CS217256B1 - Preparation of 1-Phenyl-3-methyl-4-isepropyl-5-pyrazoloa - Google Patents

Abstract

The invention relates to a method for the preparation of 1-phenyl-3-methyl-4-isopropyl-5-pyrazolene by reacting 1-phenyl-3-methyl-5-pyrazolene with acetone and hydrogenating with hydrogen over a palladium catalyst in the presence of phosphoric acid or its ammonium salts, which are added in an amount of 5 to 50% by weight, based on the amount of catalyst used. 1-phenyl-3-methyl-4-isopropyl-5-pyrazolene is an intermediate for the production of pharmaceuticals.

Description

The present invention relates to a process for the preparation of 1-phenyl-3-methyl-4-iseprepyl-5-pyrazelene by reacting 1-phenyl-3-methyl-5-pyrazelene and acetic acid and hydrogenating on a palladium catalyst, whose presence eliminates the influence of catalytic poisons.

Hydrogenaee tuner for the presence of kills Vlil. group of the perieic system of elements, because of their selectivity of the palladium and platinum heel, is a precea which finds its use even more. The advantage of this method is primarily the ecological purity of the precession, the nail does not create any by-products and impurities. Conversely, the high cost of catalysts if the chemical nature of the action requires the use of, for example, palladium or platinum is a partially inhibiting factor against an even wider spread of this method of reduction. It is therefore important that these catalysts be used as little as possible relative to the hydrogenated substance and that they can be used as long as possible. These criteria create high demands on the quality of the input catalysts, which must not contain substances which, by their chemical nature or physicochemical properties, result in loss of life or total loss of catalytic activity of the catalysts. However, this is often not fulfilled, and thus the presence of catalytic poisons in raw materials is often an insurmountable obstacle to the introduction of this modern process.

Preparation of 1-phenyl-3-methyl-4-iaeprepyl-5-pyrazelene by reaction of 1-phenyl-3-methyl-5-pyrazelene with acetone and reduction with hydrogen on a palladium catalyst proceeds as follows:

The first reaction, kendanzation of acetone with the methylenevee group of the pyrazelan, proceeds easily and quantitatively during the heating of the mixture to a reaction temperature of hydragenae of 90 ^and C, so that the reaction mixture flares as would be present for hydregonation of direct 1-phenyl-3-methyl-4. -iseprepylidenpyrazelen. However, in the res-alkylation alkylation of a number of 1-phenyl-3-methyl-pyrazelanec cremation samples, it was found that 50% of the samples taken from different batches tend to hydregonate, because the palladium catalyst loses activity due to impurities in the raw material otherwise level. The concentration of impurities was so low that the nature of the catalyst iodine was unsuccessful and the suitability for hydrogenation was unsuccessful to give a kerelaee aai with no physical raw material content, such as the content of the main component, the execution capacity, melting temperature or light permeability.

It has now been found that adding hydrogen to the reaction mixture in the presence of a palladium catalyst and additional amounts of estersic acid or its ammonium sele eliminates not only the negative effect of the catalyst poisons of the soluble heavy metal group, but also the effect of catalyst poisons failed to find.

: This knowledge is used in the process of preparation of 1-phenyl-3-methyl-4-iseprepyl-5-pyrololene

According to the invention, the novel process consists in reacting 1-phonyl-3-methyl-5-pyrazene with acetone and simultaneously hydrogenating it with hydrogen in the presence of a palladium catalyst on an inert support. The reactions are carried out in the presence of phosphoric acid or its ammonium salt which adds 5 to 50% by weight, based on the amount of catalyst used.

The addition of phosphoric acid or its ammonium sele allows not only the use of otherwise unsatisfactory types of 1-pheayl-3-netylpyrazelene, but also contributes to a significant acceleration of the roake of the compliant types.

The supposed mechanism of action of phosphoric acid and phosphates is the precipitation of soluble pigments of heavy blood cells hypothetically present in aursvia in very small amounts and by their synorgic effect of deactivating the catalyst. However, the mechanism may be different.

Using the present invention, therefore, it is not only possible to use 1-phenyl-3-methylpyrazelene for further synthetic reactions involving catalytic hydregeaaco, but at the same time to reduce the catalyst consumption and thus to further manufacture the window.

From 1-phonyl-3-methyl-4-isoprepyl-5-pyrazolone, one can. by motylation to prepare 1-phenyl-2,3-dinotyl-4-i-propyl-5-pyrazelene, an important drug of the class of drugs and anti-inflammatory drugs.

The process according to the invention is illustrated in more detail in the following examples.

EXAMPLE 1 Fit 10 liters of autofilter heated at 63 strokes per minute by supplying hydrogen from a calibrated pressure reservoir to control hydrogen supply by an automatic device and heated by means of a liquid flowing in thermostatatized ebedide, 100 g of l-phenyl-3-methyl-3-methyl-3-methyl 99.1%, melting point

127,7 * G, marked with operation number 729 · The preparation contained ions Cu, Ca, Mg, Si, Al,

Pb, Fe, determined by spectrophotemetry at a total concentration of less than 0,01%. Next, 650 ml of acetone and 1.3 g of a palladium catalyst containing 3% palladium on activated carbon in a 40% science paste were added. The autoclave was sealed, purged with nitrogen, fed with hydrogen, and the hydrogen pressure was set at 0.5 MPa. At this heel value, the pressure was automatically maintained by the control system. The mixture was heated to a reaction temperature of 90 ° C and the progress of the reaction was monitored by a hydrogen pressure packet in a reservoir from which hydrogen was fed to the autoclave. 180 minutes after the reaction temperature was reached, the pressure drop corresponded to the loss of the stoichiometric amount of hydrogen and did not decrease any further. Thus, 100% conversion of hydrogenation has been achieved over that time. The reaction was confirmed by removing the reaction mixture from the autoclave and isolating the product by crystallization by thin layer chromatography.

The product was a uniform substance consistent with the melting standard of 118 ° C.

Example 2

The experiment described in Example 1 was packed, except that 0.2 g of (NH4 / gHPO4) dissolved in 2 ml of water was added from de-phenyl-3-methylpyrazelene from the same operation as in Example 1. The reaction was terminated in this case. 30 minutes after the reaction temperature was 90 ° C.

Example 3

The experiment described in Example 1 was repeated in that 100 g of 1-phenyl-3-methylpyrazolone of the same origin but from another operation, starting at 734, were taken to react. Pyrazelene contained 99.50% of the main component, had a melting point of 127, It contained less than 0.01% of the metals listed in Example 1. After six hours of stirring the reaction mixture under standard reaction conditions (pressure of 0.5 MPa; 90 ° C), the reaction did not even partially pass.

Example 4

The experiment described in Example 3 was epacsified, but to the 1-phenyl-3-methylpyrazelene was added 0.4 g of NH4HgPO4 dissolved in 2 ml of science prior to the reaction. Hydrogenation was terminated at 210 minutes to reach the reaction temperature. The product quality was assessed in the same manner as described in Example 1 and was identical to the product obtained in the experiment of Example 1.

Example 5

The experiment described in Example 3 was repeated except that a weighed amount of 100 g of 1-phenyl-3-methylpyrazelene was ouopendevane in 100 g of 0.5% (NH 4 PO 4). The suspension was filtered and taken to dryness without drying. % conversion was achieved for 220 minutes after heating, to 90 ° C.

Example 6

The experiment described in Example 5 was repeated. However, a 0.3% phosphoric acid solution was taken to wash 1-phonyl-3-methylpyrazolone. Hydrogenation ran in 240 minutes. The reaction product was identified as identical to the product obtained according to Example 1.

Claims (1)

SUBJECT OF THE INVENTION A process for the preparation of 1-phenyl-3-methyl-4-βeprepyl-5-pyrazelene of formula CH CH, 3 \ / I want NH // \ / O N AND CH, reaction of 1-phenyl-3-methyl-5-pyrazelene with acetone and hydrogenation with hydrogen in the presence of a palladium catalyst and an inert solid support, characterized in that the reaction is carried out in the presence of phosphoric acid or its ama salt, added in an amount of 5 % to 50 wt. based on the amount of catalyst used.