Note: Descriptions are shown in the official language in which they were submitted.
1075246
This invention relates to a process for the preparation of an
optionally substituted 3-phenoxybenzaldehyde, or an acetal thereof.
The known methods for the preparation of 3-phenoxybenzaldehyde,
see, for example, Monatshefte fur Chemie, Wien, 67 (1935), 598-609, are
complicated and usually give low yields of the aldehyde.
It has now been found that 3-phenoxybenzaldehyde and certain
derivatives thereof may be readily obtained in high yield from easily
accessible starting materials.
Accordingly the present invention provides a process for the
preparation of a 3-phenoxybenzaldehyde which is either unsubstituted or
substituted by methyl, methoxy or chlorine, or an acetal thereof, which
; comprises reacting a 3-bromobenzaldehyde which is either unsubstituted or
substituted by methyl, methoxy or chlorine, or an acetal thereof, with a
phenol, or an alkali metal salt thereof, in a lar ratio of from 0.5:1 to
; 2:1, in the presence of an aprotic organic solvent and copper or a copper
compound, at a temperature from 50C to 200C~
The alkali metal salt of the phenol is preferably the sodium or
potassium salt, with the sodium salt being particularly preferred because
it gives the higher selectivity to the 3-phenoxybenzaldehyde. The salt
is preferably anhydrous since the presence of water reduces the yield of
the 3-phenoxybenzaldehyde. The anhydrous salt may be prepared by the
reaction of the phenol with an alkali metal hydroxide followed by the
removal of the water formed as an azeotrope
1O7SZ436
with toluene or xylene. Alternatively the phenol may
be reacted with an alkali metal alkoxide and the alkanol
formed may be removed by distillation.
The aprotic organic solvent may be an aromatic
hydrocarbon such as toluene or the three xylene~;
an aromatic heterocyclic nitrogen compound such as
pyridine, 2,4,6-trimethylpyridine, quinoline or pyridine-N-oxide;
a dialkylamide such as dimethylformamide or dimethyl-
acetamide; a sulphoxide such as dimethylsulphoxide
or tetrahydrothiophene 1,1-dioxide. Mixtures of these
solvents may also be used.
The copper compound may be a copper(II) compound
such as cupric fluoride, cupric chloride, cupric oxide
or cupric p-chlorobenzoate, or a copper(I) compound
such as cuprous chloride, cuprous bromide, cuprous
odide or cuprous oxide.
The 3-bromobenzaldehyde and the phenol or salt
may be used in any molar ratio; preferably the molar
ratio of benzaldehyde:(phenol or salt) is from 0.5:1
; 20 to 2:1, particularly from 0.9:1 to 1.1:1. The molar
ratio of copper compound to the 3-bromobenzaldehyde
is preferably from 1:100 to 10:100. The reaction temperature
may be from, for example, 50 and 200C, preferably
from 100 to 150C, and the reaction time from one
to five hours.
Examples of substituents which may be present
in the 3-bromobenzaldehyde or the phenol or alkali
;
, . .
'1075Z9~6
metal salt thereof are methyl and methoxy ~roups
and chlorine atoms. The acetal is preferably derived
from a dihydric alcohol such as ethylene glycol.
3-Phenoxybenzaldehyde may be reacted with hydrogen
cyanide to afford alpha-cyano-3-phenoxybenzyl alcohol
or hydrogenated to afford 3-phenoxybenzyl alcohol,
two precursors of esters which are pyrethrin-type
insecticides.
The invention is further illustrated in the
following Examples.
EXAMPLE I
Dry potassium phenolate (0.02 mol) was prepared
from phenol (0.02 mol) and potassium hydroxide (0.02
mol) followed by removal of the water formed as an
azeotrope with toluene. The phenolate, 3-bromobenzaldehyde
(0.02 mol), cuprous chloride (0.0005 mol) and pyridine
(5 ml) were heated under reflux for two hours. The
mixture was taken up in 50 ml of diethyl ether and
the ethereal solution was washed with water (3x50 ml)
and dried over anhydrous sodium sulphate. GLC analysis
revealed that 97% of the 3-bromobenzaldehyde had been
converted, with a selectivity to 3-phenoxybenzaldehyde
of 85%. Evaporation of the ethereal solution and distillation
of the residue afforded pure 3-phenoxybenzaldehyde,
boiling at 125C at 0.8 mm Hg, in a yield of 74%.
The 3-phenoxybenzaldehyde could also be purified via
bi5~/phi~
' ~ t- h ~- h ~ ' ~ h ~ ^m--~l~x
~ -. ~ v~ v ~v ~ ~
;~''''1
~, ~
'~,
,;
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'~
1075246
Comparative ExPeriment A
- The procedure of Example I was repeated using
3-chlorobenzaldehyde. A complex mixture Or products
containing only about 10% 3-phenoxybenzaldehyde was
- 5 obtained.
EXAMPLE II
The procedure of Example I was repeated using
3-bromobenzaldehyde evhylene glycol acetal and a reaction
time of 5 hours. GLC analysis indicated a 90% conversion
of starting material, with a 92% selectivity to 3-phenoxy-
benzaldehyde ethylene glycol acetal.
Comparative Experiment B
Example II was repeated using 3-chlorobenzaldehyde
ethylene glycol acetal. Less than 5% conversion was
obtained after 6 hours.
EXAMPLES III to V
The procedure of Example I was repeated using
three other solvents instead of pyridine. Table I
states the solvents used, the conversions and the
selectivities to 3-phenoxybenzaldehyde.
TABLE I
` Example Solvent Selectivity to Conversion of
3-phenoxyben- 3-bromobenzal-
zaldeh~de~% deh~de~ %
_.______ _____________________ ______ __ _____ ___ __ _______
III N,N-dimethylformamide 75 > 99
IV dimethyl sulphoxide 68 ~ 99
V a mixture of xylenes* 86 82
================================================================_
* 40 ml was used and the reflux time was 3.5 hours.
;'
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-- 6 --
EXAMPLE VI
0.05 mol of sodium hydroxide and 0.05 mol of
phenol were mixed in 75 ml of a commercial mixture
Or o-, m- and p-xylene. The water thus formed was
removed by azeotropic distillation using a Dean and
Stark apparatus. The suspension of sodium phenolate
thus prepared was mixed with 25 ml of pyridine, 0.05
mol of freshly distilled 3-bromobenzaldehyde and
0.0025 mol of cuprous chloride. The mixture was then
heated under reflux for 30 minutes. GLC analysis then
showed that 97% of the 3-bromobenzaldehyde had been
converted, with a selectivity to 3-phenoxybenzal-
dehyde of 97%.
EXAMPLE VII
The procedure of Example I was repeated using ~,
- 3-bromobenzaldehyde and potassium 4-methoxyphenolate.
The product was 3-(4-methoxyphenoxy)benzaldehyde,
` b.p. 150C at 0.1 mm Hg, yield 40%.
,
.
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