DD256130B1 - PROCESS FOR THE PREPARATION OF 2- (P-AMINOPHENYL) -2-ETHYL GLUTARIMIDE - Google Patents

Abstract

The invention relates to a process for the preparation of 2- (p-aminophenyl) -2-ethyl-glutarimide of the formula from 2- (p-nitrophenyl) -2-ethyl-glutarimide by means of hydrogen in the presence of supported nickel catalysts in organic solvents at temperatures from 323 to 423 K, preferably at 360 to 400 K and pressures of 3 to 10 MPa. The nickel-supported catalysts contain 50 to 80% nickel and as a support silica or alumina. formula

Description

For this 1 page formulas

Field of application of the invention

The present invention relates to the preparation of 2- (p-aminophenyl) -2-ethyl-glutarimide. 2- (p-aminophenyl) -2-ethylglutarimide is used as an active ingredient for the treatment of hormone-dependent tumors application.

Characteristic of the known solutions

Heretofore, various methods for producing 2- (p-aminophenyl) -2-ethyl-glutarimide have been described.

According to DL-PS 1088957 (Example 1) is 2- (p-nitrophenyl) -2-ethyl-glutarimide or the isomeric mixture consisting of 2- (p-nitrophenyl) -2-ethyl-glutarimide and the corresponding o-compound in organic Solvents and hydrogenated with hydrogen until the completion of hydrogen uptake in the presence of palladium-carbon or nickel (Raney nickel) at 50 to 7O ⁰ C.

In Ullmann's Encyclopedia of Industrial Chemistry, 4th ed., Bd.7, p.398 right column, reference is made in the paragraph "hydrogenation in liquid phase" to usual hydrogenation temperatures of 100 to 170 ⁰ C and pressures of 150 to 300bar on an industrial scale There is in the hydrogenation of nitroaromatics with sensitive two substituents, a low hydrogen pressure of only 1 to 50 bar recommended.

A disadvantage of these processes, the high catalyst costs when using palladium or the difficult handling of Raney nickel, which is present as a powder, mainly because of the risk of fire, from.

Object of the invention

The object of this invention is to find a simpler, more economical, and more technically feasible process for producing 2- (p-aminophenyl) -2-ethyl-glutarimide over the prior art.

Explanation of the essence of the invention

It is therefore an object of the present invention to find a catalyst which is easier to produce, equally effective, easier to handle and less expensive.

It has been found that the object is achieved by the catalytic hydrogenation of 2- (p-nitrophenyl) -2-ethylglutarimide in the presence of a supported nickel catalyst at temperatures of 323 to 423 K, in particular at 360 to 400 Kund a hydrogen pressure between 3 and 10 MPa until the hydrogen uptake ceases. Particularly effective are nickel-rich catalysts with 50 to 80% nickel and silica or alumina as a carrier.

These catalysts are prepared by known methods by precipitation of basic nickel carbonate on silica or alumina, drying and activation of the powder or pressed moldings by hydrogen at certain temperatures.

For hydrogenation, the nitro compound is dissolved in an organic solvent. Preference is given to aliphatic alcohols and their esters with aliphatic acids.

The advantage of the method according to the invention is that the nickel-supported catalysts used in comparison with the known palladium or nickel (Raney nickel) catalysts in their production are more economical and are characterized by additional good handling (low risk of fire).

They provide hydrogenation over Raney Nicke! the target compound in a technically favorable procedure with an equal or higher yield of 90 to 100% and higher purity, even without the recrystallization required by the prior art of 99 to 100%, expressed by the GC analysis and the several degrees higher melting point of 150

The process according to the invention can be designed batchwise or continuously, wherein the continuous feed through a spilled catalyst preferably proceeds.

The method offers no difficulties in the industrial driving style.

embodiments

The process of the invention is illustrated by the following examples.

example 1

250 g (0.95 mol) of 2- (p-nitrophenyl) -2-ethyl-glutarimide and 2.5 g of prereduced catalyst (60% nickel, 40% alumina) in 2.5 l of ethyl acetate are stirred in the stirred reactor at a hydrogen pressure of about 4 MPa Heated 383-393 K. The uptake of hydrogen starts immediately and ends after 30 minutes. Hydrogen is pressed in according to the consumption. After cooling to room temperature, the catalyst is separated off. The hydrogenation solution is concentrated, whereby the solid amino compound precipitates. The precipitate is filtered off with suction (95-100% of theory) and recrystallized from isopropanol.

Y. 199.3 g (90% of theory)

Schp. 424-425 K

GC-go. 99.9%

Example 2

4.5 kg (17.1 mol) of 2- {p-nitrophenyl) -2-ethyl-glutarimide and 45 g of prereduced catalyst (70% nickel and 30% silica) are suspended in 45 kg of ethanol and dissolved in the 50 l stirred reactor at 39.degree. 403K and about 4MPa hydrogenated. After completion of the hydrogen uptake is cooled and separated from catalyst.

The resulting reaction solution is concentrated and the precipitated reaction product is filtered off with suction.

Yield: 3.78 kg (95% of theory)

Scrip !: 423 to 424K

Example 3

A 1.5 liter tubular pressure reactor is charged with 1.41 tableted catalyst (70% nickel and 30% silica) and the catalyst is activated for 1h with hydrogen at 423-473K. Subsequently, 0.3 to 1.51 of a 20% strength solution of 2- (p-nitrophenyl) -2-ethyl-glutarimide in n-butanol in cocurrent with 2.5, over the catalyst at 383-393K and about 5 MPa hydrogen pressure per hour Nm ³ hydrogen pumped, which are completely hydrogenated under these conditions. The clear hydrogenation is worked up according to Example 2 to 2- (p-aminophenyl) -2-ethyl-glutarimide. The yield varies between 95 and 100%. The melting point in this procedure is 423 to 424K

 GC: 99.7%

Example 4 (comparative example according to the prior art)

150 g (0.57 mol) of 2- (p-nitrophenyl) -2-ethyl-glutarimide are dissolved in 20 times the amount of ethanol in the stirred autoclave and mixed with 15 g of freshly prepared Raney nickel. At 393 to 423 K and a hydrogen pressure of about 4 MPa is hydrogenated until the completion of hydrogen uptake. After cooling to room temperature, the catalyst is separated off and the reaction solution is concentrated. The precipitated amino compound is filtered off with suction.

Yield: 120 g (91% of theory)

Shp .: 417-421K

For purification is recrystallized from ethyl acetate.

Yield: 104g (79% of theory)

Sh .: 422-423 K

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c :,

Claims (2)

1. A process for the preparation of 2- (p-aminophenyl) -2-ethylglutarimide of the formula by catalytic hydrogenation of 2- (P-nitrophenyl) -2-ethylglutarimide in organic solvents at temperatures of 323 to 423 K and at a hydrogen pressure of 3-10 MPa until the cessation of hydrogen uptake, characterized in that in the presence of nickel Supported catalysts containing 50 to 80% nickel on silica or alumina is hydrogenated. 2. The method according to claim!, Characterized in that the hydrogenation is carried out continuously over a dilute catalyst of the same composition in the form of a solution.