CS217992B2 - Method of making the di-n-propylvinegar acid - Google Patents

Abstract

Di-n-propyl acetic acid is obtained in higher yields by hydrolysing di-n-propyl acetonitrile with concentrated sulphuric acid at an elevated temperature to form di-n-propyl acetamide and then reducing the concentration of the sulphuric acid in the reaction mixture and refluxing it at a generally higher temperature to convert the acetamide into di-n-propyl acetic acid. Recovery of the acid product is advantageously effected by the passage of a steam jet through the reaction mixture, since this enables a purer product to be obtained, in particular a product containing a smaller quantity of valeric acid as impurity.

Description

A process for the production of di-n-propyl acetic acid from di-n-propyl acetamide obtained by hydrolysis of di-n-propyl acetonitrile in concentrated sulfuric acid is to add water to the reaction mixture containing di-n-propyl acetamide after the hydrolysis. to reduce the sulfuric acid concentration to 60% and the mixture is heated to boiling for 4-6 hours and the resulting di-n-propyl acetic acid is separated from the reaction mixture by steaming.

The produced acid is an effective part of antiepileptic agents.

The present invention relates to a process for the preparation of di-n-propylacetic acid from di-n-propyl acetamide.

No. 197,291 discloses a process for the preparation of di-n-propylacetic acid from di-n-propylacitonitrile in the following three. successive reaction steps:

In the first step, di-n-propylacetonitrile is hydrolyzed in concentrated sulfuric acid to di-n-propylacetamide:

CH-Ce N

HzO

H * e% J

CH-NH-C "- ^C 3 ^H <

(level 1).

In the second reaction step, the di-n-propyl acetamide, without isolation, is diazotized with sodium nitrite in aqueous sulfuric acid:

Cti-C-NH _z + NaNO _z <HSO * ¹ .nC 3 * + N _z + H _z 0 + NaHSO ^

In the third step, the resulting di-n-propyl acetic acid is isolated by rectifying the reaction mixture.

However, this process has certain disadvantages. First of all, it requires the use of sodium nitrite, which is a toxic compound; its LD 50 is 180 mg / kg when administered orally in rats. In addition, nitrite and nitrate ions are formed when nitrite is used which contaminate the desired di-n-propyl acetic acid. Furthermore, the presence of valeronitrile as an impurity in the starting di-n-propyiacetonitrile leads to the formation of valeric acid during the reaction process, which confers a very indirect end product (step 2). subtle odor. Subsequently, under reaction conditions in a concentrated sulfuric acid environment, yields are reduced and thus process productivity is reduced.

With the method according to the invention, these disadvantages can be overcome.

The process for the preparation of di-n-propylacetic acid according to the invention is characterized in that it does not use sodium nitrite, but in that di-n-propyl acetamide obtained by hydrolysis of the starting di-n-propylacetonitrile with concentrated sulfuric acid is continuously hydrolysed after addition of water. -Diluted sulfuric acid according to the reaction equation:

O

CH-C-NH ₂ α- _{3 3} Н ₇ и n-C ₃ H;

H _Z O

-------->

Н ₂ ЗОц.

(60%)

3 ^ 7 \ i?

CH-C-OH ♦ (NH 4 SO 3).

In other words, the process according to the invention consists in adding, after completion of the first step of Patent No. 197 291, an amount of water to the reaction medium such that the sulfuric acid concentration is reduced to 55 to 65%, preferably to 60%, and The reaction mixture is then heated to reflux at about 125 DEG -128 DEG C. (step 3). for 4 to 6 hours to obtain a quantitative conversion of the amide to the desired acid.

The essence of the preparation of di-n-propyl acetic acid from di-n-propyl acetamide obtained by hydrolysis of di-n-propyl acetonitrile in a concentrated sulfuric acid medium according to the process of the invention is therefore that after the hydrolysis of di-n-propyl acetonitrile to di-n- propylacetamide is added to the reaction mixture containing di-n-propyl acetamide in an amount necessary to reduce the sulfuric acid concentration to 60% and this mixture is heated to boiling for 4-6 hours and the resulting di-n-propyl acetic acid is separated from the reaction mixture by exaggeration steam.

In addition to eliminating the use of nitrite and in addition to maintaining the operating conditions much more easily, the process of the invention allows to obtain di-n-propylacetic acid free of starting nitrile, and in particular free of di-n-propyl acetamide. As described in more detail in the following examples, productivity relative to di-n-propylacetic acid increases 2.5-fold and the yield increased from 92 to 98%.

Further, using the improved process, di-n-propyl acetic acid can be obtained in greater purity compared to the acid prepared according to Step 2 of Patent No. 197,291. The improvement consists in replacing the rectification of the reaction mixture by isolating the desired acid from the reaction mixture by exaggeration. with water steam.

The inventors have found that water vapor recovery is more selective with respect to residual impurities, not only with respect to the starting nitrile and amide residues, but also with respect to the valeronitrile and valeric acid residues, the content of which in the final product can be reduced in half.

Furthermore, water vapor recovery is also more economical than rectification because it requires less investment.

The beneficial effect of the method of isolation of di-n-propylacetic acid by steam steam exaggeration on its purity was experimentally proved by the following experiments:

An experimental hydrolytic medium was prepared, corresponding to the composition of the medium after carrying out the third step described above:

di-n-propylacetic acid [1 mol] containing · 0.35 ·% valeric acid 144 g 60% · sulfuric acid 730 g.

Known amounts of valeric acid were then added to said artificial environment so that the concentration of this acid gradually increased from 0.35 to 1%. Water vapor was then introduced into the media so as to keep the volume constant and to heat the mixture to 130 ° C. The volume of water required to carry out this operation was 1800 ml / mol of the final product. The yield of isolated di-n-propyl acetic acid was practically quantitative. The product was separated by decantation at room temperature and dried over anhydrous sodium sulfate. The amount of valeric acid contained in the recovered substance was then analytically determined. The results are summarized in Tables A and B below.

Table A shows the results of four experiments in which different starting amounts of valeric acid were used in experimental hydrolytic media.

Table B shows the results of one continuous operation at which the initial amount of valeric acid was used. In the above-mentioned environment was 1%. Changes in the amount of · valeric acid in each successive fraction of C1-n-pro-acetic acid obtained by steam overheating were monitored.

TABLE A experiment starting acid content amount of valeric acid in valeric acid number (%) di-n-propylacetic acid obtained by exaggeration · water vapor [%]

1 0.35 0.2 2 0.60 0.3 3 0.80 0.4 4 1.00 0.5

TABLE B

The content of valeric acid in the individual fractions obtained by steam overheating; the initial content of valeric acid in the crude di-n-propyl acetic acid before separation is

1%, i.e. 1.44 g sequential fraction number fraction weight (g) Amount of valeric acid in the di-n-propylacetic acid obtained (%) Corresponding weight of valeric acid (g) AND 36 0.9 0.324 II 34 0.6 0.204 III 42 0.2 0,084 IV 32 0.1 0,032 total 144 0,644

Regenerated valeric acid yield: 44.72%

The results of the experiments carried out show that:. using isolation of di-n-propyl acetic acid. By steam steaming according to the invention, the amount of valeric acid in the final product can be reduced by about 50%.

This advantage of the process according to the invention is of great importance in view of the very unpleasant odor which even very small amounts of valeric acid impart to the final product.

The advantages of the process according to the invention are explained in more detail in the following examples, which are not intended to limit the invention in any way.

Example!

Preparation of di-n-propyl acetic acid

To. A 1000 ml flask equipped with a stirrer, a thermometer, a dropping funnel, which can later be replaced by a water vapor feed tube, and a reflux condenser, is introduced. . 72 g of distilled water and 478 g are slowly added with stirring. 92% sulfuric acid, maintaining the temperature of the mixture below 60 ° C. Thereafter, 125.2 g (1 mol) of di-n-propyl acetonitrile are introduced in one portion and the temperature of the reaction mixture is raised to 100 ° C. This temperature is maintained for 1 hour; . during. at that time, the nitrile is almost completely hydrolyzed to the amide.

The sulfuric acid concentration is then reduced to 60% by addition. 185 g of distilled water, the reaction mixture is heated to boiling (125 DEG-130 DEG C.) and refluxed for 2 hours. for 5 hours. The reflux condenser is converted to descending distillation at atmospheric pressure and the product is separated from the mixture by introducing water vapor through a feed tube. This operation takes 2.5 hours, which is the time required to complete the separation of the product in the distillate and corresponds to consumption. 1750 g water.

Water vapor overflow is preferably performed while maintaining a constant volume in the vial, which increases yield and allows the hydrolysis to proceed completely.

The distillate is separated into two layers. The volume of distillate can be limited by occasional draining of the aqueous fraction; the use of an extraction agent is not necessary.

The organic portion was dried over azeo

Claims (2)

Subject Process for producing di-n-propyl acetic acid from di-n-propyl acetamide obtained by hydrolysis. di-n-propyl acetonitrile in concentrated sulfuric acid, characterized in that di-n-propylacetamide is added to the di-n-propylacetamide upon completion of the hydrolysis. reaction mixtures containing di-n8 by distilling off the water under reduced pressure (at 2.67 kPa and 20 ° C). 138.5 g of di-n-propyl acetic acid are obtained (yield 96.2%), which can then be further purified by flash distillation. Example 2 Production of di-n-propyl acetic acid In a 200 liter enamelled reactor equipped with a reflux device, a stirrer and a bottom outlet, with the possibility of steam heating under a pressure of 0.6 MPa and water cooling, 0.657 kg of distilled water are introduced. While stirring and maintaining the temperature in the range of 50-60 cc, 2.085 liters (3.753 kg) of 94% sulfuric acid is added. After stirring for 15 minutes, the acid concentration is checked. sulfuric; the concentration should be 80 ± 1% by weight. The temperature of the dilute acid is raised to 100 ° C and 1 kg of di-n-propyl acetonitrile is added. The reaction is exothermic and the temperature is maintained at 100 ° C by cooling the reactor with water. After addition of the nitrile, the temperature of the reaction mixture was maintained at this temperature with stirring for 1 hour. The sulfuric acid concentration is then reduced to 60% by adding 1.470 kg of distilled water while maintaining the temperature by gentle heating to 100 ° C. The reaction mixture is heated to boiling at 125 to 128 ° C, refluxed for 6 hours and then cooled to about 30 ° C. Stirring is stopped and the mixture is allowed to separate into two. layers for about 30 minutes; after this time, the lower mother liquor containing the sulfuric acid is drained. About 3.5 liters, i.e. about 5 kg of mother liquors are obtained which contain 59% sulfuric acid as determined by titration. Organic. the batch is washed with 1.333 kg of distilled water, with which it is stirred at 30 ° C for about 30 minutes. After an additional 30 minutes of standing, the separated lower aqueous layer (1.4 kg) is drained. Then, the crude di-n-propyl acetic acid * containing a small proportion of water is also drained and filtered. 1.12 kg of di-n-propyl acetic acid is obtained, containing about 1% of water; yield 97 to 98 percent. VYNALEZU propyl acetamide water in an amount necessary to reduce the sulfuric acid concentration to 60% and this mixture is heated under vacuum for 4 to 6 hours and the resulting di-n-propyl acetic acid is separated from the reaction mixture by steaming.