Process for preparing trans-.beta.-benzoylacrylic acid ester

A process for preparing trans-.beta.-benzoylacrylic acid ester having the general formula (I): ##STR1## wherein R is alkyl group or aralkyl group, which comprises dealcoholizing .beta.-benzoyl-.alpha.-alkoxypropionic acid ester having the general formula (II): ##STR2## wherein R is above, in the presence of an acid catalyst to give trans-.beta.-benzoylacrylic acid ester having the general formula (I). According to the process of the present invention, the by-product (II) produced in the esterification reaction of .beta.-benzoylacrylic acid (III) with the alcohol (V) by the dehydration reaction can be converted into the compound (I) by the dealcoholization reaction in the presence of the acid catalyst and thus trans-.beta.-benzoylacrylic acid ester (I) with a high purity can be produced in an industrially advantageous manner.

BACKGROUND OF THE INVENTION 
The present invention relates to a process for preparing 
trans-.beta.-benzoylacrylic acid ester having the general formula (I): 
##STR3## 
wherein R is an alkyl group or aralkyl group. The purpose of the present 
invention is to provide a process for preparing the compound (I) in an 
industrially advantageous manner, the compound (I) being an important 
intermediate compound for the production of the medicines and the 
perfumes. 
Hitherto, the most commonly known method for synthesizing the ester has 
been the method by the dehydration reaction between carboxylic acid and 
alcohol. This method has been used for synthesizing .beta.-benzoylacrylic 
acid ester, for example, ethyl .beta.-benzoylacrylate. In case of the 
dehydration reaction between .beta.-benzoylacrylic acid and ethanol, 
though it has been reported that ethyl .beta.-benzoylacrylate is obtained 
with a good yield, geometrical isomerism, i.e. cis-form and trans-form, of 
the starting material and of the product as well as the concrete procedure 
have not been described [Nippon Kagakukaishi, 88, 224 (1967)]. On the 
contrary, other report describes that the product of the 
ethyl-esterification reaction of .beta.-benzoylacrylic acid with ethanol 
is hardly purified [J. Amer. Chem. Soc., 45, 222 (1923)], while another 
report describes that ethyl .beta.-benzoyl-.alpha.-ethoxypropionate was 
obtained in the usual ethyl-esterification reaction [Bull. Chem. Soc. 
Japan, 42, 1353 (1969)]. Therefore, the above-mentioned method for 
synthesizing .beta.-benzoylacrylic acid ester by the dehydration reaction 
between 8-benzoylacrylic acid and alcohol is not suited for the method for 
industrially effective production of .beta.-benzoylacrylic acid ester 
since it has various problems to be solved such as unclearness of 
geometric isomerism of the product, of a kind of the products and of a 
quantitative ratio of the products. Under such circumstances, several 
different methods for preparing trans-.beta.-benzoylacrylic acid ester 
have been studied by many research workers. For example, a method by the 
aldol condensation reaction between acetophenone and glyoxylic acid ester 
(Japanese Unexamined Patent Publication No. 192622/1982) and a method by 
halogenating .beta.-benzoylpropionic acid ester and then 
dehydrohalogenating the resultant [J. Amer. Chem. Soc., 45, 222 
(1923)]have been proposed. However, these methods are also disadvantageous 
for an industrial application since, in the former method, the product is 
not easily produced and very expensive glyoxylic acid ester is employed 
and, in the latter method, the reaction is carried out in a multiple step 
including a preparation of .beta.-benzoylpropionic acid ester and the 
yield is low. Also a method by esterifying trans-.beta.-benzoylacrylic 
acid by means of dialkyl sulfate or halogenated alkyl is not suited for 
the industrial production since it has various drawbacks such as noxious 
reaction agent and liquid-waste treatment after the reaction. 
In order to establish the industrial process for preparing 
trans-.beta.-benzoylacrylic acid ester endowed with excellent 
operatability, safety and economical advantage, the present inventors have 
studied a condition for predominantly producing trans-form of the ester 
and surpressing the by-product in the reaction between 
.beta.-benzoylacrylic acid and alcohol. 
As the result of the continuous effort of the present inventors, now it has 
been found that in the esterification reaction of .beta.-benzoylacrylic 
acid having the formula (III): 
##STR4## 
with the alcohol having the general formula (V): 
EQU ROH (V) 
wherein R is as above, by the dehydration reaction, considerable amount of 
.beta.-benzoyl-.alpha.-alkoxypropionic acid ester having the general 
formula (II): 
##STR5## 
wherein R is as above, is by-produced in addition to desired 
trans-.beta.-benzoylacrylic acid ester having the general formula (I): 
##STR6## 
wherein R is as above, and that the by-product (II) can be easily 
converted into the desired compound (I) by the dealcoholization reaction 
in the presence of an acid catalyst. 
SUMMARY OF THE INVENTION 
According to the present invention, there is provided a process for 
preparing trans-.beta.-benzoylacrylic acid ester having the general 
formula (I): 
##STR7## 
wherein R is an alkyl group or aralkyl group, which comprises 
dealcoholizing .beta.-benzoyl-.alpha.-alkoxypropionic acid ester having 
the general formula (II): 
##STR8## 
wherein R is as above, in the presence of an acid catalyst. According to 
the process of the present invention, the by-product (II) produced in the 
esterification reaction of .beta.-benzoylacrylic acid (III) with the 
alcohol (V) by the dehydration reaction can be converted into the compound 
(I) by the dealcoholization reaction in the presence of the acid catalyst 
and thus trans-.beta.-benzoylacrylic acid ester (I) with a high purity can 
be produced in an industrially advantageous manner. 
DETAILED DESCRIPTION OF THE INVENTION 
The process of the present invention is illustrated in the following 
reaction scheme. 
##STR9## 
In the above reaction scheme, R is as above, the compound (III) is 
trans-form, cis-form or a mixture thereof of .beta.-benzoylacrylic acid. 
In the dehydration reaction between trans-.beta.-benzoylacrylic acid (III) 
and the alcohol, both desired trans-.beta.-benzoylacrylic acid ester (I) 
and a considerable amount of the alcohol addition product, 
.beta.-benzoyl-.alpha.-alkoxypropionic acid ester (II), as the by-product 
are produced as shown in the following scheme. 
##STR10## 
Hitherto, this by-production of the alcohol addition product has been an 
obstacle for effectively producing the desired compound (I) with a high 
purity. 
However, now it has been found that the desired compound (I) and the 
alcohol addition product (II) are mutually conversible and they are in 
equilibrium with each other under control of a concentration of the 
alcohol as shown in the following reaction scheme. 
##STR11## 
The removal of the alcohol (V) from the reaction system in the presence of 
an acid catalyst shifts the equilibrium to the desired compound (I), 
finally the compound (II) being quantitatively converted into the compound 
(I), and thus the desired compound (I) can be obtained with a high purity 
in an extremely easy way. 
In this way, the compound (II) can be converted into the desired compound 
(I) by the acid catalyst at room temperature or under heating. However, if 
the produced alcohol is not removed from the reaction system, the 
conversion of the compound (II) into the desired compound (I) becomes 
incomplete. When the equilibrium is shifted to the desired compound (I) 
by, for example, distilling away the produced alcohol under normal or 
reduced pressure, the desired compound (I) can be effectively obtained. 
In case that the same esterification reaction is carried out on 
cis-.beta.-benzoylacrylic acid (III), cis-.beta.-benzoylacrylic acid ester 
(IV), trans-.beta.-benzoylacrylic acid ester (I) and the alcohol addition 
product (II) are obtained as shown in the following reaction scheme. 
##STR12## 
In the above reaction, the side-produced alcohol addition product (II) can 
be converted into the desired compound (I) as mentioned above. It was 
found that the concurrently produced compound (IV) can be easily 
isomerized into the desired trans-.beta.-benzoylacrylic acid ester (I) by 
the acid catalyst under the same reaction condition as in case of the 
dealcoholization reaction. 
From the practical point of view, the esterification reaction is preferably 
conducted while removing water produced as the reaction proceeds from the 
reaction system together with an azeotropic solvent in a conventional 
manner so that the equilibrium is shifted to the esterification. 
Further, when .beta.-benzoylacrylic acid is esterified with around 
stoichiometric amount (for example, 1.0 to 1.5 equivalent amount) of the 
alcohol while removing water by means of the azeotropic solvent, the 
esterification (dehydration) reaction proceeds effectively through removal 
of produced water and at the same time a decreased concentration of the 
alcohol in the reaction system accelerates the conversion of the alcohol 
addition product into the desired compound as shown in the following 
reaction scheme. 
##STR13## 
In this manner, by-production and accumulation of the alcohol addition 
product is surpressed and thus the desired compound (I) can be efficiently 
obtained. 
When cis-.beta.-benzoylacrylic acid is employed, the by-produced compound 
(IV) is isomerized into the desired compound (I) as mentioned above. 
##STR14## 
Therefore, according to the present invention, any .beta.-benzoylacrylic 
acid in trans-form, in cis-form or in a mixture thereof can be converted 
into trans-.beta.-benzoylacrylic acid ester with an extremely high purity. 
As mentioned above, in the process for preparing 
trans-.beta.-benzoylacrylic acid ester by the esterification reaction 
between .beta.-benzoylacrylic acid and alcohol, the process of the present 
invention is characterized in that the by-product and cis-isomer are 
converted into the desired compound by distilling away the alcohol which 
constitutes .beta.-benzoyl-.alpha.-alkoxypropionic acid ester in the 
presence of the acid catalyst. 
In the conversion reaction of the compound (II) or of the compound (IV) 
into the desired compound (I), examples of the substituent R are a linear 
alkyl group such as methyl group, ethyl group, n-propyl group, n-hexyl 
group or n-octyl group; a branched alkyl group such as isopropyl group, 
isobutyl group or isoamyl group; a cycloalkyl group such as cyclohexyl 
group; an aralkyl group such as .beta.-phenylethyl group. 
The conversion reaction of the compound (II) or of the compound (IV) into 
the desired compound (I) can be conducted without solvent or in an inert 
solvent such as benzene or toluene. The reaction solvent may be benzene, 
toluene or the like in a single form or may be a mixed solvent containing 
other solvent without interfering with the proceeding of the reaction 
together with benzene, toluene or the like as a main solvent. Examples of 
the acid present in the reaction system are, for example, an inorganic 
acid such as sulfuric acid or hydrochloric acid, an organic acid such as 
paratoluenesulfonic acid, Lewis acid such as boron trifluoride etherate, 
and the like. Though the reaction temperature may range from 20.degree. to 
150.degree. C., it is preferably not less than 40.degree. C. from the view 
point of the reaction rate, and preferably not more than 100.degree. C. 
from the view point of decomposition or coloration of the product. An 
amount of the acid is generally 0.02 to 40 % (W/V) based on the reaction 
mixture in case of a non-volatile acid such as paratoluenesulfonic acid, 
or 10 to 50 % (W/V) in case of a volatile solvent such as hydrochloric 
acid. The reaction is usually carried out for the time ranging from a few 
minutes to about 5 hours. 
The proceeding of the reaction can be followed by means of a thin layer 
chromatography. After completion of the reaction, desired 
trans-.beta.-benzoylacrylic acid ester (I) can be obtained by extraction 
or distillation. 
In the conversion reaction, the alcohol addition product (II) and 
cis-.beta.-benzoylacrylic acid ester can be separately or simultaneously 
converted into the desired compound (I). Trans-form of 
.beta.-benzoylacrylic acid (III) is reacted with the alcohol in the 
presence of the acid to produce the compounds (I) and (II) or, if cis-form 
of .beta.-benzoylacrylic acid is employed, to produce the compounds (I), 
(II) and (IV) in the reaction system and then the compound (II) and/or the 
compound (IV) are converted into the desired compound (I) while distilling 
away the excessive unreacted alcohol and the alcohol produced in the 
conversion reaction from the reaction system under normal or reduced 
pressure, finally only the desired compound (I) being isolated. 
In the esterification (dehydration) reaction between .beta.-benzoylacrylic 
acid and the alcohol employing the azeotropic solvent, an amount of the 
alcohol is preferably about 1.0 to about 1.5 equivalent amount based on 
.beta.-benzoylacrylic acid with consideration of remaining 
.beta.-benzoylacrylic acid and by-produced 
.beta.-benzoyl-.alpha.-alkoxypropionic acid ester. Benzene, chloroform, 
1,1,1-trichloroethane or the like can be employed as the azeotropic 
solvent in the usual way. A kind of the acid present in the reaction 
system and an amount of the acid are as mentioned above. The reaction is 
carried out for the time ranging from about 1 hour to 5 hours. After 
completion of the reaction, desired trans-.beta.-benzoylacrylic acid ester 
(I) can be obtained by extraction or distillation. 
Any .beta.-benzoylacrylic acid can be employed in cis-form, in trans-form 
or in a mixture thereof. 
The present invention is more particularly described by the following 
Examples and Reference Example. However, it should be understood that the 
present invention is not limited to the Examples and the Reference Example 
and various changes and modifications can be made without departing from 
the scope and spirit of the present invention.

EXAMPLE 1 
A mixture of 268 mg of methyl .beta.-benzoyl-.alpha.-methoxypropionate, 150 
mg of paratoluenesulfonic acid monohydrate and 5 ml of toluene was stirred 
at 80.degree. C. for 1 hour. A pressure was reduced with an aspirator and 
a total amount of the resultant was reduced to 1/2 by concentration. The 
resultant was stirred at 80.degree. C. for 20 minutes and was left for 
cooling. The reaction mixture was distributed between ethyl acetate and 
water and the ethyl acetate layer was washed with a saturated solution of 
NaHCO.sub.3 and then with water, and was dried with anhydrous magnesium 
sulfate. The solvent was distilled away to give 206 mg of methyl 
trans-.beta.-benzoylacrylate as a yellow oil. 
.sup.1 H NMR (CDCl.sub.3,.delta.): 8.15 to 7.32 (m, phenyl), 7.95 (d, 
olefinic proton), 6.88 (d, olefinic proton) and 3.85 (s, ester methyl). 
EXAMPLE 2 
A mixture of 6.45 g of ethyl trans-.beta.-benzoylacrylate, 3.55 g of ethyl 
.beta.-benzoyl-.alpha.-ethoxypropionate and 1.80 g of sulfuric acid was 
stirred at 100.degree. C. while reducing the pressure to 20 mmHg with the 
aspirator and distilling away produced ethanol. The reaction was continued 
for 10 minutes and then cooled, followed by the procedure as in Example 1 
to give 7.76 g of ethyl trans-.beta.-benzoylacrylate. 
EXAMPLE 3 
A mixture of 6.79 g of ethyl trans-.beta.-benzoylacrylate, 1.97 g of ethyl 
.beta.-benzoyl-.alpha.-ethoxypropionate and 0.12 g of sulfuric acid was 
subjected to distillation under reduced pressure. 7.02 g of ethyl 
trans-8-benzoylacrylate was distilled out at 123.degree. to 134.degree. 
C./3 mmHg. 
EXAMPLE 4 
A mixture of 7.75 g of trans-.beta.-benzoylacrylic acid, 25.8 ml of ethanol 
and 1.63 g of sulfuric acid was stirred at 62.degree. C. for 3 hours. A 
pressure was gradually reduced with the aspirator and ethanol was 
distilled away for 20 minutes. After a pressure was finally reduced to 20 
mmHg, the resultant was stirred at 62.degree. C. for 1.5 hours and then 
cooled, followed by the procedure as in Example 1 to give 8.18 g of ethyl 
trans-.beta.-benzoylacrylate. 
EXAMPLE 5 
A mixture of 5.00 g of trans-.beta.-benzoylacrylic acid, 1.67 ml of 
n-propanol and 1.05 g of sulfuric acid was stirred at 100.degree. C. for 
1.5 hours. A pressure was gradually reduced with the aspirator and 
n-propanol was distilled away for 15 minutes. After a pressure was finally 
reduced to 20 mmHg, the resultant was stirred at 100.degree. C. for 10 
minutes and then cooled, followed by the procedure as in Example 1 to give 
5.78 g of n-propyl trans-.beta.-benzoylacrylate. 
.sup.1 H NMR (CDCL.sub.3,.delta.): 8.13 to 7.33 (m, phenyl), 7.94 (d, 
olefinic proton), 6.88 (d, olefinic proton), 4.20 (t, --OCH.sub.--2 
CH.sub.2 CH.sub.3, methylene), 2.77 (m, --OCH.sub.2 CH.sub.--2 CH.sub.3, 
methylene) and 1.00 (t, --OCH.sub.2 CH.sub.2 CH.sub.--3, methyl) 
EXAMPLE 6 
A mixture of 200 mg of ethyl cis-.beta.-benzoylacrylate, 200 mg of boron 
trifluoride etherate (about 47 %) and 10 ml of toluene was stirred at 
80.degree. C. for 45 minutes and then cooled, followed by the procedure as 
in Example 1 to give 175 mg of ethyl trans-.beta.-benzoylacrylate as a 
yellow oil. 
.sup.1 H NMR (CDCl.sub.3, .delta.): 
8.10 to 7.35 (m, phenyl), 7.90 (d, olefinic 
proton), 6.85 (d, olefinic proton), 4.28 (q, --OEt, methylene) and 1.33 (t, 
--OEt, methyl). 
EXAMPLE 7 
A mixture of 3.00 g of .beta.-benzoylacrylic acid (cis/trans =1/2 according 
to .sup.1 H NMR analysis), 10 ml of ethanol and 0.63 g of sulfuric acid 
was refluxed for 2 hours. A pressure was gradually reduced with the 
aspirator and ethanol was distilled away for 10 minutes. After a pressure 
was finally reduced to 20 mmHg, the resultant was stirred at 85.degree. C. 
for 40 minutes and then cooled, followed by the procedure as in Example 1 
to give 2.45 g of ethyl trans-.beta.-benzoylacrylate. 
EXAMPLE 8 
A mixture of 7.50 g of trans-.beta.-benzoylacrylic acid, 2.36 g of ethanol, 
0.50 g of sulfuric acid and 30 ml of chloroform was refluxed for 5 hours 
while azeotropically removing water produced from the reaction system. 
After cooling, the reaction mixture was washed with a saturated solution 
of NaHCO and then with water. The solvent was distilled away to give 8.08 
g of ethyl trans-.beta.-benzoylacrylate. 
REFERENCE EXAMPLE 
A mixture of 7.75 g of trans-.beta.-benzoylacrylic acid, 25.8 ml of ethanol 
and 1.63 g of sulfuric acid was stirred at 62.degree. C. for 3 hours. 
After cooling, the resultant was diluted with water and was then extracted 
with ethyl acetate. The ethyl acetate layer was washed with a saturated 
solution of NaHCO.sub.3 and then with water and was dried with anhydrous 
magnesium sulfate. The solvent was distilled away to give 7.86 g of a 
mixture of ethyl trans-.beta.-benzoylacrylate and ethyl 
.beta.-benzoyl-.alpha.-ethoxypropionate (3 : 1 according to .sup.1 H NMR 
analysis).