Process for producing 1,2-propanediol

The present invention provides a process for obtaining 1,2-propanediol or optically active substances thereof in high yields and at a low cost using readily available starting materials. According to the process of the present invention, 3-halogeno-1,2-propanediol of the general formula [I] is catalytically hydrogenated in an alcoholic solvent having two or more carbon atoms in the presence of a base of an equivalent or less to the starting material to give 1,2-propanediol of the formula [II]. In the formula [I], X stands for a halogen atom. ##STR1##

TECHNICAL FIELD 
The present invention relates to a process for producing 1,2-propanediol, 
particularly, optically active substances thereof, which are useful 
compounds as a synthetic intermediate of medicines, agricultural chemicals 
and the like. 
BACKGROUND OF THE INVENTION 
1,2-Propanediol is a known substance as an industrially useful compound. As 
a conventional process for producing the compound, it is reported that 1) 
3-chloro-1,2-propanediol is converted into glycidol in a solution of 
potassium hydroxide-methanol and then glycidol is catalytically 
hydrogenated to give the object substance (M. Ochiai, Biochem. Z., 293 
(1935)). 
Known processes for producing optically active substances of 1, 
2-propanediol are 2) reduction of natural ethyl lactate (J. Amer. Chem. 
Soc., 107, 5210 (1985)), 3) reduction of hydroxyacetone in the presence of 
a chiral catalyst (J. Amer. Chem. Soc., 110, 629 (1988)), 4) asymmetry 
reduction of hydroxyacetone with yeast (Japanese Laid-open Patent 
Publication No. 059592/1995), 5) resolution of racemate with enzyme 
(Japanese Laid-open Patent Publication No. 030790/1994), etc. 
In the case of the above-mentioned conventional processes, however, since 
1.2 equivalents of the base is used to the starting compound in the 
process 1), it leads to forming by-products such as polymers and 
3-methoxy-1,2-propanediol. Since it is difficult to separate these 
by-products from the object substance, the yield of the object substance 
is low (72%). Actually, when the reaction 1) was carried out on a large 
scale, the yield was lower (47% (see Comparative Example 2 mentioned 
later)). The process 2) has disadvantages in that both of optically active 
substances of 1,2-propanediol cannot arbitrarily be obtained because the 
starting material is a natural optically active substance and in that it 
is necessary to use lithium aluminium hydride, which is difficult to 
handle in a practical use and expensive, as a reducing agent. In the 
process 3), the optical purity of the obtained object substance is low 
(92%ee), and it needs troublesome steps wherein the optical purity is 
improved by recrystallization after conversion into a derivative in order 
to obtain the object substance having high optical purity. In the 
processes 4) and 5), only one optically active substance is obtained. 
In view of the above-mentioned various problems, the object of the present 
invention is to provide a process for obtaining 1,2-propanediol or the 
optically active substances thereof, both arc the object substance, in 
high yields and at a low cost, using a readily available compound as a 
starting material. 
DISCLOSURE OF THE INVENTION 
Doing studies continuously to attain the above-mentioned object, the 
inventors found a process for producing 1,2-propanediol, particularly, 
optically active substances thereof advantageously using 
3-halogeno-1,2-propanediol as a starting compound and accomplished the 
present invention. 
The present invention relates to a process for producing 1,2-propanediol 
characterized in that 3- halogeno-1,2-propanediol represented by the 
following general formula [I] is catalytically hydrogenated in an 
alcoholic solvent having two or more carbon atoms in the presence of a 
base of 0.9 to one mole with respect to one mole of 
3-halogeno-1,2-propanediol to give 1,2-propanediol represented by the 
following formula [II]. In the general formula [I], X stands for a halogen 
atom. 
##STR2## 
3-Halogeno-1,2-propanediol [I] can be obtained by any processes. Optically 
active 3-halogeno-1,2-propanediol can easily be prepared according to 
processes described in Japanese Examined Patent Publication Nos. 
73998/1992 and 73999/1992. 
The halogen atom X of 3-halogeno-1,2-propanediol [I] is preferably a 
chlorine atom or a bromine atom. Accordingly, preferred 
3-halogeno-1,2-propanediol, which is the starting material, is 
3-chloro-1,2-propanediol or 3-bromo-1,2-propanediol. 
The "alcoholic solvent" means a solvent which comprises alcohol(s) having 
two or more carbon atoms in the present specification. Namely, the solvent 
can contain the other omponent(s) than alcohol(s) having two or more 
carbon atoms, unless the other components substantially influence the 
fundamental and novel characteristic of the present invention. For 
example, the alcoholic solvent can comprise a large part of the alcohol(s) 
having two or more carbon atoms and a small part of other solvent(s) which 
is (are) compatible with the alcohol(s). However, the larger the 
proportion of the other solvent(s), the m ore liable to occur are side 
reactions. As a result, a yield of the object substance tends to decrease. 
Accordingly, a range of the proportion of the other solvent(s) is decided 
so that the yield of the object substance is not lower than a desired 
value. 
The hydrocarbon group of the alcohol(s) can be straight, branched or 
cyclic, and can have substituent(s). 
The alcohol can be monohydric or polyhydric depending on a number of 
hydroxyl groups, and can be any of an n-alcohol, a sec-alcohol and a 
tert-alcohol depending on a position of the hydroxyl group. 
A preferred alcoholic solvent is essentially composed of monohydric 
alcohol(s) having two to four carbon atoms. A particularly preferred 
alcoholic solvent is essentially composed of an alcohol selected from the 
group consisting of propanol, isopropanol, n-butanol, isobutanol, 
sec-butanol and tert-butanol, or combination of two or more thereof. When 
methanol is used as the solvent, glycidol, which forms in the reaction 
process, reacts with methanol to give a by-product, which lowers the yield 
of the object substance. 
The base used in the process of the present invention can be a substance 
which exhibits basicity (including Lewis bases). Examples of the base are 
hydroxides of alkali metals or alkali earth metals such as lithium 
hydroxide, sodium hydroxide, potassium hydroxide, magnesium hydroxide and 
calcium hydroxide: carbonates of alkali metals or alkali earth metals such 
as lithium carbonate, sodium carbonate, potassium carbonate, magnesium 
carbonate and calcium carbonate; hydrogencarbonates of alkali metals such 
as lithium hydrogencarbonate, sodium hydrogencarbonate and potassium 
hydrogencarbonate; hydrides such as sodium hydride, potassium hydride and 
calcium hydride; alkali alkoxides such as sodium methylate, sodium 
ethylate, potassium methylate, potassium ethylate, potassium t-butoxide: 
and amines such as triethylamine, pyridine, 2, 6-lutidine, 
dimethylaniline, diazabicycloundecene and diazabicyclononene. These can be 
used individually or in combination. Among them, hydroxides of alkali 
metals, particularly sodium hydroxide and potassium hydroxide are 
preferable. 
An amount of the base used is 0.9 to one mole, preferably 0.95 to one mole 
with respect to one mole of the starting material 
3-halogeno-1,2-propanediol [I]. When the amount of the base is more than 
one mole with respect to one mole of the starting material, undesirable 
by-products form. On the contrary, when the amount of the base is less 
than 0.9 mole, 3-halogeno-1,2-propanediol [I] remains and the yield of 
1,2-propanediol decreases. 
A catalyst used in catalytically hydrogenating 3-halogeno-1, 2-propanediol 
in the process of the present invention can be a usual catalyst for 
catalytic hydrogenation. Examples of the catalyst are palladium-carbon, 
Raney nickel, platinum oxide, etc. Palladium-carbon is preferable among 
them. 
An amount of the catalyst used is suitably 1 to 100 g with respect to one 
mole of 3-halogeno-1,2-propanediol [I]. When the amount of the catalyst 
used is less than 1 g to one mole of the starting material, the reaction 
proceeds slowly, and sometimes the practical operation cannot be carried 
out. On the contrary, when the amount is more than 100 g, the cost 
increases. 
Hydrogen gas for catalytic hydrogenation can be supplied from a usual 
hydrogen source. Hydrogen gas in a hydrogen cylinder or ammonium formate 
can be used as the hydrogen source. Since removal of excess of ammonium 
formate after the reaction requires troublesome steps in the latter case, 
it is preferable to use hydrogen gas. Though a theoretical amount of 
hydrogen is one mole to one mole of 3-halogeno-1,2-propanediol [I], the 
practical amount is usually in excess of the theoretical amount, and 
preferably once to three times as much as the theoretical amount. It is 
preferable to adjust the amount of supplied hydrogen according to the 
state of progress of the reaction. When ammonium formate is used as the 
hydrogen source, it is preferable to add about 10 moles of ammonium 
formate to one mole of the starting material because ammonium formate is 
solid matter. 
There are two ways which are different in the addition order of the base 
and catalytic hydrogenation; a process wherein the catalytical 
hydrogenation is carried out after the addition of the base is finished; 
and a process wherein the catalytic hydrogenation is carried out 
simultaneously with the addition of the base. Good results arc obtained in 
both ways. 
The catalytic hydrogenation can be carried out under norm al pressure and 
can also be carried out under elevated pressure, for example, under 
hydrogen pressure of 10 Kgf/cm.sup.2 (gauge pressure) or lower. 
Reaction temperature is preferably -20.degree. to 80.degree. C., and m ore 
preferably 0.degree. to 50.degree. C. When the reaction temperature is 
lower than -20.degree. C., the progress of the reaction is slow, and 
viscosity of a reaction liquid tends to increase. On the contrary, when 
the reaction temperature is higher than 80.degree. C., a dimer of the 
starting material, etc. form, and the yield of 1,2-propanediol is apt to 
decrease. 
After the reaction is completed, the object substance is obtained by the 
conventional method. For example, insoluble matter such as the catalyst is 
filtered out, an excessive solvent is evaporated under reduced pressure, 
and the obtained residue is usually treated, e.g. distilled to give object 
substance 1,2-propanediol. The above-mentioned reaction is carried out 
using 3-halogeno-1,2-propanediol which is the optically active substance 
as a starting material to give desired optically active 1,2-propanediol 
with little decrease in optical purity. 
A reaction mechanism of the process of the present invention is not 
definite. However, it is considered that a successive reactions occur 
wherein 3-halogeno-1,2-propanediol [I] is converted into glycidol with the 
base and then 1,2-propanediol [II] is formed by the catalytic 
hydrogenation. 
BEST MODE FOR CARRYING OUT THE INVENTION 
The present invention is practically described by Examples below, but the 
present invention is not limited to these Examples. Comparative Example 1 
is an example wherein methanol is used as a solvent. Comparative Example 2 
is an example wherein methanol is used as a solvent and an excessive base 
is used to a starting material. Comparative Example 3 is an example 
wherein isopropanol is used as a solvent and the excessive base is used to 
the starting material.

EXAMPLE 1 
a) In a flask of 200 ml, 10 g (90.5 mmol) of 3-chloro-1,2-propanediol was 
dissolved in 50 ml of isopropanol. To the solution was added 7.2 g (86.4 
mmol) of a 48% aqueous NaOH solution dropwise in an ice bath over 30 
minutes. The mixture was stirred at 25.degree. C. for 30 minutes, and then 
1 g of 10% palladium-carbon (50% wet product) was added thereto. The 
atmosphere in the flask was replaced with hydrogen, and the mixture was 
stirred at 40.degree. C. for further three hours. 
b) Then the reaction mixture was filtered to remove insoluble matter, the 
filtrate was concentrated under reduced pressure, and the residue is 
purified by distillation to give 6.0 g (yield 87.2%) of 1, 2-propanediol. 
EXAMPLE 2 
In an autoclave of 1000 ml, 50 g (0.45 mol, optical purity 99.6%ee) of 
(S)-3-chloro-1,2-propanediol was dissolved in 250 ml of isopropanol. To 
the solution was added 35.8 g (0.43 mol) of a 48% aqueous NaOH solution 
dropwise in an ice bath over 30 minutes. The mixture was stirred at 
25.degree. C. for 30 minutes, and then 5 g of 10% palladium-carbon (50% 
wet product) was added thereto. Then hydrogen gas was supplied to the 
autoclave so that hydrogen pressure was always kept at 5 Kgf/cm.sup.2.and 
the mixture was stirred at 25.degree. C. for further two hours. 
Next the same operation as in the step b) of Example 1 was repeated to give 
31.8 g, (yield 92.4%, optical purity 99.3%ee) of (R)-1, 2-propanediol. 
EXAMPLE 3 
In a flask of five liters, 500 g (4.52 mol. optical purity 98.2%ee) of 
(R)-3-chloro-1,2-propanediol was dissolved in 2240 ml of isopropanol. To 
the solution was added 360 g (4.32 mol) of a 48% aqueous NaOH solution 
dropwise in an ice bath over one hour. The mixture was stirred at 
25.degree. C. for 30 minutes, and then 49 g of 10% palladium-carbon (50% 
wet product) was added thereto. The atmosphere in the flask was replaced 
with hydrogen, and the liquid was stirred. The stirring was continued at 
40.degree. C. for further seven hours. 
Then the same operation as in the step b) of Example 1 was repeated to give 
313 g (yield 91.0%, optical purity 98.0%ee) of (S)-1, 2-propanediol. 
EXAMPLE 4 
In a flask of five liters, 500 g (4.52 mol, optical purity 99.6%ee) of 
(S)-3-chloro-1,2-propanediol was dissolved in 2240 ml of isopropanol. To 
the solution was added 49 g of 10% palladium-carbon (50% wet product). The 
atmosphere in the flask was replaced with hydrogen, 360 g (4.32 mol) of a 
48% aqueous NaOH solution was added to the mixture dropwise with stirring 
at 40.degree. C. over 10 hours. and the mixture was stirred for further 
one hour. 
Then the same operation as in the step b) of Example 1 was repeated to give 
310 g (yield 90.0 %, optical purity 99.2%ee) of (R)-1, 2-propanediol. 
Comparative Example 1 
In a flask of 30 liters, 3.75 kg (33.9 mol, optical purity 99.6%ee) of 
(S)-3-chloro-1,2-propanediol was dissolved in 14 liters of methanol. To 
the solution was added 2.70 kg (32.4 mol) of a 48% aqueous NaOH solution 
dropwise in an ice bath over two hours. The mixture was stirred at 
25.degree. C. for one hour, and then 375 g of 10% palladium-carbon (50% 
wet product) was added thereto. The atmosphere in the flask was replaced 
with hydrogen, and the mixture was stirred at 40.degree. C. for further 11 
hours. 
Then the same operation as in the step b) of Example 1 was repeated to give 
1.62 kg (yield 62.8%, optical purity 99.0%ee) of (R)-1,2-propanediol. 
Comparative Example 2 
In a flask of 10 liters, 500 g (4.52 mol, optical purity 99.6%ee) of 
(S)-3-chloro-1,2-propanediol was dissolved in 2.5 liters of methanol. To 
the solution was added 1.5 liters (5.36 mol) of a 20% KOH/methanol 
solution dropwise in an ice bath over one hour. The mixture was stirred at 
25.degree. C. for 30 minutes, and then 50 g of 10% palladium-carbon (50% 
wet product) was added thereto. The atmosphere in the flask was replaced 
with hydrogen, and the mixture was stirred at 40.degree. C. for further 
eight hours. 
Then the same operation as in the step b) of Example 1 was repeated to give 
162 g (yield 47.1%, optical purity 98.8%ee) of (R)-1, 2-propanediol. 
Comparative Example 3 
In a flask of 1000 ml, 50 (0.45 mol, optical purity 99.6%ee) of 
(S)-3-chloro-1,2-propanediol was dissolved in 250 ml of isopropanol. To 
the solution was added 45 kg (0.54 mol) of a 48% aqueous NaOH solution 
dropwise in an ice bath over 30 minutes. The mixture was stirred at 
25.degree. C. for 30 minutes, and then 5 g of 10% palladium-carbon (50% 
wet product) was added thereto. The atmosphere in the flask was replaced 
with hydrogen, and the mixture was stirred at 40.degree. C. for further 
four hours. 
Then the same operation as in the step b) of Example 1 was repeated to give 
22.4 g (yield 66.4%, optical purity 99.6%ce) of (R)-1, 2-propanediol. 
Industrial Applicability 
The present invention provides a process for advantageously obtaining 
1,2-propanediol, which is a useful compound as a synthetic intermediate of 
medicines, agricultural chemicals, etc. 
According to the present invention, 1,2-propanediol can be obtained in a 
higher yield at a lower cost compared with conventional methods. In 
particular, optically active substances can be obtained without decreasing 
purity thereof.