JPS5913764A - Preparation of 5-(2-cyanoethyl)-2,4-imidazolidinedione - Google Patents

Abstract

PURPOSE:In preparing the titled substance useful as an intermediate for synthesizing glutamic acid, etc. by reacting 4-oxobutanenitrile as a raw material with NH4, CO2, prussic acid, etc., to improve its purity and yield economically, by making a feed amount of the raw material with high concentration based on a solvent, adjusting the reaction solution to >= a given pH after the reaction. CONSTITUTION:At least one of 4-oxobutanenitrile, 2-hydroxypentanedinitrile, and 2-aminopentanedinitrile as a raw material is used as a raw material, and water or a mixed solvent such as water-methanol, etc. is used as a solvent. 15-40wt%, preferably 20-35wt% raw material based on the solvent is reacted with ammonia and/or ammonium salt, carbon dioxide and/or carbonate and prussic acid and/or its salt. After the reaction is over, the reaction solution is adjusted to <=9pH, preferably 1-9 with a mineral acid, so that crystal of the desired compound is precipitated, and collected by filtration.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing 5-(2-cyanoethyl)-2,4-imidazolidine silone. In particular, the invention relates to the so-called BUCLIERER-BE
JtUS) By reaction, (a) 4-oxobutanenitrile, 2-hydroxypentanedinitrile and 2-
At least one type of aminopentanedinitrile, (b)
ammonia or/and ammonium salt, (C) carbon dioxide or/and carbonate and (d) hydrocyanic acid or/
and its salt to form 5-(2-cyanoethyl)
5-(2-cyanoethyl)-2, which is an intermediate for the synthesis of various useful organic compounds such as glutamic acid, ornithine, and tryptophan. It is an object of the present invention to provide a method for producing 4-imidazolidinedione economically and industrially.

A method for synthesizing 5-substituted-2,4-imitasolidinesions by reacting carbonium compounds, cyanide compounds, and ammonium carbonate (or ammonium bicarbonate) in water or a water-organic solvent has been known for a long time. This method was subsequently improved and systematized as a general synthesis method for 5-substituted-2,4-imitazolidine ions, and since then it has generally been used as
B1 No. I (called Gs reaction).

U.S. time π [Specification No. 8168558, Japanese Patent Publication No. 391
9805'19 Publication Oyohi Special Publication lIe 40-2258
No. 2 publication Niha, Kono r3. f c o I! ;1u;
1t-r3F'; H,OS reaction 'e is used to obtain L5(2-Schif/y-f)-2,4-imitazolysinthion (hereinafter abbreviated as CF: rD). 3. In all of these known methods, the amount of 4-oxobutanenitrile, 2-hy[-loxybencundinitrile, or 2-aminopentanedinitrile based on the solvent is about 10% or less After performing the reaction at a relatively low concentration and evaporating a large amount of solvent to dryness after the reaction, CE 1. i) The method of isolating is adopted. However, if these methods are to be adopted as an industrial production method, they are economically disadvantageous because they require complicated operations and wasteful energy for evaporating a large amount of solvent. The inventors have overcome these drawbacks and developed a more economically advantageous OE II)
As a result of various studies on the industrial production method of After the seeding and reaction, the PR of the reaction product solution was adjusted to 9 or less with mineral acid without distilling off the solvent, and CE I 1
) to achieve high yield and high purity, it was considered optimal to charge the aldehyde or cyanohydrin in an amount of about 10% by weight or less relative to the solvent. However, as a result of detailed study of these reaction conditions f1 in the synthesis of CEID, the present inventors found that CEID
Regarding the synthesis of IJ1, the charging amount of at least one of 4-oxbutanenitrile, 2-hydroxypentanedinitrile and 2-aminopentanedinitrile to a solvent consisting essentially of water is 15 wt% to 40 wt%. Month,%
It has been found that even if the reaction is carried out under such high concentration conditions, the reaction proceeds at a good yield without any problem.

On the other hand, the present inventors also conducted detailed studies on the method for isolating CEID crystals after the reaction.

Usually, the B20HE RE JL-13E RG S reaction is carried out in the presence of an excess of ammonium blown acid or ammonium bicarbonate, and these ammonium salts should not remain in the reaction solution after the reaction. Under these conditions, the electrolysis of the product CEID with respect to water is extremely large, and CEID crystals cannot be isolated simply by cooling the reaction solution, or some of them may remain as crystals. is large, resulting in poor yield.The conventional method has the same effect.

As described above, the method used was to evaporate the solvent to dryness after the reaction and then isolate CEID. By the way, the inventor has 0
As shown in Figure 1, as shown in Figure 1, the solubility of Eil) was significantly increased near pH 9. After the synthesis reaction, the pH of the reaction solution was adjusted with mineral acid.
It has been found that CEID can be isolated in a good yield by adjusting the value to 9 or less and precipitating crystals of CEII). The method of the present invention, which combines the above two new discoveries, completely eliminates the need for solvent evaporation as in conventional methods, greatly simplifies operation, and significantly reduces energy costs. The economic efficiency was significantly improved. Furthermore, in the conventional method of evaporating the solvent to dryness, side reactions and other impurities are mixed into the total 10EID, so some kind of purification was necessary in order to obtain highly pure CEID. However, in the method of the present invention, 0Ei
Because D is crystallized from water, which is the reaction solvent, trace amounts of impurities remain dissolved in the solvent, and 0EID simply precipitates.
It is possible to obtain highly pure CEID simply by passing the crystals through the mouth.

The 4-oxobutanenitrile used as a raw material in the method of the present invention can be synthesized by a known method, for example, one synthesized from acrylCFdiI-lyl, -carbon oxide and hydrogen or from acrolein and hydrocyanic acid or a salt thereof.

For 2-hydroxypentanedinitrile, 4-oxobutanenitrile and hydrocyanic acid were prepared using a known method.
2-aminopentanedinitrile is easily synthesized from 2-hydroxypentanedinitrile and ammonia by a known method. In demonstrating the method of the present invention, 4-oxobutanenitrile may be used as the starting material, or 2-hydroxypentanedinitrile may be synthesized from 4-oxobutanenitrile and hydrocyanic acid and used as the starting material. Furthermore, there is no problem even if it is carried out in the presence of 4-oxobutanenitrile and 2-hydroxypentanedinitrile. Alternatively, 2-aminopencundinitrile may be synthesized from 2-hydroxypentanedinitrile and ammonia and used as a starting material. Examples of ammonia or ammonium salts include ammonia gas, liquid ammonia, ammonium carbonate, ammonium hydrogen carbonate, ammonium chloride, ammonium bromide, ammonium acetate, ammonium carbamate, ammonium cyanide, and the like. Regarding the usage amount (, 'not limited, normal B/cHbJtnu
, -di (the amount used in the ERG8 reaction may be used, for example, 1 mol or more per 1 mol of the above (a), preferably 1 to 5
Moles are used. As carbon dioxide or carbonate,
For example, carbon dioxide, ammonium carbonate, ammonium hydrogen carbonate, sodium carbonate, sodium hydrogen carbonate, potassium carbonate, potassium hydrogen carbonate, etc. are used. There is no particular limit on the amount used, and the usual Boo HE RE
The amount used in the R-B E RG S reaction may be used, for example, 1 mol or more, preferably 1 to 5 mol of F(a), is used. Ammonia or ammonium salt and carbon dioxide or carbonate are used. Flj to the 9 relationship of! l
There is no Iiμ. As hydrocyanic acid or its salt, hydrogen cyanide, sodium cyanide, potassium cyanide, ammonium cyanide, etc. are used. There is no particular restriction on the amount used, and normal B//(3HE几ER-I3E I(,
It may be used in the GS reaction. For example, when 4-oxobutanenitrile is used as a starting material, it is used in an amount of 1 mol or more, preferably 1 to 2 mol, per 1 mol of 4-oxobutanenitrile.

Although the solvent used in the method of the present invention is essentially water, there is no problem if a small amount of a water-soluble organic solvent is mixed in. For example, water-methanol, water-ethanol,
Mixed solvents such as water and tentonitrile can also be used. The amount of solvent used is the raw materials 4-oxobutanenitrile, 2-hydroxypentanedinitrile and 2-
The amount of at least one of the aminopencundinitriles is 15% to 40% by weight, and the amount of the appropriate amount is 20% by weight to 20% by weight.
It is important to adjust the ratio to 85%. If the amount of the solvent is above this range, loss due to dissolution during crystallization of CEID will increase and the yield of the product will decrease. If the amount of the solvent is less than this range, side reactions will increase and the reaction yield of CEID will decrease, as well as the purity of the product will decrease, which is not preferable.

The mineral acids used in the method of the present invention include sulfuric acid, hydrochloric acid, nitric acid, etc., and there are no particular restrictions on their concentrations. colour.

υ B, 3'C11ERER-BER when carrying out the present invention
The pH after the G8 reaction should be adjusted to 9 or less, preferably 1 to 9, to give better results. Although the present invention may be practiced at a pH below 1, there are no particular advantages unless the CEID is used in the next step under acidic conditions.

There are no particular restrictions on the reaction temperature and reaction time in the method of the present invention, and ordinary B, yOHE RE R-B
For example, to allow the ERGS reaction to occur at room temperature to 15
There is no particular restriction on the crystallization temperature and crystallization time when crystallizing CE ID in the method of the present invention. When crystallization is performed, losses due to dissolution increase, so it is usually carried out at a temperature of 60° C. or lower, preferably 30° C. or lower, and higher than the freezing temperature of the solution. A crystallization time of 10 minutes to 8 hours is usually sufficient, but there is no problem if the crystallization is allowed to stand for more than a month. As for the method for removing o) CE]D after crystallization, a conventional crystal separation method can be used, and for example, a method using a centrifuge, a supertecanter, etc. is employed. Regarding the operating pressure when carrying out the method of the present invention: 1. There are no particular restrictions, and it can be done under normal pressure, and it can also be done with a pressurizer. Operations can also be performed in batch mode,
It is also possible to carry out continuous operation. Furthermore, it is also possible to recycle a portion of the money after crystal separation, either after concentrating it or as is, as is commonly done.

EXAMPLES The present invention will be explained in more detail with reference to the following Examples, but the present invention is not limited by these Examples. In addition, the yields shown in the Examples (@ are shown on a molar basis).

Example 1 1 (1 flask with stirrer and reflux condenser, 2302 ammonium bicarbonate, 490 ml of hydrocyanic acid 0.3y-1 water)
2 with a purity of 98.8 MI amount% by heating to 72°C.
-Hydroxypentanedinitrile 111.4y-50
After charging over several minutes, the reaction was carried out at 85° C. for 50 minutes.

After cooling the reaction solution to room temperature, the pJ of the reaction solution was adjusted to 7 with 97% sulfuric acid, and crystallization was performed at 5°C for 3 hours.
Ko. When the obtained slightly yellow crystal was analyzed by liquid chromatography, the yield was 81.2%.

Example 2 The same operation as in Example 1 was carried out except that 30% by weight hydrochloric acid was used instead of 97% sulfuric acid.
'), 'Ii rate i, t, 80.1 n; r h
F-ko.

Example 97 The same operation as in Example 1 was carried out except that 201■ nitric acid was used instead of Ichikawa-type sulfuric acid, and the yield was 7.
It was 8.3%.

%/M Example 4 Purity 〇 instead of 98.8% by weight of 2-hydrodipenter/dinyl-1-lyl], 11.45' 7.
2-Aminobenzenedinitrile 11
．． ], 8.9 was used, and the yield was 82.0%, which was 17 tons. ammonium carbonate 1505r, t[0,4F-.

Pour 400 m of water and keep it at 40℃ while stirring.
Purity 98.13 (amount f52-hydroxypentanedinitrile 112.1 fi') was charged over 1 hour, immediately heated to 62°C, and reacted for 4 hours. After cooling the reaction solution to room temperature, it was taken out from the autoclave. The pH of the reaction solution was adjusted to 4.5 with 7OiK leaf% sulfuric acid, and after cooling to 2°C, crystallization was performed for 2 hours. When the obtained pale yellow crystals were analyzed by liquid chromatography, the yield was determined. The rate is 88.6
%Met.

Example 6 A flask equipped with a stirrer and a reflux condenser was charged with 144 P of ammonium carbonate, 28.45 P of hydrocyanic acid, and 800 P of water.
Subsequently, 85.69 ml of 4-ochinobutanenitrile having a purity of 97.0% by weight was charged at room temperature with stirring, and then the mixture was immediately heated to 77° C. and reacted for 3 hours. After cooling the reaction solution to room temperature, the pH was adjusted to 6 with 50% by weight sulfuric acid, and the pH was adjusted to 7 at 10°C.
Time crystallization was performed. When the obtained pale yellow crystals were analyzed by liquid chromatography, the yield was 76.5%.

Example 7 The same procedure as in Example 6 was carried out except that 1255 ml of ammonium carbonate and 230 ml of water were used instead of 1445 ml of ammonium carbonate and 800 ml of water. Yield is 73.
It was 2%.

Example 8 Instead of ammonium carbonate 144 yen and water 800 ml,
The same procedure as in Example 6 was carried out except that 192 g of ammonium carbonate was used and 500 g of water was used. Yield is 72.9
CF).

[Brief explanation of drawings]

FIG. 1 shows the relationship between the solubility of C E I D in water I and pB at 5°C.

Claims (1)

[Claims] (a) at least one of 4-oxobutanenitrile, 2-hydroxypentanedinitrile and 2-aminopentanedinitrile, (b) ammonia and/or ammonium, (C) carbon dioxide or/and 5-(2-cyanoethyl)-2,4-imidazolidinedione is produced by reacting carbonate and (d) hydrocyanic acid or/and its salt, and the raw material is added to a solvent consisting essentially of water. The reaction was carried out under conditions -F until the amount of (Fl) charged was 15 to 40% by weight, and after the reaction, the i-mount of the reaction product solution was adjusted to 9 or less with mineral acid, and 5-(2-cyanoethyl) -Production method of 2,4-imidazolidinedione.