JPS6017776B2 - Production method of γ-chloro-β-hydroxybutyric acid alkyl ester - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a process for preparing y-chloro-8-hydroxybutyric acid alkyl esters, in particular, the preparation of y-chloro-3-hydroxybutyric acid alkyl esters using epichlorohydrin, carbon monoxide and an aliphatic alcohol using a cobalt carbonyl catalyst. The present invention relates to a method for producing an alkyl butyrate.

Conventionally, y-amino-8-hydroxybutyric acid, which is useful as an anti-defining nerve agent, has been mainly produced from y-chloro-8-hydroxybutyric acid alkyl ester.

The method for producing this y-chloro-8-hydroxybutyric acid ester is well known.

For example, '11 A method in which epichlorohydrin and hydrocyanic acid are reacted to form y-chloro-8-hydroxybutyronitrile, and this is heated in alcohol in the presence of an acid (F. Bi dish n, P
．． BrMkneret al “B mountain 1.Soc.chi
m. '2' A method of reacting epichlorohydrin and carbon monoxide in toluene in the presence of a hydrocobalt tetracarbonyl catalyst, and esterifying this with an aliphatic alcohol and iodine, (Y. Watahada beetal “Bull, C
hem, SoC, Japan” 371964 No. 672
Page) ■ A method of reacting epichlorohydrin, carbon monoxide, and an aliphatic alcohol at a carbon monoxide pressure of about 600 atm using dicobalt octacarbonyl as the main catalyst and a quaternary ammonium salt as a promoter (J.D. .Mcclur
e,''J. ○rg. Chem. 32, 1967, p. 388) [4'Epichlorohydrin, carbon monoxide and an aliphatic alcohol using bis(tributylphosphine) dicobalt hexacarbonyl as a main catalyst and a quaternary ammonium salt as a co-catalyst, A method of reacting at a carbon monoxide pressure of about 42 atmospheres (US Pat. No. 3,259,647).

In these methods, '1} has a low yield and is not practical due to the use of hydrocyanic acid, '21 has an extremely low yield, and both {31 and However, the yield is as low as around 50%, and there is a disadvantage that an expensive co-catalyst is used.

The present invention is aimed at solving these drawbacks, and involves producing an alkyl chloro-8-hydroxybutyric acid ester from epichlorohydrin, carbon monoxide and an aliphatic alcohol in the presence of a cobalt carbonyl catalyst. In this regard, the present invention provides a method for producing a y-chloro-8-hydroxy acid alkyl ester in good yield by using an alkali metal compound and/or an alkali metal compound. That is, the present invention provides an alkali metal compound and a y-chloro-6-hydroxybutyric acid alkyl ester in which epichlorohydrin, carbon monoxide, and an aliphatic alcohol are used under normal pressure or pressure using a cobalt carbonyl catalyst. It is characterized by the presence of/or an alkali metal compound.

The present invention will be explained in more detail below.

The present invention relates to a method for producing an alkyl y-amino-8-hydroxybutyric acid ester using epichlorohydrin, carbon monoxide, and an aliphatic alcohol under normal or elevated pressure as a catalyst and cobalt carbonyl. Known means can be applied to any of these raw material manipulation methods.

First, the raw material epichlorohydrin preferably has high purity, but is not limited to this.

Although carbon monoxide may be a mixed gas of hydrogen, inert gas, etc., it is preferable that the carbon monoxide be of high purity. Also,
Regarding the aliphatic alcohol, the alcohol serving as the ester moiety is preferably selected from methanol, ethanol, isopropanol, and n-butanol, but is not limited thereto.

Further, an inert solvent such as an aliphatic hydrocarbon or an aromatic hydrocarbon acetone can also be made to coexist with these. The amount of aliphatic alcohol added is 1 to 2 per mole of epichlorohydrin.
0 mol, preferably 5 to 10 mol.

The cobalt carbonyl used as a catalyst in the present invention can be selected from dicobalt octacarbonyl, hydrocobalt tetracarbonyl, their sodium salts, and aliphatic alcohol or acetone solutions of cobalt tetracarbonyl anions.

The amount of cobalt carbonyl used is 0.005 to 1 mol, preferably 0.01 to 1 mol, per 1 mol of epichlorohydrin.
At 0.25 mol. As the base, an alkali metal compound or an alkali metal compound that exhibits basicity in the reaction system is used, and these may be used in combination.

Specific examples include their oxides, hydroxides, carbonates, bicarbonates, phosphates, organic acid salts, fatty acids, and aromatic alcoholates, such as sodium carbonate, potassium carbonate, sodium hydrogen carbonate, and hydrogen carbonate. Potassium, sodium acetate, etc. are preferred. These bases are used in an amount of 0.01 to 1 mol, preferably 0.03 mol, per 1 mol of epichlorohydrin.
~0.1 mol may be used to maintain the reaction system at pH 7 or higher to maintain catalyst activity and the reaction to proceed with high selectivity.

Further, even if these bases are not completely dissolved and are partially undissolved, they do not impede the reaction. The reaction temperature is 0~
It is 100q0, preferably 10 to 40q0, and side reactions are suppressed within this range. The reaction pressure is from normal pressure to 20 atmospheric pressures, usually from normal pressure to 100 atmospheric pressures, and particularly preferably from 5 to 3 atmospheric pressures.

The reaction product liquid contains the target substance y-chloro-8-hydroxybutyric acid alkyl ester and a cobalt carbonyl catalyst. As a post-treatment, the cobalt catalyst is decomposed with sulfuric acid and the excess alcohol is removed, followed by treatment with water, for example. The desired ester can be obtained in pure form by extracting the organic component with a solvent such as chloroform and distilling it. As explained above, the present invention uses epichlorohydrin, carbon monoxide, and an aliphatic alcohol as a cobalt carbonyl catalyst to produce an alkyl ester of y-chloro-8-hydroxybutyrate. It is characterized by the presence of a metal compound, and according to the present invention, y-chloro-8-hydroxybutyric acid alkyl ester can be obtained in good yield.

Note that the percentages described in the specification are expressed in mol% unless otherwise specified.
The present invention will be further explained below with reference to Examples.

Example 1 2.0 mol of epichlorohydrin and 0.0 mol of potassium bicarbonate were placed in a stainless steel autoclave having an internal volume of IZ.
1 mol, cobalt tetracarbonyl anion (0.08
100 moles of methanol solution and 10 moles of methanol were charged, and the reaction was carried out for 4 hours at a carbon monoxide pressure of 20k9/kg and a temperature of 25:00.

After completion of the reaction, gas chromatography analysis revealed that the conversion rate of epichlorohydrin was 100% and the selectivity of y-chloro-8-hydroxy acid tertyl acid was 73%. Comparative example
1. In a stainless steel autoclave with an internal volume of 500 ml, 1.0 mol of epichlorohydrin and 50 ml of a methanol solution of cobalt tetracarbonyl anion (0.04 mol),
5 moles of methanol was charged and a reaction was carried out for 2 hours at a carbon monoxide pressure of 30 k9/d and a temperature of 4000, but epichlorohydrin hardly reacted.

Example 2 Internal volume: 5.0 mol of epichlorohydrin and 0.2 mol of sodium carbonate in the stainless steel autoclave
5 mol, methanol solution of cobalt tetracarbonyl anion (0.2 mol) 250ml [, 34 mol of methanol was charged, carbon monoxide pressure 10k9/carp, temperature 38℃
Anchor time reactions were performed.

The conversion rate of epichlorohydrin is 100%, y-chloro-
The selectivity for methyl 8-hydroxybutyrate was 67%. Example 3 Into a stainless steel autoclave with an internal volume of 5, 3.0 mol of epichlorohydrin, 0.5 mol of sodium carbonate,
240 methanol solution of cobalt carbonyl anion (0.24 mol), 55 mol of methanol were charged, carbon monoxide pressure was 6k9/base, 3 was 0 for 7 hours, and then 25q0
As a result of conducting the reaction for 1 hour, the conversion rate of epichlorohydrin was 75%, and the selectivity of methyl y-chloro-8-hydroxybutyrate was 79%.

Example 4 Inner volume 1 Into the stainless steel autoclave, 1.0 mol of sodium carbonate, 100 methanol solution of cobalt tetracarbonyl anion (0.08 mol), and 10 mol of methanol were charged, and the carbon monoxide pressure was 10×9/2. 2.0 mol of epichlorohydrin was added at a constant rate over 9 hours at a temperature of 55°C.

After the addition was completed, the reaction was continued for 1 hour under the same conditions. After the reaction was completed, the conversion rate of epichlorohydrin was 91%, and the selectivity of methyl y-chloro-8-hydroxybutyrate was 40%. Example 5 A methanol solution of 1.0 mol of epichlorohydrin, 0.1 mol of sodium acetate, and 0.04 mol of cobalt tetracarbonyl anion (5 mol of methanol) was placed in a stainless steel autoclave with an internal volume of 1. When the reaction was carried out for 46 hours at a carbon monoxide pressure of 20k9/ground and a temperature of 25o0, the conversion rate of epichlorohydrin was 1.
00%, the selectivity for methyl y-chloro-6-hydroxybutyrate was 72.5%.

Example 6 Internal volume 1 Into the autoclave, 10 moles of methanol was charged over a methanolic solution of 2.0 moles of epichlorohydrin, 0.1 moles of sodium carbonate, and a cobalt carponyl anion (0.08 moles), The reaction was carried out for 4 hours at a carbon monoxide pressure of 20k9/kg and a temperature of 260°C.

Conversion rate of epichlorohydrin is 99%, y-chloro-8
The selectivity for methyl -hydroxybutyrate was 81%. Example 7 Example 6 except that 100% of an acetone solution of cobalt carbonyl anion (0.08 mol) was used as the catalyst.
As a result of carrying out the reaction in the same manner as above, the conversion rate of epichlorohydrin was 100%, and the selectivity of methyl y-chloro-8-hydroxybutyrate was 80%.

Example 8 The reaction was carried out in the same manner as in Example 6, except that 0.08 mol of dicobalt octacarponyl crystals were used as a catalyst, and the conversion of epichlorohydrin was 100.
%, the selectivity for methyl y-chloro-8-hydroxybutyrate was 78%.

Example 9 Fill the autoclave with 1 volume of epichlorohydrin.
0 mole, sodium carbonate 0.05 mole, cobalt tetracarbonyl anion (0.04 mole) in acetone solution 5
3 people, prepare 5 moles of methanol, 70% carbon monoxide,
A mixed gas having a composition of 30% hydrogen was supplied at a pressure of 9k9', and while purging the gas in the system at a rate of 0.4 hours per hour, a reaction was carried out for 9 hours at a temperature of 25 minutes.

Claims (1)

[Claims] 1 In producing γ-chloro-β-hydroxybutyric acid alkyl ester using epichlorohydrin, carbon monoxide, and aliphatic alcohol under normal pressure or increased pressure, using a cobalt carbonyl catalyst, an alkali metal compound and/or
Alternatively, a method for producing a γ-chloro-β-hydroxybutyric acid alkyl ester, which comprises the presence of an alkaline earth metal compound.