CS196365B2 - Process for preparing di-n-propylacetonitrile - Google Patents

Abstract

Process for the preparation of di-n-propyl acetonitrile of the formula : whereby, in a single step, sodium n-propylate in n-propanol medium is added to a reaction medium which is formed of a cyanacetate of general formula : in which R represents an alkyl radical having from l to 4 carbon atoms, and n-propyl bromide or iodide, the alkylation reaction taking place under reflux, the crude ester obtained is saponified with a 10 to 20 % solution of sodium hydroxide or potassium hydroxide, the resulting salt is acidified with a strong acid, to give crude di-n-propyl cyanacetic acid, which is decarboxylated by heating at a temperature between 140.degree.C and 190.degree.C, so as to obtain the di-n-propyl acetonitrile.

Description

The present invention relates to a novel process for the preparation of di-n-propyl acetonitrile of formula I

СНз — СНг — СНг \ ·

CH — CN (1),

CHs — СНг — СНг and intermediates of its synthesis.

. Di-n-propyl acetonitrile is a well-known product which is of particular importance for the preparation of compounds with significant pharmacological properties. For example, di-n-propylacstonitrile can be used to prepare di-n-propyl acetamide, which has particularly important neuropsychotropic properties, as described in French Patent No. 2442 M.

Di-n-propylacetamld be a di-n-propyl easily produced in high yields, of the order of about 83%, in such a way that the _four latter compound hydrolyzed, e.g., an aqueous, about 75 to .80% sulfuric acid solution at 80 130 [deg.] C.

Conventional processes for the preparation of di-n-propyl acetonitrile are generally complex and require the use of reaction components that are hazardous to the operator.

For example, to prepare di-n-propyl acetonitrile from n-propyl ketone as the starting material.

...

Sodium cyanide is an extremely toxic substance.

In addition, some stages of the process require hydrogenation, which is always difficult to carry out on an industrial scale.

The need to find an industrial process for the production of di-n-propyl acetonitrile is therefore extremely important.

To date, only the synthesis of acetonitrile substituted in the α-position by two isopropyl groups has been described using a cyanoacetic acid ester as a starting material, and this is also on a laboratory scale. This procedure has been described by Marshall [J. Chem. Soc., 2754-2761 (1930)], and Brown and colleagues [}. Am. Chem. Soc. 77, 1038-1089 (1955)] and Newman et al., [Am. Chem. Soc. 82, 873-875 (1960)].

The above described processes are characterized by successive three or four rather different reaction stages or steps, starting from the canoctanoic acid ester starting material:

(1) the phase of acetylation, common to all three processes described, to obtain a diisopropylcyanoacetic acid ester;

2) a monoalkylated ester separation phase; ,

(3) the saponification phase of the diisopropyl propyl cyanacetic acid ester in the case of the procedures described by Marshall and Newman and colleagues; and

4) decarboxylation, either decarboxylation of the diisopropylcyanoacetic acid ester in the case of the procedure described by Brown and co-workers, or decarboyoylation of the nitopropylcyanoacetic acid, in the case of the procedures described by Marshall and Newman and co-workers.

According to Marshall, diisopropylacetonitrile is prepared from cyanoacetic acid ester by treating the alcoholic solution of said ester with sodium and allowing the resulting mixture to react with excess isopropyliodide for several hours. The monoalkyl product thus formed is removed by shaking the mixture with 10% sodium hydroxide solution and the crude dialkyl ester thus obtained is saponified by treatment with 35% aqueous sodium hydroxide solution for 16 hours. Acidification of the reaction mixture yields diisopropylcyanacetic acid, which is decarboxylated by distillation in the presence of twice its molten weight. potassium hydroxide.

Bro-wn and coworkers obtained nitopropylacetonitrile by first treating isopropyl iodine with a solution of cyanoacetic acid ester in n-propanol in the presence of sodium n-propylate for 2 hours while heating the reaction mixture to reflux, and then added again. sodium n-propylate solution in. of n-propanol and isopropyl iodide and the reaction mixture were again heated to reflux for 3 hours. The methylated product was removed by shaking with a 10% sodium hydroxide solution and crude. the diisopropylcyanoacetic acid ester was pre-distilled several times in the presence of twice its weight. potassium hydroxide.

Later . Newman - '· se. The co-workers prepared the diisoprbpylacetomtril by first heating the isopropyliodide with a solution of ethyl cyanoacetate in ethanol in the presence of sodium ethylate for 3 hours to reflux, then adding additional sodium ethylate and isopropyl iodide and reheated the reaction mixture for 3 hours. Then. added sodium ethylate and · isopropyl iodide and heated · mixture for another · · 2 hours to boiling, · crude · washed diisopropylderivative with 15% · · potassium hydroxide solution, saponified the ester · 26-hour boiling with 3% alcoholic · with potassium hydroxide solution and the obtained diisopropyl-cyanacetic acid decarboxylated by heating to 180-200 ° C in the presence of powdered copper.

Due to the great similarity of the chemical structure of diisopropylacetonitrile with di-n-propyl acetonitrile, the inventors have attempted to prepare the latter compound by applying the procedures described above for the preparation of diisopropylacetonitrile.

In the experiments carried out by the method described by Marshall, pure di-n-biphenyl (zetonitail only in non-significant yields, of the order of about 20%) was obtained. if each of the synthesis intermediates were purified, and in about 30% yield when the intermediates were used in the crude state, said yields being calculated based on the starting cyanoacetic acid ester The intermediates prepared in this way were further contaminated with impurities which prevented their use in the crude state. For example, it has been found that the crude di-n-pabpyicyanoacetic acid prepared by the method of Marshall or Newman and Associates is contaminated with 18-25% and 32-34%, respectively, of a by-product, which is probably a di-n-ester. -prbpylfoamamidoocíové.

The method described by Brown and co-workers does not appear to be suitable for the preparation of di-n-propyl acetonitrile, since it requires a twice-repeated alkylation phase; using this method, the pure product was obtained in yields ranging from 28 to 44% calculated on the starting cyanoacetic acid methyl ester.

Subsequently, according to the method of Newman and co-workers, which requires a triple alkylation phase and is particularly time consuming, pure di-n-propyl acetonitrile was obtained only in yields of about 40%, calculated on the starting cyanoacetic ester. It has also been observed that the saponification of the di-n-propylcyanacetic acid ester results in a mixture of 10 percent di-n-propyl cyanacetic acid and 5 percent di-n-propyl cyanacetamide.

In conclusion, all of the above methods, applied to the preparation of di-n-prop-acetonitrile, are essentially characterized in that they are complex and time-consuming, and that impurities occur at different stages of the process. necessary impurities prior to subsequent reaction. and that the final di-n-propyl acetyl cocktail is obtained only in low yields.

It was therefore essential to find a process for the preparation of di-n-propyl acetonitrile having the following advantages: - simplicity of the process, - shorter overall execution time, - higher yields.

- low production costs, if possible, so that they can be used effectively on an industrial scale. '

The present inventors have now found that di-n-propyl acetonitrile can be prepared in such a way from a cyanoacetic acid ester as a starting material and that this process can be used industrially. *

According to the process of the invention, di-n-propyl acetonitrile can be prepared by adding, in one step, in sodium n-propanol n-propylate to the cyanacetic acid ester of formula II.

. CN.:

/

HzC (II)

COORve - which R - denotes. C 1 -C 4 alkyl, preferably methyl or ethyl, and. . n-propyl bromide or n-propyl iodide, the crude ester obtained. se.zmýdelní. 10 to 20% solution. sodium or potassium hydroxide, the resulting salt is acidified with hydrochloric acid, and the crude di-n-propylcyanacetic acid obtained is decarboxylated by heating to a temperature in the range of 140 to 190 ° C to form di n-petroleum acetonitrile.

The starting materials of formula (II) are either known compounds which are described in the above-mentioned publications. or ‘- They are substances that lie; Prepare - by known methods. in · * · '·' ·, · .. ·. '<.

If it concerns the alkylation phase. The reactants were reacted in such a way that from 2 to 2.2 parts of h-propylate. sodium. in n-propanol is added at a temperature of 45 to 55 ° C to the reaction medium formed by the ester moiety. and - 2 to. 2.3 parts of n-propyl halide ··. The alkylation reaction is then completed by heating the reaction mixture to reflux for hodin 3 hours.

Saponification of debris-ester. The di-n-propyl cyanacetic acid is preferably carried out at a temperature in the range of from 60 to 70 ° C for 3 hours, using an amount of -1.25 to 2 moles of sodium hydroxide. - 1-mol-ester. The subsequent acidification is carried out, for example, with a 36% hydrochloric acid solution. at a temperature slightly below 40 ° C. Alternatively, the saponification can be carried out. in the presence of a quaternary ammonium salt, for example trimethylcetyl ammonium bromide, benzyltrimethylammonium chloride or lauryltrimethylammonium bromide. n-Propyl cyanoacetic acid - Concerning the saponification temperature and reaction. the time required for this operation varies depending on the amount of quaternary ‘ammonium salt used.

If Quaternary is used,. ammonium salt in an amount of 0.1 mol per 1 mol - ester, saponification takes place for 3 hours at a temperature. 30 ° C, and - at a concentration ‘0,005. mole of ammonium salt per mole of ester is completed in 1 hour at 60-65 ° C.

Regarding the decarboxylation phase,. this reaction is carried out by heating the crude di-n-propylcyanoacetic acid to a temperature of 140 ° C to 190 ° C, preferably 175 ° C to ‘190 ° C.

The latter operation can be modified to decarboxylate. di-n-propyl cyanacetic acid is carried out in a continuous manner. the acid is heated to a temperature of 185 ° C to 190 ° C, and as the decarboxylation commences, further acid is introduced continuously and the liberated carbon dioxide and the resulting di-n-propyl acetonitrile are removed simultaneously. '·.

The process according to the invention exhibits undeniable advantages compared to the known processes previously described.

In particular, the process according to the invention provides the possibility of obtaining pure di-n-propyl acetonitrile in good yields. The yields, calculated on the starting cyanoacetic acid esters, are above 80%, while it is not possible to obtain the product in a manner known per se. higher yields than 50% calculated on the same starting ester. . ’

The process according to the invention is furthermore undoubtedly simpler than the aforementioned Malshall processes described above with Brown et al. Neeman with coworkers. For example, the process of the invention allows the alkylation phase to be carried out in ‘a single operation involving the use of alkali metal-n-propyl halide α-propylate.

In contrast, the procedure described by Brown and coworkers - - requires two successive additions of alcoholate - and a halide, and in the process - described by Newman - and coworkers even in ‘three successive steps.

The reaction time required to carry out the alkylation and the saponification is considerable in the processes described in the Newman method. and co-workers require at least 8 hours for the alkylation phase and 26 hours for the saponification phase. · ·. .

In contrast, at. According to the process according to the invention, it is possible to carry out the corresponding alkylation and saponification phases. much faster than using the methods described.

. As far as the saponification phase is concerned, the time required for this operation can be advantageously reduced by carrying out the reaction in the presence of quaternary ammonium salts, for example trinomethylcytyl ammonium bromide. The use of this quaternary ammonium salt also has the advantage of reducing the risk of the hydrolysis of the nitride function of the di-n-propyl cyanacetic acid ester.

In the known processes, furthermore, in the decarboxylation phase, not to mention the application of higher temperatures, additives such as potassium hydroxide or powdered copper have to be used. In the process according to the invention, the decarboxylation phase is carried out simply by heating di-n-propylcyanoacetic acid.

Another disadvantage in the processes described in the literature, in particular the disadvantage of the alkylation phase of these processes, is the regeneration of the solvents, the regeneration of the reaction. and - v - removing the by-products of the reaction.

Regeneration, which is very difficult, when a mixture of sodium ethylate with ethanol or a mixture of sodium methylate with methanol is used in the reaction. is easier to use when used. reacting a mixture of sodium n-propylate with n-propanol; in the latter case, there is a greater possibility of separation by distillation. nezréagovaný. n-propyl halide,. at. re*

198385 the action of the ether and alcohol liberated by transesterification of the cyanoacetic acid ester with n-propanol. .

Due to all these disadvantages of the previously described processes, the amount of material required for the production, the labor required and the energy consumption are increased, resulting in a further increase in production costs.

Among the disadvantages of the known processes, it is certainly not negligible that they produce difficult side-effects at various stages. . ₄ ·

These by-products, which are formed in each stage of the known processes, make it extremely difficult to carry out these processes. These impurities have to be eliminated at each reaction stage, thus increasing the demands on the intermediate operations, which is on an industrial scale. always costly.

For example, in the procedure of. described methods are needed. at the end of the alkylation phase, remove the monoalkylated compound from the product by shaking with 10% sodium hydroxide.

If the alkylation is carried out according to the process of the present invention, it is not necessary to purify the resulting intermediate, i.e., the di-n-propyl cyanacetic acid ester, and can be used for the next reaction phase in crude form. . ,

The inventors have found that it is particularly advantageous to react the reactants in the alkylation process according to the invention, i.e. essentially by adding a solution of sodium n-propylate in n-propanol to the ester medium of formula II and n-propyl halide, since this process suppresses the formation of a monopropylcyanacetic acid ester, which is produced in much larger amounts, when the n-propyl halide is added to the mixture of the cyanacetic acid ester with sodium n-propylate. The monopropyl cyanoacetic acid ester may, if the mixture is further processed, optionally provide - valeronitrile, - which is a particularly difficult by-product and must be removed. '

When the reaction components are reacted in the alkylation process according to the invention, the valeronitrile content of the final di-n-propyl acetonitrile is substantially reduced from about 3.6% to only 0.3% in the process of the invention.

The inventors have further found that the use of a solution of sodium n-propylate in n-propanol in the process of the invention is far more advantageous than a solution of sodium ethylate in ethanol or a solution of sodium methylate in methanol, as described in the previously described procedures.

Indeed, it has been found that the content of the monopropylcyanacetic acid ester in the crude v - further leads to valeronitrile, increases, and - can range up to 2 to 5% if the reflux temperature of the reaction mixture during alkylation is - too low, which occurs when methanol or ethanol is used as the reaction medium. ,

It has also been found that when a solution of sodium ethylate in ethanol is used, an insignificant amount (about 1%) of the n-propyl cyanacetic acid ethyl derivative is formed during the alkylation phase.

As mentioned above, the saponification of the crude di-n-propylcyanoacetic acid ester under the conditions described by Newman and co-workers, or Marshall, i.e. by treatment with 35% potassium hydroxide for 16-26 hours, yields - crude acid di-n-propylcyanacetic acid containing 18 to 34% by-product, which is - probably - dl-n-propylformamidoacetate, which must be removed. This by-product does not provide di-n-propyl acetonitrile in decarboxylation, but di-n-propyl acetamide.

In carrying out the process according to the invention, this disadvantage is again eliminated and the crude di-n-propylcyanacetic acid obtained is not necessary to be purified. ,.

While verifying the scope of the invention, the inventors have also attempted to combine some of the phases characteristic of the method of the invention with - some of the phases used in the above-mentioned - previously described processes. , - 'r.

For example, - if done -. The process according to the invention is followed by a process of distillation followed by a decarboxylation phase of the di-n-propylcyanocetic acid by melting twice its weight of 85% potassium hydroxide. at a temperature in the range of 190 to 360 ° C according to the method described by Marshall, only 11% of di-n-propyl acetonitrile, calculated on the starting cyanoacetate ester, was obtained. In this modification of the process, the majority of di-n-propyl cyanoacetic acid was converted to di-n-propyl acetamide and din-propyl acetic acid. _of

The di-α-propylcyanoic acid prepared by the process of the invention was also decarboxylated by a variation of the method described by Marshall, i.e. by heating, in the presence of twice its weight of 98% sodium hydroxide. Distillation at 37.0 ° C for two and a quarter hours (this mixture gave only 38.3% di-n-propyl acetonitrile, calculated on the usable starting di-n-propylcyanobutic acid) '

Furthermore, the decarboxylation of the di-n-propylcyanacetic acid methyl ester prepared by the process of the invention was tested by distillation in the presence of potassium hydroxide, as described by Brown and co-workers. . ..

Using twice the weight of -97.7% potassium hydroxide per ester weight, only 28.4% pure di-n-propyl acetonitrile was obtained by heating the mixture at 380 ° C for two and a quarter hours. calculated on the starting cyanoacetate ..

In a similar experiment ^, using the same amount of 98% sodium hydroxide instead of potassium hydroxide, otherwise under the same temperature and time conditions, di-n-propyl acetonitrile was obtained in yield. 44.4%, calculated. to the starting cyanoacetate. . .

Of the above. From the results, it is clear that the process of the invention has undeniable advantages over the known processes described. . Furthermore, it has been shown that the process according to the invention is superior to. . known. . methods for the preparation of di-n-pi-acetyl acetonitrile described in the literature. . .

The process according to the invention is explained in more detail below in the examples, which, however, do not limit its scope. '·. .

. Examples

He did

Preparation of dl-n-propyl acetonitrile

(a) dl-n-propylcyanacetic acid.

At first they prepare. sodium n-propylate solution in such a way that:. A mixture of 7.42 g (0.322 mol) of sodium and 180 ml of anhydrous solution was added. The n-propanol is heated to gentle boiling until the sodium is completely dissolved.

In a 500 ml round - bottomed flask, fitted with a dropping funnel, mechanical stirrer, rim, thermometer and reflux condenser. 16.95 g (0.141 mol) of ethyl cyanoacetate and 40.69 g (0.33 mol) are added. of n-propyl bromide. The mixture is heated to 45 ° C and then sodium n-propylate solution prepared as described above is added slowly and with stirring. se. temperature. reaction. maintains the mixture by gentle external cooling in the range of 50-55 degrees. Celsius...

After addition of all the alcoholate solution, the reaction mixture was refluxed for 30 minutes and refluxed for 3 hours. Then. n-propanol. distillation and distillation is interrupted when the temperature of the distillation residue reaches 115 ° C.

A solution of 7.5 g of flaky sodium hydroxide in 67.5 ml of water is added to the crude ester obtained in this way, the mixture is transferred to a 250 ml round-bottom flask equipped with a reflux condenser, and the solution is slowly heated to 60-70 ° C.

The reaction mixture is kept at this temperature for 3 hours, then cooled to about 50 ° C and hydrolysed. the ethanol formed and the n-propanol residues are distilled off at a pressure of about 10 mm Hg. The remaining solution was cooled to 20 ° C and acidified with stirring by adding 26.25 g of 36% hydrochloric acid. . During this operation, the temperature of the reaction mixture is kept below 40 ° C by cooling. The mixture was stirred for 30 minutes and then allowed to stand for a further 30 minutes. An oily layer of di-n-propyl cyanacetic acid. The mixture was decanted and the aqueous portion was shaken with toluene. The toluene extract was combined. decanted. di-n-propyl cyanacetic acid and the solution is washed in a separatory funnel with a solution of 1.5 g of sodium chloride in 14 ml of water. The toluene fraction is. The solvent is removed by distillation at atmospheric pressure. 25 g of crude product are obtained. . of n-propyl cyanoacetic acid.

b) Dii ^ -j ^ p ^ <^] ^ p ^ y ^ a ^ e ^ ec ^ i ^ nii ^ il · .... ., .....

Into a round .. flask o. 100. 25 ml of the crude di-n-propyl cyanoacetic acid prepared above are introduced into a thermometer and reflux condenser. mentioned. . procedure. and the flask is heated to oil. . bath.

Decarboxylation. starts at temperature. about 140 degrees Celsius, 'Blend. The mixture was heated to temperature. boiling,. i.e. at about 160 ° C first. and then during 2 · hour to raise the temperature .At 190 ^Q C. The latter temperature is then maintained until the end. evolution of gases, which 'takes' and 2 hours.

The resulting di-propyl acetometric is then slowly distilled off and the fraction is collected. passing '. between. 165 až. 175 ° C. . Acquired. the product is repeatedly distilled. . ,

That procedure ... shall:. 14.7 g. di-n-Polyacetonitrile v. 170 [deg.] C. Yield: 83 percent, calculated from the starting point. Kyaipoct-an. . ethyl. . ..

Example 2 '

Preparation of di-n-propyl acetonitrile

(a) Di-n-propyl cyanacetic acid

First, a solution of sodium n-propylate is prepared by mixing. mixture 50 g. (2 mol of 10%) sodium and 804 g (1000 ml) of anhydrous n-propanol were heated at 50-55 ° C for 60-90 minutes.

Place 99.1 grams in a 2 liter round-bottomed flask. (1 mol) methyl cyanacetate a

270.6 g (2.2 mol) of n-propyl bromide are added, the mixture is heated to 45-50 ° ^C and stirred at this temperature. temperature at a uniform rate as above. by the method prepared a solution of sodium n-propylate in n-propanol; this operation lasts. about 60 to 75 minutes.

Mon. by introducing the alcoholate solution, the reaction mixture was heated at reflux for 3 hours and then n-propanol was distilled off until the temperature of the distillation residue reached. '120 to. 125 ° C. K 'obtains'. 500 g of 10% aqueous sodium hydroxide solution and 0.36 g of cetyltrimethylammonium bromide are then added to the crude crude ester.

Heat the mixture 1. 1 hour under reflux, then cooled to about 50 ° C. the alcohols present are distilled off under reduced pressure (at a pressure of 6.67 to 13.33 kPa).

The solution obtained is cooled and acidified. 175 g of 36% hydrochloric acid such that the temperature did not exceed 40 ° C. The mixture was allowed to stand for 30 minutes and then. the di-n-propyl cyanacetic acid was decanted. The lower aqueous layer is shaken. 250 g. toluene, toluene. The extract is combined with the first organic fraction, the solution is shaken once with 100 g of distilled water and the solvent is removed.

196385 distilled under reduced pressure. 154.5 g of crude di-n-propyl cyanacetic acid are obtained.

(b) Di-n-propyl acetonitrile:

The crude dl-n-propylcyanoacetic acid prepared above was transferred to a 250 ml round flask and heated gradually to boiling until the mass temperature in the flask reached 175-180%; the last traces of toluene are removed by means of a DeánStark adapter. The decarboxylation begins at about 140% and the reaction is complete after practically 1 hour of boiling. The mixture was boiled for a total of 2 hours; the temperature of the mass in the flask rises to 205 to 210% during the first few minutes of refiuxing, then drops again to a level of about 185%. After this time, the di-n-propylocetonitrile formed is distilled off at atmospheric pressure.

102.5 g of di-n-propyl acetonitrile are obtained. The yield of crude product is 82% based on the starting cyanoacetic acid methyl ester.

The yield of pure product is 80%.

Example 3

Production of di-n-propyl acetone-tril

30 kg of di-n-propyl cyanacetic acid are added to a 50-liter enamel kettle, the contents are heated to boiling at 185-190 ° ^C with stirring, and the temperature is maintained for 15 minutes. The resulting di-n-propyl acetonitrile is then distilled off and a total of 69.4 kg of di-n-propyl cyanacetic acid is continuously introduced into the reaction vessel.

The rate of acid addition is controlled depending on the rate of distillation of the nitrile, and the temperature of the mass in the cauldron is maintained at 185-190%. The acid addition takes about four and a half hours, during which time 40.9 kg of crude di-n-propyl acetonitrile distills off. Distillation is then continued while the mass temperature is gradually raised to 206% until the end of the distillation. This operation lasts 6 hours, during which 16.350 kilograms distill and then another 8.980 kg of crude di-n-propylacetonitrile.

The apparatus is then connected to a vacuum source and a further 1.640 kg of di-n-propylacetonitrile is distilled off under reduced pressure (about 13.33 kPa).

A total of 67.87 kilograms of crude di-n-proyl acetonitrile is obtained.

Example 1 and 4

Preparation of di-n-propyl acetonitrile

(a) Di-n-propyl cyanacetic acid

First of all. prepare a solution of sodium n-propylate by heating a mixture of 7.42 g (0.322 mol) of sodium and 100 ml of anhydrous n-propanol until boiling until complete dissolution of the sodium.

Into a 500 - ml round - bottomed flask fitted with a dropping funnel, mechanical stirrer, thermometer and. 17.9 g (0.141 mol) of n-propyl cyanoacetate and 40.69 g (0.33 mol) of n-propyl bromide are added via a reflux condenser with a chlorocarbon cap. The mixture is heated to 45% and then sodium n-propylate solution prepared as described above is added slowly and with stirring while maintaining the temperature of the reaction mixture by gentle cooling in the range of 50-55 ° C. After addition of all the alcoholate solution, the reaction mixture is brought to reflux for 30 minutes and refluxed for 3 hours. The n-propanol is then distilled off and distillation is stopped when the temperature of the distillation residue reaches 115%.

A solution of 7.5 g of flaky sodium hydroxide in 67.5 ml of water is added to the crude ester obtained in this way, the mixture is transferred to a 250 ml round-bottom flask equipped with a reflux condenser and the solution is slowly heated to 60-70%. The reaction mixture is kept at this temperature for 3 hours, then cooled to about 50% and the n-propanol formed by hydrolysis is distilled off at a pressure of about 50 mm Hg. The remaining solution was cooled to 20% and acidified with stirring by adding 26.25 g of 36% hydrochloric acid. During this operation, the temperature of the reaction mixture was kept below 40% by cooling. The mixture was stirred for 30 minutes and then allowed to stand for a further 30 minutes. The oily layer of di-n-propylcyanoacetic acid was separated by decantation and the aqueous portion was shaken with toluene. The toluene extract was combined with decanted di-n-propyl cyanacetic acid and the solution was washed in a separatory funnel with a solution of 1.5 g of sodium chloride in 14 ml of water. The toluene fraction was separated and the solvent was distilled off at atmospheric pressure.

23.9 g of crude di-n-piropropylcyanoic acid are obtained.

bj Di-n-propyl acetonitrile

A 100 ml round flask equipped with a thermometer and a reflux condenser was charged with 23.9 g of crude di-n-propylcyanoacetic acid prepared as described above and heated in an oil bath.

Decarboxylation begins at a temperature of about 140 degrees Celsius. The mixture is heated to boiling, i.e. first to about 160%, and then the temperature is raised to 190% over 2 hours. The latter temperature is then maintained so. until gas evolution is complete, which takes about 2 hours. The resulting di-n-proplacetonitrile is then slowly distilled off and the fractions passing over are collected; ranging from 165 to 175%. The product obtained is. distilling again.

14.2 g of n-propyl acetonitrile are obtained. Yield: 81% based on n-propyl cyanate starting material.

1.96 3 65

Example 5

Preparation of di-n-propylacetonitrile

(a) Di-n-propyl cyanacetic acid

First, a solution of sodium n-propylate is prepared by heating a mixture of - 7.42 g (0.322 mol) of sodium and 180 ml of anhydrous n-propanol until boiling until complete dissolution of the sodium.

- In a 500 ml round-bottomed flask fitted with a dropping funnel, mechanical stirrer and reflux condenser with a chlorine-calcium cap, add 19,8 g - (0,141 mol) of cyanoctane · n-butyl and 40,69 g ( 0.33 mol) of n-propyl bromide. The mixture is heated to 45 ° C and then the sodium n-propylate solution prepared above is added slowly and with stirring as described above, while maintaining the temperature of the reaction mixture by gentle external cooling in the range of 50-55 ° C. Noc: 2 ° C. After the addition of the alcoholate solution, the reaction mixture is started to be white. to reflux for 30 minutes and refluxed for 3 hours. The n-propanol is then distilled off and distillation is stopped when the temperature of the distillation residue reaches 115 ° C. .

A solution of 7.5 is added to the crude ester obtained by the above process. g of flaky sodium hydroxide in 67.5 ml of water, transfer the mixture to a 250 ml round-bottom flask equipped with a reflux condenser, and slowly heat the solution to 60-70 ° C. Reaction mixture. The mixture is kept at this temperature for 3 hours, then cooled to about 50 DEG C. and the resulting n-butanol and the n-propanol residues are distilled off under a pressure of about 50 psig. The remaining solution is cooled to 20 DEG C. and acidified with stirring by adding 26.25 g of 36 percent hydrochloric acid. During this operation, the temperature of the reaction mixture is kept below 40 ° C by cooling. The mixture was stirred for 30 minutes and then allowed to stand for an additional 30 minutes. The oily layer of di-n-propylcyanacetic acid was decanted, canted and the aqueous portion was shaken with toluene. The toluene extract was combined with decanted di-n-propyl cyanacetic acid and the solution was washed in a separatory funnel with a solution of 1.5 g of sodium chloride in 14 ml of water. The toluene fraction was separated and the solvent was distilled off at atmospheric pressure.

22.8 g of crude di-n-propyl cyanacetic acid are obtained.

b) Di-n-propyl acetonitrile

Into a 100 ml round-bottom flask equipped with a thermometer and a reflux condenser was charged 22.8 g of crude di-n-propylcyanoacetic acid prepared as described above and the flask was heated in an oil bath.

Decarboxylation begins at about 150 degrees Celsius. The mixture is heated to boiling point, i.e. first to about 160 ° C and then raised to 190 ° C over 2 hours. The latter temperature is then maintained until gas evolution ceases, which takes about lodines. The wicked d-propyl acetonitrile is then slowly distilled and the fractions passing between 165 and 175 ° C are collected. The product obtained is distilled once more.

13.8 g of di-n-propyl acetonitrile are obtained. Yield 78.5% based on n-butyl cyanacetate starting material.

Example-6

Preparation. di-n-propyl acetonitrile

a) Di-n-propyl cyanacetic acid

First, a solution of sodium n-propylate is prepared by heating a mixture of 50 g (2 mol - (- 10%) sodium and 804 g (1000 ml) of anhydrous n-propanol at 50 to 55 ° C for 60-90 minutes. .

Place 99.1 grams (1 mol) of methyl naathocyan cyanate in a 2 liter round-bottomed flask.

373.7 g (2.2 mol) of n-propyliodide, the mixture is heated to 45-50 ° C and a solution of sodium n-propylate in n-propanol prepared as described above is added at a uniform rate at that temperature with stirring; said operation takes about 60 to 75 minutes.

After the alcoholate solution is introduced, the reaction mixture is refluxed for 3 hours and then n-propanol is distilled off until the temperature of the distillation residue reaches 120-125 ° C. To the obtained crude ester was then added · · 500 g of a 10% aqueous solution OyOroxidu ^ч srdnéhr and 0.36 · g · cetyltrimethyaamoniumbromidu. · The mixture 'was heated for 1 hour under reflux, then cooled to about 50 ° C and · the alcohols present are distilled off under reduced pressure (at 10 to 50 psig). The solution obtained is cooled and acidified with 175 g of 36% hydrochloric acid such that the temperature does not exceed 40 ° C. The mixture was allowed to stand for 30 minutes and then the oily n-propylcyanoacetic acid was decanted off. . Shake the lower aqueous layer with 250 g of toluene, combine the toluene extract with the first organic phase, shake the solution once with 100 ml of distilled water, and distil off the solvent under reduced pressure. 154.5 g of crude di-n-propylcyanoacetic acid are obtained.

(b) Di-pgyopylacetrniiril

The crude di-n-propylene cyanoacetic acid prepared above was transferred to a 250 ml round-bottomed flask and gradually heated to boiling until the temperature of the reaction mixture reached 175-180 ° C; the last traces of toluene are removed by means of a Dean-Stark trap. The decarboxylation begins at about 140 ° C and the reaction is complete after about 1 hour of boiling. The mixture is refluxed for a total of 2 hours; . the temperature of the reaction mixture in the flask rises to 205 ° to 210 ° C in the first few minutes, then drops again and stabilizes at 185 ° C.

198365 ¹⁵

After this time, the di-n-propyl acetonitrile formed is distilled off at atmospheric pressure.

102 g of di-n-propyl acetonitrile are obtained. Crude yield

Claims (9)

Process for the preparation of di-n-propyl acetonitrile of the formula I ' CH3 — CH2 — CH2 CH - CN (I),. - / CH3 — CH2 — CH2 ... characterized in that, in a single step, 2 to 2.2 parts of sodium n-propylate in n-propanol are added to the reaction medium at a temperature of 45 to 55 ° C, consisting of 1 part of the cyanoacetate of the formula II CN / HdC. . (II), COOR in which. . R is C1 -C4 alkyl and 2- to 2.3 parts by weight of n-propyl bromide or n-propyl iodide, wherein the alkylation is carried out by heating the reaction mixture to reflux, the crude ester obtained is saponified for 10 to 10 minutes. 20% sodium or potassium hydroxide solution, preferably in the presence of a quaternary ammonium salt, the resulting salt is acidified with hydrochloric acid to give the crude di-n-propyl cyanacetic acid, which is decarboxylated by heating to 140-190 ° C, preferably 175 ° C. to 190 ° C to give the di-n-propyl acetonitrile of formula I. 2. The process according to claim 1, wherein the ¹⁶ product is 81.5% based on the methyl cyanacetate starting material. The yield of the pure product is 79.9%. The use of methyl cyanoacetate or methyl cyanoacetate is used as the cyanoacetate of formula II. 3. A process according to claim 1, wherein the saponification is carried out using sodium or potassium hydroxide in a ratio of 1.25 to 2 moles per 1 mol of crude ester at a temperature in the range of 60 to 70 [deg.] C. 4. The process according to claim 1, wherein the saponification is carried out in the presence of a quaternary ammonium salt, preferably trimethylcetylaminium bromide, benzyltrimethylammonium chloride or lauryltrimethylammonium bromide. -. 5. The process according to claim 4, wherein the saponification is carried out in the presence of 0.005 to 0.1 moles of quaternary ammonium salt per mole of crude ester. _; ' 6. The process of claim 4 wherein the saponification is carried out in the presence of 0.005 mol of quaternary ammonium salt per mole of crude ester at a temperature in the range of 60-65 degrees Celsius. , 7. The process of claim 4 wherein the saponification is carried out in the presence of 0.1 mole of quaternary ammonium salt per mole of crude ester at 30 ° C. 8. The process of claim 1, wherein the acidification of the di-n-propylcyanacetic acid salt is carried out with a 36% hydrochloric acid solution at a temperature of up to 40 ° C. 9. A process according to claim 1, wherein the decarboxylation is carried out by continuously feeding di-n-propylcyanacetic acid to the decarboxylation medium and simultaneously removing the resulting di-n-propyl acetonitrile.