7
620 Lu et al.
Asian J. Chem.
J = 7.83, 1H, ArH), 7.01-7.17 (m, 5H, ArH), 6.39 (d, 1H, J =
5.96 Hz, CHCO
E)-Methyl 3-(3-phenoxyphenyl)-2-propenoate (4): A
solution of (E) -3-(3- phenoxyl phenyl) acrylic acid (3) (29 g,
.12 mol), p-toluene sulfonic acid (7 g, 40 mmol), in absolute
methanol (300 mL, 0.50 mol) was refluxed with stirring for
8 h. The methanol was removed in vacuo and the residue
phenyl) propan-1-ol (5) (7.6 g, 33.3 mmol) and dichloro-
methane (50 mL). The reaction mixtures were stirred at room
temperature for 4 h, after reaction, added saturated brine water,
extracted with dichloromethane (100 mL × 3). The combined
1
2
)
(
0
4
organic extracts were dried (anhyd. MgSO ) and concentrated
under reduced pressure. The resulting residue was purified by
flash chromatography (95:5 petroleum ether: ethyl acetate) to
afford 1-(3-iodopropyl)-3-phenoxy benzene (6) (10.5 g,
1
taken up in ethyl acetate (250 mL) and washed with a saturated
aqueous sodium bicarbonate solution (120 mL × 2). The
washes were back-extracted with ethyl acetate (250 mL × 2)
and the combined extracts washed with brine, dried over
anhydrous sodium sulfate and filtered. The filtrate was
evaporated in vacuo to give (30.4 g, 93.6 % in yield) (E)-
methyl 3-(3-phenoxyphenyl)-2-propenoate (4) as a yellow oil,
1
93.2 % in yield) as a colourless oil. H NMR: (300 Hz, CDCl
3
),
δ (ppm), 7.22-7.27 (m, 3H, ArH), 7.12 (t, 1H, ArH), 6.95-
7.01 (m, 3H, ArH), 6.83 (d, 2H, J = 1.62Hz, ArH), 3.17 (t, J =
6.82 Hz, CH
1
2
), 2.70 (t, 2H, J = 7.32 Hz, CH ), 2.06-2.15 (m,
2
2 3
2H, CH ); C NMR: (100 Hz, CDCl ), δ (ppm), 142.49, 129.93,
129.57, 123.38, 118.76, 36.10, 34.65, 6.14.
1
which was used without further purification. H NMR: (300
Hz, CDCl
3
), δ(ppm), 7.64 (d, J = 15.2 Hz, 1H, ArCH), 7.01-
.38 (m, 9H, Ar), 6.37 (d, 1H, J = 15.2 Hz, CHCO ), 3.87 (s,
H, CH ).
-(3-phenoxyphenyl) propan-1-ol (6): A stirring solution
RESULTS AND DISCUSSION
7
3
2
Recently studies the phosphonosulfonates and a key inter-
mediate 3-(3-phenoxyphenyl) propan-1-ol (4) showed that the
reduction of (E)-methyl 3-(3-phenoxyphenyl)-2- propenoate
(3) using sodium borohydride in the present of PEG-400
affords 3-(3-phenoxy phenyl)propan-1-ol (4) in good yields.
The optimization of the synthetic conditions for 1-(3-iodo-
propyl)-3-phenoxy benzene (2) and 1-(3-iodopropyl)-3-
phenoxy benzene (5) were examined.
3
3
of methyl 3-(3-phenoxyphenyl) propanoate (4) (13.4 g, 50
mmol) in polyethylene glycol (PEG-400) (250 mL) was added
in small batch sodium borohydride (6 g, 160, mmol) at room
temperature. The reaction mixture was allowed to stir at 65 °C
for another 10 h and then added dropwise 10 % hydrochloric
acid (300 mL) to no bubbles, extracted with ethyl acetate (200
mL × 3) and washed with saturated sodium chloride solution.
The combined extracts were dried over anhydrous sodium
sulphate and concentrated by evaporation of the solvent under
The condensation of substituted benzaldehyde and
malonic acids in the presence of pyridine and piperidine gave
the expected cinnamic acids in good yields according to the
literature. The yield of condensation of 3-phenoxybenzal-
dehyde and malonic acid was 82.5 %. It was found that the p-
toluene sulfonic acid was a good esterification catalytic to yield
(E)-methyl 3-(3-phenoxyphenyl)-2-propenoate (3). The yield
of esterification was 93.6 %.
reduced pressure to yield 3-(3-phenoxyphenyl) propan-1-ol
(
1
5) (8.6 g, 77.2 % in yield) as a colourless oil. H NMR: (300
Hz, CDCl
3
), δ(ppm), 7.09-7.35 (m, 4H, ArH), 7.09-7.12 (m,
H, ArH), 7.06 (d, 2H, ArH), 6.86 (d, 1H, J = 1.5Hz, ArH),
.83 (m, 2H, ArH), 3.66 (t, J = 6.42 Hz, CH ), 2.67 (t, 2H, J =
.74 Hz, CH ), 1.84-1.89 (m, 2H, CH ), 1.47 (s, 1H, OH), C
), δ(ppm), 156.28, 142.91, 128.69,
28.60, 122.35, 122.12, 117.89, 117.81, 115.32, 61.19, 33.02,
0.93.
-(3-Iodopropyl)-3-phenoxybenzene (6): Mixtures of
1
6
7
2
13
Lithium aluminium hydride is an excellent reagent for
the reduction and hydrolysis of certain polar groups, but it
was a highly flammable solid and may ignite in moist or heated
air. It is a dangerous reagent in the process for reduction. In
the paper, the relative safety of reductive reagent, sodium
borohydride, was be used. The yield of reduction was 77.2 %.
Iodination of 3-(3-phenoxy phenyl) propan-1-ol using
iodine in the present of KI, KI can improve the yield of iodi-
nation under the imidazole as catalyst, the yield of iodination
is 93.2 % (Scheme-I).
2
2
NMR: (100 Hz, CDCl
3
1
3
1
phenyl phosphine (13.1 g, 50 mmol), iodine (12.8 g, 50 mmol),
potassium iodide (0.8 g, 5 mmol) and dichloromethane (250
mL) were stirred at room temperature under nitrogen
atmosphere for 20 min. To the reaction solution was added
imidazole (6.82 g, 100 mmol) and continued to stirring for
another 20 min and then added the solution of 3-(3-phenoxy-
O
O
O
CHO
a.
b
O
O
OH
O
(93.6%)
(82.5%)
2
4
3
c
O
O
d
OH
I
(77.2%)
(
93.2%)
5
1
Scheme-I: Reagents (a) malonic acid, pyridine, piperidine (b) methanol, p-toluene sulfonic acid (c) NaBH , PED-400 (d) l
4
2
3
, KI, P(Ph) , imidazole