JPH0379350B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a method for stabilizing α-acetyl-α-chloro-γ-butyrolactone (hereinafter abbreviated as chlorlactone), which is famous as an intermediate raw material for pharmaceuticals. Chlorlactone is generally α-acetyl-γ
- butyrolactone in the presence or absence of a solvent,
It is produced by chlorination with chlorine, and the resulting reaction solution is a slightly viscous, pale yellow liquid with a purity of approximately 95%.
Depending on the use, this product can be provided directly. However, in this reaction, hydrogen chloride is inevitably produced as a by-product, and most of it escapes from the system along with unreacted chlorine during the reaction.
Contains ~4% hydrogen chloride. This reaction solution is very unstable, and if left in this state at room temperature, the purity and hue of the reaction solution will drop significantly, as shown in Reference Example-1. On the other hand, it is possible to purify chlorlactone by distilling the reaction solution under high vacuum;
Since the boiling point of chlorlactone at normal pressure is as high as 225°C, approximately 10% of chlorlactone decomposes even if it is distilled under a high vacuum such as a pressure of 5 Torr and a tower top temperature of 105°C, making it difficult to purify by distillation over time. It is not necessarily suitable because it is subject to changes and causes a large decrease in yield, which is economically disadvantageous. Therefore, stabilization of the reaction solution has long been desired in the art for direct use of the reaction solution, which is economically advantageous. First, the present inventors investigated the cause of quality deterioration of chlorlactone in a hydrogen chloride coexistence system, and
I discovered the following facts. That is, the raw materials α-acetyl-γ-butyrolactone and chlorlactone easily undergo a ring-opening reaction with hydrogen chloride at room temperature, and are decarboxylated and converted into halogenated ketones. For example, the ring-opening reaction of chlorlactone is expressed as follows. Next, this halogenated ketone undergoes a condensation reaction characteristic of ketones in the presence of a trace amount of hydrogen chloride, such as a catalytic amount, and turns into a colored substance. Since the molecular weight of hydrogen chloride is about 1/5 smaller than that of chlorlactone, it can be seen that even the presence of a trace amount of hydrogen chloride significantly affects the quality deterioration of chlorlactone. The relationship between the hydrogen chloride concentration in chlorlactone and its quality is as shown in Example-1. That is,
When left at room temperature for two months, the purity decreases almost quantitatively as the hydrogen chloride concentration increases, but the hue changes to Gardner No. 10 when the hydrogen chloride concentration increases to 0.15% or more.
It gets worse. From this, it was found that the reaction solution could be stored stably by reducing the hydrogen chloride concentration in the reaction solution to 0.1% or less. Next, the present inventors investigated specific methods for removing hydrogen chloride, such as physical methods such as washing with water and aeration with inert gas, and chemical methods such as neutralization. However, chlorlactone hydrolyzes when it comes into contact with water, causing ketone decomposition in acidic solutions and acid decomposition in alkaline solutions, so washing with water and treatments involving water caused a decrease in purity and were inappropriate. Furthermore, treatment with an anion exchange resin and neutralization with tertiary amines such as triethylamine and pyridine are undesirable because the treatment solution becomes colored. As an example of a physical method, as shown in Reference Example 2, hydrogen chloride could be removed to 0.14% by aerating the reaction solution with nitrogen for a long time at room temperature, but this was insufficient. However, it can be used as a pretreatment to remove hydrogen chloride. Therefore, when we investigated vacuum aeration, we were able to reduce hydrogen chloride to a maximum of 0.04% by vacuum aerating the reaction solution at room temperature and at a pressure of 100 Torr or less, as shown in Example-2. In this case, at a pressure of 200 Torr, it was difficult to reduce hydrogen chloride to 0.1% or less even with vacuum aeration at about 30°C. Also, it is thought that it is possible to reduce hydrogen chloride to 0.1% or less by increasing the temperature;
When vacuum aeration was performed at a temperature of approximately 50°C, a decrease in purity was observed, probably due to thermal changes over time. The actual operating conditions are appropriately determined through experiments based on the hydrogen chloride concentration of the target chlorlactone, capacity, treatment equipment, time, etc. In this way, by reducing the hydrogen chloride concentration in the chlorlactone reaction solution to 0.1% or less, the quality that can be used as an industrial raw material can be maintained for more than 3 months, and therefore industrially it is extremely easy to operate and can be used at room temperature.
We discovered that hydrogen chloride in the reaction solution can be removed by vacuum aeration at a pressure of 100 Torr or less,
The present invention has now been completed. The present invention will be specifically described below with reference to Reference Examples and Examples. Reference Example-1 1920 g of α-acetyl-γ-butyrolactone was placed in a 2-4 neck round bottom flask equipped with a stirrer, a thermometer, a chlorine inlet tube, and a condenser connected to the exhaust gas absorption tower.
(15 mol) and added chlorine at a reaction temperature of 8 to 12℃.
Blow for 9 hours (15 mol) at a rate of 37.3N/Hr,
The reaction was carried out to obtain 2455 g of a reaction solution. Gas chromatography analysis values (area percent) of the reaction solution showed 95.1% chlorlactone, 0.3% α-acetyl-γ-butyrolactone, and 3.7% high-boiling substances. Further, hydrogen chloride was determined to be 2.54% by silver nitrate titration. Next, Table 1 shows the purity and hue of the reaction solution at 18 to 25°C over time.

[Table] Example 1 Table 2 shows the changes in hue and purity of purified chlorlactone containing hydrogen chloride shown in Table 2 over a period of 2 months at 18 to 25°C.

[Table] Reference Example 2 Add 500g of the reaction solution obtained in Reference Example-1 to 15-19℃.
By aerating nitrogen at a rate of 40N/Hr for 4 hours, hydrogen chloride decreased from 2.54% to 0.15%. Aeration was continued for another 3 hours under the same conditions, but hydrogen chloride decreased by only 0.14%. Example 2 500 g of the reaction solution obtained in Reference Example 2 was subjected to vacuum aeration while changing the temperature and pressure shown in Table 3. The results are shown in Table-3.

[Table] Next, Table 4 shows changes in hue and purity over time at 18 to 25°C for the 3-4 treatment solution.

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Claims (1)

[Claims] 1 α-acetyl-α-chloro-γ-butyrolactone obtained from chlorination of α-acetyl-γ-butyrolactone, which is characterized in that it is stored in a state substantially free of hydrogen chloride. Method for stabilizing chloro-γ-butyrolactone.