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3,4,5-Trimethoxyphenyl isocyanate (1 g, 4.80 mmol, 1.1 equiv.) and PrOH (0.33 ml, 264 mg, 4.40 mmol,
1 equiv.) were dissolved in anh. toluene (40 ml) and refluxed for 2 h. The solvent was then removed, and the
resulting crude material was purified on silica gel (AcOEt/hexane 3 :7) to yield the trimethoxy derivative
(1.07 g, 4.00 mmol, 91%). M.p. 90 918. UV/VIS (MeOH): lmax 273.0 (950). IR (KBr): 3342 (NÀH), 1720
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(CO), 660 (NÀH), 1128 (CÀO). H-NMR (CDCl3): 0.98 (t, J 7.25, Me); 1.69 (s, J 7.25, CH2); 3.81 (s, p-
MeO); 3.84 (s, 2 m-MeO); 4.12 (t, J 6.80, CH2O); 6.63 (m, NH); 6.69 (s, 2 Ho). 13C-NMR (CDCl3): 10.98
(Me); 22.94 (CH2); 56.73 (m-MeO); 61.63 (p-MeO); 67.52 (CH2); 97.02, 134.82, 154.11 (arom. C); 154.30 (CO).
Anal. calc.: C 57.98, H, 7.11, N 5.20, found: C 58.28, H 7.16, N 5.30.
Cleavage of MeO groups was performed as described for 1a. The protected compound (1.88 g, 7.00 mmol,
1 equiv.) and 1m BBr3 (42 ml, 42.00 mmol, 6 equiv.) lead, after recrystallization in AcOEt/hexane, to 2a (1.45 g,
6.39 mmol, 91%). M.p. 55 55.28. UV/VIS (MeOH): lmax 281.0 (3210). IR: (KBr): 3300 (OÀH), 1701 (CO),
669 (NÀH). 1H-NMR ((D6)DMSO): 0.93 (t, J 7.5, Me); 1.62 (m, J 7.3, 6.5, CH2); 3.98 (t, J 6.5, CH2); 6.47
(s, 2 Ho); 9.10 (s, NH). 13C-NMR ((D6)DMSO): 10.26 (Me); 21.94 (CH2); 65.21 (CH2O); 98.23, 128.33, 130.59,
145.97 (arom. C); 153.51 (CO).
N-(3',4',5'-Trihydroxyphenyl) Amides 3a 3c. A typical procedure is presented for N-(3',4',5'-Trihydroxy-
phenyl)octaneamide (3b).
3,4,5-Trimethoxyaniline (500 mg, 2.73 mmol, 1 equiv.) was dissolved in dist. CH2Cl2 (30 ml). Et3N (0.4 ml,
276 mg, 2.73 mmol, 1 equiv.) was poured dropwise under N2 and under cooling to a soln. of octanoyl chloride
(0.52 ml, 488 mg, 3.00 mmol, 1.1 equiv.) in CH2Cl2 (10 ml). After 12 h at r.t., the solvent was removed, and the
crude oil was dissolved in AcOEt (40 ml). The org. phase was washed successively 3 Â with 1n HCl (10 ml), aq.
NaHCO3 (10%, 10 ml), and dried (Na2SO4). The resulting material was purified on silica gel (AcOEt/hexane:
35 :65) to yield, after recrystallization (MeOH/H2O), the expected product (480 mg, 1.55 mmol, 57%). M.p.
62 638. UV/VIS (EtOH): lmax 273.0 (3730). IR (KBr): 3291 (NÀH), 1655 (CO), 723 (NÀH), 1134 (CÀO).
1H-NMR (CDCl3): 0.89 (t, J 7.5, Me); 1.26 (m, 4 CH2); 1.73 (m, CH2); 2.34 (t, J 7.50, COCH2); 3.81 (s, p-
MeO); 3.85 (s, 2 m-MeO); 6.84 (s, 2 Ho); 7.05 (s, NH). 13C-NMR (CDCl3): 14.73 (Me); 23.30 32.37 (CH2);
38.58 (CH2); 56.85 (m-MeO); 61.65 (p-MeO); 98.19 (o-CH); 134.77, 154.07 (m-MeO); 172.50 (CO). Anal. calc.:
C 65.99, H 8.80, N 4.53, found: C 66.27, H 9.3, N 4.09.
Cleavage of MeO groups was performed as described for 1a. The trimethoxy derivative (1.65 g, 5.34 mmol,
1 equiv.) and 1m BBr3 (32 ml, 32.00 mmol, 6 equiv.) lead to 3b (1.00 g, 3.75 mmol, 70%). M.p. 1358 (dec.). UV/
1
VIS (EtOH): lmax 275.4 (3950). IR (KBr): 3330 (OÀH), 1655 (CO), 723 (NÀH). H-NMR ((D6)DMSO):
0.87 (t, J 6.6, Me); 1.27 (m, 4 CH2); 1.56 (m, CH2); 2.22 (t, J 7.3, CH2); 6.63 (s, 2 Ho); 9.38 (s, NH). 13C-NMR
((D6)DMSO): 13.94 (Me); 22.10 36.46 (6 CH2); 99.10 (o-CH); 128.87, 130.94, 145.80 (m-COH); 170.49 (CO).
3,4,5-Tribenzyloxybenzoic Acid. Gallic acid (1 g, 5.88 mmol, 1 equiv.) was solubilized in dry acetone
(60 ml). K2CO3 (3.6 g, 25.88 mmol, 4.4 equiv.) and PhCH2Br (3.1 ml, 4.4 g, 25.88 mmol, 4.4 equiv.) were added
to the soln. The mixture was heated under stirring for 12 h. After adding H2O (200 ml), the mixture was
extracted 3 Â with AcOEt. The solvent was removed in vacuo, and the residual oil was recrystallized (EtOH) to
yield the perbenzylated derivative (2.48 g, 4.69 mmol, 80%). M.p. 93.5 94.58. UV/VIS (MeOH): lmax 275.8
(10694). IR (KBr): 1711 (CO), 1219 (CÀO, ester), 1130 (CÀO, ethers). 1H-NMR (CDCl3): 5.12 (s, 3 CH2);
5.32 (s, COOCH2); 7.40 (m, 22 arom. H). 13C-NMR (CDCl3): 67.43 (COOCH2); 71.99 (m-CH2O); 75.82 (p-
CH2O); 110.05 (o-CH); 125.84 153.23 (arom. C); 166.41 (CO).
The above benzyl ester (1 g, 1.89 mmol) was refluxed for 12 h in 3n KOH in MeOH (50 ml). The basic soln.
was then acidified at r.t. with 3n HCl (pH 3 4). The resulting precipitate was filtered, dissolved in AcOEt
(40 ml), washed 3 Â with H2O (30 ml), and dried (Na2SO4). After recrystallization (MeOH), the product was
isolated (357 mg, 0.81 mmol, 95%). M.p. 193.5 193.78. UV/VIS (MeOH): lmax 272.6 (16038). IR (KBr): 1686
(CO), 1431 (CÀO, acid), 1128 (CO, ethers). 1H-NMR (CDCl3): 5.07 (s, p-CH2O); 5.08 (s, 2 m-CH2O); 7.30
(m, 17 arom. H). 13C-NMR (CDCl3): 71.99 (m-CH2O); 75.86 (p-CH2O); 110.43 (o-CH); 124.75 (CCOOH);
128.25 129.25 (arom. C); 137.26 (m-CCH2); 138.08 (p-CCH2); 143.94 (p-COCH2); 153.31 (m-COCH2); 171.15
(COOH).
3,4,5-Trihydroxy-N-[tris(hydroxymethyl)methyl]benzamide (4a). To a soln. of 3,4,5-tribenzyloxybenzoic
acid (1.00 g, 2.27 mmol, 1 equiv.) and EEDQ (620 mg, 2.50 mmol, 1.1 equiv.) in freshly distilled MeOH (40 ml),
[tris(hydroxymethyl)amino]methane (300 mg, 2.50 mmol, 1.1 equiv.) was added. The mixture was heated under
stirring for 12 h. Purification on silica gel (AcOEt) followed by recrystallization (AcOEt/hexane) gave the
expected product (500 mg, 0.92 mmol, 95%). M.p. 129.2 129.58. UV/VIS (MeOH): lmax 273.4 (17757). IR
(KBr): 3325 (OÀH), 1637 (CO), 1122 (CÀO, ether). 1H-NMR (CDCl3): 3.71 (s, CH2OH); 4.61 (s, 3 OH
(arom.)); 5.10 (s, p-CH2O); 5.13 (s, 2 m-CH2O); 7.20 (m, 17 H, o-CH, arom. H). 13C-NMR (CDCl3): 62.44 (quat.
C); 63.24 (CH2OH); 72.17 (m-CH2O); 75.88 (p-CH2O); 107.75 (p-CH); 128.27 129.76 (CCONH, arom. C);