 1H), 6.30
(br s, 1H), 3.43 (q, J ) 6.3 Hz, 2H), 1.68-1.58 (m, 2H), 1.38-
1.34 (m, 4H), 0.92 (t, J ) 6.6 Hz, 3H); 13C NMR δ 68.7, 160.5,
136.7, 127.8, 120.5, 115.9, 110.1, 39.9, 29.1, 29.0, 22.3, 13.9. Anal.
Calcd for C12H16BrNO2: C, 50.37; H, 5.64; N, 4.89. Found: C,
50.54; H, 5.57; N, 4.84.
1-Hydroxynaphthalene-2-carboxylic acid N-phenethylamide
(10c): pale yellow microcrystals from ethyl acetate (94%); mp
125-126 °C; IR (neat) ν ) 3417, 1615, 1594, 1542, 1501 cm-1
;
1H NMR δ 13.84 (s, 1H), 8.42 (d, J ) 7.1 Hz, 1H), 7.73 (d, J )
7.9 Hz, 1H), 7.59-7.49 (m, 2H), 7.36-7.11 (m, 7H), 6.34 (br s,
1H), 3.75 (q, J ) 6.6 Hz, 2H), 2.96 (t, J ) 6.8 Hz, 1H); 13C NMR
δ 170.6, 160.6, 138.5, 136.2, 128.9, 128.8 (2C), 127.3, 126.8, 125.8,
125.6, 123.8, 120.6, 118.1, 106.6, 40.8, 35.6. Anal. Calcd for C19H17-
NO2: C, 78.33; H, 5.88; N, 4.81. Found: C, 77.94; H, 5.94; N,
4.86.
5-Bromo-2-hydroxy-N-methyl-N-octylbenzamide (7d): cream
microcrystals from ethyl acetate (82%); mp 92-93 °C; IR (neat) ν
1
) 3125, 2927, 2855, 1612, 1490 cm-1; H NMR δ 9.74 (s, 1H),
7.40-7.37 (m, 2H), 6.87 (d, J ) 9.5 Hz, 1H), 3.50-3.45 (m, 2H),
3.11 (s, 3H), 1.68-1.64 (m, 2H), 1.29 (br s, 10H). 0.88 (t, J ) 6.2
Hz, 3H); 13C NMR δ 170.2, 157.7, 134.9, 130.5, 119.8, 119.6,
110.1, 31.7, 29.2, 29.1, 27.3, 26.6, 22.6, 14.1. Anal. Calcd for
C16H24BrNO2: C, 56.15; H, 7.07; N, 4.09. Found: C, 56.46; H,
7.35; N, 4.10.
(1-Hydroxynaphthalen-2-yl)pyrrolidin-1-ylmethanone
(10d): white microcrystals from ether (97%); mp 93-94 °C; IR
(neat) ν ) 3445 (br w), 2972, 2877, 1584, 1438 cm-1; 1H NMR δ
12.87 (s, 1H), 8.40 (d, J ) 8.1 Hz, 1H), 7.74 (d, J ) 7.9 Hz, 1H),
7.58-7.47 (m, 3H), 7.24 (d, J ) 8.6 Hz, 1H), 3.77-3.73 (m, 4H),
1.97-1.92 (m, 4H); 13C NMR δ 171.2, 159.4, 135.5, 128.5, 127.1,
125.5, 125.3, 123.9, 123.7, 116.9, 109.5, 48.9, 25.5. Anal. Calcd
for C15H15NO2: C, 74.76; H, 6.27; N, 5.80. Found: C, 74.28; H,
6.30; N, 5.85.
2,4-Dihydroxy-N-pentylbenzamide (7e): white microcrystals
from ethyl acetate (96%); mp 104-105 °C; IR (neat) ν ) 3385,
1
1637 cm-1; H NMR (DMSO-d6) δ 13.06 (s, 1H), 10.03 (s, 1H),
8.51 (br t, J ) 6.2 Hz, 1H), 7.67 (d, J ) 8.8 Hz, 1H), 6.28 (dd, J
) 8.8, 1.8 Hz, 1H), 6.22 (d, J ) 1.8 Hz, 1H), 3.24 (q, J ) 6.1 Hz,
2H), 1.54-1.50 (m, 2H), 1.29 (br s, 4H), 0.87 (t, J ) 6.4 Hz, 3H);
13C NMR (DMSO-d6) δ 169.4, 162.7, 162.1, 128.8, 106.9, 106.6,
102.7, 39.5, 28.7, 21.9, 13.9. Anal. Calcd for C12H17NO3: C, 64.56;
H, 7.67; N, 6.27. Found: C, 64.77; H, 7.89; N, 6.28.
3-Hydroxynaphthalene-2-carboxylic acid allylamide66 (10e):
pale yellow microcrystals from ethyl acetate (75%); mp 121-122
°C; IR (neat) ν ) 3374, 1657, 1584, 1509 cm-1; 1H NMR δ 11.72
(s, 1H), 7.97 (s, 1H), 7.72 (d, J ) 8.4 Hz, 1H), 7.67 (d, J ) 8.2
Hz, 1H), 7.47 (dt, J ) 6.9, 1.1 Hz, 1H), 7.31-7.26 (m, 2H), 6.70
(br s, 1H), 6.03-5.09 (m, 1H), 5.33 (dq, J ) 17.0, 1.2 Hz, 1H),
5.25 (dq, J ) 10.2 Hz, 1.2 Hz, 1H), 4.14 (tt, J ) 5.8, 1.5 Hz, 2H);
13C NMR δ 169.6, 156.6, 137.0, 133.3, 128.5, 128.4, 126.8, 126.7,
126.2, 123.9, 117.5, 116.8, 112.4, 42.2. Anal. Calcd for C14H13-
NO2: C, 73.99; H, 5.77; N, 6.16. Found: C, 73.69; H, 5.86; N,
6.17.
2,4-Dihydroxy-N-methyl-N-phenylbenzamide (7f): white mi-
crocrystals from chloroform (93%); mp 150.0-152.0 °C; IR (neat)
ν ) 3350, 1664, 1624, 1502 cm-1; 1H NMR δ 11.65 (s, 1H), 7.37-
7.31 (m, 2H), 7.28-7.26 (m, 1H), 7.15-7.12 (m, 2H), 6.53 (d, J
) 8.8 Hz, 1H), 6.37 (d, J ) 2.6 Hz, 1H), 5.88 (dd, J ) 8.8, 2.6
Hz, 1H), 5.67 (br s, 1H), 3.46 (s, 3H); 13C NMR δ 171.7, 162.9,
160.0, 145.3, 132.3, 129.7, 127.1, 126.6, 108.3, 106.3, 103.6, 39.5.
Anal. Calcd for C14H13NO3: C, 69.13; H, 5.39; N, 5.76. Found:
C, 68.77; H, 5.43; N, 5.77.
4-(Morpholin-4-ylcarbonyl)benzene-1,3-diol (7g): white mi-
crocrystals from chloroform (94%); mp 179.0-181.0 °C; IR (neat)
ν ) 3378, 1620, 1578 cm-1; 1H NMR δ 9.60 (s, 1H), 8.19 (s, 1H),
7.05 (d, J ) 8.4 Hz, 1H), 6.34 (d, J ) 2.3 Hz, 1H), 6.30 (dd, J )
8.4, 2.3 Hz, 1H), 3.68-3.65 (m, 8H); 13C NMR δ 170.9, 160.0,
158.7, 129.9, 110.2, 107.4, 103.8, 66.7, 46.0. Anal. Calcd for C11H13-
NO4: C, 59.19; H, 5.87; N, 6.27. Found: C, 58.83; H, 5.99; N,
6.19.
(3-Hydroxynaphthalen-2-yl)morpholin-4-ylmethanone64
(10f): white needles from ethyl acetate (70%); mp 216-217 °C;
1
IR (neat) ν ) 3095, 2967, 2855, 1594, 1483 cm-1; H NMR δ
8.93 (s, 1H), 7.74 (d, J ) 7.8 Hz, 1H), 7.73 (s, 1H), 7.66 (d, J )
8.2 Hz, 1H), 7.47 (t, J ) 7.7 Hz, 1H), 7.34 (t, J ) 7.8 Hz, 1H),
7.32 (s, 1H), 3.83-3.76 (m, 8H); 13C NMR δ 170.2, 154.1, 135.8,
128.7, 128.3, 128.1, 126.9, 126.4, 124.1, 119.7, 112.3, 66.9 (2C).
Anal. Calcd for C15H15NO3: C, 70.02; H, 5.88; N, 5.44. Found:
C, 69.70; H, 5.95; N, 5.44.
2-Hydroxy-3-methyl-N-(3-methylbutyl)benzamide (7h): col-
orless oil (93%); IR (neat) ν ) 3384, 2962, 2926, 2875, 1633, 1609,
General Procedure for the Synthesis of Hydroxy Aryl-/Alkyl-
and Thio Esters (11a-g) from Hydroxy Acids. The (N-hy-
droxyacyl)benzotriazole was prepared as described in the synthesis
of the hydroxy carboxamides.
The appropriate alcohol/thiol (6 mmol) was treated with NaH
(60% dispersion in oil) (6.2 mmol) in 12 mL of anhydrous THF
and stirred for 30 min. The supernatant of the benzotriazolating
mixture/hydroxy acid was carefully syringed out and added
dropwise to the sodium salt of the alchohol/thiol while under inert
1
1588, 1541 cm-1; H NMR (DMSO-d6) δ 12.65 (s, 1H), 7.25 (d,
J ) 6.4 Hz, 1H), 7.20 (d, J ) 7.9 Hz, 1H), 6.73 (t, J ) 7.7 Hz,
1H), 6.39 (br s, 1H), 3.42-3.21 (m, 2H), 2.26 (s, 3H), 1.73-1.62
(m, 1H), 1.53-1.39 (m, 1H), 1.28-1.14 (m, 1H), 0.97-0.91 (m,
6H); 13C NMR (DMSO-d6): δ 170.6, 159.9, 134.8, 127.7, 122.6,
(112) Paris, G. Y.; Chambers, C. H. J. Med. Chem. 1966, 9, 1.
3372 J. Org. Chem., Vol. 71, No. 9, 2006