Note: Descriptions are shown in the official language in which they were submitted.
H.27('0~/28230
- ~8i~Z730 :
THE PRESENT INVENTION relates to the produc-tion
of an aromatic alcohol, in particular -to -the production
of 3-hydroxymethyldiphenyl ether.
3-hydroxymethyldiphenylether is an intermediate
which is used in the manufacture of pyrethrum type insec-
icides by esterification with a chrysanthemic acid
(cyclopropane carboxylic acid) such as 2,2-dimethyl-3-
(2,2-dichlorovinyl) cyclopropane carboxylic acid. -
According to the present invention 3-hydroxy~
methyldiphenylether is produced by a four-stage process
in which:-
`, (a) phenol is condensed with meta-cresol to yield
` 3-methyldiphenylether,
~, (b) the 3-methyldiphenylether is oxidised to 3-carb- :
1 15 oxydiphenylether,
(c) the 3-carboxydiphenylether is esterified, and
(d) the ester is reduced to y~eld the 3-hydroxy-
methyldiphenyl ether.
~ The condensation of phenol and meta-cresol
`~ 20 suitably takes place at a temperature in the ~ange 200
to 650C, preferably 350 to 550C over a dehydration
catalyst such as thoria preferably at atmospheric pressure. -~
The condensation reaction gives rise to three products,
the desired 3-methyldiphenylether together with diphenyl-
~ , . ...
ether and ~,3'-dimethyldiphenylether. We have found
that the best distribution of products from the point
of view of obtaining the monc-methyl derivative is
obtained when the phenol to meta-cresol ratio is 0.5 to
- 2 -
.. ~e . .
~, ',
~1.'7(~0,/~iO
~ ~Z 7 3~
3 : 1 and all other factors being equal, this range
of ratios is preferred for use in the process.
Diphenylether itself, however, is a commercial
product so advantage may lie in operating at a phenol
to meta-cresol ratio of greater than 3 : 13 say up -to
6 : 1 or higher when the production of the unwanted
dimethyl derivative would be minimised at the expense
o~ increased diphenylether production.
After completion of the step (a) reaction the
diphenylether is generally separated from the mono-
; methyl derivative by distillation. I~ the dimethyl
content of the monomethyl product is not too greàt
the dimethyl derivative may be left to be removed at
a later stage, particular]y between step (c) and (d).
Otherwise the dimethyl derivative may also be removed
by distillation.
~` Any 3,3~-dimethyldiphenylether which may be
formed and which is a product of little intrinsic
value may be converted either to meta-cresol, which
` 20 can if wished be recirculated to the process, or to
, ~ .
3~methyldiphenylether. This may be acco~plished by
heating at least a part of the 3,3'-dimethyldipheny- - ~
lether in the presence of water or phenol to produce ;
. .
l ` meta-cresol or 3-methyldiphenylether respectively. ~
;` '
The 3,3'-dimethyldiphenylether may be heated ;~
with the water or phenol to a -temperature in therange
; 200 to 650C pre~erably 350 to 550C. The heating is ~ -
' ~ preferably carried out over a catalyst 9 particularly a ~;~
- 3 -
,....
.. . .
., : .. :
:
H.27603/28230
~ L~6273~
:
hydration/dehydration catalyst eg thoria.
The molar ratio of water to dime-thyldipheny-
lether is preferably 0.5:1 to 50:1 more preferably
1:1 to 20:1 and the molar ratio of phenol to
dimethyldiphenylether is preferably 1:1 to 6:1.
A preferred method of carrying out the process
is to recirculate the 3,3'-dimethyldiphenylether to the
phenol/meta-cresol condensation reaction together with
phenol and with or without water when the dimethyldip-
henylether takes part in the condensation reaction
; and provides at least a part of the meta-cresol required.
The 3-methyldiphenylether is readily oxidised
to the 3-carboxydiphenylether by oxygen at a tempera-
ture suitably in the rang~a 50 to 350C, preferably 100
to 250 and under,a pressure of 0.1 to 100 ats.
` preferably 1 to 50 ats. oxygen. The oxidising agent
is preferably oxygen which may be used as a mixture
with an inert gas such as nitrogen e.g. in the form of
air. The reaction is suitably carried out in the
liquid phase, preferably in a solvent which may be a
lower (C2 to c8j alkanoic acid such as acetic acid. It
, is preferred to carry out the oxidation in the presence
;~ ~ of a catalyst which may be a transition metal such as
~'! vanadium, chrQmium, manganese or, particularly, cobalt -~
which may be added as a suitable salt such as a carb~
~i oxylate, e.g. cobalt naphthenate or a C2 -to C20
alkanoate such as cobalt stearate or manganese acetate.
The oxidation reaction is suitably initiated by a
. .
- 4-- ~ ~
.- ', : : ,
.', .
H.27603/28230
7 3~
:
compound such as a peroxide which is commonly used
for the ini-tiation of oxidation reactions.
A preferred method of carrying out the
oxidation step (b~ involves the use of bromine as
catalyst in conjunction with a heavy metal.
:
The "heavy metals" are defined in the "Hand- -
book of Chemistry" by Lange 10th Edition 1961 pages
56 and 57. The preferred heavy metals are manganese,
: cobalt, nickel, chromium, vanadium, molybdenum,
tungsten, tin and cerium or mixtures thereof and the
metal may be used in elemental, compound or ionic
form preferably in a form which is soluble in -the
reaction medium e.g. oxide; carbonate; hydroxide; palide,
particularly bromide; or carboxylate, pre~erably C2 to
.
~` 15 C alkanoate.
. 6
The bromine may be provided in elemental, ionlc,
~ .
`~ organic or inorganic form, eg as an alkali metal or
` ammonium bromate or bromide, as a heavy metal bromide
;' - ~ eg manganese bromide, benzyl bromide, bromobenzene or
;i - - 20 tetrabromoethane.
The oxidation reaction is suitably carried out
in an inert liquid medium which may be an alkanoic acid
contalning 2 to 8 carbon atoms, preferably 2 to 4 carbon
,i; .
~ atoms eg acetic acid or it may be benzoic acid. --
, 1
~; 25 The amount of heavy metal used in the process is
~ suitabl~ 0.~1 to 10~ by weight of the 3-methyldipheny-
.,!i lether preferably 0.03 to 2% by weight. The amount of
; bromine may be 100:1 to 1:100 expressed as atoms of
~ ~ 5 ~
.; . -':-: :
~: '' ' '
.. ~. . .
. . .
: . -
H.27603/28230
l~iZ~30 ,,
bromine per atom of the heavy metal preferably 10:1
to 1:10. -
The temperature of the oxidation reaction
may be 80 to 300C preferably 100 to 250C. The
pressure may be in the range 1 to 400 atmospheres
(ats) preferably 2 to 100 ats. The partial pressure
of the oxygen may be 1 to 10 ats and the oxidising
- gas may contain inerts such as argon, nitrogen, carbon
dioxide and methane which may be controlled so as to
` 10 avoid the formation of explosive mixtures.
; The 3-carboxydiphenylether is esterified
: .,,
preferably to a lower alk~ (C1 -to C6) ester, particu-
larly to the methyl or ethyl ester. The esterification
is carried out by reacting the carboxy-derivative with
a suitable alcohol, preferably at 50 to ~50C in the
presence of an esterifica-tion catalyst such as a `
., .
tltanate, e.g. tetraisopropyltitanate or other known
esterlfication catalyst 9 e.g. an acid such as p-toluene
` ~ sulphonic acid~ sulphuric acid or phosphoric acid. The
:: ,
- 20 esteri~ication is preferably carried out under the
autogenous pressure of the reactants at the temperature
:- :
of the reaction eOg. a pressure up to 20, preferably up
to 10 atmospheres. Any 3,3'-dicarboxydiphenylether
which may be present ls esteri~fied~at the same time;as
the 3-carboxydiphen~lether and following the esterif-
ication the mono- and di-esters may readily be
separated as there is a substantial difference in their
boiling points. Thus, ~ractional distillation serves
~` - 6 - ~
: ~:
'' ;"','; `:
~ 7(-0~,/2~230
~ ;Z7~
to remove the mono ester which is then ready for the
reduction step (d).
Although a number of reducing agents may be
used to accomplish the step (d) reduction, e.g.
lithium aluminium hydride, sodium in alcohol, or a
complex of sodium borohydride and aluminium chloride
we have found a cheap, readily available catalyst
that gives high yields. This is a copper, preferably
a copper chromite catalyst used with gaseous hydrogen.
The reduction may in general be carried out at an
elevated temperature; e.g. 50 to 5500C, preferably
100 to 250C and at an elevated hydrogen pressure,
` e.g. 10 to 1000 ats., preferably 100 to 500 ats. The
catalyst concentration is suitably 0.001 to 50
`~` 15 preferably 0.001 to 30 wt.% based on the ester being
reduced and the reaction is generally carried out in
the liquid phase in a suitable solvent which may be an
excess of the alcohol corre~ponding ~o the alcohol
'! . -
c' moiety of the ester, eOg. ethanol. The copper chromite
catalyst comprises copper oxide and chromium oxide
which~may be present in ratio of 1 : 10 to 10 : 1. A
;~ small amcun~ (eg 2 to 20% by weight) of a barium ~ ;
compound, e.g. barium oxide, may also be included in
the catalyst as a promoter. An alternative copper
catalyst which may be used is the catalyst produced
- ... ,. :
~ by treating COPAL (copper/aluminium alloy) with aqueous ~-
..
~ alkali. The copper catalyst may be supported or -
.i . ..
j unsupported and may be pre-reduced by hydrogen before
.
_
* Trade Mark
A
` H.27603/28230
Z~3~ ::
:`
.` .
treatment of the es-ter.
; The invention will now be further described
with reference to the following Examples.
EXAMPLE 1
.
Step (a~
Mixture of m-cresol and phenol were vaporised
and passed through a glass tube containing 10 mls. of
gg.9% by wt. thorium oxide pellets. The pellets had
previously been activated by heating them in a stream
of air at 550C for 12 hours. The rate o~ passage of
mixture through the tube was 30 mls/hr. and the
temperature in the tube 450C. The reaction product
leaving the tube was condensed, analysed by gas-liquid
chromatography and ~inally separated into its
components by distillation. The results are given in
the following Table:-
~i ` . , .
.~i . .... ,, :.
,.:' . .:: .
;i ~ . . .: .
.i . . . .
i . .
`~: : ' , .... ~
'~ .~.' '''
;~
.: , .
~` ' "' '" '
i, ,:: ~,:
' :' '~''~
H~ 27603/28230
2~;'3~
~ .
* ~ ~ ~ ~ o
* I ~ ~ ~ CO ~
- ~ ~ ~ ~
,-~ . . . _ . ..
**
,; ~ ~ ~ ~ o
o ,.
.
,` $ * o o o o
.. . ~ __ ~
: .,1 ~ ~ ~ ~D
~ æ ~
., ~ _ ~ .,
', , ~
,,, ~ a) ~ D
~ h ~ ~ C`.l
,'~
, , __ . _ _ ~ ,~: ,:'
j . r~ h ~1 . . .
,,j ~0 C~ D
~: a) QD ~I C-- 1~ +~ O :: . '.
,'.:: ~ ` ' i~ Ir~ . ,1 ~ ''.'' ,.
.~ h C~
-- - - ~
~` . ~ o;~,~ ~
~j h !~ .. .. .. ~o ~ +'
r _. ~ 1~ 11 11 11 ~ ;~
~ ;~ ~ ~ ~ Q ~ : ~
.''. . . _ _~ _ , ~ ~ + ' "' '.
`' ~ * * .~ , .
` ~ ' ' ' :,'
~, ' -,
'( - ,'' ~ :
H.27603/28230
. . ,:
Z7301
..: . .
Step (b)
500 grams of 3-methyldiphenylether from l(a)(i)
were mixed with 500 grams acetic acid, 6.96 grams
cobalt acetate tetrahydrate (Co(oAc)24H20) and
5 heated to 165C under nitrogen at a pressure of 14 -
atmospheres. 10% by volume oxygen in nitrogen was
passed into the mixture and the oxida-tion reaction
was started by the addition of 5mls. di-tert. bu~
peroxide in 100 mls. acetic acid. Af-ter 3 hours the
up-take of oxygen ceased and the reactor was cooled
and discharged. The 3carboxydiphenylether (360 grams)
was filtered off and washed with a little cold acetic
; acid. The washings and mother liquor were then - :
~, bulked and diluted with water (500 mls.) when crude
' 15 3-carboxydiphenyl ether (176 grams) precipitated.
24 grams of 3-methyldiphenylether were recovered. The
conversion of the 3-me-thyl to 3-carboxyderivative was
95% representing a yeild of 96% on converted material.
Ste~ (c~
A mixture of 214 grams of 3-carboxydiphenyl-
ether and 1.9 gram p-toluene eulphonic acid was
! ~ heated to 135 to 160 C when the ether was molten. ~
~- Ethanol was then gradually added as a liquid to the -
molten reaction mixture over a period of 7.5 hours,
At the end of this time the mixture was cooled~ washed -
with sodium hydroxide solution and water and then
distilled under vacuum to recover the ethyl ester of
3-carboxydiphenylether.
:
. .
., - .
.: . - .. . .- . . . i . . - . . .
H.27603/28230
730
Step (d)
10 grams of the ethyl ester from step (c)
and 40 mls. of e~hanol were agitated in an autocla~e
-~ at 155C under 250 atmospheres of hydrogen in the
presence of a copper chromite catalyst (32.3% copper,
30.1% chromium and 8.1% barium). After 20 hours the
catalyst was removed by filtration and the ethanol
distilled off. The reaction product was analysed by
gas-liquid chromatography and nuclear magnetic
resonance spetroscopy. It was found that 74% by
weight conversion of the ethyl ester had occurred,
` 92% of which was to 3-hydroxymethyldiphenylether. -
`~ EXAMPLE 2
A mixture comprising 3,3'-dimethyldiphenyl-
ether (obtained by the process of Example l(iv))and
~ water ~1:18 molar ratio) was vapourised and passed `i
.. .
~ over a bed o~ thoria catalyst at a space velocity o~ -
."
4 hr 1 and at a temperature of 450C. The vapour ~ -
leaving -the catalyst bed was condensed and analysed by
gaslliquid chromatography. The conversion of the
3,3'-dimethylether was 53% and the yield of meta-cresol
85%.
Example2 ~ was repeated except that
the space velocity of the mixture over the catalyst
bed was 8.5 hr 1.
The conversation of the 3 7 3'-dimethyldiphenyl- ~
` ~ ether~was 41% and the yield o~ meta-cresol 82~. `
--
H.27603/28230
~Z73~
EXAMPLE 4
A mixture comprising 3,3'-dimethyldiF~enyl
ether (obtained by the process of Example l(iv)),
water and phenol (molar ratio 1:1:6) was vapourised
and passed over a bed of thoria catalyst at a space
velocity of 3 hr 1 and at a temperature of 450C.
The vapour leaving the catalyst bed was condensed
and anaylsed by gas/liquid chromatography.
The reaction product contained 47.5% phenol,
19.3% diphenylether, 7.4% meta-cresol, 7.7% 3-methy-
ldiphenylether and 14.5% 3,3'-dimethyldiphenylether
(aI1 percen-tages are by weight). The conversation
of the 3,3'-dimethyldiphenylether was 43%.
EXAMPLE 5
A mixture comprising phenol and 3,3'-dimethyl-
diphenylether (obtained by the process of Example
l(iv)) (6:1 molar ratio) was vapourised and passed
- over a bed o~ thoria catalyst at 450C and at a
.
space velocity of 3 hr 1. The vapours leaving the
catalyst bed were condensed and analysed by gas/liquid
- chromatography. The composition o~ the reaction
product was phenol 41.5%, diphenylether 28.0%~ me-ta- ~
cresol 6.4% 3-methyldiphenylether 8.9% and 3,3'-dim- -
~t : ethyldiphenylether 13.5% (all percentages are by ~ ;
~ 25 weigh-t.
:t~ EXAMPLE 6
t' Example 1 (a)(i) was repeated, steps (b), (c)
and (d) being as follows:-
- 12 -
:
.
H.27603/28230
;Z73~
A mixture of 3-methyldiphenylether (400 gram),
glacial acetic acid (400 grams), cobaltous acetate
(0.55 gram) manganous acetate (0.15 gram) and potassium
bromide (0.05 gram) was oxidised with air at 160C and -
10 atmospheres pressure until absorption of oxygen
ceased. The reaction mixture was then cooled to 120C
~ and discharged into a large excess of water. The solid
`~ so produced was filtered, washed well with water and
air dried at 100C to give 460 grams of fawn coloured
crystals mpt 140-145C.
Step (c)
100 grams of the 3-carboxydiphenylether was
mixed with me~thanol (56 grams) and concentrated
sulphuric acid (1.5 grams) and pressured with nitrogen
to 1.5 atmospheres. The mixture was then heated at
110 C i~ a sealed vessel for 10 hours, cooled and the
- aqueous methànol layer separated. The ester product
~; ~ was finally distilled under vacuum from the oily res- -
idues.
` ~ A reducing solution was prepared by adding
sodium borohydride (22.6g) to a well stirred diglyme
;l -
solution (240 mls) of aluminium chloride (26.4 grams)
;' 25 under nitrogen at 0 to 5C. The ester (120 grams)
.. .
~ ~ in toluene (120 mls) was added dropwise with stirring
; to the reducing solution allowing the temperature to
rise to 50C. After the addition was complete the
mixture was stirred ~or 60 minutes at 40 to 50C and
.! - 13 - ~
:.:
. , .. ., . . , .. . . , .. . . . . - . . . . .. . . . . . .. .. .. . . .. ..
~ H.27603/28230
, .
~6;2 73~
~' .
- was then poured with care into a mixture of water
(120 mls) and concentrated hydrochloric acid (75 mls).
The aqueous layer was separated, extracted with
toluene,the toluene layer water washed until neutral
and the toluene finally distilled o~f together with
` any remaining diglyme. The residual crude 3-hydroxy-
methyldiphenylether was finally purified by distillation
under vacuum ~b pt. 220.4C/32.5 mm.)
EXAMPLE 7 - -
Example 6, steps (a), (b) and (c~, was
repeated. Step (d) was as follows:-
100 grams of the methyl ester of 3-carboxy-
:, . ~ .:
diphenylether and methano:L (400 grams) were agitated
ln an autoclave at 160 C ~md 200 atmospheres hydrogen
~` 15 in the presence of the barium promoted copper chromite
.
catalyst used in Example :L (50% by weight of the
~' ester). After 24 hours the catalyst was removed by
~ : .
!; filtration and the methanol distilled off.
The reaction product was analysed by gas-
~' 20 liquid chromatography when it was found that 98.8%
conversion of the ester had occurred, the yield of
- alcohol being 92~. ~
:~ j
~XAMPLE 8
`~ Example 6, steps (a~ (b) and (c), was
`~ ~ 25 repeated. Step (d) was as follows:-
lOO grams of the methyl ester of 3-carboxy-
;~ diphenylether were agitated in an autoclave at 180C
and 100 atmospheres hydrogen in the presence of the
~'~ barium promoted copper chromite catalyst used in Example
`~ 1 (10% by weight of the ester~. After 12 hours the
- - 14 -
, ' , . ' " "~
- - . . , . :
H.27603/28230
3L~6Z73~ ;
catalyst was removed by ~iltration and the methanol
distilled off. . - -
The reaction produce was analysed by gas-
liquid chroma-tography when it was found that 53%
conversion of the ester had occurred, the yield of
alcohol being 78%. ~-.
' ~ . .
'
'' '
.~ .
. ~ , ,.
,
9:~ .
': : -. ' :
!~ .,: .
~i . ,' ~' .',
:: ' ' .,
.: .' :' "'
, ~ . '. ..
: - '; '
.! . ~: .
;; - :.
~ - 15 ~
.i ~ ';
, . .:
. . :.. : ~
~ ~.
-. . . ,.... . . .... . . .. " , , , ~
