Note: Descriptions are shown in the official language in which they were submitted.
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Pre~aration Process of Cinnamic Acids
The present invention relates to a preparation
process of cinnamic acids by the hydrolysis of an alkyl
ester of the cinnamic acids.
Cinnamic acids are technically important as
materials for perfumes, photosensitive polymers and
various organic or biochemical products.
Regarding the processes for the synthesis of
cinnamic acid and its derivatives, a variety of methods
has been known up to the present time.
For instance, these processes are methods of
preparing cinnamic acid and it~ derivative~ from
benzaldehydes as a main raw material by Perkin reaction,
Knoevenagel reaction or Claisen condensation (as
described in, for example, Organic Reactions, vol. 1,
217 (1942)), and from benzene or its derivatives and
acrylate esters as raw materials (as described in, for
example, Japanese Patent Publication No. 50611/'72,
~b
, .i
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lZ9Z997
Japanese Patent Laid-Open No. 59927/'83, USP 3783I40.and -;
3922299). Besides a method has also been proposed
recently where.in styrene or its derivatives are reacted
with carbon monoxide, alcohol and oxygen in the presence
of a catalyst (as described in Japanese Patent
Publication Nos. 5570/'84 and 23661/'85).
Cinnamate esters are always formed as an
intermediate in such processes as Claisen condensation
which used benzaldehyde and acetate esters, a method
of using benzene or its derivatives and acrylate esters
as the raw materials, and a method of employing styrene
or its derivatives, carbon monoxide, alcohol and oxygen
as the raw materials. Therefore hydrolysis of cinnamate
esters is necessary for preparing free cilmamic acids.
Concerning the hydrolysis of cinnamate esters
a method has recently been proposed which applies an
acid as the catalyst (as described in Japanese Patent
Laid-Open No. 12736/'85). The hydrolysis, however,
is generally performed by use of alkali such as sodium
hydroxide in a homogeneous system which contains
aqueous mixture of alcohol, dioxane or acetone (as
described in Japanese Patent Laid-Open No. 102614/'74).
On the hydrolysis of cinnamaté esters with
an acid catalyst a long reaction time is generally
required becausé of a low reaction rate. On the other
hand, the alkali hydrolysis is, as described above,
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carried out in a homogeneous system employing the x
aqueous mixture of organic solvents. Therefore,
procedures such as extraction and concentration are
required for the isolation of desired products.
5 Furthermore, the solvents used for the extraction
should be recovered in the industrial application.
Besides a step of acidifying the resultant
alkaline solution with mineral acids after alakli
hydrolysis is required in order to finally obtain the
lO cinnamic acids.
In the prior arts, mineral acids are added
to the aforesaid alkaline ~olution of alkali cinnamate
containing the organic solvents.
In these cases, however, acidification must
15 be performed in a low concentration which is diluted
with a large amount of water as a result of employing
a dilute aqueous alkali cinnamate solution, using a
dilute aqueous solution of the acid or diluting the
system with a special addition of water. Otherwise
20 the system becomes a slurry having a high viscosity
on the way of acidification and in extreme cases
stirring is inhibited by the solidification of total
system. Therefore it becomes difficult to conduct
the acidification of aqueous solution of the alkali
25 cinnamate with the mineral acid in a high concentration
and the amount of products produced per unit volume of
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the reaction vessel is reduced.
Furthermore, the use of organic solvents
described in the prior art results in the loss due to
dissolving of desired product into the solvents and
hence cause the reduction of yield.
This invention is directed towards the
provision of an industrial method of preparing a
cinnamic acid by the hydrolysis of a cinnamate ester
with an alkali.
The present inventors have made an intensive
effort on the study of alkali hydrolysis of cinnamate
esters. As a result, it has been found that the
cinnamic acid having an excellent quality can be
favorably obtained by alkali
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hydrolysis in the heterogeneous binary-phase liquid
system with the aqueous solvent in the absence of
organic solvents, and followed by acidifying the
resultant aqueous alkaline solution so that the pH value
of the solution obtained by the reaction was not more
than the specific value.
Besides the following facts have also been
found. When the acidification of aforementioned
aqueous alkaline solution is conducted either by
adding the aqueous alkaline solution into the mineral
acid or by continuously chargi~g the aqueous alkaline
solùtion and said mineral acid into the reaction
ve~sel so as to keep the pH value at not more than the
specific value in the mixture obtained by acidifying
and continuously discharging the product, this method
can decrease the ~uantity o~ water in use, and thus
the amount of product produced per unit volume of the
reaction vessel can be increased, the environmental
problems on drainage is mitigated, the loss of the
product by dissolving in the drainage is reduced and
the cinnamic acids having an excellent quality can be
obtained in good efficiency.
That is, the present invention is a process
of preparing a cinnamic acid by the hydrolysis of a
cinnamate ester with an alkali which comprises starting
the hydrolysis reaction of the alkyl cinnamates with
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the alkali in the heterogeneous binary-phase liquid
system with an aqueous solvent in the absence of
organic solvents, and acidifying the resultant aqueous
alkaline solution so as to obtain the pH value of not
more than 4 in the solution after acidification.
More preferably, the present invention
includes a process for preparing the cinnamic acid
which comprises either adding the aqueous alkaline
solution obtained by the alkali hydrolysis of the
cinnamate ester into the mineral acid, or continuously
charging the aqueous alkaline solution and the mineral
acid into the reaction vessel to keep the pH value of
not more than 4 in the solution after acidification and
continuously discharging the reaction mixture.
According to the process of this invention,
the hydrolysis of the cinnamic acid ester with the
alkali can be started in the heterogeneous binary-phase
liquid system with the aqueous solvent in the absence
of organic solvents. Therefore, recovery of the
organic solvents is not required and easy separation
of the resultant cinnamic acid can be attained.
Besides in accordance with the process of
this invention, the aqueous alkaline solution of the
alkali cinnamate obtained by the alkali hydrolysis of
the cinnamic acid ester can be acidified at a high
concentration, the quantity of products per unit volume
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of the reaction vessel can be increased, the quantity of
water in use can be reduced, the environmental problems
of drainage can be mitigated and the loss by dissolving
the products into the drainage can be decreased. Hence
the cinnamic acid having good quality can be obtained
efficiently and in good yield.
Therefore the method of this invention is
technically very advantageous for preparing the cinnamic
acid.
The cinnamate esters useful for the practise
of the process of this invention are represented by the
following formula:
(R )n ~Co2R4
(wherein n is an integer of 1 to 5, R1 is hydrogen or at
least one kind of substituent on the aromatic ring and
represents halogen, hydroxyl, alkyl of 1 to 4 carbon
atoms or alkoxy of l to 4 carbon atoms, and where n is
not less than 2, each R1 is the same or different.
R2 and R3 may be the same or different groups and
..
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represent respectively hydrogen or alkyl of 1 to 6
carbon atoms.
R4 represents unsubstituted or substituted alkyl group.)
The cinnamate esters include, for example,
methyl cinnamate, ethyl cinnamate, propyl cinnamate,
butyl cinnamate, ethyl ~-methyl-~-phenylacrylate,
methyl a-propyl-~-chlorophenylacrylate, methyl ~-3,4-
dimethoxyphenylacrylate, methyl ~-4-methoxyphenylacrylate
and benzyl cinnamate.
The cinnamate esters mentioned above can be
prepared by various methods. For example, as
aforesaid, these can be prepared by Claisen condensation
from benzaldehydes and acetate ester, by the oxidative
carbonylation reaction of styrene compounds, by the
reaction of benzene or its derivatives with acrylate
ester and further by the separation from natural
storax.
The alkali for use in the alkali hydrolysis
of this invention includes, for example, sodium hydroxide,
potassium hydroxide, calcium hydroxide and barium
hydroxide. Sodium hydroxide or potassium hydroxide is
preferably employed among these compounds. The alkali
can also be applied as a mixture of two or more The
quantity of alkali in use is at least one equivalent to
the cinnamate ester.
The hydrolysis reaction of cinnamate esters
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with alkali in the process of this invention is started
in the heterogeneous binary-phase liquid system,
which consists of melted cinnamate ester and aqueous
alkali solution. Although alkali cinnamates formed
in the hydrolysis are rather easily dissolved in
water, insulfficient quantity of water in use causes
incomplete dissolution. As a result a homogeneous
solution cannot be formed and in the extreme cases
the operation is substantially inhibited as a result
of solidification. While excessive quantity of water
leads to the reduction of yield.
Therefore, for the technically effective
application of the method of this invention, it is
required to u~e water in such quantity that the
concentration of the alkali cinnamate is 1 to 20% by
weight in the aqueous solution. It is preferably
in the range of 2 to 15% by weight.
For the hydrolysis reaction of the cinnamate
ester with aqueous solution of the alkali, any operation
can be applied which includes a batchwise or semi-
batchwise operation of charging both components in a
lump or separately into the reaction vessel and a
continuous operation of continuously charging these
components.
The reaction temperature is preferably in the
range of 40 to 120C and more preferably 60 to 100C.
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The reaction pressure is normally atmospheric
and yet in some cases slightly decreased or increased
pressure is effective.
The reaction time depends upon reaction
temperature and pressure and is preferably in the range
of 1 to 120 minutes, and more preferably 3 to 30
minutes.
Vigorous stirring is effective for the process
of this invention because the hydrolysis reaction of the
alkyl cinnamate with the alkali starts in the hetero-
geneous binary-phase liquid system except that special
cinnamate esters are used as raw materials. The mixture
generall~ forms a homogeneous solution after ending the
reaction.
In the method of this invention, alcohols
generated in the course of the hydrolysis reaction may
optionally be recovered, for example, by distilling from
the system during or after the reaction.
An example of the effective manner for removing
alcohol is to distill generated alcohol out of the system
together with exhaust gas by feeding inert gas into the
reaction solution.
In the process of this invention, the cinnamic
acids can be precipitated by acidifying the resultant
aqueous alkaline solution with the mineral acid and
the reaction mixture forms a slurry or suspension. The
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cinnamic acids can be separated from the mixture by
suitable means, for example, filtration, decantation
and the like.
Water soluble mineral acid which is usually
available in industry can be used in the acidification
of the alkali cinnamate solution. The mineral acid
includes, for example, hydrochloric acid, sulfuric
acid and phosphoric acid.
In order to afford high yield of the
cinnamic acid in the method of this invention, the alkali
cinnamate and the mineral acid are required to react so
as to keep the pH value at not more than 4 and preferably
at not more than 3 in the solution after endin~ the
acidification reaction.
When the pH value is more than 4, precipitation
of the desired product is incomplete even in acidic
conditions and thus the yield is reduced. Therefore
the acidification reaction of the alkali cinnamate
solution is suitably carried out by maintaining the
system always in acidic conditions, that is, at the pH
value of not more than 4 and preferably not more than 3.
In the process of this invention, the
acidification of aqueous alakline solution of the
alkali cinnamate can be performed by the batchwise,
semi-batchwise or continuous operation. The embodiments
of acidification reaction are, for example, the operation
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of adding said mineral acid into the aqueous alkaline
solution of alkali cinnamate, the operation of adding
the aqueous alkaline solution of alkali cinnamate into
the mineral acid and the operation of continuously
charging both components. Any of these operations
can be applied.
In the operation of adding the mineral acid
into the aqueous solution of alkali cinnamate, however,
the reaction mixture often forms a slurried liquid
having a high viscosity. In the extreme cases the
stirring is inhibited. As a result the product is
deteriorated in quality and the yield tends to decrease.
Therefore, to avoid aforesaid problems in
the batchwise or semi-batchwise operation, the alkaline
solution of alkali cinnamate is preferably added into
the mineral acid.
Besides the acidification reaction of this
invention is also preferably conducted by the continuous
operation. The term continuous operation mentioned
herein is different from what is called batchwise
operation in which raw materials are charged in a lump
and discharged after ending the reaction. It means
the operation of discharging the reaction product while
charging the raw materials. The charge or discharge
operation may not always be continuous. The operation
may be intermittent with a suitable interval so long as
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the operation does not make~this invention invalid.
For example, quantity of the raw materials
can be set so as to obtain the pH value of not more
than 4 after the reaction. And the materials may be
fed continuously or intermittently at a certain rate.
On conducting the acidification reaction of
this invention, the continuous reaction may optionally
be started after previously charging the sufficient
quantity of aqueous solution of the mineral acid for
stirring the reactant. Vigorous stirring is more
effective for the acidification.
The suspension of the cinnamic acid formed
by the acidification of this invention is continuously
di~charged, and optionally, it may be discharged
intermittently. As a concrete method, for example,
from a flooding port equipped on the reaction vessel,
the suspension may be discharged by an overflow mode,
or may also be discharged by use of a pump.
The separation step of the cinnamic acid
from the suspension may be carried out batchwise or
continuously.
In the acidification reaction of aquéous
alkaline solution of the alkali cinnamate by the method
of this invention, the quantity of water in use is
adjusted so that the concentration of the produced
cinnamic acid is preferably 1 to 20% by weight and
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more preferably 2 to 15% by weight of the suspension.
The concentration outside of this range cannot
sufficiently achieve the object of this invention.
That is, the yield of the product reduces at less than
1~ by weight, while a highly concentrated slurry is
formed at more than 20% by weight and causes insufficient
stirring, incomplete reaction and deterioration in the
purity of product.
In the acidification of this invention, the
batchwise or semi-batchwise operation wherein the
aqueous solution of alkali cinnamate is added into the
mineral acid, or the continuous operation wherein the
reaction is conducted by maintaining the pH value of
the system at not more than 4, has the advantage of
performing the acidification in the higher concentration
of the produced cinnamic acid in the suspension.
The temperature in the acidification reaction
is suitably 10 to 80C. The reaction is normally
carried out under atmospheric pressure and may also
be performed under slightly reduced or increased
pressure.
The present invention is further illustrated
by the following Examples and Comparative examples.
Example 1
A separable flask equipped with a stirrer was
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charged with 16.2 grams (0.10 mol) of methyl cinnamate,
and a solution of 4.3 grams of 97 wt.% sodium hydroxide
in 200 grams of water, and the mixture was reacted at
80~C for 15 minutes with vigorous stirring. The aqueous
alkaline solution of sodium cinnamate thus obtained was
added slowly under stirring into 200 ml of aqueous
sulfuric acid solution containing 0.056 mol of sulfuric
acid. The formed suspension had pH of approximately 1.5
after cooling to room temperature. The precipitates
were filtered with suction, washed with 50 ml of water
by stirring in a beaker, filtered again and dried under
reduced pressure. Cinnamic acid thus obtained was 14.6
grams (98.5~ yield) and had purity of more than 99.9%
according to analysis.
ComDarative example 1
The procedure o~ Example 1 was repeated except 64
grams of water were used in the hydrolysis. As a
result, the reaction solution was entirely solidified at
around 5 minutes after starting the hydrolysis reaction
of methyl cinnamate with sodium hydroxide, and further
proceeding of the reaction was failed.
Comparative example 2
The procedure of Example 1 was repeated except 2100
grams of water in the hydrolysis and 200 grams o~
~P
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aqueous sulfuric acid solution containing 0.08 mol of
sulfuric acid were used in acidification. Consequently,
cinnamic acid obtained was 13.8 grams and the yield was
reduced to 93.2~.
Comparative example 3
The procedure of Example 1 was repeated
except 2000 ml of aqueous sulfuric acid solution
containing 0.085 mol of sulfuric acid were used in
place of the aqueous acid solution in acidification.
Consequently, cinnamic acid obtained was 13.9 grams
and the yield was reduced to 93.8%.
Example 2
The same reaction procedure as in Example 1
was carried out except 230 grams of water was used
in hydrolysis. After heating for 15 minutes with
stirring, the flask was fitted with a Liebig's
condenser and further heated to give 30 grams of
distillate. The distillate contained 3.1 grams of
methanol according to the analysis by gas chromatography.
Example 3
The same reaction procedure as in Example 1
was carried out except 17.6 grams (0.1 mol) of ethyl
cinnamate was used in place of methyl cinnamate.
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Consequently, cinnamic acid obtained was 14.5 grams
(97.9% yield) and had purity of above 99.9~.
Example 4
The procedure of Example 1 was repeated except
6.9 grams of 85~ potassium hydroxide was used in place
of sodium hydroxide in hydrolysis. Consequently,
cinnamic acid obtained was 14.5 grams (97.9% yield)
and had purity of above 99.9%.
Example 5
The procedure of Example 1 was repeated except
0.112 mol of hydrochloric acid was used in place of
0.056 mol of sulfuric acid in acidification. Consequent-
ly, cinnamic acid obtained was 14.4 grams (97.2% yield)
and had purity of above 99.9%.
Example 6
A 300 ml separable flask was charged with
16.2 grams (0.10 mol) of methyl cinnamate, and a
solution of 4.3 grams of 97 wt.% sodium hydroxide in
140 grams of water. The mixture was reacted at 80C
for 15 minutes with vigorous stirring. The aqueous
alkaline solution of sodium cinnamate thus obtained
was poured into a hot funnel which was previously kept
at 80C. The solution was added dropwise with stirring
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to a beaker having 20 ml of aqueous sulfuric acid
solution containing 0.053 mol of sulfuric acid. The
resultant suspension was cooled to room temperature
and filtered with suction. The crystals were washed
with 50 ml of water by stirring in a beaker, filtered
and dried under reduced pressure. Cinnamic acid
obtained was 14.7 grams (99.9% yield). The purity was
above 99.9~ according to analysis.
Example 7
The procedure of Example 6 was repeated except
17.6 grams (0.1 mol~ of ethyl cinnamate was used in
place of methyl cinnamate. Consequently cinnamic acid
thus obtained was 14.6 grams (98.5~ yield) and had
purity of above of 99.9%.
Example 8
The procedure of Example 6 was repeated except
6,9 grams of 85 wt.% potassium hydroxide in place of
sodium hydroxide. Consequently cinnamic acid thus
obtained was 14.5 grams (97.9%) and had purity of above
99 . 9% .
Example 9
25The procedure of Example 6 was repeated except
0.102 mol of hydrochloric acid was used in place of
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0.053 mol of sulfuric acid in acidification. Conse-
quently cinnamic acid thus obtained was 14.4 grams
(97.2% yield) and had purity of above 99.9~.
Example 10
A 1 Q round bottomed flask equipped with a
stirrer was charged with 100.0 grams (0.617 mol) of
methyl cinnamate and 700 grams of aqueous solution
containing 25.9 grams (0.647 moi) of sodium hydroxide
and vigorously stirred for 15 minutes at 80C. Then
the resultant aqueous alkaline solution of sodium
cinnamate having concentration of 13.1% by weight
was transferred to a hot dropping funnel kept at 80C.
A round bottomed flask having an overflow
lS port of about 20 mm in diameter in the middle of the
vessel (the volume below the port was about 130 ml)
was respectively equipped with a stirrer, an electrode
of pH meter, a discharge orifice of tube pump capable
of delivering 25 wt.% aqueous sulfuric acid solution at
a constant flow rate, and an orifice of hot dropping
funnel containing aqueous alkaline solution of sodium
cinnamate.
After charging about 20 grams of sulfuric
acid in the flask in advance, the aqueous alkaline
solution of sodium cinnamate was added dropwise with
stirring until pH of 2 was indicated. Then the aqueous
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solution of sodium cinnamate and 25 wt.% aqueous sulfuric
acid solution were added dropwise at a rate of 13 grams
per minute and 2.0 grams per minute respectively.
The reaction was always carried out at the pH of not
more than 2 and terminated after one hour. The concen-
tration of cinnamic acid in the reaction vessel was
about 10 wt.%.
The slurry flowed out of the overflow port
and cinnamic acid finally remained in the flask were
filtered with suction, washed with water and dried
under reduced pressure. Cinnamic acid thus obtained
was 90.0 grams (98.5~ yield) and had purity of above
99.9% according to the analysis of liquid chromatography.
The quantity of cinnamic acid produced was 116 g/Q to
one liter of water used, and about 700 g/Q to the unit
volume of reaction vessel.
An aqueous alkaline solution of sodium cinnamate
was obtained by the same method as described above. The
solution was distilled at about 100C, a fraction of 98
to 99C was collected, and 17.8 grams of methanol were
recovered as an aqueous solution.
Comparative example 4
A 3 Q flask equipped with a stirrer was
charged with 100.0 grams (0.617 mol) of methyl cinnamate
and 1260 grams of aqueous solution containing 25.9 grams
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21
(0.647 mol~ of sodium hydroxide and vigorously stirred
for 15 minutes at 80C. To the obtained aqueous
alkaline solution of sodium cinnamate having
concentration of 7.7% by weight were added in a lump
1240 ml of aqueous sulfuric acid solution containing
0.35 mol of sulfuric acid. The resultant slurry having
concentration of 3.4% by weight was cooled to room
temperature and measured pH to give a value of about 2.
The total reaction mixture was discharged and filtered
with suction. The separated precipitates were 87.8
grams (96.0% yield) and had purity of above 99.9%. The
quantity of cinnamic acid produced per 1 of water used
and per unit volume of the reaction vessel were 36 g/l
and 35 g/l respectively.
E~a~ Lll
The procedure of Example 10 was repeated except 19
wt.% hydrochloric acid was used in place of 25 wt.%
sulfuric acid and pH was kept at not more than 3 in the
reaction vessel in acidification. Consequently cinnamic
acid obtained was 89.5 grams (97.9% yield) and had
purity of above 99.9%.
Comparative example 5
The procedure of Example 10 was repeated except the
dropwise addition rate of aqueous sulfuric
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acid solution was reduced and pH of the reaction
mixture was kept at 5 in acidification. As a result,
the separated cinnamic acid was 85.5 grams and the
. "
yield was reduced to 93.5%.
