ؒ
The ketones were subsequently converted to the required
alcohols in a mixed aldol condensation reaction. Potassium
carbonate (0.1 g) was dissolved in 50 mL of absolute ethanol
and the solution was left to cool to 0 ЊC in an ice bath. The
dibenzylketone (R = H, 4-CH3) or phenylacetone (R = 4-OCH3,
4-Cl, 4-F) derivative was subsequently added (4.5 mmol) and
the mixture was left to stir for a further 30 minutes. Formalde-
hyde (40% aqueous solution; 3 molar equivalents per CH2OH
group added) diluted with 5 mL ethanol was added dropwise
with continuous stirring. After 1 to 4 hours, the reaction was
quenched by adding cold brine (20 mL) and then extracted
three times with diethyl ether (30 mL). The combined organic
layers were dried with magnesium sulfate and the solvent
removed under reduced pressure. The crude product mixtures
were purified by flash column chromatography using ethyl
acetate–hexane mixtures, or by cold recrystallization from ethyl
acetate–hexane mixtures.
(0.10); EIMS m/z (%) 270.1 (M ϩ, 0.20), 240 (10), 121 (52), 105
(5), 104 (100), 103 (27), 91 (10); HRMS: found 270.1264
0.0008) u, calculated 270.1256 u for C17H18O3.
To prepare the mesylate derivatives, the alcohols (2.5 mmol)
(
were dissolved in a mixture of pyridine (25 mmol) and CH2Cl2
(3.5 mL). When cooled to 0 ЊC, methanesulfonyl chloride
(10 mmol) diluted in CH2Cl2 (2 mL) was added dropwise to
the reaction mixture with continuous stirring. Progress was
monitored by NMR spectroscopy and reaction times ranged
between 2.5–6.5 hours. The reaction was quenched with the
addition of ice water and the mesylate product extracted using
CH2Cl2. The organic layer was washed twice with 5% aqueous
H2SO4, twice with saturated aqueous NaHCO3, and twice with
ice water. The organic fractions were combined and dried with
MgSO4, filtered and the solvent evaporated under reduced
pressure. The crude product was purified using flash column
chromatography on silica gel and eluted with ethyl acetate–hex-
ane solvent mixtures. Alternatively, repetitive cold recrystalliz-
ations in ethyl acetate–hexane mixtures were carried out to
purify the crystalline mesylate products. Dimesylates were syn-
thesized similarly using the corresponding diols in a 1 : 8 : 20
molar ratio of diol–methanesulfonyl chloride–pyridine. All
compounds were stored in the dark at 0 ЊC.
All materials were characterized by 1H- and 13C-NMR
(Bruker 250 MHz) using CDCl3 as the solvent.
3-(4-Fluorophenyl)-4-hydroxy-2-butanone
Pale yellow oil, enantiomeric mixture; 1H NMR δ 2.07 (1H, s),
2.66 (1H, broad peak), 3.62–3.71 (1H, m), 3.84–3.96 (1H, m),
4.03–4.13 (1H, m), 7.01–7.19 (4H, AAЈBBЈ pattern); 13C NMR
δ 29.61, 60.68, 63.94, 116.01, 116.36, 130.14, 130.28, 131.41,
131.47, 162.46 (d, J = 248.0 Hz), 209.00; UV (CH3CN)
2-(4-Chlorophenyl)-3-oxobutyl methanesulfonate (2a)
C11H13O4SCl; clear oil; 1H NMR δ 2.14 (3H, s, CH3), 2.98 (3H,
s, SCH3), 4.10–4.76 (3H, m, CH and CH2), 7.15–7.38 (4H, m);
13C NMR δ 29.48 (CH3), 37.24 (SCH3), 57.25 (CH), 69.17
(CH2), 129.77, 129.86, 132.02, 134.82, 204.55 (CO); UV
(CH3CN) λmax (nm) 267.0.
λmax (nm) 264 (1.80), 270 (1.61); EIMS m/z (%) 182 (M ϩ, 0.6),
ؒ
139 (3), 123 (6), 122 (100), 121 (4), 109 (7), 42 (20); HRMS:
found 182.0742 ( 0.0008) u, calculated 182.0743
C10H11FO2.
u
for
3-(4-Methoxyphenyl)-4-hydroxy-2-butanone
2,4-Diphenyl-3-oxopentyl 1,5-dimethanesulfonate (2b)
1
Fine white powder, enantiomeric mixture; mp 50–51 ЊC; H
NMR δ 2.08 (3H, s), 2.32 (1H, dd, J = 5.50, 7.93 Hz), 3.62–3.72
(1H, m), 3.79 (3H, s), 3.80–3.86 (1H, m), 4.05–4.15 (1H, m),
6.86–7.13 (4H, AAЈBBЈ system); 13C NMR δ 29.53, 55.42,
60.83, 64.18, 114.75, 127.62, 129.74, 159.40, 209.67; UV
(CH3CN) λmax (nm) 277 (1.53), shoulder at 283 (1.33); EIMS
C19H22O7S2; fine white crystals; mp 114–116 ЊC; 1H NMR
δ 2.99 (6H, s), 4.23–4.33 (4H, m), 4.73–4.82 (2H, m),
6.88–7.14 (10H, m); 13C NMR δ 37.42 (CH3), 57.91 (CH),
69.58, 128.42, 128.65, 128.98, 132.40, 205.13 (CO); UV
(CH3CN) λmax (nm) 253.0 (0.38), 293.0 (0.19); EIMS m/z (%)
Mϩ not observed, 234 (100), 205 (43), 128 (31), 104 (54),
103 (31), 91 (45).
m/z (%) 194 (M ϩ, 16), 151 (86), 134 (79), 133 (72), 121 (100),
ؒ
119 (36), 91 (91), 77 (45); HRMS: found 194.0945 ( 0.0008) u,
calculated 194.0943 u for C11H14O3.
2-(4-Fluorophenyl)-3-oxobutyl methanesulfonate (2c)
1
C11H13FO4S; clear yellow oil; H NMR δ 2.14 (3H, s, CH3),
3-(4-Chlorophenyl)-4-hydroxy-2-butanone
2.98 (3H, s, CH3), 4.12–4.31 (2H, m), 4.70–4.78 (1H, dd,
J = 8.54, 9.76 Hz), 7.03–7.33 (4H, m); 13C NMR δ 29.27
(CH3), 36.99 (SCH3), 56.86 (CH), 69.33 (CH2), 116.23,
116.57, 129.36, 129.41, 130.14, 130.27, 160.71, 164.65,
204.81 (CO); UV (CH3CN) λmax (nm) 263 (0.538), 269
(0.471); EIMS m/z (%) 165.1 (1.24), 123.0 (19.07), 122.0
(100.00), 121.0 (17.14), 109.1 (10.57), 101.1 (9.09), 42.0
(49.93); HRMS: found 165.0709 ( 0.0008) u, calculated
165.0716 u for C10H10OF.
1
Pale yellow oil; H NMR δ 2.07 (3H, s), 3.62–3.71 (1H, m),
3.80–3.85 (1H, m), 4.02–4.16 (1H, m), 7.04–7.36 (4H, AAЈBBЈ
system); 13C NMR δ 29.72, 58.6, 63.8, 129.7, 130.2, 133.4,
134.3, 209.8; UV (CH3CN) λmax (nm) 267 (0.45), shoulder at
275 (0.37), 296 (0.28); EIMS m/z (%) 198 (M ϩ, 0.6), 155 (43),
ؒ
140 (18), 138 (100), 125 (17), 35 (16); HRMS: found 198.0482
(
0.0008) u, calculated 198.0476 u for C10H11O2Cl.
2,4-Bis(4-methylphenyl)-1,5-dihydroxy-3-pentanone
2,4-Bis(4-methylphenyl)-3-oxopentyl 1,5-dimethanesulfonate
(2d)
Fine colorless needles, diastereomeric mixture; mp 92–93 ЊC; 1H
NMR δ 1.99 (1H, dd, J = 6.10, 7.63 Hz), 2.11 (1H, dd, J1 = 6.1
Hz, J2 = not resolved), 2.28 and 2.35 (6H, s), 3.59–4.20 (6H, m),
6.82–7.19 (8H, two sets of AAЈBBЈ patterns); 13C NMR δ 21.10,
58.56, 60.99, 63.86, 64.97, 128.72, 129.33, 130.11, 131.89,
137.29, 211.11, 211.78; UV (CH3CN) λmax (nm) 264 (0.76), 272
C21H26O7S2; white powder; mp 91–92 ЊC; 1H NMR δ 2.25
and 2.36 (6H, two singlets with ratio 16 : 84, Ar–CH3), 2.82
and 2.99 (6H, two singlets, 16 : 84, SCH3), 4.00–4.80 (6H, m),
6.76–6.95 and 7.03–7.22 (8H, AAЈBBЈ, two sets of aromatics
with ratio 16 : 84); 13C NMR δ 21.28 (CH3), 37.24 (SCH3),
55.09 (CH), 68.81 (CH2), 128.74, 129.44, 129.66, 130.53,
139.11, 203.15 (CO); UV (CH3CN) λmax (nm) 263.9 (0.307),
292.7 (0.188).
(0.66), 292 (0.40); EIMS m/z (%) 298 (M ϩ, 52), 268 (100), 135
ؒ
(39), 118 (62), 117 (17); HRMS: found 298.1561 ( 0.0008) u,
calculated 298.1569 u for C19H22O3.
2,4-Diphenyl-1,5-dihydroxy-3-pentanone
2-(4-Methoxyphenyl)-3-oxobutyl methanesulfonate (2e)
Colorless needles, diastereomeric mixture; mp 85–86 ЊC; 1H
NMR δ 3.66–3.75 (4H, m), 4.09–4.31 (4H, m), 6.91–7.13 (10H,
m); 13C NMR δ 61.70, 64.73, 127.48, 128.57, 128.76, 129.33,
129.60, 134.94, 211.28; UV (CH3CN) λmax (nm) 259 (0.13), 297
C12H16O5S; clear oil; 1H NMR δ 2.12 (3H, s, CH3), 2.97 (3H, s,
SCH3), 3.80 (3H, s, OCH3), 4.06–4.76 (3H, m, CH and CH2),
6.88–7.15 (4H, AAЈBBЈ); 13C NMR δ 29.25 (CH3), 37.07
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 1 9 7 2 – 1 9 7 9
1978