JPS5826737B2 - Method for producing bromoacetic acid and its ester - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a process for producing bromoacetic acid and its esters from chloroacetic acid.

Conventionally, as a method for producing bromoacetic acid, Berichte Vol. 9, 5
61 (1876) describes the reaction of chloroacetic acid and hydrobromic acid in a sealed tube, and U.S. Patent No. 313,022.
No. 2 (1964) describes a method of blowing hydrogen bromide gas into an aqueous solution of chloroacetic acid and hydrobromic acid.

In addition, in general, organic, ensesis collection volume 3 3
The reaction of acetic acid and bromine in acetic anhydride and pyridine solution is known as described in the section on bromoacetic acid synthesis on page 81 (1943).

However, these methods have disadvantages such as relatively complicated operations or long reaction times and low yields.

Further, U.S. Patent No. 2,876,255 (1959
) describes the reaction of α-hydroxycarboxylic acid compounds with hydrogen bromide.

This method is based on the discovery that α-hydroxycarboxylic acid compounds can be converted to the corresponding monobromocarboxylic acids without using bromine. The following will be implemented.

However, since the α-hydroxycarboxylic acid compounds used as starting materials for this reaction have both hydroxyl and carboxyl functional groups in their molecules, they are relatively highly reactive and may cause side effects such as decomposition or polymerization, especially when heated. Reactions are likely to occur and careful handling is required, and therefore the production method is not necessarily industrially advantageous in terms of operation and yield. It is obtained by boiling in an aqueous system in the presence of an alkali metal hydroxide, which is uneconomical due to its high cost.

The present inventors previously proposed a method for producing bromoacetic acid from chloroacetic acid and an alkali metal bromide or ammonium bromide in Japanese Patent Application No. 112381/1982, but subsequently, the inventors proposed a method for producing bromoacetic acid from chloroacetic acid and an alkali metal bromide or ammonium bromide. We investigated the production of acetic acid and found that bromoacetic acid can be produced with sufficient selectivity under conditions where the reaction between chloroacetic acid and hydrobromic acid in an aqueous system is mild, and the reaction rate is significantly improved, especially in a concentrated system. As a result of extensive research, we have completed the present invention.

The present invention provides a method for producing bromoacetic acid using inexpensive raw materials in a single reaction vessel and with extremely simple and easy operations. The present invention provides a method for obtaining the desired results.

In producing fromoacetic acid from chloroacetic acid, the present invention heats chloroacetic acid and an aqueous solution of hydrobromic acid in an organic solvent that is azeotropic with water, and at the azeotropic temperature of water and the organic solvent,
The present invention provides a method for producing bromoacetic acid, which is characterized in that the reaction is carried out while gradually removing water and by-product hydrogen chloride, and then fromoacetic acid is separated from the residue.

Furthermore, the present invention provides a production method in which alcohol is directly added to the above residue and reacted in the presence of an esterification condensing agent to obtain a fromacetate.

Furthermore, according to the present invention, after separating bromoacetic acid from the above residue, alcohol and fresh organic solvent are added,
The present invention provides a manufacturing method in which a bromoacetic acid ester is obtained by reacting in the presence of an esterification condensing agent.

According to the method of the present invention, bromoacetic acid can be obtained with a high yield of 90% or more and a high purity of 95% or more with extremely simple operations.

In the method for producing bromoacetic acid of the present application, chloroacetic acid and hydrobromic acid are mixed in a reactor and heated while stirring, so that halogen substitution proceeds while the temperature of the liquid increases, and as a result, halogen substitution proceeds while the temperature of the liquid increases. The temperature rises to the azeotropic temperature of the organic solvent and water.

After azeotropic distillation of both, the two are separated, and while the organic solvent is refluxed into the reactor, water is gradually removed from the reaction system, and at the same time hydrogen chloride produced as a by-product is removed from the system in gaseous form or as hydrogen chloride water. The reaction is allowed to proceed, and the S azeotropic distillation is continued to remove most of the water, thereby completing the reaction.

In this method, for example, in the equimolar reaction of chloroacetic acid and hydrobromic acid (hydrogen bromide content 47%), the halogen substitution reaction proceeds even at low temperatures around 25°C, and the liquid temperature is maintained at 100°C or higher by heating. The reaction proceeds in the same way.

However, in this case, the reaction rate was approximately 30% in the former and approximately 60% in the latter, and no matter what other temperature conditions were applied, the above reaction rate did not improve and water and chloride by-produced from the reaction system. By removing hydrogen and gradually transferring to a concentration system, the reaction can proceed and be completed to achieve a yield of 90% or more.

Therefore, in the present method, there are no particular restrictions on the temperature to be maintained in the reaction layer and the time required for azeotropic dehydration as long as the temperature raising operation is carried out in a common sense.

Further, the time required for azeotropic dehydration should preferably be kept long enough to allow the reaction to proceed smoothly, but this depends on the concentration of hydrobromic acid used.

The concentration of hydrobromic acid that can ensure reactivity is 10
%, therefore, in this application, it is possible to use not only commercially available hydrobromic acids but also all low-concentration hydrobromic acids that are produced in large quantities as a by-product in various processes for producing bromine compounds using bromine as a brominating agent. It is possible.

However, considering the time required for dehydration and distillation, it is preferable that the concentration is as high as possible, and usually a saturated aqueous solution of about 47% is suitably used.

The reaction between chloroacetic acid and hydrogen bromide is an equimolar reaction, and the molar ratio used is preferably 1:1, and approximately 1.4 times the mole of hydrogen bromide to chloroacetic acid is preferably used.

However, as long as unreacted raw materials are reused, there is no problem in changing the molar ratio.

However, if the hydrogen bromide content is greatly excessive, hydrogen bromide gas will escape in the high temperature range where the reaction ends, resulting in loss, or there will be disadvantages in terms of operation.

In view of the above-mentioned facts, the organic solvent that can be used in the present invention is one that promotes the progress of the rogane substitution reaction and maintains conditions such that the azeotropic fraction with water is distilled off under mild conditions. Preferably, a substance having a boiling point close to the boiling point of water is selected so as to drip, and suitable and preferable examples include benzene, toluene, xylene, trichlene and perchlene.

In the method of the present invention, the distillation of water is completed at the azeotropic temperature of water and the organic solvent, and unreacted hydrogen bromide is also sufficiently removed to complete the reaction, and then only the organic solvent is removed. Distill and remove to obtain bromoacetic acid in a container.

This product has a purity of 95% or more and can be used as it is as an intermediate for drug production or for other purposes, but if necessary, it can be easily reduced to 99% by redistilling under reduced pressure.
% or more of bromoacetic acid is obtained.

In the method for producing fromoacetic acid ester, which is an invention provided separately in this application, in carrying out the reaction method for bromoacetic acid described above, alcohol and an esterification condensation agent are added after azeotropic dehydration, and the reaction is carried out by heating or An alcohol and a new organic solvent can be added to the obtained bromoacetic acid and reacted in the presence of an esterification condensing agent to yield bromoacetic acid ester.

The reaction carried out here can be carried out by directly applying the well-known esterification reaction, and therefore, as the condensing agent, p-toluenesulfonic acid or sulfuric acid, which is used in general esterification reactions, is used.

Further, as the alcohol, any alcohol corresponding to the desired ester can be suitably used.

By way of example, all types of mono-, di- or polyhydric alcohols commonly used as esterifying agents can be used.

Namely, n-hexyl alcohol, n-lauryl alcohol, ethylene glycol, 1,4-butanediol,
Aliphatic saturated alcohols such as glycerin, allyl alcohol, propargyl alcohol, cis-2-butene-
Aliphatic unsaturated alcohols such as 14-diol and trans-2-butenate 4-diol, aliphatic alcohols such as 2-chlorobrobanol, Halogenated alcohols, aliphatic nitro alcohols such as 2-nitro-2-methylpropanol, fats such as cyclohexanol, 2-ethylcyclohexanol, cysuto-2-cyclohexanediol, 2-cyclohexenol, and 2-chlorocyclohexanol. Heterocyclic allyl alcohols such as benzyl alcohol, p-methylbenzyl alcohol, cinnamyl alcohol, p-chlorobenzyl alcohol, aromatic alcohols, furfuryl alcohol, and tetrahydrofurfuryl alcohol, ethylene glycol monobutyl ether , glycol monoalkyl ethers such as propylene glycol monoethyl ether, and the like.

Note that when bromoacetic acid is separated and led to an ester, it is desirable to use the organic solvent used in the production of bromoacetic acid as the newly added solvent.

In addition to the various advantages already mentioned, the method of the present invention has the advantage that the time required for the reaction is shorter than that of conventional methods when the reaction is carried out using a saturated aqueous solution of hydrobromic acid, making it significant as an industrial process. is big.

Next, the present invention will be explained with examples.

Example 1 A thermometer, a stirrer, a reflux condenser, and a water metering receiver were attached to the lower end of the eleven three-necked flask.

To this were added 1 mol of 97.5 f chloroacetic acid (purity 97%), 206.61 ml (1.2 mol) of 47% hydrobromic acid, and 100 ml of toluene and stirred rapidly.

Next, it is heated in an oil bath, and when the internal temperature reaches 94°C, water-toluene azeotropy begins, and at this time, hydrogen chloride gas that is trapped in the halogen exchange begins to be generated, and the generated gas is transferred to the top of the cooling tube. 500rrL of 10% sodium hydroxide aqueous solution
An absorption tank filled with 1.5 liters of hydrogen chloride was provided to completely absorb the generated hydrogen chloride without leaking it out of the reaction system.

Due to water-toluene azeotropy, toluene is continuously returned to the reactor and water is removed from the reaction system.

The dehydration temperature at this time was 102 to 115°C, and dehydration required 2 hours.

The desired product, bromoacetic acid, was thus obtained from the reaction mixture.

As a result of analysis by gas chromatography, this synthetic bromoacetic acid was found to have a purity of 97.0%, and an additional 1.0 m
Distilled at 91-92℃ under reduced pressure of mHg to obtain purity of 99.
．． 5% bromoacetic acid 133.4S' was obtained.

This is 95.5% compared to the theoretical production amount from chloroacetic acid.
% yield.

The obtained bromoacetic acid is a colorless transparent crystal with a melting point of 50°C and a specific gravity of D2g-1,9335.

Examples 2 to 12 Bromoacetic acid was prepared in the same manner as in Example 1 by changing the concentration of hydrobromic acid, hydrogen bromide/chloroacetic acid molar ratio, organic solvent, dehydration time, and dehydration temperature as shown in the following table. It bottomed out.

Note that the reaction scale was 1 mol reaction.

Further, the reaction yield refers to the amount of bromoacetic acid obtained by distillation, the purity was measured by gas chromatography analysis, and the yield was calculated based on the amount of chloroacetic acid.

Examples 13-15 In a 500 ml three-necked flask, add 48.61 chloroacetic acid (
97% purity, reagent grade, 0.5 mol), hydrobromic acid 103
．． 5y' (47% aqueous solution, reagent grade, 0.6 mol) and 100 Ttl of toluene were heated on an oil bath with stirring in a reaction apparatus equipped with a thermometer and a water quantitative receiver at the lower end of the reflux condenser tube. The reaction was carried out.

The operations during the reaction** and to the completion of the reaction to produce bromoacetic acid were similar to those described in Example 1.

Next, 0.5 mole amount of alcohol was added to the residue after the reaction was completed.
p-)luenesulfonic acid 0.5P as esterification catalyst
was processed, esterification progressed to synthesize bromoester, and the reaction product was distilled to obtain bromoester.

The results are shown in the table below.

Example 16.17 The reaction was carried out under the reaction conditions shown in the table below according to the procedure described in Example 1. The residue after the reaction was distilled to obtain bromoacetic acid having a melting point of 50'C1 and a specific gravity of D2F of 1.933. Obtained.

Add the desired varnish※※ Terni compatible sulfur alcohol 0.5 mol, toluene 100
TrLl and hibaradruenesulfonic acid 0.5'? was added and heated to carry out an esterification reaction to obtain bromoacetic acid ester with the results shown in the following table.

Claims (1)

[Scope of Claims] 1. In producing fromacetic acid from chloroacetic acid and hydrobromic acid, water and by-product chloride A method for producing bromoacetic acid, which comprises carrying out the reaction while gradually removing hydrogen, and then separating fromoacetic acid from the residue. 2. The method of claim 1, wherein the aqueous hydrobromic acid solution is an aqueous solution containing about 40-47% hydrobromic acid. 3. A method according to claim 1 or 2, wherein an aqueous solution containing about 47% hydrobromic acid is used. 4. Heating chloroacetic acid and an aqueous hydrobromic acid solution in an organic solvent that is azeotropic with water, and carrying out the reaction while gradually removing water and by-product hydrogen chloride at the azeotropic temperature of water and the organic solvent, A method for producing bromoacetic ester, which is characterized in that alcohol is then directly added to the residue and reacted in the presence of an esterification condensing agent to lead to bromoacetic ester. 5. The method of claim 4, wherein the aqueous hydrobromic acid solution is an aqueous solution containing about 40-47% hydrobromic acid. 6. Process according to claim 4 or 5, using an aqueous solution containing about 47% hydrobromic acid. 7 Heating chloroacetic acid and an aqueous hydrobromic acid solution in an organic solvent that is azeotropic with water, and carrying out the reaction while gradually removing water and by-product hydrogen chloride at the azeotropic temperature of water and the organic solvent, A method for producing bromoacetic ester, which comprises separating fromoacetic acid from the residue, adding alcohol and a new organic solvent, and reacting in the presence of an esterification condensing agent to produce bromoacetic ester. 8. The method of claim 7, wherein the aqueous hydrobromic acid solution is an aqueous solution containing about 40-47% hydrobromic acid. 9. Process according to claim 7 or 8, using an aqueous solution containing about 47% hydrobromic acid.