Note: Descriptions are shown in the official language in which they were submitted.
1~57778
A process for the production of 2-alkoxy-4-propen-1yl phenols
There are already various processes for producing 2-
alkoxy-4-propen-1-yl phenols (isoeugenol and ethyl isoeugenol):
1) Isomerising eugenol or ethyl eugenol with alkalis
(Piscepromisdat 1939, page 303) or under the influence
of catalysts, for example nickel, palladium carbon or
ruthenium chloride(German Offenlegungsschrift No.1,936,
727).
2) Reacting vanillin with ethyl magnesium bromide to form
guaiacol ethyl carbinol which may be dehydrated in the
presence of glycerol and potassium carbonate (Russian
Patent No.114,197; cf. also CA53, 1959, 14 140e) or in
the presence of aluminium oxide (Russian Patent No
126,879, cf. also CA 54, 1960, 19596c) to form isoeugenol.
3) Working up various plant extracts or lignin with alkalis
- (Holz, Roh- und Werkstoff 23. 237 - 40, 1965, cf.C
1966, (28) 1047). But these processes suffer from serious
disadvantages.
The present invention relates therefore to a new pro-
~ess for the production of 2-alkoxy-4-propen-1-yl phenols
corresponding to the formula (I)
OH
, (I)
H=CH-CH3
in which
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R represents the methyl or ethyl radical.
The process according to the invention is characterised by
the fact that 2-alkoxy phenols corresponding to the formula (II)
H0 ~ (II)
R0
in which
R is as defined in reference to formula I,
are initially condensed with propionaldehyde in the presence of acid ca-
talysts at a temperature in the range from 0C to 100C, and the resulting
condensation product is subsequently split by heating at a temperature in
the range from 180C to 250C in the presence of a basic catalyst.
2-Methoxy phenol and 2-ethoxy phenol are used as starting com-
pounds for the first stage of the process according to the invention.
Acid catalysts suitable for use in the condensation reaction in-
clude, in particular, medium-strength to strong proton acids, acid ion
exchangers, acid anhydrides of inorganic acids or Lewis acids.
The following are mentioned as examples of medium-strength to
strong proton acids: inorganic acids such as sulphuric acid, acids of
phosphorus, for example orthophosphoric acid, pyrophosphoric acid, meta-
phosphoric acid, polyphosphoric acid, phosphortungstic acid or phos-
phormolybdic acid, also hydrohalic acids, for example hydrofluoric, hydro-
chloric and hydrobromic acid, and amidosulphonic acid; strong organic
acids such as sulphonic acids, for example p-toluene sulphonic acid, ~-
methoxy benzene sulphonic acid, also oxalic acid, trifluoroacetic acid
and picric acid.
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The following are mentioned as examples of acid ion
exchangers: inorganic cation exchangers such as natural
hydrosilicates of aluminium, for example montmorillonites,
glauconites or zeolites, prepared (for example by acid
treatment) hydrosilicates of aluminium (cf. Ullmanns
Enzyklopadie der technischen Chemie, Vol. 8, 3rd Edition
(1957). page 801), mineral cation exchangers produced on a
commercial scale from silicates, such as kaolin or feld-
spar, and al~lmina minerals, such as bauxite, silica and
sodium hydroxide or soda (cf. Ullmann, Vol.8 3rd Edition
(1957), page 802), the aluminium compounds being replaceable
either wholly or in part by iron, tin, lead, zirconium,tit-
anium, chromium, tungsten, vanadium or boron compounds
(cf. Ullmann, Vol. 8, 3rd Edition (1957), page 802); or
carbon-based exchangers activated with sulphuric acid, or
organic cation exchangers, for example polycondensation
resins based on phenolformaldehyde or polymerisation resins
based on styrene or alkyl-, alkoxy- or halogen-substituted
styrenes containing carboxyl or phosphoric acid groups, also
copolymers of polystyrene, acrylic acid, methacrylic acid or
maleic acid containing sulphonic acid, carboxyl or phosphoric
acid groups (cf. Ullmann, Vol. 8, 3rd Edition (1957), pages
806-810).
Acid anhydrides of inorganic acids are, in particular,
solid acid anydrides of inorganic non-oxidising acids, for
example phosphorus pentoxide.
The following are mentioned as examples of Lewis acids:
aluminium chloride, antimony trichloride, antimony pentachloride,
iron (III) chloride, boron fluoride, zinc chloride or phospho-
rus halides, such as PC13 or PC15.
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~57778
It is also possible to use mixtures of the aforementioned
catalysts.
The acid catalysts are used in quantities of from
0.001 to 10% by weight~ preferably in quantities of from 0.1
to 5% by weight and more especially in quantities of from
0.1 to 3% by weight, based on the weight of propionaldehyde
used.
The condensation reaction is carried out at temperatures
in the range from about 0C , to 100C , preferably at
temperatures in the range from 60C to 90C. and, more
especially, at temperatures in the range from 65C to 85C.
Basicallvv, the pressure applied is not critical. In
general, the reaction is carried out under normal pressure
although, in special cases, it may be advantageous to carry
out the reaction either under reduced pressure or excess
pressure. For example, the water formed during the con-
densation reaction is easier to remove where the reaction is
carried out under reduced pressure, thereby providing for an
increase in conversion. On the other hand, the reaction tem-
perature and, hence, the reaction velocity may be increased
when the reaction is carried out under excess pressure.
The 2-alkoxy phenols of general formula II are generally
used in excess. For example, it is advantageous to react
about 3 to 10 mols of the phenol with 1 mol of propionalde-
hyde. On completion of the reaction, the unreacted phenol
may readily be separated off from the condensation product
formed, for example by distillation.
In the condensation reaction, 2 mols of alkoxy phenol
(II) react with 1 mol of propionaldehyde to form the corres-
ponding l~l-bis-(hydroxy alkoxy phenyl)- propanes in accord-
ance with the following scheme:
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2 ~0 ~ ~ ~H ~ 0
R0 I R0 CH R
CH3 , ~H2
CH3
(III)
The bis-(hydroxy alkoxy phenyl)-propanes (III) are
formed in high yields. Since the H-atom of the benzene
nueleus in the p-position to the hydroxy group is prefer-
ably substituted by the earbonyl carbon atom of the aIdehyde,
l,l-bis-(4-hydroxy-3-alkoxy phenyl)- propanes are the main
produets. Accordingly, the condensation products consist
essentially of l,l-bis-(4-hydroxy-3-methoxy phenyl)-propane
or of l,l-bis-(4-hydroxy-3-ethoxy phenyl)-propane.
In the seeond stage of the process aeeording to the
invention, these condensation products are subjected to
thermal splitting at 180C to 250C , preferably at 210C
to 240C , in the presence of a basic eatalyst.
Suitable basie eatalysts inelude oxides, hydroxides,
alcoholates, phenolates, alkyl earboxylates, earbonates, amides
or hydrides of aluminium, zinc, eadmium or lead and, in
partieular, of alkali metal and alkaline-earth metals.
It has proved to be partieularly effective to use alkali
metal hydroxides,such as lithium, sodium and potassium
hydroxide, and alkali metal alcoholates, such as lithium,
sodium and potassium methylate and ethylate. It is preferred
to uRe potassium hydroxide. Mixtures of the afore~entioned
basie eatalysts may also be used.
The basie eatalysts are generally used in quantities of
from about O.Ol~ to 10% by weight and preferably in quantities
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of from 0.1% to 5~ by weight, based on the amount of conden-
sation product.
Splitting of the l,l-bis-(hydroxy alkoxy phenyl)- prop-
anes (III) is carried out under normal pressure or, preferably,
under reduced pressure. A reduced pressure of about 0.1 to
700 mm Hg has proved to be effective depending upon temperature.
At temperatures in the range from 200C to 250C , for ex-
ample, it has proved to be particularly effective to apply
a reduced pressure of from about 0.1 to 100 mm Hg.
It has also proved to be of advantage ~ carry out
splitting in an inert-gas atmosphere, for example in
nitrogen.
To carry out the process according to the invention,
the condensation product is heated with the catalyst, and
the propenyl phenol (I) formed is distilled off from the
reaction mixture together with the 2-methoxy phenol or
2-ethoxy phenol formed at the same time.
Separation of the compound mixture accumulating during
splitting is preferably carried out by fractional distillation
or recrystallisation from solvents, for example alcohols,
such as methanol and ethanol, hydrocarbons such as ligroin
cyclohexane, benzene, toluene and xylene or water or mi~-
tures o~ these solvents.
2-Methoxy-4-propen-1-yl phenol (isoeugenol) is used as
an odorant and a flavouring (S. Arctander, Perfume and
Flavour Chemicals, Montclair 1969). Isoeugenol is also used
as an intermediate product in the preparation of vanillin
(German Patent No. 517,539) and medicaments, for example methyl
dopa.
2-Ethoxy-4-propen-1-yl phenol is used as an intermediate
product in the production of 4-hydroxy-3-ethoxy benzaldehyde
(ethyl vanillin), employed a~ a flavouring.
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1~)5777~
The advantage of the process according to the invention
over known processes is that it enables 2-alkoxy-4-
propenyl phenols to be readily obtained in excellent yields,
even on a commercial scale, from readily available starting
compounds. When it is taken into consideration that the
unreacted starting materials are continuously recycled to
the corresponding reaction stages both during condensat~n and
during thermal splitting, an almost complete conversion of
the starting compounds is obtained.
The condensation of guaiacol and propionaldehyde and
the thermal splitting of the product of condensation in the
presence of an acid catalyst, is described in the Dissertation
by K. Remesat, Berlin 1931, more especially pages 29, 56 and
58. However, it is propyl guaiacol and not propenyl guaiacol
which is obtained by this process.
The production of 4-alkenyl phenols by subjecting bis-
(4-hydroxy phenol)-alkanes to thermal splitting in the
presence of basic catalysts, is known from British Patent
Specification No.905,994.
The thermal splitting reaction used in the process ac-
cording to the invention di~fers from the splitting reaction
described in British Patent Specification No.905,994 in that
3-alkoxy-4-hydroxy phenol propanes, i.e. pyrocatechol
derivatives, are used in it. It is known from numerous
reactions~ that the pyrocatechol compounds behave fundamentally
differently from the corresponding phenol compounds.
Accordingly, the thermal splitting reaction used in
accordance with the invention was not suggested by the
splitting reaction described in this British Patent Specificat-
ion. Rather had it been expected that dealkylation of the
alkoxy group and rearrangomont reactions will occur under the
de#cribed reaction condltion~. It ha~ surprisingly been found
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1~)57778
that these rearrangement reactions do not take place, so that
the required 2-alkoxy-4-propen-1-yl phenols are obtained not
only in high yields, but also in the commercially interesting
form.
EXAMPLE 1
A mixture of 8 mols of guaiacol (2-methoxy phenol), 1
mol of propionaldehyde and 500 g of anhydrous cation exchanger
in the H+-form (Lewatit SC 104/H+), was introduced into the
reaction vessel equipped with stirrer, thermometer, inlet-
tube and outlet-tube. Further quantities of 8 : 1 guaiacol-
propionaldehyde-mixture were introduced via a metering unit
through the inlet-tube at a reaction temperature of 55C to
70C and at such a rate that 525 g/h of reaction product could
be removed through the outlet-tube. In order to avoid entrain-
ment of liquid reaction mixture by the of~-going product
stream the outlet-tube is equipped with a frit at the end
facing the reaction vessel.
Following removal of the water of reaction and unreacted
guaiacol by distillation at 110C/10 Torr, 990 g of conden-
sation product, consisting mainly of 1,1-bis-(4-hydroxy-3-
methoxy phenyl)-propane, were obtained from 4 kg of reaction
product.
~00 mg of NaOH were added to 600 g of this condensation
product in a distillation apparatus provided with a 30 cm
Vigreux column attachment, followed by heating under nitrogen~
500 g of a mixture of guaiacol and isoeugenol of b.p~ 110 -
140C/10 Torr, distilled over at a sump temperature of 220
to 240C/10 Torr.
The isoeugenol can be isolated in pure form from the mix-
3 ture by fractional distillation at b.p. 140 C - 142C/13 Torr.
7rc2 ~ é.f7?a rk
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The yield of isoeugenol (cis-trans mixture) amounted to 307
~ g (90~ of the theoretical yield, based on the condensate used,
and 81~ based on the gu~iacol consumed). The trans-isoeugenol
content of the isomer mixture amounted to 85~ - 90~.
EXAMPLE 2
A mixture of 1240 g (10 mols) of guaiacol (2-methoxy
phenol), 20 g of acetic acid, 300 g of 65~ by weight H2S04
and 10 g of ~-mercaptopropionic acid, was introduced into a
three-necked flask equipped with a thermometer, stirrer and
dropping funnel, followed by the addition over a period of
3 hours at 5C to 10C of 145 g (2.5 mols) of propionaldehyde.
After stirring for 24 hours at the same temperature, the
reaction mixture was extracted with 1 litre of methylene
chloride to isolate the condensation product. In addition
to methylene chloride and unreacted starting materials,
distillation of the organic phase at 110C/10 Torr gave 424 g
of condensation product (b.p. 200 - 210C/0.1 - 0.5 Torr)
which consisted mainly of l,l-bis-(4-hydroxy-3-methoxy phenyl)-
- propane, and 12 g of residue. 200 g of the condensation
product were heated under nitrogen with 200 mg of KOH in a
distillation apparatus provided with a 10 cm Vigreux column
attachment. A mixture of guaiacol and isoeugenol (b.p.
100 - 140C/10 Torr) distilled off at a sump temperature of
220C to 240C. Yield of distillate: 117 g (64 g of un-
split condensation product were recovered from the distillation
residue by distillation at b.p. 200 - 210C/0.1 - 0.5 Torr.)
66.1 of isoeugenol (58~ of the theoretical yield9 based on
the condensate used) were obtained from the 117 g of distillate
by fractional distillation at 140 - 142C/13 Torr.
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EXAMPLE 3
138 g of 1,1-bis-(4-hydroxy-3-methoxy phenyl)-propane
(m~p. 120 - 121C) were heated under nitrogen with 200 mg
of KOH in a distillation apparatus. A mixture of guaiacol
and isoeugenol (b.p. 110 - 140C/10 Torr) distilled off at
a sump temperature of 220C -240C. Yield of distillate:
115.5 g; distillation residue: 16 g 65.8 g of isoeugenol
were recovered from the distillate by fractional distillation
at 140 - 142C13 Torr (corresponding to a yield of 83.8
of the theoretical yield, based on the condensate used).
EX~PLE 4
545 g of the condensation product of guaiacol (2-methoxy
phenol) and propionaldehyde prepared in accordance with Example
1 were heated in a distillation apparatus following the
addition of 1 g of LiOH. 365 g of a guaiacol/isoeugenol
mixture (b.p. 110C - 140C/10 Torr) distilled off at a sump
temperature of 220C -240C. The yield of the pure isoeugenol
isolated from this mixture by fractional distillation amounted
to 58.3~ of the theoretical yield.
EXAMPLE 5
(Comparison Example; K. Remesat~s method, cf.
Dissertation, Berlin, 1931, pages 28,29 and 58).
Following the addition of 5 g of Tonsil AC, 100 g of
the condensation product of guaiacol and propionaldehyde
prepared in accordance with Examplc 1 were heated in a
distillation apparatus. 90.7 g o~ product (b.p. 220 -
240C/8 Torr) distilled over at a sump temperature of 220C-
240C The distillate consisted predominantly of starting
material and a little guaiacol. Distillation residue: 9 g
When the sump temperature was increased to beyond 250C
during splitting, propyl guaiacol, guaiacol and resin~like
secondary products were predominantly formed.
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EXAMPLE 6
996 g (7 mols) of guaethol (2-ethoxy phenol) and 150
g of anhydrous cation exchanger in the H+ - form (Lewatit
SC 102/H+) were introduced into a three-necked flask
equipped with a stirrer, condenser~ dropping funnel, thermomet-
er, 30 cm Vigreux column attachment and heating system, followed
by the addition over a period of 30 minutes at 65C of 58
g (10 mols) of propionaldehyde. After stirring for 1 hour
at the same temperature, the mixture was filtered off from the
ion exchanger and water of reaction, unreacted propionaldehyde
and excess guaethol subsequently distilled off at 110 C/10
Torr, leaving 123 g of condensation product consisting mainly
of l,l-~is-(4-hydroxy-3-ethoxy phenyl)-propane.
The 123 g of condensation product were then heated
following the addition of 200 mg of NaOH. A mixture of
guaethol and p-propen-l-yl guaethol (b.p. 120 - 150C/10
Torr) distilled off at a sump temperature of 220 to 250C/10
Torr. Yield of distillate: lOOg. 48.5 g-of pure p-propen-l-
yl guaethol were obtained from the distillate by fractional
destillation (corresponding to a yield of 70 % of the theoretic-
al yield).
"Lewatit" is a trade mark o~ ~ayer AGo
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