This has a very mild method for cleaving di phenolic ethers(end of article) and a prep for 2,4,6-(MeO)3C6H2Br.
An unusual cleavage of diaryl ethers.
Mayer, Walter; Fikentscher, Rolf; Schmidt, Johannes; Schmidt, Otto Th.
Chem. Ber. (1960), 93 2761-76.
CAN 55:27689 AN 1961:27689
Abstract
Dehydrodigallic acid (I) and valoneaic acid dilactone were cleaved non-hydrolytically by alkali on the diphenyl ether bridge. This cleavage of diphenyl ethers was apparently dependent on the presence of 3 vicinal, free OH groups on one of the 2 phenyl radicals. The cleavage was an intramol. disproportionation and its mechanism regarded as a bor vinylogous b-elimination. 2,3-HO(MeO)C6H3CO2H (II) (3.5 g.) in 60 cc. Et2O treated with CH2N2-Et2O and refrigerated 2 hrs. yielded 3.4 g. Me ester (III) of II, m. 67° (2:1 MeOH-H2O) (all m.ps. are cor.). III (3.4 g.) dissolved with 1.31 g. MeOK in abs. MeOH and evapd., a 3.7-g. portion of the residue in 60 cc. abs. MeOH stirred 20 hrs. at 65° with 7 g. [Ph2I]Br, concd., and worked up with H2O and Et2O yielded 1.8 g. 3,2-MeO(PhO)C6H3CO2Me (IV), rodlets, m. 114-16° (3:2 MeOH-H2O). IV (1.5 g.) in 20 cc. C6H6 treated with stirring with 2 g. AlBr3 in 8 cc. C6H6, refluxed 4 hrs., and treated dropwise with cooling with 25 cc. 2N HCl, and the product isolated with Et2O gave 0.46 g. 3-OH analog (V) of IV, prisms, m. 74-6° (3:1 (MeOH-H2O). V (0.23 g.) and 30 cc. 2N NaOH refluxed 6 hrs. under a stream of H, cooled, and acidified with 2N HCl gave 0.17 g. 3,2-HO(PhO)C6H3CO2H, m. 154° (cyclohexane). 3,4-(MeO)2C6H3Br (30 g.), 26 g. PhOK, and 4 g. Cu bronze heated slowly to 170-80°, kept 2 hrs. at this temp., cooled, and decompd. with dil. aq. KOH, and the product isolated with Et2O yielded 15.5 g. 3,4-(MeO)2C6H3OPh (VI), leaflets, m. 47° (petr. ether). VI (10 g.) in 50 cc. C6H6 refluxed 5 hrs. with 25 g. AlBr3 in 100 cc. C6H6 yielded 7.6 g. 3,4-(HO)2C6H3OPh, prisms, m. 104-6°, green with FeCl3 in MeOH. 3,4,5,2-(MeO)3(PhO)C6HCO2Me (9.5 g.) in 100 cc. C6H6 refluxed 4-5 hrs. with 25 g. AlBr3 in C6H6 and poured into 100 cc. concd. HCl and 200 g. ice gave 3,4,5,2-(HO)3(PhO)C6HCO2Me.H2O (VII.H2O), rodlets, m. 92-6° (H2O), which dried at 65°/1 mm. over P2O5 yielded 5.6 g. VII, m. 128-9°, deep blue with FeCl3.
VII (2 g.) in Et2O treated dropwise with CH2N2Et2O, refrigerated 2 hrs., concd., and chromatographed on Al2O3 and then on silicone-impregnated cellulose powder yielded 0.180 g. 3,5,4,2-(HO)2(MeO)(PhO)C6HCO2Me (VIII), m. 117° (H2O). VIII (0.107 g.) and 30 cc. 2N NaOH refluxed 6 hrs. under a stream of H, acidified, and extd. 24 hrs. with Et2O, and the ext. worked up gave 3,5,4,2(HO)2(MeO)(PhO)C6HCO2H (IX), prisms, m. 155-7° (H2O). The Rf values (given) in 10:2:4 BuOH-AcOH-2H2O and in 2% aq. AcOH, and the color (given) with diazotized sulfanilic acid were detd. for the following compds.: VIII, 0.90, 0.74, orange; IX, 0.86, 0.74, orange-yellow; 3,5,4(HO)2(MeO)C6H2CO2H, 0.76, 0.60, red-brown. 3,4,5,2-(MeO)3(PhO)C6HCO2H (7 g.) in 100 cc. C6H6 refluxed 4 hrs. with stirring with 25 g. AlBr3 in 100 cc. C6H6, cooled, treated dropwise with 10 cc. H2O and 4 cc. concd. HCl, and filtered, the residue dissolved in 250 cc. H2O and extd. continuously with Et2O, and the ext. worked up gave 4.25 g. 3,4,5,2(HO)3(PhO)C6HCO2H (X), prisms, m. 172-95° (decompn.), deep blue with FeCl3. X (2.85 g.) in 50 cc. Me2NH heated 1 hr. at 190-200° in a stream of H, cooled, treated with 500 cc. 2N H2SO4, and extd. 12 hrs. with Et2O gave 2.0 g. 2,3,4-(HO)3C6H2OPh (XI), yellowish prisms, m. 125-7° (H2O), which with CH2N2 gave 2,3,4-(MeO)3C6H2OPh, leaflets, m. 56-8°. Syringic acid Me ester (4.3 g.) and an equiv. amt. 4N KOMe evapd., the residue in MeOH treated with 7.2 g. [Ph2I]Br, refluxed 20 hrs. with stirring, concd., dild. with H2O, and extd. with Et2O, and the residue from the ext. refluxed 4 hrs. with 4N NaOH and acidified gave 2 g. 4,2,6-HO2C(MeO)2C6H2OPh (XII), rodlets, m. 207-9° (H2O). XII (1.3 g.) in 80 cc. C6H6 treated in the usual manner with 5 g. AlBr3 gave 0.7 g. 4,2,6-HO2C(HO)2C6H2OPh, m. 196-8°, orange-red with diazotized sulfanilic acid. 3,4,5-(MeO)3C6H2I (8 g.), an equiv. amt. PhOK, and 2 g. Cu bronze heated slowly to 150-60°, kept 2 hrs. at 150-60 and 2 hrs. at 180-90° and cooled yielded 1.9 g.
3,4,5(MeO)3C6H2OPh (XIII), prisms, m. 84-6°. XIII (2.6 g.) in 65 cc. C6H6 cleaved with 9 g. AlBr3 yielded 1.2 g. 3,4,5(HO)3C6H2OPh, leaflets, m. 135-7° (C6H6), gray-blue with FeCl3. 1,3,5-C6H3(OMe)3 (10 g.) in 120 cc. CHCl8 (8, thats what is says, but I assume its chloroform) treated dropwise with stirring with 3 cc. Br gave 10 g. 2,4,6-(MeO)3C6H2Br (XIV), m. 97-9° (1:1 EtOH-H2O). XIV (8 g.) and 4.4 g. PhOK heated with 2 g. Cu bronze 2 hrs. at 150-70°, 2 hrs. at 180-90°, and 2 hrs. at 200-10°, and worked up in the usual manner gave 0.6 g. 2,4,6-(MeO)3C6H2OPh (XV), m. 94-5° (aq. MeOH). XV (2.4 g.), 20 cc. AcOH, 10 cc. Ac2O, and 25 cc. 57% HI refluxed 3 hrs. in the presence of a small amt. of red P, cooled, and dild. with 40 cc. H2O, and the product isolated with Et2O, sublimed at 150-70°, and recrystd. from C6H6 yielded 1.13 g. 2,4,6-(HO)3C6H2OPh, rodlets, m. 175-7°, red-brown with diazotized sulfanilic acid. 1,2,3-C6H3(OH)3 (XVI) (5 g.), 12 g. Na2SO3, and 1.6 g. NaOH in 100 cc. H2O treated 5-6 hrs. with a stream of air, acidified with 6N HCl, extd. 48 hrs. with Et2O, treated with Ba(OAc)2, filtered, passed through Amberlite IR-120, treated with C, and evapd., and the residue dried 48 hrs. at 70°/0.2 mm. over P2O5 yielded 4 g. 4(5)-SO3H deriv. (XVII) of XVI, m. 158-60° (decompn. from 115°), Rf 0.86 (10% aq. AcOH), blue with FeCl3, and ruby-red with aq. KCN. XVII and 4N HCl heated 3 hrs. at 140° gave a resin and XVI, Rf 0.71 (10% AcOH). XVII (1 g.) with CH2N2-Et2O kept 2 hrs. in the refrigerator yielded 1 g. tetra-Me ester (XVIII) of XVII, prisms, m. 123-4° (MeOH). X (1.1-1.4 g.) added under H to 50 cc. 2N KOH, heated 6 hrs. at 100° under a stream of H, and acidified with 2N HCl gave 31% PhOH; 24-hr. heating gave 49.5% PhOH. X and 2% aq. Na2CO3 heated 6 hrs. at 100° gave 62% PhOH, 49% 3,4,5-(HO)3C6H2CO2H (XIX), and 22% unchanged X; 24-hr. heating yielded 77% PhOH and 47% XIX. X and NaOAc-AcOH buffer of pH 5.7 heated 6 hrs. at 100° resulted in the decarboxylation of X to XI; after 12 hrs., small amts. (5%) of PhOH and XIX were formed.
X (1.7 g.) in NaOAc-AcOH buffer heated 72 hrs. yielded in addn. to PhOH, XIX, and XI 0.022 g. unidentified solid which sublimed from 265° with darkening, but without melting. The Rf values were detd. for the following compds. in 2% AcOH and in 10:2:4 BuOH-AcOH-H2O: XIX, 0.40, 0.63; X, 0.65, 0.82. XI and 2% aq. Na2CO3 heated 6 hrs. at 100° gave 8.2% PhOH; XIII gave similarly 14% PhOH. XIII and 2N NaOH heated 6 and 20 hrs. at 100° gave 20% PhOH in both cases. I and 3.8% aq. Na2CO3 refluxed 4 hrs. gave 0.59 g. XIX; the mother liquor methylated with CH2N2 and sapond. with alkali gave 0.015 g. (MeO)3C6H2CO2H and 0.070 g. 1,2,3-C6H3(OMe)3. I (1.48 g.), 1.2 g. Na2CO3, and 2.0 g. Na2SO3 in 60 cc. H2O refluxed 4 hrs. under a stream of H, treated with 10 cc. 6N HCl, and extd. continuously with Et2O, and the ext. evapd. gave 0.69 g. XIX[/b]; the aq. phase treated with BaCl2, filtered, passed through Amberlite IR-120, and evapd. gave 0.4 g. XVII. X (0.080 g.), 0.6 g. Na2CO3, 1 g. Na2SO3, and 30 cc. H2O refluxed 6 hrs. gave XIX, m. 236-7°, and XVIII.
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