Synthesis of 5-Substituted Resorcinol Derivatives Via Cross-Coupling Reactions
15, s). Ϫ C11H18O2Sn (301): calcd. C 43.90, H 6.13; found C 44.05, the solvent was evaporated. The residue was crystallized from ben-
FULL PAPER
H 6.01.
zene/hexane yielding 7.7 g (80%) of a yellow solid, m.p. 112Ϫ114°C
(ref.[12] 117°C). Ϫ IR (KBr): ν˜ ϭ 3626 (w, OH) cmϪ1, 3272 (br,
OH),1605, 1491, 1473, 1300, 1196, 1153, 1094. Ϫ 1H NMR ([D6]a-
3,5-Dimethoxyphenyl Boronic Acid (11): A mixture of 2 g of Mg
and 5 g (29.5 mmol) of 4 in 10 ml of THF was refluxed for 24 h.
The brown slurry was cooled to room temp., diluted with 20 ml of
THF, filtered and added to a cooled (Ϫ78°C) solution of 5 ml of
B(OMe)3 (44.3 mmol) in 40 ml of THF. The grey suspension was
allowed to warm to room temp. overnight. The reaction mixture
was poured onto 20 ml of 1 of HCl and 50 ml of diethyl ether.
After separation the water layer was washed with 30 ml of diethyl
ether and the collected organic layers were washed twice with 25
ml of 1 of NaOH. After washing twice with 10 ml of CH2Cl2,
the water layer was acidified with conc. HCl and extracted twice
with 25 ml of CH2Cl2. The organic fraction was dried with MgSO4
and evaporated to dryness. Yield 2.4 g (45%) of a white solid , m.p.
200.7Ϫ201.7°C. Ϫ IR (KBr): ν˜ ϭ 3284 (m, OH) cmϪ1, 3010Ϫ2840
(w), 1589, 1448, 1422, 1364, 1336, 1202, 1158, 1060, 1041. Ϫ 1H
NMR ([D6]acetone): δ ϭ 7.28 (s, OϪH), 7.15 (d, 2 H, 4J ϭ 2.3
Hz), 6.64 (t, 1 H, 4J ϭ 2.3 Hz), 3.88 (s, 6 H, OϪCH3). Ϫ 13C NMR
([D6]DMSO): δ ϭ 161.1 and 161.0 (CϪO), 142.6 and 137.4 (CϪB),
112.6 and 111.9, 103.4 and 102.5, 56.0 (OϪCH3). Ϫ C8H11BO4
(182.0): C 52.80, H 6.09; found C 53.15, H 6.13.
4
cetone): δ ϭ 8.74 (s, 2 H, HϪO), 6.48 (d, 2 H, J ϭ 2.1 Hz), 6.41
(t, 1 H, 4J ϭ 2.1 Hz). Ϫ 13C NMR ([D6]acetone): δ ϭ 164.2 (CϪO),
139.4 (CϪCl), 112.1, 106.4. Ϫ MS; m/z: 144, 146 [Mϩ].
5-Iodoresorcinol (5a): A solution of 2.5 g of 5 (9.5 mmol) and 12
ml (57 w%) of HI (90 mmol) was refluxed for 3 h. The dark brown
solution was cooled to room temp. and diluted with 20 ml water,
followed by addition of 20 ml of diethyl ether. The organic layer
was separated and washed twice with 10 ml of 1 of sodium thio-
sulfate and once with 10 ml of demineralized water. After drying
with MgSO4 the solvent was evaporated yielding 2 g of a white
solid (89%), m.p. 84.6Ϫ85°C (ref.[12] 92.3°C). Ϫ IR (KBr): ν ϭ
˜
3589 (m, OH) cmϪ1, 3239 (br, OH), 1610, 1586, 1480, 1473, 1344,
1
1165. Ϫ H NMR ([D6]acetone): δ ϭ 8.62 (s, 2 H, HϪO), 6.83 (d,
2 H, 4J ϭ 2.2 Hz), 6.44 (t, 1 H, 4J ϭ 2.2 Hz). Ϫ 13C NMR ([D6]ace-
tone): δ ϭ 160.1 (CϪO), 117.6, 103.9, 95.2 (CϪI). Ϫ MS; m/z: 236
[Mϩ]. Ϫ C6H5IO2·0.5 H2O (236.0): calcd. C 29.41, H 2.47; found:
C 29.25, H 2.74.
5-Phenylresorcinol (8a): The same procedure as for 5a was used,
with 0.86 g (4 mmol) of 8 and 5 ml of HI (40 mmol). After workup
the yellow oil was purified by column chromatography using silica
gel (eluent 40%, EtOAc/PE). Yield 0.54 g (73%) of a white solid,
5-Allyl-1,3-dimethoxybenzene (7)[27]: A mixture of 17 g of 6 (56
mmol), 7 ml of allyl chloride (90 mmol) and 25 mg of Pd(Ph-
BIAN)(DMFU) (0.043 mmol) in 120 ml of dry DMF was heated
overnight at 50°C. The solution was cooled to room temp. and
poured onto a mixture of 150 ml of H2O and 100 ml of hexane.
The water layer was washed twice with 50 ml of hexane and the
collected hexane layers were washed three times with 50 ml of H2O.
The organic layer was dried with MgSO4, evaporated and distilled.
Yield 8 g (99%) of a colorless oil b.p. 68°C/0.25 Torr. Ϫ IR (neat):
ν˜ ϭ 3079Ϫ2837 (w) cmϪ1, 1608, 1589, 1462, 1430, 1346, 1323,
m.p. 157°C (ref.[7] 157°C). Ϫ IR (KBr): ν ϭ 3308 (br, OH) cmϪ1
,
˜
1624, 1603, 1339, 1201, 1158, 1148, 1000. Ϫ 1H NMR: δ ϭ 8.35
3
3
(s, 2 H, HϪO), 7.56 (d, 2 H, J ϭ 7.2 Hz), 7.41 (t, 2 H, J ϭ 7.05
3
Hz), 7.31 (t, 1 H, J ϭ 7.2 Hz), 6.65 (br, 2 H), 6.40 (br, 1 H). Ϫ
13C NMR: δ ϭ 159.9 (CϪO), 144.1 (CϪC), 142.1 (CϪC), 129.6,
128.2, 127.6, 106.5, 102.6. Ϫ MS; m/z: 286 [Mϩ]. Ϫ C12H10O2
(186.2): calcd. C 77.40 , H 5.41; found C 77.34, H 5.44.
1
4
1295, 1207. Ϫ H NMR: δ ϭ 6.37 (d, 2 H, J ϭ 2.1 Hz), 6.33 (d,
5-(4Ј-Methylphenyl)resorcinol (9a): The same procedure as for
5a was used, with 0.91 g (4 mmol) of 9 and 5 ml of HI (40 mmol).
After workup the yellow oil was purified by column chromatogra-
phy using silica gel (eluent 40%, EtOAc/PE). Yield 0.58 g (72%) of
a white solid, m.p. 163.2Ϫ164°C. Ϫ IR (KBr): ν˜ ϭ 3360 (br, OH)
1 H, 4J ϭ 2.1 Hz), 5.95 (m, 1 H, HϪOl), 5.1 (m, 2 H, HϪOl), 3.79
(s, 6 H, OϪCH3), 3.34 (d, 2 H, CH2, J ϭ 6.7 Hz). Ϫ 13C NMR:
3
δ ϭ 161.1 (CϪO), 142.7 (CϪC), 137.3, 116.2 (OlCH2), 106.9, 98.4,
55.6 (OϪCH3), 40.7 (CH2). Ϫ MS; m/z: 178 [Mϩ].
1
cmϪ1, 1631, 1611, 1482, 1259, 1162, 1010, 1002. Ϫ H NMR: δ ϭ
5-Bromoresorcinol (3a): A solution of 2 g of 3 (9.2 mmol) dis-
solved in 25 ml of dry CH2Cl2 was cooled to Ϫ78°C. Hereafter 19
mmol of BBr3 (19 ml of a 1 solution in CH2Cl2) was added and
the reaction mixture was allowed to warm to room temp. overnight.
The brown solution was cooled on ice and 50 ml of water was
slowly added. The two layers were separated and the water layer
was washed twice with 40 ml of CH2Cl2. The collected organic
layers were washed once with 30 ml of 1 solution of sodium
thiosulfate and once with 50 ml of water, dried with MgSO4 and
evaporated to dryness. After purification via column chromatogra-
phy using silica gel (eluent 40%, EtOAc/PE) the residue was crys-
tallized from CHCl3 yielding 1.4 g (78%) of a grey-brown light
sensitive solid[12], m.p. 85Ϫ86.4°C (ref.[12] 87°C). Ϫ IR (KBr): ν˜ ϭ
3620 (m, OH) cmϪ1, 3268 (br, OH), 1599, 1473, 1297, 1197, 1154.
8.28 (s, 2 H, HϪO), 7.44 (d, 2 H, 3J ϭ 6.82 Hz), 7.21 (d, 2 H, 3J ϭ
6.82 Hz), 6.61 (br, 2 H), 6.35 (br, 1 H), 2.33 (s, 1 H, CH3). Ϫ 13C
NMR: δ ϭ 159.8 (CϪO), 144.1 (CϪC), 139.3 (CϪC), 137.8
(CϪC), 130.3, 127.5, 106.3, 102.4, 21.1 (CH3). Ϫ MS; m/z: 214
[Mϩ]. Ϫ C13H12O2 (202.1): calcd. C 77.98, H 6.04; found C 77.74,
H 6.12.
5-(4Ј-Chlorophenyl)resorcinol (10a): The same procedure as for
5a was used, with 1.0 g (4 mmol) of 10 and 5 ml of HI (40 mmol).
After workup the yellow oil was purified by column chromatogra-
phy using silica gel (eluent 40%, EtOAc/PE). Yield 0.7 g (79%) of
a white solid, m.p. 151.9Ϫ152.3°C. Ϫ IR (KBr): ν˜ ϭ 3265 (br, OH)
1
cmϪ1, 1625, 1605, 1481, 1473, 1165, 1153, 1004. Ϫ H NMR: δ ϭ
8.38 (s, 2 H, HϪO), 7.57 (d, 2 H, 3J ϭ 6.42 Hz), 7.41 (d, 2 H, 3J ϭ
6.42 Hz), 6.59 (br, 2 H), 6.39 (br, 1 H). Ϫ 13C NMR: δ ϭ 160.0
(CϪO), 142.8 (CϪC), 140.9 (CϪC), 133.7 (CϪCl), 129.7, 129.3,
106.4, 103.0. Ϫ MS; m/z: 224, 222 [Mϩ]. Ϫ C12H9ClO2 · 0.5 H2O
(220.7): calcd. C 62.76, H 4.39; found C 62.78, H 4.49.
1
Ϫ H NMR ([D6]acetone): δ ϭ 8.63 (s, 2 H, HϪO), 6.53 (d, 2 H,
4J ϭ 2.1 Hz), 6.33 (t, 1 H, 4J ϭ 2.1 Hz). Ϫ 13C NMR ([D6]acetone):
δ ϭ 160.2 (CϪO), 123.1 (CϪBr), 111.0, 102.7. Ϫ MS; m/z: 188,
190 [Mϩ]. Ϫ C6H5BrO2 (189): calcd. C 38.13, H 2.67; found C
37.76, H 3.32.
5-Allylresorcinol (7a): A mixture of 5.6 g of aluminium (210
5-Chlororesorcinol (4a): A solution of 11 g of 4 (66.7 mmol) and mmol) and 42 g of iodine (168 mmol) in 400 ml of carbon disul-
80 ml (57 w%) of HI (623 mmol) was refluxed for 90 min. The
solution was cooled to room temp. and diluted with 100 ml water
phide was heated at reflux for 2 h. The brown reaction mixture was
cooled on an ice bath and 10 g of 7 (56 mmol) in 20 ml of carbon
and 100 ml of diethyl ether was added. The organic layer was sepa- disulphide was slowly added. The reaction mixture was refluxed
rated and subsequently washed twice with 10 ml of 1 of sodium
thiosulfate and once with 50 ml of brine. After drying with MgSO4
overnight and then cooled on an ice bath, 100 ml of ice water was
added and the mixture was stirred for 30 min. After addition of
Eur. J. Org. Chem. 1998, 359Ϫ364
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