DE883899C - Process for the preparation of basic substituted 1-phenyl-1-cyclohexyl-propanols - Google Patents

Description

Process for the preparation of basic substituted 1-phenyl-l-cyclohexyl-propanols The compound i-cyclohexyl-i-phenyl-3-piperidyl- (i) -propan-i-ol is according to literature an effective spasmolyticum (antispasmodic) and a effective remedy in cases of paralysis agitans (paralysis). It has previously been produced by a process which involved the formation of the i-phenyl-3-piperidyl- (i) -propan-i-one and the reaction of this compound with a cyclohexyl Grignard reagent. The yields obtained in the necessary series of operations are low, especially because the cyclohexyl Grignard reagents are not very reactive. Experiments on the catalytic hydrogenation of compounds of the general formula where R denotes a piperidyl (i) or pyrrolidyl (i) group led to the finding that the reaction was continuous (without any interruption in the hydrogen absorption, which would correspond to the reduction of only one of the two phenyl radicals) to to the fully saturated product of the general formula progresses, but it is possible by stopping the reaction in an intermediate stage, the semi-saturated derivative of the general formula to be separated in pure form.

According to the invention, the catalytic hydrogenation of a compound broken off from the general formula (I) as soon as a little more than 3 mol of hydrogen, based on i mol of the starting compound, have been absorbed, and then the resulting compound of the formula (III) isolated.

It was found that the extent of hydrogen absorption of depends on a number of factors. The reaction works in various solvents at different speeds in front of you; it is faster in glacial acetic acid, for example than in aqueous acetic acid or in ethanol, and it has been found that with Salts formed in hydrochloric acid are hydrogenated faster than the free bases. Farther an increase in the amount of catalyst used gives a faster reaction rate.

If proper consideration is given to the above factors, it is possible to choose the operating conditions so that the reaction to the end products of formula (III) above. After stopping the Ueaktion, after a little Excess over 3 moles of hydrogen acted to completely eliminate the Starting material (I) can ensure the semisaturated derivative produced (III) isolated and purified e.g. B. by crystallization from a solvent, such as B. Light petroleum, in which it is sparingly soluble and in which the fully saturated Product (II) is considerably more soluble.

Both the compound i-cyclohexyl-i-phenyl-3-piperidyl- (i) -propan-i-ol as well as the previously unknown compound i-cyclohexyl-i-phenyl-3-pyrrolidyl- (i) -propan-i-ol have been found to be effective in the treatment of paralysis agitans (paralysis); They can be used pharmaceutically as salts of acids, which are used for the compound used dosage are not toxic.

The present invention will now be illustrated in more detail by the following examples. Example ii - i-Diphenyl-3-piperidyl- (i) -propan-i-ol (5 g) was dissolved in glacial acetic acid (5o cm3) to which platinum oxide (Adam's catalyst) (1.3 g) had been added and shaken in a hydrogen atmosphere. After absorption of a hydrogen equivalent of 3.4 mol per mol of the compound, the catalyst was filtered off and the filtrate was diluted with water (150 cm '). The solution was made strongly alkaline with concentrated potassium hydroxide solution while cooling in an ice bath and extracted with ether. The essential extract was washed with water, dried over anhydrous sodium sulfate and concentrated. The residue (q., 96 g) was crystallized twice from light petroleum (boiling point 80 to 100 °), after which i-cyclohexyl-i-phenyl-3-piperidyl- (i) -propani-ol with a melting point of 110 ° (4th , 3 g) was obtained. Example 2 i - i-Diphenyl-3-piperidyl- (i) -propane-i-o1 (5 g) was dissolved in glacial acetic acid (5 cm '), which contained water (50 cm3) and platinum oxide (Adam's catalyst) (0.9 g) had been added, dissolved and shaken in a hydrogen atmosphere. After absorption of a hydrogen equivalent of 3.3 mol per mol of the compound, the reaction product was worked up as described in the previous example, i-Cyclohexyl-i-phenyl-3-piperidyl- (i) -propani-ol (4g) being isolated became.

Example 3 ii-Diphenyl-3-piperidyl- (i) -propan-i-ol (iog) was added in ethanol (i25 cm3) to which concentrated hydrochloric acid (3.4 cm3) and Adam's catalyst (2.4 g) were added were suspended. The mixture was at an initial hydrogen pressure of 29 atm. hydrogenated. As soon as the amount of hydrogen absorbed had risen to 3.5 mol, the catalyst was filtered off from the solution and the filtrate was evaporated to dryness in vacuo. The residue was dissolved in water and the solution made basic. Working up as described above gave i-cyclohexyl-i-phenyl-3-piperidyl- (i) -propan-i-ol (8.3 g). Example 4 i - i-Diphenyl-3-piperidyl- (i) -propan-i-ol (509) was dissolved in glacial acetic acid (250 cm3) and in the presence of Adam's catalyst (3.45 g) at an initial hydrogen pressure of 67 atm . hydrogenated. After absorption of 3.5 mol of hydrogen, the product was separated off as described above and gave i-cyclohexyl-i-phenyl-3-piperidyl- (i) -propane- i -o1 (42 g). (Recrystallized from light petroleum). Example 5 i - i-Diphenyl-3-pyrrolidyl- (i) -propan-i-ol (3o g) was dissolved in glacial acetic acid (12o cm3), then Adam's catalyst (6 g) was added and the mixture shaken in a hydrogen atmosphere until the equivalent of 3.4 moles per mole of compound had been taken up. Water was added, the catalyst removed by filtration, an excess of ammonia added and the liberated base extracted with ether. The ethereal extract was dried and evaporated, and the residue was recrystallized from light petroleum (boiling point qo to 60 °). The i-cyclohexyl-i-pheny1-3-pyrrolidyl- (i) -propane-1-o1 (1 g, 3 g) obtained in this way had a melting point of 85.5 to 86.5 °. The hydrochloride recrystallized from a mixture of ethanol and ethyl acetate melted with decomposition at 226 to 227 °.

Claims (1)

PATENT CLAIM: Process for the preparation of basic substituted i-phenyl-i-cyclohexyl-propanols of the general formula wherein R is a piperidyl (i) or a pyrrolidyl (i) group, characterized in that a compound of the general formula in which R has the above meaning, is subjected to a catalytic hydrogenation, the reaction is terminated as soon as a little more than 3 mol of hydrogen, based on 1 mol of starting compound, have been absorbed, and the compound (III) thus formed is isolated.