Method for producing hydroxyphenylpropionic acid ester

Method for producing 3,9-bis{2-[3-(3-tert-butyl-4-hydroxy-5-methylphenyl)propionyloxy]-1,1-dime thylethyl}-2,4,8,10-tetraoxaspiro[5.5]undecane by ester exchange of a 3-(3-tert-butyl-4-hydroxy-5-methylphenyl)-propionic acid ester with 3,9-bis(2-hydroxy-1,1-dimethylethyl)-2,4,8,10-tetraoxaspiro[5.5]-undecane at a temperature of 170.degree.-250.degree. C. using a calcium compound as a catalyst in an amount of 0.05-1.5 moles per mole of the 3,9-bis(2-hydroxy-1,1-dimethylethyl)-2,4,8,10-tetraoxaspiro[5.5]-undecane.

The present invention relates to a novel method for producing 
3,9-bis{2-[3-(3-tert-butyl-4-hydroxy-5-methylphenyl)propionyloxy]-1,1-dime 
thylethyl}-2,4,8,10-tetraoxaspiro[5.5]undecane represented by the 
structural formula (III) (hereinafter referred to as 
"hydroxyphenylpropionic acid ester"), 
##STR1## 
It is well known that the hydroxyphenylpropionic acid ester represented by 
the structural formula (III) can effectively be used to prevent various 
kinds of synthetic resin from deterioration such as softening, 
embrittlement, surface crack, discoloration, etc. caused by the action of 
heat, light and oxygen at the time of processing and use [Japanese Patent 
Application Kokai (Laid-open) Nos. 25826/84 and 231089/84]. As such 
synthetic resins, there may be mentioned polyolefins such as polyethylene, 
polypropylene, etc., styrene series synthetic resins such as polystyrene, 
impact-resistant polystyrene, ABS, etc., engineering plastics such as 
polyacetal, polyamide, etc., and polyurethane. 
Hitherto, nothing is directly known about a method for producing such 
hydroxyphenylpropionic acid ester represented by the structural formula 
(III), but, to produce 
3,9-bis{2-[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionyloxy]-1,1-dimethyl 
ethyl}-2,4,8,10-tetraoxaspiro[5.5]undecane similar to said ester (III) and 
represented by the structural formula (IV), 
##STR2## 
such a method is known that methyl 
3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate and 
3,9-bis(2-hydroxy-1,1-dimethylethyl)-2,4,8,10-tetraoxaspiro[5.5]undecane 
represented by the structural formula (II), 
##STR3## 
are ester-exchanged at 140.degree.-150.degree. C., under reduced pressure 
if necessary, using lithium amide as a catalyst [Japanese Patent 
Application Kokai (Laid-open) No. 25826/84]. 
However, when the compound represented by the structural formula (III), an 
object of the present invention, is produced by this method, the purity, 
color, etc. of the product obtained are not satisfactory, and in some 
cases, the product can not be even obtained. This method therefore is 
unsatisfactory as an industrial method. 
Generally, in order to obtain a certain substance in good purity on a 
commercial scale, it is a common practice to purify the substance at the 
steps subsequent to the prescribed chemical reaction, making use of 
differences in physical properties between said substance and the 
impurities, although it is of course not necessary to conduct such 
purification if the substance already has a desired purity at the stage 
when it is obtained as a reaction product of said reaction. Specifically, 
methods such as recrystallization, distillation, adsorption, sublimation, 
etc. are used for such purification. 
In the production of the desired hydroxyphenylpropionic acid ester 
represented by the structural formula (III), the product is generally low 
in purity, so that the subsequent purification is necessary. Since, 
however, said compound is very low in vapor pressure, distillation or 
sublimation is not suitable as a purification method. Purification by 
adsorption is an effective means, but in order that this method may 
succeed, the selectivity and amount of adsorbant are so important that the 
compound to be purified should be of considerably high purity. 
Purification by adsorption, therefore, cannot be used as an industrial 
purification method excet in those cases wherein economy is sacrified or 
impurities and colored products to be removed are luckily very small in 
amounts. Thus, the only remaining purification method for the 
hydroxyphenylpropionic acid ester represented by the structural formula 
(III) is recrystallization. 
However, the hydroxyphenylpropionic acid ester represented by the 
structural formula (III) is a compound which is very difficult to 
crystallize, and it takes a glassy form at room temperature when obtained 
by the usual methods. 
As a result of an extensive study, the present inventors have found that 
said ester of the structural formula (III) takes a certain crystalline 
form at room temperature. Thus, purification by recrystallization from 
solvent has come to be possible in principle. However, the present 
inventors have found at the same time that, in actual operation, 
impurities formed by the reaction disturb crystallization, so that the 
recrystallization is impossible unless the purity of said ester is 
previously raised to a very high level at the step of reaction. 
However, when the ester exchange proposed in the foregoing Japanese Patent 
Application Kokai No. 25826/84 is applied using the catalyst and reaction 
condition described therein, it is impossible to obtain the product 
containing such a low amount of impurities as to make it possible to 
successfully apply the purification by recrystallization. The present 
inventors have made a further extensive study to solve these problems, and 
as a result, found that the product of excellent quality can be obtained 
simply and economically by carrying out the reaction at a particular 
temperature using a particular kind of catalyst. Based upon this finding 
the present invention has been accomplished. 
An object of the present invention is to provide a method for producing 
3,9-bis{2-[3-(3-tert-butyl-4-hydroxy-5-methylphenyl)-propionyloxy}-1,1-dim 
ethylethyl}-2,4,8,10-tetraoxaspiro[5.5]undecane represented by the 
structural formula (III), 
##STR4## 
by the ester exchange of a 
3-(3-tert-butyl-4-hydroxy-5-methylphenyl)-propionic acid ester represented 
by the general formula (I), 
##STR5## 
wherein R.sup.1 represents a C.sub.1 -C.sub.3 alkyl group, with 
3,9-bis(2-hydroxy-1,1-dimethylethyl)-2,4,8,10-tetraoxaspiro[5.5]undecane 
represented by the structural formula (II), 
##STR6## 
characterized in that said ester exchange is carried out at a temperature 
of from 170.degree. to 250.degree. C. using an element belonging to the 
Group II of the periodic table or its compound as a catalyst. 
In the general formula (I), R.sup.1 includes methyl, ethyl, n-propyl and 
isopropyl groups. Specifically, said ester represented by the general 
formula (I) is the methyl, ethyl, n-propyl or isopropyl ester of 
3-(3-tert-butyl-4-hydroxy-5-methylphenyl)propionic acid. 
The amount of the ester of the general formula (I) is preferably in 
stoichiometrically a slight excess, i.e. about 2.1 to about 6 times by 
molar ratio based on the dihydric alcohol of the structural formula (II). 
Since, however, the ester exchange reaction itself is an equilibrium 
reaction, the reaction proceeds by removing an alcohol, R.sup.1 OH, 
resulting from the ester of the general formula (I). Therefore the amount 
of the ester is not critical. Further, in the present invention, the 
excess of the ester of the general formula (I) can easily be recovered by 
distillation in high yield and in high quality, there being little loss 
due to the use of excessive amount of the ester. 
In the present invention, elements belonging to the Group II of the 
periodic table or their compounds are used as a catalyst for the ester 
exchange reaction. Specific examples thereof include beryllium, calcium, 
magnesium, the oxides, hydrides, hydroxides and carbonates of these 
elements, and the salts of these elements with organic acids (e.g. acetic 
acid, propionic acid). For example, there may be mentioned beryllium 
oxide, calcium, calcium oxide, calcium hydroxide, calcium hydride, calcium 
carbonate, calcium salts of organic acids (e.g. calcium acetate, calcium 
propionate), magnesium, magnesium oxide, etc. among which calcium oxide, 
calcium hydroxide and calcium hydride are particularly preferred. Of 
course, these catalysts can be used in combination, or together with other 
catalysts. 
The amount of the catalyst is preferably 0.05 to 1.5 times by molar ratio 
based on the alcohol of the structural formula (II). When the amount is 
less than 0.05 time by mole, the reaction does not proceed substantially, 
while when it exceeds 1.5 times by mole, undesirable side reactions such 
as decomposition of the material and product are caused. 
The reaction temperature is preferably from 170.degree. to 250.degree. C. 
When the temperature is lower than 170.degree. C., the reaction does not 
proceed substantially, while when it exceeds 250.degree. C., undesirable 
side reactions such as decomposition of the material and product are 
caused. 
Generally, the reaction is carried out under atmospheric pressure. Of 
course, it may be carried out under reduced pressure in accordance with 
necessity. In order to expel the alcohol, R.sup.1 OH, resulting from the 
ester of the general formula (I) out of the system, it is possible to 
remove the alcohol by passing an inert gas (e.g. nitrogen, helium, argon, 
carbon dioxide, gaseous organic substances) through the system, or to 
distill the alcohol out of the system together with a solvent. 
A reaction solvent may or may not be used. When it is used, solvents having 
a high boiling point and a high polarity such as N,N-dimethylformamide, 
dimethyl sulfoxide, sulfolane, N,N-dimethylacetamide, N-methylpyrrolidone, 
etc. are preferred. 
The ester exchange reaction is continued until the alcohol, R.sup.1 OH, is 
not substantially formed from the ester of the general formula (I), and it 
is generally carried out for a period of time from 5 to 20 hours. 
The reaction product obtained is after-treated by neutralization, washing 
with water, etc., and if necessary, the excess of the ester represented by 
the general formula (I), used as a material, is recovered. 
According to the method of the present invention, the desired 
hydroxyphenylpropionic acid ester represented by the structural formula 
(III) occupies 94 to 98% of the reaction product thus obtained. Other 
substances present in the reaction product are 0 to 2% of the ester of the 
general formula (I) used as a material, 0 to 1% of an intermediate ester 
and a very small amount, as 1 to 2%, of other byproducts. 
In contrast thereto, when the hydroxyphenylpropionic acid ester represented 
by the structural formula (III) is produced using the conventional 
catalyst and reaction temperature, the content of the desired ester of the 
structural formula (III) in the reaction product obtained is at best 90%, 
byproducts being present in as large an amount as 6 to 10% or more, and 
also said ester is of bad color and low quality. In addition, since the 
ester of the structural formula (III) is difficult to crystallize as 
described above, purification of the ester by recrystallization becomes 
substantially impossible because of such an increase in by-products. The 
conventional method is therefore completely unsatisfactory as a 
commercial-scale production method. 
As described above, the method of the present invention is very 
advantageous to commercially produce the hydroxyphenylpropionic acid ester 
represented by the structural formula (III) with good purity, which was 
difficult to obtain on the commercial scale by the conventional method. 
The present invention will be illustrated in more detail with reference to 
the following specific examples.

EXAMPLE 1 
To a 500-ml four-necked flask equipped with a stirrer, a condenser, a 
thermometer and a nitrogen-introducing pipe were charged 200.3 g (0.8 
mole) of methyl 3-(3-tert-butyl-4-hydroxy-5-methylphenyl)-propionate and 
60.88 g (0.2 mole) of 
3,9-bis(2-hydroxy-1,1-dimethyl-ethyl)-2,4,8,10-tetraoxaspiro[5.5]undecane, 
and the mixture was heated at 150.degree. C. for 30 minutes with stirring 
in nitrogen atmosphere to form a solution. After adding 2.25 g (0.04 mole) 
of calcium oxide to this solution, the solution was heated up to 
190.degree. C. and kept at the same temperature for 6 hours while 
distilling out formed methanol to complete the reaction. After completion 
of the reaction, the reaction solution was diluted with toluene, 
neutralized with aqueous dilute hydrochloric acid and washed with water. 
After removing toluene by evaporation, 97.1 g of methyl 
3-(3-tert-butyl-4-hydroxy-5-methylphenyl)propionate, a material present in 
excess, was distilled off to obtain 148.3 g of a pale yellow highly 
viscous product. Analysis of this highly viscous product showed that said 
product contained 96.4% of 
3,9-bis{2-[3-(3-tert-butyl-4-hydroxy-5-methylphenyl)propionyloxy]-1,1-dime 
thylethyl}-2,4,8,10-tetraoxaspiro[5.5]undecane, the yield being 96.5% based 
on 
3,9-bis(2-hydroxy-1,1-dimethylethyl)-2,4,8,10-tetraoxaspiro[5.5]undecane. 
The highly viscous product also contained methyl 
3-(3-tert-butyl-4-hydroxy-5-methylphenyl)propionate which was a starting 
material and other by-products in the amounts of 1.2% and 2.4%, 
respectively. 
EXAMPLES 2 AND 3 
Procedure was repeated in the same manner as in Example 1 except that 
calcium oxide was replaced by each of 2.97 g (0.04 mole) of calcium 
hydroxide (Example 2) or 1.69 g (0.04 mole) of calcium hydride (Example 
3). The results are shown in Table 1. 
COMATIVE EXAMPLES 1 AND 2 
Procedure was repeated in the same manner as in Example 1 except that 
calcium oxide was replaced by each of 2.25 g (0.02 mole) of potassium 
tert-butoxide (Comparative example 1) or 0.46 g (0.02 mole) of lithium 
amide (Comparative example 2), and that the reaction was completed at 
150.degree. C. under a pressure of 5 mmHg. The results are shown in Table 
1. 
COMATIVE EXAMPLES 3 AND 4 
Procedure was repeated in the same manner as in Example 1 except that the 
temperature at which the reaction was completed was changed to 160.degree. 
C. (Comparative example 3) or 260.degree. C. (Comparative example 4). The 
results are shown in Table 1. 
COMATIVE EXAMPLES 5 AND 6 
Procedure was repeated in the same manner as in Example 1 except that the 
amount of calcium oxide was changed to 0.45 g (0.008 mole) (Comparative 
example 5) or 17.95 g (0.32 mole) (Comparative example 6). The results are 
shown in Table 1. 
COMATIVE EXAMPLE 7 
Procedure was repeated in the same manner as in Example 1 except that 
methyl 3-(3-tert-butyl-4-hydroxy-5-methylphenyl)propionate was replaced by 
234 g (0.8 mole) of methyl 
3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate. The result is shown in 
Table 1. 
EXAMPLE 4 
Fifty grams of the highly viscous product obtained in Example 1, 150 g of 
cyclohexane and 2.5 g of ethyl acetate were stirred to form a solution 
while heating at 70.degree. C. for 1 hour. After rapidly cooling the 
resulting uniform solution to 30.degree. C., 0.1 g of a seed crystal was 
added, and the solution was stirred at the same temperature for further 7 
hours for crystallization. The formed crystals were filtered off, washed 
with cyclohexane and dried to obtain 46.4 g of white crystals having a 
melting point of 103.degree.-107.degree. C. Analysis of the white crystals 
showed that said crystals contained 98.6% of the desired 
3,9-bis{2-[3-(3-tert-butyl-4-hydroxy-5-methylphenyl)propionyloxy]-1,1-dime 
thylethyl}-2,4,8,10-tetraoxaspiro[5.5]-undecane and 1.4% of by-products, 
and that the crystals contained no methyl 
3-(3-tert-butyl-4-hydroxy-5-methylphenyl)propionate which was used as a 
starting material. 
COMATIVE EXAMPLES 8 TO 13 
Recrystallization was repeated in the same manner as in Example 4 except 
that 50 g of each of the highly viscous products obtained in Comparative 
examples 1 to 6 was used. The results are shown in Table 2. 
TABLE 1 
__________________________________________________________________________ 
Temperature 
Amount of 
for comple- 
Reaction 
Purity (wt. %) Yield of 
Kind of 
catalyst 
tion of 
time Desired desired 
catalyst 
(molar ratio)*.sup.1 
reaction (.degree.C.) 
(hr) product*.sup.2 
Material*.sup.3 
Intermediate*.sup.4 
Others 
product 
__________________________________________________________________________ 
(%)*.sup.1 
Example 
1 CaO 0.2 190 6 96.4 1.2 0.8 1.6 96.5 
2 Ca(OH).sub.2 
0.2 190 6 94.3 2.6 1.2 1.9 93.2 
3 CaH.sub.2 
0.2 190 6 96.1 1.6 0.7 1.6 96.0 
Comparative 
example 
1 KOBu--t 
0.1 150 6 87.5 1.4 0.7 10.4 
85.8 
2 LiNH.sub.2 
0.1 150 6 88.9 1.5 0.8 8.8 87.5 
3 CaO 0.2 160 12 52.4 1.2 45.2 1.2 40.1 
4 CaO 0.2 260 6 91.5 0.5 1.1 6.9 88.5 
5 CaO 0.04 190 24 65.9 0.9 32.3 0.9 56.3 
6 CaO 1.6 190 6 94.2 1.3 0.7 3.8 93.5 
7 CaO 0.2 190 10 90.5*.sup.5 
4.4*.sup.6 
3.5*.sup.7 
1.6 85.2 
__________________________________________________________________________ 
*.sup.1 Based on 
3,9bis(2-hydroxy-1,1-dimethylethyl)-2,4,8,10-tetraoxaspiro[ 5.5]undecane 
*.sup.2 
3,9Bis{2[3(3-tert-butyl-4-hydroxy-5-methylphenyl)propionyloxy1,1-dimethyl 
thyl2,4,8,10-tetraoxaspiro[5.5]undecane 
*.sup.3 Methyl 3(3-tert-butyl-4-hydroxy-5-methylphenyl)propionate 
*.sup.4 
3{2[3(3-Tert-butyl-4-hydroxy-5-methylphenyl)propionyloxy1,1-dimethylethyl 
-(2-hydroxy-1,1-dimethylethyl)-2,4,8,10-tetraoxaspiro[5.5]undecane 
*.sup.5 
3,9Bis{2[3(3,5-di-tert-butyl-4-hydroxyphenyl)propionyloxy1,1-dimethylethy 
2,4,8,10-tetraoxaspiro[5.5]undecane 
*.sup.6 Methyl 3(3,5-di-tert-butyl-4-hydroxyphenyl)propionate 
*.sup.7 
3{2[3(3,5-Di-tert-butyl-4-hydroxyphenyl)propionyloxy1,1-dimethylethyl9-(2 
hydroxy-1,1-dimethylethyl)-2,4,8,10-tetraoxaspiro[5.5]undecane 
TABLE 2 
______________________________________ 
Purity of Time 
Weight of 
desired required for 
Melting 
crystal product crystalli- point 
(g) (wt. %) zation (hr) 
(.degree.C.) 
______________________________________ 
Example 4 
46.4 98.6 7 103-107 
Comparative 
example 
8 32.2 94.2 24 92-98 
9 35.3 93.9 24 90-98 
10 0* 144* 
11 42.5 96.2 12 95-100 
12 0* 144* 
13 43.8 96.8 12 97-101 
______________________________________ 
*Did not crystallize.