JPH0692917A - Improved method of synthesizing glycine - Google Patents

Abstract

PURPOSE: To provide the improved synthesizing process of glycine by which high purity crude crystal glycine is produced in a high yield of 90% or more, saving energy and more economically compared with conventional glycine synthesis processes.

CONSTITUTION: The improved process for synthesizing glycine comprising (A) a process to form monochloracetatic acid by chlorinating acetic acid with neutral red phosphorous as a catalyst, (B) a process to obtain melted crude monochloroacetic acid by removing unreacted acetic acid in the reaction products and (C) a process to obtain crystalline glycine by completing the total process by feeding crude-to-refined monochloroacetic acid still in melted state into the reactor vessel, allowing it to react with tert. alkyl amine which is added after adding a lower alkanol as a solvent thereto, mixing and dissolving paraformaldehyde at 35 to 40°C and subsequently allowing ammonia gas to be introduced into the reaction system and to react at 40 to 45°C, and further raising the temp. after the introduction, thereby to obtain crystallized glycine.

COPYRIGHT: (C)1994,JPO

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an improved synthetic method for glycine, and more specifically, it uses acetic acid as a starting material and chlorinates it to selectively synthesize monochloroacetic acid, which is then crystallized. Without passing through the process, it is recovered in a molten state by distillation, and the monochloroacetic acid in the molten state is reacted with a tertiary amine in an alkanol solvent to produce an intermediate product tertiary ammonium ammonium chloride. Further, it relates to an improved synthetic method of glycine which is obtained by reacting paraformaldehyde and ammonia to obtain glycine in a short time in a high yield and a high purity.

[0002]

2. Description of the Related Art Conventionally, a method for producing monochloroacetic acid from acetic acid or the like as a starting material and synthesizing glycine using the same is as follows. First, acetic acid is chlorinated to synthesize monochloroacetic acid. The target glycine was produced by the various methods described below. As a method for synthesizing monochloroacetic acid by chlorinating this acetic acid, red phosphorus, sulfur, or a mixture of sulfur and acetic anhydride chloride is used as a catalyst, and 100% acetic acid is obtained under the condition of 100 to 110 ° C in the presence of light. A method of chlorinating to a close degree and then crystallizing (it may take several months to completely crystallize because it gradually crystallizes) to obtain crude monochloroacetic acid crystals is generally performed.

However, as described above, 100% of acetic acid is added.
When chlorinated to a close degree, a large amount of dichloroacetic acid, trichloroacetic acid, etc. are produced as side reaction products in the reaction product in addition to monochloroacetic acid, and other impurities such as polymers are also considerably formed. Therefore, not only the ultimate yield (intensity unit) per charged acetic acid is lowered, but also the purity of the crude crystal is low, and the crude crystal cannot be used as it is as a raw material for glycine production. How was it?

Therefore, generally, the crude crystalline monochloroacetic acid has been purified by a fractional recrystallization method or rectified by a distillation method to obtain a higher purity monochloroacetic acid. However, the fractional recrystallization purification method requires not only a large amount of a solvent for fractional recrystallization, but also equipment such as a recrystallization tank, and a complicated operation step for handling solid crystals or rally. The cost will be increased economically.

On the other hand, even when the crude crystalline monochloroacetic acid is subjected to fractional purification by distillation, these impurities, especially di- or trichloroacetic acid, have boiling points of 192 to 3 ° C. and 19 respectively.
Since it is close to 7.5 ° C. and the boiling point of monochloroacetic acid (189.3 ° C.), a rectification column equipped with a large number of plates is required to separate them by the distillation method.

These chlorinated acetic acid derivatives, particularly di- and trichloroacetic acid, require a rectification column made of a corrosion-resistant alloy or a special corrosion-resistant metal, which is significantly more corrosive to metals than mono-substituted products and is expensive. Also, in the operation, various disadvantages are inevitable such as installation of special protective equipment for avoiding contact with human body.

Next, as a method for synthesizing glycine from monochloroacetic acid, until now, various methods described below are already known. One is the classical and laboratory method for synthesizing glycine from monochloroacetic acid and aqueous ammonia (Organic Synthesis).
Vol II). US Pat. No. 3,190,914 discloses a method for synthesizing glycine from monochloroacetic acid, formalin solution, and ammonia water. Further, JP-A-58-22055 discloses that NH ₄ Cl, (NH ₄ )
An invention of a method for synthesizing glycine by using monochloroacetic acid and about 10 times the amount of ammonia water with respect to the monochloroacetic acid using ₂ CO ₃ or the like as a catalyst is disclosed. Furthermore, there is also known a method of producing acetic acid tertiary ammonium chloride from monochloroacetic acid and a tertiary alkylamine, and reacting this with aminomethanol in an alkanol solvent to synthesize glycine (Republic of China Patent No. 45037). ing.

However, among the above-mentioned fourth methods, that is, methods other than the method of reacting acetic acid tertiary ammonium chloride with aminomethanol, all produce a large amount of ammonium chloride as a by-product. The reaction has a drawback that it takes a very long time or the yield is low, and it is not suitable as a practical method for producing glycine.

The above-mentioned fourth method has good yield and purity of glycine, but in this method, the reaction product obtained by reacting monochloroacetic acid and a tertiary amine is passed through ammonia gas at 60 ° C. Since the absorption of ammonia gas is carried out at a high temperature of 60 ° C. in the step of producing glycine, the reaction between formaldehyde and ammonia gas becomes insufficient, and most of the introduced ammonia gas is discharged without being fixed. Therefore, there is a disadvantage that a recovery device for the unreacted exhausted ammonia gas is required, and thus an initial cost for manufacturing and installing the recovery device and an ordinary cost required for operation are extra.

[0010]

Therefore, the present inventor has improved the above-mentioned drawbacks of the conventional method, and can economically synthesize crystalline glycine of high yield and high purity from acetic acid in a short time. As a result of intensive studies on the method, the inventors have found that the method described below solves the drawbacks of the conventional method and achieves the above-mentioned objects, and thus completed the present invention.

[0011]

According to the present invention, when chlorinating acetic acid in the presence of a catalyst at a temperature of 95 to 110 ° C. to obtain monochloroacetic acid as a main reaction product, oxide is removed as the catalyst. Step (A) in which the reaction product is obtained by using the above-mentioned neutral red phosphorus and terminating the reaction when the acetic acid standard conversion of the monochloroacetic acid is 90% or less, and collecting unreacted acetic acid in the reaction product. To obtain molten crude monochloroacetic acid, or to rectify the reaction product, or to further distill the crude monochloroacetic acid to obtain molten purified monochloroacetic acid, and the crude or purified monochloroacetic acid. Is fed into the synthesis reaction tank in a molten state, an alkanol having 1 to 4 carbon atoms is added as a solvent, and then a tertiary alkylamine having 2 to 3 carbon atoms is added to produce acetic acid tertiary ammonium chloride, Continue to 3 After adding and dissolving paraformaldehyde at a temperature of 40 to 40 ° C, ammonia gas is introduced into the reaction system at the reaction temperature of 40 to 45 ° C to cause reaction, and after the ammonia gas is introduced, the temperature is further raised to complete the reaction. And a step (C) of obtaining crystalline glycine, the method for synthesizing glycine is provided.

[0012]

The present invention is a method for synthesizing glycine using acetic acid as a starting material and using monochloroacetic acid obtained by chlorinating the acetic acid, which is used as a chlorination catalyst in the chlorination of acetic acid in step (A). Chlorination reaction at a reaction temperature of 95 ° C to 110 ° C using neutral red phosphorus from which substances have been removed,
The first feature is that the reaction is stopped when the conversion ratio of monochloroacetic acid to input acetic acid is within 90% to obtain a reaction product mixture.

It is already known to use either red phosphorus or sulfur, or a mixture of sulfur and acetic anhydride chloride or phosphorus trichloride as a catalyst in the synthesis of monochloroacetic acid by chlorinating acetic acid. The inventor conducted comparative experiments on the performance of each of these catalysts. When red phosphorus was used as the catalyst, the desired reaction was completed in about 4 to 5 hours, while sulfur or sulfur and acetic anhydride were used. It has been found that when a mixture with chloride or the like is used as a catalyst, it takes a dozen hours or more, and there is a marked difference in the chlorination rate.

As the red phosphorus used as a catalyst, it is necessary to use a neutral one from which oxides have been removed. When a red phosphorus containing an oxide is used as a catalyst, acetic acid In chlorination, a large amount of impurities such as polymers are produced, and the selectivity is deteriorated.

Many commercially available red phosphorus whose surface is oxidized and contains an oxide, and when this is used, after the oxide is changed to an acid by a treatment such as boiling with water, hot water or the like is used. It is preferable that the washing water is washed several times until it becomes neutral, and this is used as a catalyst. By using the neutral red phosphorus from which the oxide has been removed as a catalyst, monochloroacetic acid can be selectively produced in the chlorination reaction of acetic acid,
When the conversion rate is about 90%, the production rate of the polymer can be suppressed to 2% or less.

In the acetic acid chlorination reaction step (A) of the present invention, the reaction is stopped when the conversion rate of monochloroacetic acid based on acetic acid is 90% or less to obtain a reaction product. By stopping the chlorination reaction at this point using the above-mentioned catalyst of the present invention, the production of di- or trichloroacetic acid, which is a by-product of the chlorination reaction, can be suppressed to substantially zero, and It is possible to suppress the generation of impurities as a polymer to 2% or less.

Therefore, the crude monochloroacetic acid obtained by distilling off unreacted acetic acid from this reaction product mixture has a considerably high purity and can be used as it is as a raw material for the glycine synthesis step. However, since the crude monochloroacetic acid still contains a very small amount of polymer and other impurities, if the product glycine is required to have a particularly high purity, the crude monochloroacetic acid should be purified by redistillation. It is necessary to rectify the reaction product mixture to obtain high-purity monochloroacetic acid.

Next, the second feature of the method of the present invention is obtained by subjecting the above-mentioned reaction product mixture to crude distillation of crude monochloroacetic acid obtained by distilling off unreacted acetic acid to redistillation or rectification. That is, the purified monochloroacetic acid is fed into the reaction tank of the next glycine synthesis reaction step (C) in a molten state. As a result, the produced monochloroacetic acid can be used as a raw material for the next reaction step without time loss, and not only the time required for producing glycine from acetic acid can be significantly shortened but also crystallization can be achieved. It is possible to omit steps and achieve considerable energy saving.

The third feature of the method of the present invention is that (C)
Step, that is, a step of synthesizing glycine from the monochloroacetic acid in a one-step reaction step. The elementary reactions of the step (C) are shown in the reaction formulas as follows.

[0020]

[Chemical 1]

That is, in the step (C), the molten monochloroacetic acid is fed into the reaction tank in a molten state,
An alkanol solvent is added to and dissolved in this, and a tertiary alkylamine is gradually added and reacted at 60 ° C. to 70 ° C. to generate acetic acid tertiary ammonium chloride (the above elementary reaction (i)). To 40 ° C., paraformaldehyde is added and dissolved sufficiently, and then ammonia gas is introduced into the reaction system while maintaining the temperature at 40 to 45 ° C.

First, the introduced ammonia gas first reacts with paraformaldehyde dissolved in the system (primary reaction (ii)) to give aminomethanol, and this aminomethanol immediately reacts with acetic acid tertiary ammonium chloride present in the system. React to react with HOCH ₂ NHCH ₂ COOH and R
₃ N HCl is produced (elementary reaction (iii), but the temperature in the system at this time is 40 to 45 ° C.).

HOCH ₂ NHCH ₂ COOH produced
Is decomposed into glycine and HCHO by the catalytic action of HCl separately generated in the elementary reaction (iv) (elementary reaction (v)). HCHO produced by this decomposition reaction (v)
Has a high reaction activity, and immediately re-bonds with the unreacted ammonia gas dissolved in the system to fix the dissolved ammonia gas in the system (elementary reaction (vi)). Since the target product glycine produced in the reaction system is substantially insoluble in the alkanol solvent, it undergoes phase separation as a solid phase upon production,
Therefore, the reaction solution becomes cloudy with the formation of glycine, and eventually becomes a slurry. About 2.
After introducing 0 to 2.1 equivalents of ammonia gas and fixing them in the solution, the temperature is raised to about 60 ° C. to 65 ° C. to complete the glycine production reaction (elementary reaction (ii
i) later stages).

In the above step (C) of the present invention,
It is particularly important to dissolve paraformaldehyde in the tertiary ammonium chloride after it is sufficiently formed and then to introduce ammonia gas at a temperature of 40 to 45 ° C. That is, acetic acid tertiary ammonium chloride (ClR ₃ N.CH ₂ CO) present in the above reaction system.
The Cl group of OH) is activated and is highly reactive, and it sufficiently reacts with the —NH ₂ group of aminomethanol even at a temperature of about room temperature. Therefore, the progress of this reaction (the above elementary reaction (iii))
1) mainly depends on the production rate (concentration) of aminomethanol.

On the other hand, the production of aminomethanol depends on the dissolved concentration of the introduced ammonia gas in the reaction liquid, and if the temperature of the reaction liquid is too high, the dissolution of ammonia gas in the liquid becomes insufficient, Therefore, this gas dissolving step becomes rate-determining, and the reaction between ammonia and paraformaldehyde or the recombination with formaldehyde desorbed in the elementary reaction (v) does not proceed at a sufficient rate. Therefore, for example, if the introduction of the ammonia gas is performed at a high temperature of about 60 ° C. or higher, most of the introduced ammonia gas is discharged unreacted.

On the other hand, the introduction of ammonia gas is 40
When carried out at ˜45 ° C., the introduced ammonia gas is temporarily dissolved in the system in a free state, and is rapidly bound and immobilized with the dissolved paraformaldehyde and desorbed formaldehyde during this period.

Therefore, in the step (C) of the present invention, substantially no ammonia gas is discharged unreacted,
Therefore, a facility for collecting unreacted ammonia gas is not required. In the step (C) of the present invention, in order to smoothly proceed the production of glycine by the reaction of the acetic acid tertiary ammonium chloride and aminomethanol, p of the reaction solution is
H is preferably in the range of 7.0 to 10.0, p
When H is 7.0 or less, the cause is not clear, but the reaction does not proceed smoothly. The pH is adjusted by adjusting the amount of tertiary amine and the amount of ammonia gas introduced. It is not preferable to add another alkaline substance for pH adjustment.

Further, in the step (C) of the present invention, HCl is eliminated and generated in the reaction process of the acetic acid tertiary ammonium chloride and aminomethanol, and this HCl selectively and immediately binds to the alkyl tertiary amine. However, it is also a remarkable feature of the method of the present invention that ammonium chloride is not produced.

[0029]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention will be described in more detail below. (I) Chlorination of acetic acid [Step (A)] In the chlorination step of acetic acid of the present invention, neutral red phosphorus from which oxides have been removed is used as a catalyst. Many red phosphorus, especially commercially available red phosphorus, contains oxides due to surface oxidation, and when red phosphorus containing such oxides is used as a catalyst, many impurities such as polymers are generated during chlorination. However, the reaction selectivity decreases. The method for removing the harmful oxides from the surface of red phosphorus is not limited to this. For example, red phosphorus is sufficiently boiled with water to convert the oxides into acids. Then, a method of washing with hot water a plurality of times until the pH of the wash water (hot water) becomes neutral is used.

When the reaction is carried out under the chlorination conditions of the present invention using the neutral catalyst from which the oxide is completely removed, the chlorination reaction proceeds smoothly and impurities such as the above-mentioned polymer are also produced. It can be kept as low as 2% or less.

In the chlorination step of the present invention, it is not necessary to irradiate a light ray which is generally required in a known method, and chlorination proceeds at a sufficient rate even without irradiating a light ray. In the chlorination step of the present invention, the above-mentioned red phosphorus catalyst is not necessarily limited, but it is preferable to use about 2 to 3% with respect to the amount of acetic acid added. The reaction temperature in the chlorination step of the present invention is 95 ° C to 110 ° C, preferably 100 to 1
Perform at 05 ° C. Chlorination of acetic acid starts at a temperature of 75 ° C or higher, but a practical reaction rate is 95%.
℃ or above. If the reaction temperature exceeds 110 ° C,
Not only is the selectivity of the reaction product lowered, but there is a case where acetic acid escapes from the backflow condenser together with hydrochloric acid, which is not preferable. It is preferable to introduce chlorine by installing a chlorine flow meter, a chlorine backflow prevention trap, or the like between the chlorine supply cylinder and the chlorination reaction tank. By adjusting the chlorine introduction rate to be constant with a chlorine flow meter, the chlorination rate and reaction temperature can be stabilized at appropriate values, and the hydrochloric acid generation rate can be stabilized.

In the chlorination step of the present invention, the chlorine introduction rate in the initial stage of the reaction is preferably adjusted to a rate at which chlorine is not mixed in the produced HCl gas, and the progress of chlorination is determined by high performance liquid chromatography (HPLC). The rate of chlorine introduction is halved at the time when the production of monochloroacetic acid reaches 60%, and the chlorination reaction is performed at the time when the conversion rate reaches a maximum of 90%, preferably 80 to 85%. Stop and end.

In the chlorination step in the method of the present invention, it is important to terminate and terminate the reaction when the conversion rate of monochloroacetic acid is 90% or less for the above-mentioned reason. When the conversion is stopped within 90%, dichloroacetic acid, trichloroacetic acid and the like are not detected even by the analysis result of the reaction product by high performance liquid chromatography.

On the other hand, the conversion rate of monochloroacetic acid is 90
%, Dichloroacetic acid begins to be formed, and when completely chlorinated, the production rates of di- and trichloroacetic acid reach about 7% dichloroacetic acid and about 1% trichloroacetic acid. In this chlorination reaction, about 3% acetyl chloride is produced as a by-product, which can be returned to acetic acid by adding water after chlorination, and can be recovered by distillation as acetic acid. The time required for the chlorination step of the present invention varies depending on the reaction conditions, but is usually 4 to 5 hours.

[II] Molten crude monochloroacetic acid, molten refinement
Monochloroacetic acid produced by [Process (B)] The reaction product mixture produced in the above chlorination step was analyzed by high performance liquid chromatography, and the typical composition ratio was acetyl chloride: acetic acid: monochloroacetic acid = 3 to
It is about 4: 6 to 15:80 to 85. In addition to the above, about 1 to 2% of a polymer is produced (the polymer cannot be analyzed by HPLC and is recovered as a distillation residue). In the conventional known method, separation of monochloroacetic acid after chlorination of acetic acid is performed by a crystallization method. Crystallization was performed, and this was further purified by recrystallization or distillation to obtain monochloroacetic acid. This is because, in the conventional known method, a large amount of by-products such as di- or trichloroacetic acid are produced in addition to monochloroacetic acid, and these are mixed as a contaminant in the crude crystal of monochloroacetic acid, and therefore, the following glycine This is because it cannot be used as a raw material in the synthesis process.

In the present invention, chlorination is stopped at a conversion rate of monochloroacetic acid within 90%, preferably 80 to 85% to suppress the production of side reactions, and water is added to the reaction solution after completion of chlorination to convert acetyl chloride into acetic acid. Instead, the reaction mixture is distilled to distill off acetic acid, and crude monochloroacetic acid in a molten state is used as a bottom product fraction, which is used as it is as a raw material for the next glycine synthesis step. The acetic acid distilled off at this time contains phosphorus trichloride, which can be reused with the recovered acetic acid as the next chlorination raw material. The purity of crude monochloroacetic acid in this case is usually 95 to 97%. When a product with higher purity such as glycine is required, the crude monochloroacetic acid is redistilled or the reaction mixture is rectified to obtain purified monochloroacetic acid having a purity of 99% or more. Also in this case, the purified monochloroacetic acid is transferred to the next step in a molten state and used as a raw material.

[III] Synthesis of glycine and content of glycine
Separation [Step (C)] (III-1) Solvent In the glycine synthesis step of the present invention, the number of carbon atoms is 1 to 4
Of alkanol is used as a solvent. The solvent used in the glycine synthesis step of the present invention has no direct reactivity with each reaction raw material, reaction reagent, etc., and includes monochloroacetic acid, aminomethanol and formaldehyde produced during the reaction, acetic acid tertiary amine chloride, etc. It can dissolve various substances completely in a hot solution state, has almost no solubility for glycine, which is the target product, and can almost completely phase-separate in a solid phase state. It is required to satisfy requirements such as convenience in operations such as washing, and it is preferable that the boiling point is relatively low, the collection is easy, and the price is not so high.

In the present invention, an alkanol having 1 to 4 carbon atoms is used as a solvent suitable for such purpose. Specific examples include methanol, ethanol, propanol, isopropanol, butanol, isobutanol, secondary butanol, and tertiary butanol. The amount of the solvent used is preferably 2.0 times (volume) or more, and particularly preferably 2.0 to 3.0 times (volume) the amount of monochloroacetic acid. Within the above range, glycine is a crystalline precipitate, but the others are in a completely dissolved state, which is useful for allowing the reaction to proceed smoothly. It is of course possible to use a mixture of the abovementioned alkanols as solvent.

[III-2] Tertiary amine In the glycine synthesis reaction step of the present invention, one of the features is that a tertiary amine is added to monochloroacetic acid to form a tertiary ammonium chloride. The conditions required for the tertiary amine used in the present invention are that it is poorly soluble in water, has a specific gravity lower than that of water, has a low boiling point, is easy to purify, and is inexpensive. For this purpose, in the present invention, at least one selected from tertiary alkylamines having 2 to 3 carbon atoms is used.

Specific examples of such a tertiary alkylamine include triethylamine and tripropylamine. The tertiary alkylamine is 1.1 to 1.2 mol per mol of monochloroacetic acid,
Preferably, 1.02 to 1.05 mol is used.

When the amount of the tertiary alkylamine used is within the above range, the reaction of monochloroacetic acid can be completely progressed, and at the same time, the pH of the reaction solution during the reaction can be increased.
To maintain the preferred state of 7.0 to 10.
Also, a tertiary alkylamine hydrochloride (R ₃ N
-HCl) can be used for the next reaction after distilling off the solvent and adding a caustic soda solution to recover the poorly water-soluble tertiary alkylamine and further dehydrating it. Tertiary amines other than tertiary alkylamines having 2 to 3 carbon atoms, such as triethylamine, can be used, but are not practically preferable because they are gaseous at room temperature and easily soluble in water. The recovered tertiary alkylamine does not need to be purified through a distillation process or the like, and can be separated from the soda solution, dehydrated with a dehydrating agent and used as it is in the next reaction.

[III-3] Glycine Synthesis Step and Separation Step Crude monochloroacetic acid or purified monochloroacetic acid obtained by chlorination in [II] is transferred to a glycerin synthesis reaction tank in a molten state, and the alkanol is used as a solvent. In addition, make a solution. The liquid temperature is 60 to 70 ° C., preferably 60 to 65 ° C., followed by a slight excess (1.1 to 1.2 mol / mol) of the equivalent weight.
The above-mentioned tertiary alkylamine (monochloroacetic acid) is gradually added and reacted. During the reaction, it is preferable to always maintain the temperature of the reaction liquid at 60 to 70 ° C., particularly preferably 60 to 65 ° C., by means such as cooling from the outside in order to prevent the liquid temperature from rising due to heat generation.

After the addition of the tertiary amine is completed, another 2
The reaction of heating and stirring for 0 to 30 minutes is completed to complete the reaction for forming the reaction product tertiary ammonium chloride of acetic acid while maintaining the above temperature. Subsequently, the temperature is lowered to 35 to 40 ° C. and paraformaldehyde is added and dissolved. When the paraformaldehyde is dissolved, the liquid temperature is kept at 40 ° C. or lower, and then stirred for 20 to 30 minutes to completely dissolve the paraformaldehyde, and then the liquid temperature is adjusted to 40 to 45 ° C. and ammonia gas is introduced. The temperature gradually rises with the introduction of ammonia gas, but the reaction temperature is kept in the range of 40 to 45 ° C. by an operation such as cooling or adjusting the introduction rate of ammonia gas.

When introducing this ammonia gas,
The pH of the reaction solution along with the solution temperature is 7.0 to 10.0, preferably 7.0 to 9.0, and more preferably 8.5 to 9.5.
The introduction rate of the ammonia gas is adjusted so that it falls within the range. In this reaction step, the reason why the pH of the reaction solution is 7.0 or less, that is, the acid side is not clarified, but the reaction hardly progresses, and therefore glycine is hardly produced. The pH of the reaction solution is adjusted by the addition amount of the tertiary alkylamine and the introduction rate of ammonia gas. It is not preferable to add another alkaline substance for adjusting the pH. The total amount of ammonia gas introduced is 2.0 to 2.1 with respect to the amount of monochloroacetic acid input.
An equivalent range is preferred.

After the introduction of the ammonia gas, when about 60% of the charged monochloroacetic acid is converted into glycine, the temperature of the reaction solution is raised to 60 to 65 ° C. and stirring is continued. When the conversion rate of monochloroacetic acid reached about 50 to 60%, most of the excess dissolved ammonia present in the reaction system was converted into aminomethanol, and almost no free ammonia was present. No, it is not discharged unreacted. The completion of the glycine conversion reaction is determined by using the time point at which the amount of residual monochloroacetic acid in the reaction solution as measured by high performance liquid chromatography is 0.5% or less as a measure of the end point.

The time required for the glycine synthesis step varies depending on the reaction temperature and other reaction conditions such as pH control and is not fixed, but is usually about 2 to 3 hours when the reaction is carried out under standard conditions. finish. The reaction time becomes longer as the reaction temperature becomes lower.
The glycine produced after completion of the reaction is not necessarily limited to this, but for example, a method of separating the glycine by filtering the product mixture after the reaction in a hot state is used. The solubility of glycine in alkanol at 60 ° C. is about 0.5% or less, but unnecessary substances by-produced by the reaction, such as aminomethanol, tertiary alkylamines and tertiary amine hydrochlorides, and small amounts of All the polymers and the like are easily dissolved in the hot alkanol, and remain dissolved in the hot alkanol solution after filtration of glycine. The glycine after filtration can therefore be washed once or twice with hot alkanol to remove contaminants, and glycine having a purity of 98% or more can be obtained as crude crystalline glycine.

According to the method of the present invention, the yield of glycine is 90%.
The fact that glycine having a purity of 98% or more and a yield of 90% or more obtained in the above-described one-step operation was first achieved in the method of the present invention, and can be achieved in other conventional methods. I couldn't do it. In order to make the reaction procedure, operation, etc. of the method of the present invention described above easier to understand, the outline of the method of the present invention is shown as a block diagram in FIG. Next, the present invention will be described more specifically by way of examples.

[0048]

【Example】

(Analysis method) In Examples and Comparative Examples described below, acetic acid as a raw material (abbreviated as AA in the following description,
The same applies in parentheses), monochloroacetic acid (MCA), and aminomethanol, tertiary amine hydrochloride, glycine, etc. produced during the reaction by high performance liquid chromatography (HPL).
C) was measured and identified under the following conditions. In the identification confirmation of each of the above-mentioned compounds and the like, the identification by HPLC and the melting point measuring method were also used together as necessary.

HPLC measurement conditions (1) Column: Zorbax Sax: Strong anion exchange resin (Shimadzu No: 228-00764-91, 46)
mmID × 15 cm) (2) Mobile phase 0.005 mol KH ₂ PO ₄ in methanol / water (4/9
6) Solution (3) pH: 2.0 (4) Flow rate: 1.0 ml / min (5) Temperature: Room temperature (6) Detection device: UV 210 μm

Example 1 As a device, a 500 cc four-necked flask was equipped with a backflow condenser, 1
A 50 ° C. thermometer and a chlorine inlet tube (insert near the bottom of the flask) are attached, and the whole is placed on a magnetic stirrer. From the top outlet of the backflow condenser, connect to a blank flask by a polyethylene tube or a copper tube, further connect to a HCl gas absorption bottle containing water, and finally pass through a gas absorption bottle containing caustic soda solution. A chlorine backflow trap and a chlorine flow meter are placed between the chlorine cylinder and the 500 cc flask, and the chlorination reaction is carried out in a draft.

This four-necked 500 cc flask was charged with A. A 200 gms was added, and the mixture was further boiled with hot water for a while to decompose the oxide, and then the same with hot water to a pH of 6.0.
After washing to 7.0, add 6 gms of dried red phosphorus and stir it. After heating to 95 ° C, add 300 cc / min of chlorine.
Pass at the flow rate of. Since HCl gas begins to come out from the top outlet and the temperature becomes 105 ° C. or higher, the temperature is kept at 100 to 105 ° C. Prevent A from distilling. At this time, if the cooling of the backflow cooler is poor, A. A and acetyl chloride are distilled from the top outlet.

In about 2 hours, the result of the HPLC test was about 50-
It can be confirmed that 60% has been converted to MCA. The HCl generated during chlorination is absorbed in water and finally collected with soda solution. At this point, change the flow rate of chlorine to 150 cc / min
To prevent local dichloride formation. Then, chlorine is passed at this flow rate for about 2 hours, and MCA is performed by HPLC.
Stop chlorination after confirming that the conversion rate to 84.5% has reached 84.5%. The color of the liquid at this time was pale yellow. As a result of weighing, the content weight was 305 gms, the purity test by HPLC was 82.6%, the calculated amount of MCA was 251.9 gms, and the unreacted A. A25.5gms, Acetyl chloride
e 10.5 gms (A.A 8.5 gms equivalent) MCA
Converted to A. The amount of A is calculated to be about 166.5 gms.
The conversion rate of MCA to A is

[0053]

[Equation 1]

This chlorinated solution 305 gms (component 8
Acetyl chloride was first distilled off and recovered with a rotary bath evaporator at a water bath temperature of 80 ° C. and a vacuum degree of 100 mmHg, and distilled until the distillate stopped producing 240.5 gms of residue and 55. 0
Get gms. Distillation loss 9.5 gms, Purity: residue 9
5.8%, distillate A. A: MCA = 63.4: 36.
6. This residue (ie crude MCA) 120 gms, purity 9
5.8% was distilled further at a water bath temperature of 100 ° C. and a vacuum degree of 20 mmHg to obtain 113.6 gms of colorless MCA with a purity of 99.1%.
Got

Example 2 49.5 gms of crude MCA obtained in Example 1 (purity 9
(5.8%, 0.5M) of the melt was placed in a 500cc three-necked flask (backflow condenser, thermometer, equipped with a 100cc separating funnel), 130cc of methanol was added, and 52gms (0.52M) of triethylamine was added. When the solution is gradually dropped from the liquid funnel, the temperature gradually rises and rises to 60 ° C or higher. Therefore, external cooling is performed, keeping the temperature at 60 to 65 ° C, the dropping is completed, and the temperature is kept stirring at the same temperature for 30 minutes.

Then, cooled paraformaldehyde (24.5 gms, purity: 92%, 0.75M) was added at 35 ° C., and the mixture was stirred and dissolved, and then NH ₃ was passed through. 40-45 during NH ₃ introduction
Hold at ° C. Amount of NH ₃ introduced 19 gms (1.117
M), NH ₃ discharged without being absorbed was absorbed and measured in a H ₂ SO ₄ solution, and NH ₃ was about 2 gms (60-6).
The NH ₃ discharged NH ₃ introduced at 5 ° C. to about 15gms). The pH at this time was about 9.0, and then the temperature was kept at 60-65 ° C. and stirred for about 1.5 hours, and MCA was about 0.5% by HPLC test, so the reaction was stopped at this point. Since the liquid becomes a slurry, it is subjected to hot filtration and then rinsed, filtered, and dried twice with hot methanol to obtain white glycine crystalline powder.
Yield 36.0 gms, purity 98.7%, yield 94.7.
%, M.I. P. 726.5-729.0 ° C

Example 3 47.7 gms of purified MCA obtained in Example 1 (purity 9
9.1%, 0.5M) melt with a backflow condenser, thermometer,
A 500 cc three-necked flask equipped with a separating funnel is placed, and subsequently 130 cc of ethanol is placed. After that, the operation reaction according to Example 2 resulted in the following. Yield 35.
3 gms, purity 98.6%, yield 92.7%, M.I. P.
126.5-129.0

Example 4 55 gms of distillate obtained by distillation after chlorination in Example 1
(AA: MCA = 63.4: 36.6) was placed in a 500 cc flask similar to that in Example 1, and A.M.A. A 150gm
s was added, and 3 gms of red phosphorus that had been washed and dried to pH 6 to 7 was added, and chlorination was performed in the same manner as in Example 1. 31.0 gms of chlorinated solution of acetyl chloride: AA: MCA = 3.5: 14.5: 82 was obtained. 67 g of distillate
ms, (AA: MCA = 61.3: 38.7, separately C
H ₃ COCl 9 gms recovered) Residue (crude MCA) 23
5 gms (purity 96.3%) were obtained.

Example 5 The crude MCA (purity 96.3%) obtained in Example 4 was melted to obtain 49.0 gms (0.5 M) in the same manner as in Example 1.
Transfer to a 00 cc flask and add 130 cc of butanol. Tripropylamine 7 as tertiary alkyl amine
6.5 gms (0.52M) was added, and an experiment was conducted in the same manner as in Example 1 and the results were as follows. Glycine yield 3
5.0 gms, purity 98.4%, yield 91.8%, M.I.
P. 226.0-229 ° C

Example 6 The filtrate after separating glycine in Example 5 was left at 3 ° C. overnight, and the resulting crystals were filtered and dried to obtain 22.1 g. HP
It was confirmed by LC that monoaminomethanol 86% and tripropylamine hydrochloride 7.0 were contained.
(The rest are unknown components) Crude MCA obtained in Example 4 by the same operation as in Example 1
22.5 gm of the above monoaminomethanol in a methanol solution of triethylammonium acetate acetate synthesized from 49.0 gms (purity 96.3%, 0.5M).
s and 5gms of paraformaldehyde were added and dissolved,
Pass NH3 ₉ gms at 40-45 ° C. MC by HPLC
After confirming that at least 50% of A was produced, the temperature was increased to 6
After the temperature was raised to 0-65 ° C. and stirring was completed for about 1.5 hours, glycine production was completed, glycine was obtained by hot filtration and hot washing, and the yield, purity and yield after drying were as follows. Yield: 35.1
gms, purity: 98.6%, yield 92.2%, M.P. P.
226.7 to 229.3 ° C

Comparative Example A. A200 gms was chlorinated in the same manner as in the example,
A. A. by HPLC inspection. As a result of passing chlorine until the A peak disappears, the peak appearing on the HPLC chart is MC
Outside of A, 4.0% of acetyl chloride, 7.3% of dichloroacetic acid, and 1.3% of trichloroacetic acid were distilled to distill off the MCA, which was 3.2% of dichloroacetic acid, 0.6% of trichloroacetic acid, and MCA96. .2%, polymer (residue) is 1
It was 3.5 gms (vs A.A 6.75%).

[0062]

According to the present invention, glycine crystals having a purity of 98% or more can be obtained from acetic acid via monochloroacetic acid in a high yield of 90% or more, and energy saving and economically. it can.

[Brief description of drawings]

FIG. 1 is a block diagram illustrating steps and operating procedures of a method of the present invention.

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[Procedure amendment]

[Submission date] August 27, 1992

[Procedure Amendment 1]

[Document name to be amended] Statement

[Name of item to be corrected] 0002

[Correction method] Change

[Correction content]

[0002]

2. Description of the Related Art Conventionally, a method for producing monochloroacetic acid from acetic acid or the like as a starting material and synthesizing glycine using the same is as follows. First, acetic acid is chlorinated to synthesize monochloroacetic acid. The target glycine was produced by the various methods described below. As a method for synthesizing monochloroacetic acid by chlorinating this acetic acid, red phosphorus, sulfur, or a mixture of sulfur and acetic anhydride chloride is used as a catalyst, and 100% acetic acid is obtained under the condition of 100 to 110 ° C in the presence of light. A method of chlorinating to near, and then crystallization (it may take several days to completely crystallize due to gradual crystallization) to obtain crude monochloroacetic acid crystals is generally performed.

[Procedure Amendment 2]

[Document name to be amended] Statement

[Correction target item name] 0042

[Correction method] Change

[Correction content]

[III-3] Glycine Synthesis Step and Separation Step Crude monochloroacetic acid or purified monochloroacetic acid obtained by chlorination in [II] is transferred to a glycine synthesis reaction tank in a molten state, and the alkanol is used as a solvent. In addition, make a solution. At a liquid temperature of 60 to 70 ° C., preferably 60 to 65 ° C., the tertiary alkylamine, which is slightly in excess of the equivalent (1.1 to 1.2 mol / monochloroacetic acid), is gradually added and reacted. During the reaction, it is preferable to always maintain the temperature of the reaction liquid at 60 to 70 ° C., particularly preferably 60 to 65 ° C., by means such as cooling from the outside in order to prevent the liquid temperature from rising due to heat generation.

[Procedure 3]

[Document name to be amended] Statement

[Correction target item name] 0056

[Correction method] Change

[Correction content]

Then, cooled paraformaldehyde (24.5 gms, purity: 92%, 0.75M) was added at 35 ° C., and the mixture was stirred and dissolved, and then NH ₃ was passed through. 40-45 during NH ₃ introduction
Hold at ° C. Amount of NH ₃ introduced 19 gms (1.117
M), NH ₃ discharged without being absorbed was absorbed and measured in a H ₂ SO ₄ solution, and NH ₃ was about 2 gms (60-6).
The NH ₃ discharged NH ₃ introduced at 5 ° C. to about 15gms). The pH at this time was about 9.0, and then the temperature was kept at 60-65 ° C. and stirred for about 1.5 hours, and MCA was about 0.5% in the HPLC test, so the reaction was stopped at this point. Since the liquid becomes a slurry, it is subjected to hot filtration and then rinsed, filtered, and dried twice with hot methanol to obtain white glycine crystalline powder.
Yield 36.0 gms, purity 98.7%, yield 94.7.
%, M.I. P. 226.5-229.0 ° C

[Procedure amendment 4]

[Document name to be amended] Statement

[Name of item to be corrected] 0057

[Correction method] Change

[Correction content]

Example 3 47.7 gms of purified MCA obtained in Example 1 (purity 9
9.1%, 0.5M) melt with a backflow condenser, thermometer,
A 500 cc three-necked flask equipped with a separating funnel is placed, and subsequently 130 cc of ethanol is placed. After that, the operation reaction according to Example 2 resulted in the following. Yield 35.
3 gms, purity 98.6%, yield 92.7%, M.I. P.
126.5-129.0 ° C

Claims (4)

[Claims] 1. Acetic acid in the presence of a catalyst at 95 to 110 ° C.
At the time of chlorination at a temperature of 10 to obtain monochloroacetic acid as the main reaction product, neutral red phosphorus from which oxides have been removed is used as the catalyst, and the reaction is carried out at an acetic acid standard conversion of the monochloroacetic acid of 90% or less. Step (A) of stopping to obtain a reaction product, distilling off unreacted acetic acid in the reaction product to obtain a molten crude monochloroacetic acid, or rectifying the reaction product, or the crude monochloroacetic acid. Is further distilled to obtain a molten purified monochloroacetic acid (B), and the crude or purified monochloroacetic acid is fed into the synthesis reaction tank in a molten state, and alkanol having 1 to 4 carbon atoms is added as a solvent. , C2 to C3
To produce acetic acid tertiary ammonium chloride, followed by addition of paraformaldehyde at a temperature of 35 to 40 ° C. to dissolve it, and then in a reaction system at a reaction temperature of 40 to 45 ° C. A method of synthesizing glycine, which comprises the step (C) of introducing ammonia gas into the reaction mixture to react the mixture, and further raising the temperature to complete the reaction to obtain crystalline glycine. 2. The alkanol solvent having 1 to 4 carbon atoms used in the step (C) is at least one selected from the group consisting of methanol, ethanol, propanol, isopropanol, butanol, secondary butanol, isobutanol and tertiary butanol. The method for synthesizing glycine according to claim 1, which is an alkanol solvent, and the tertiary alkylamine having 2 to 3 carbon atoms is at least one selected from triethylamine and tripropylamine. 3. The amount of paraformaldehyde used in the step (C) is 1.0 to 2.0 mol per mol of pure or purified monochloroacetic acid, and the amount of ammonia used is paraformaldehyde 1. 1.0 per mole
To 2.0 moles, the amount of the tertiary alkylamine used is 1.1 to 1.2 moles per mole of pure monochloroacetic acid, and the temperature is 60 to 60 after introducing ammonia at 40 to 45 ° C. The method for synthesizing glycine according to claim 1, wherein the temperature is raised to 65 ° C to complete the reaction. 4. The method for synthesizing glycine according to claim 1, wherein the pH of the reaction solution after the introduction of ammonia in the step (C) is in the range of 7.0 to 10.0.