JPS6025955A - Production of gamma-chloroacetoacetic acid ester - Google Patents

Abstract

PURPOSE:To obtain the titled compound useful as an intermediate of quinacridone (a red pigment) or a raw material of pharmaceuticals, etc., in high yield, by reacting gamma-chloroacetoacetyl chloride with an alcohol while removing the by- produced hydrogen chloride from the reaction system. CONSTITUTION:gamma-Chloroacetoacetyl chloride is made to react with an alcohol (e.g. methanol, ethanol, propanol, butanol, n-hexanol, etc.) in an inert solvent (e.g. dichloroethane) at -20-0 deg.C for 5-60min while removing the by-produced hydrogen chloride from the system, to obtain the objective gamma-chloroacetoacetic acid ester. The removal of hydrogen chloride can be carried out e.g. by the addition of a hydrogen chloride absorbent to the system, the evacuation of the system or the introduction of an inert gas (e.g. N2, argon, etc.) into the reaction system.

Description

DETAILED DESCRIPTION OF THE INVENTION T-1' loracetoacetate is useful as an intermediate for quinacridone, which is a red pigment, and as a raw material for pharmaceuticals and other synthetic materials.

The ester is produced by reacting T-chloroacetoacetic acid chloride with alcohol, and the above esterification is not only for the production of intermediates, but also for the purpose of stabilizing T-chloroacetoacetic acid chloride and improving its storage stability. Implemented.

However, when the present inventors investigated this method, it was confirmed that hydrogen chloride produced as a by-product during the reaction acts as a catalyst for various side reactions, which causes a decrease in the yield of T-chloroacetoacetate. discovered that the desired product could be obtained in good yield if the reaction was carried out while removing the hydrogen chloride from the system.

That is, in the present invention, when alcohol is added dropwise to T-chloroacetoacetic acid chloride to produce T-chloroacetoacetic ester, the reaction is carried out while removing by-product hydrogen chloride from the system.

The reaction between T-chloroacetoacetic acid chloride and alcohol is usually carried out in an inert solvent such as dichloroethane, and some of the by-product hydrogen chloride is naturally released from the system.
With this level of release, no improvement in the yield of the target product can be expected. In the present invention, it is further essential to actively remove hydrogen chloride present in the system.

Any method can be used to remove the hydrogen chloride, such as adding a hydrogen chloride absorbent into the system, conducting a reaction under reduced pressure, or introducing an inert gas into the system. Ru.

Industrially, the reaction is advantageously carried out under reduced pressure or preferably under the introduction of an inert gas (nitrogen, argon, etc.).

In the former case, it is carried out under reduced pressure of d[1[1°H] or less. In the latter case, 0.5 to 5
Double the amount of inert gas is introduced into the reaction solution.

In the reaction of T-10 acetoacetic acid chloride and alcohol, a solvent such as dichloromethane, dichloromethane, dichloropropane, carbon tetrachloride, chloroform, liquid sulfur dioxide, or the like is used. This solvent can also serve as a reaction solvent when producing the raw material T-chloroacetoacetic acid chloride from digtene and chlorine, so it is usually diketene,! l
: Producing T~tacroacetoacetate chloride from chlorine,
T-chloroacetoacetate can be produced by subsequently adding dropwise alcohol to the reaction solution without removing the reaction solvent for chlorination.

Any alcohol can be used, including aliphatic alcohols, alicyclic alcohols, and aromatic alcohols. Typical alcohols include methanol, ethanol, propatool, butanol, n-hexanol, and the like.

Esterification reaction It5 is 5 at a temperature of about -2C1℃~o℃
The event will last approximately 60 minutes. The reaction format can be either punch type or continuous type.

After the reaction is complete, the desired product can be obtained by removing trace amounts of remaining hydrogen chloride and distilling off the solvent.

Next, the method of the present invention will be explained in more detail by giving examples.

Example 1 Dichloroethane + 240f and diguten 566y (4,
Dissolve chlorine 287 (!00 mol) at a temperature of L-10°C.
(4,0 4 mol) was prepared over 2.5 hours.
- Chloracetoacetic acid chloride was produced.

Next, nitrogen gas was blown into the resulting reaction solution 1B65f (containing about 4.0 mol of T-taloacetoacetoacetyl chloride) at a rate of 6 CJl/hour at a temperature of 0 to -10°C for bag ringing. While doing so, methanol 649 (2,00 mol) was added dropwise over 60 minutes. After the reaction was completed, dehydrochlorination was performed and dichloroethane was further distilled off at 60° C. under 100 to 20 OaHf. As a result of gas chromatography analysis, the yield of the obtained methyl T-chloroacetoacetate was 86%.

Incidentally, when the same reaction as in Example 1 was carried out without carrying out nitrogen gas bagging, the yield of the target product was only 80%.

Example 2 Using the same T-chloroacetoacetic acid chloride reaction solution as in Example 1, a reaction was carried out by adding methanol dropwise over 5D minutes at a temperature of 0 to -10°C and under reduced pressure of 9°C. The yield of gtylated T-chloroacetoacetate was 92%.

Example 5 When the pressure was changed to 680 Hg in Example 2, T
-Yield of glutyl chloroacetoacetate was 9,196.

Examples 4-5 In Example 2, methanol was replaced with i-getanol (Example 4)
The same experiment was conducted except that cyclohexanol (Example 5) was used.

The yield of gtyl T-chloroacetoacetate was 87%, and the yield of cyclohexyl T-chloroacetoacetate was 8,696.

Claims (1)

[Claims] 1. In producing T-chloroacetoacetic ester by dropping alcohol into T-chloro/L/acetoacetic chloride, the reaction is carried out while removing by-product hydrogen chloride from the system. A method for producing T-chloroacetoacetic ester, characterized by: 2. The manufacturing method according to claim 1, wherein the reaction is carried out under reduced pressure. 6. The production method according to claim 1, wherein the reaction is carried out under the introduction of an inert gas.