SU512712A3 - The method of obtaining 1,4-disubstituted piperazines - Google Patents

Description

the compound can be converted by reacting with an alkylating or aralkylating reagent i into a compound of the general formula containing an alkyl group having from 1 to 3 carbon atoms, or an alkyl group containing from 1 to 3 carbon atoms and substituted by a hydroxyl group, a beneyl group or ben a group substituted by a halogen atom as a substituent.

If the resulting compound of the general formula .1 presumes that it can be converted into a salt formed by the addition of an acid by reaction with an acid, or the salt can be converted into a free base by reacting with a strong base with another acid .

The free bases of the general formula, 1, are purified before the formation of salts thereof, preferably by recrystallization or distillation. a vacuum, however, can be used raw to form a salt. Formula I.

When starting compounds are compounds of formula I, where R represents a hydroxyl, amino or alkoxy group. Having from 1 to 4 carbon atoms, they preferably react with compounds of the general formula W at 140,250 °. The reaction can be carried out in the absence of a solvent or in the presence of solvents such as ethylene glycol, formamide, dimethylformamide, ben ethyl alcohol having a higher temperature.

In the case of using the starting compounds of the general formula P containing a halogen atom as substituent 1, the reaction is preferably carried out at a temperature from 0 to 100 ° C in the absence of a solvent or in the presence of a neutral solvent such as diethyl ether, dioxane, benzene or carbon tetrachloride .

Example 1. Getting N-picolinyl. ,

A mixture of 27.4 g (0.2 mol) of picolinic acid methyl ether (or 30.2 g (0.2 mol) of picnic acid ethyl ester, or 35.8 g (0.6 mol) of pilin c-nyl butyl ester and 51.6 g (0.6 mol) of anhydrous piperazine were kept for 25 hours at 135-145 s, the excess piperazine was distilled off in an oil bath at. The residue was subjected to fractional distillation at a pressure of 0.1 mM Hg. In this way, 21- 23 g () of N-picolinyl piperazine with a melting point of 152-155 ° C (0.1 mHg). The product crystallizes on aging, mp 72-73 ° C

Analytical data (M "191,24)

Calculated% i, N21.97,

Found,%: H21.65. The white, crystalline H-picolinyl pipbrazin dihydrochloride melts after recrystallization with decomposition.

Analytical data (, 17)

Calculated,%: N15.91; Ct 26,34

Found,%; N15.95; CE 26.35. EXAMPLE 2. Preparation of N-picolinoylpiperazine.

; A mixture of 8.6 g (0.1 mol) anhydrous piperazine and 12.2 g (0.1 mol) amide of picolinic acid is refluxed for 20 hours in an oil bath with a temperature of from 150 to, after which the mixture is subjected to fractional distillation at a pressure of 0.1 mm Hg, St, 21 g (55%) are obtained. N-picolinoyl piperazine. The product is identical to the product obtained in example 1.

Froze Preparation of N - (6-mfetiJ picolynil) - And -methyl piperazine.

A mixture of 33.0 g (0.2 mol) of ethyl bicyl picolic acid and 20.0 g (0.2 ml) of N-methyl piperazine is heated; with a reflux condenser for 20 hours in an oil bath at 40–200 ° C and pressure 0, 4 mm Hg. 19f5-22 g (45-50%) oily are obtained as the main product. N - (6-methyl-picolinyl) - N-methyl-piperazine, light yellow.

Analytical data (M 219.29) Calculated,%: N19.16 Found,%: N19.10.

After recrystallization from ethanol, the crystalline dichlorohydrate

N - (6-methyl-picolinyl) -N-methyl-piperazine melts at 247-248 s with decomposition.

Analytical data (M 292.22) Calculated,%: N14.23; se24,27 Found,%: M14,28; Ct 24,57

Note 4. Preparation of K-picolinbenzylpiperazine.

Claims (1)

A mixture consisting of 15.95 g (0.1 mol) of picolinic acid hydrochloride and from 17.6 g (0.1 mol) of M-benzylpiperazine kept in the apparatus for 5 hours at 160-170 4 ::. The N-picolinyl-N-benzylpiperazine monohydrochloride obtained is dissolved in 200 ml of hot absolute ethanol and the solution is acidified at a temperature of 50-70 ° C with absolute ethanol saturated with hydrogen chloride. The value of the solution is controlled by using an indicator paper. The mixture was kept for several hours, in the refrigerator, after which the separated crystals were filtered off, washed with two portions of ethanol rid of 20 ml and dried. In this case, 20.3 g (58%) of digidrochloride, N-picolinyl-N-benzylpiperazine, melted at 214215 ° C with decomposition, are obtained. After overgrowth from absolute ethanol, the decomposition temperature rises to 216-217 C. Analysis results, 29) Calculated,%: N11.86, se20.01. Found,%: N11.91, ce 19.70, Maleinate N-picolinyl-N-benzylpiperazine (C, 7Hi,) melts false l66-nO ° Cf while fumarate .N-picolynil - N-benzylpiperaznn tC H NjO -G HO) melts at. Example 5, Preparation of N-picolinyl-M-benzylpiperazine, k a hot solution of 19.1 g (0.1 mol) of N-picolinyl piperazine (prepared according to the method described in example 1) in 150 ml of absolute dioxane Within 1 hour, 2.3 g of sodium metal powder was added in separate portions while stirring. The mixture was kept at room temperature for one day. Within 1 hour, when external cooling is added, dropwise 0, 1 mol of benzyl chloride is added to the previously obtained N - picol nilpiperazine sodium, after which the mixture is heated to the dope. Separated chloride. the sodium is filtered off, the solvent is removed from the c) t, and the residue is subjected to fractional distillation in vacuo. In this case, 18.2 g (65%) / N-picolinyl of H-benyl piperazine melted at 218-220 ° C under a pressure of 0.1 mm Hg is produced. The product is identical with the product obtained by Example 4. Example L6-12. Compounds that are directly applied to the table can be obtained in a manner similar to that described in the preceding examples. Example 13. Obtaining N - (pyridyl- (2) -acetyl) - N-methyl piperazine. A mixture consisting of 30.2 g (0.2 mol) of pyridine-2-acetic acid methyl ester or from 38 g (0.2 mol) of pyryl-2-acetic acid n-butyl ester and from 20 g (0.2 mole) methylpiperazine is heated at reflux temperature. Analysis results (M «402.77) Calculated,%: 10.48, C 26.41) Found,% 10.18, ce 26.31 Example 14. Preparation of L- (pyridyl) - (2) -acetyl) - N-benzylpiperazine. A distillation of 17.6 g (0.1 mol) of N-free nsylpiperazine is added in separate portions, while stirring for 0.5-1 hour, 19.25 g (0.1 mol) of pyridyl (2) -acetic acid hydrochloride acid. The reaction mixture is boiled for 1 hour, then cooled and basified with a solution of 10 g of sodium hydroxide in 60 ml of water. The benzene phase containing the desired product is separated, then the benzene is distilled off and the residue is subjected to fractionated distillation under vacuum. In this case, 12.7 g (43%) of yellow-yellow, oily N - (pyridyl- (2) -acetyl) -benzylpiperazine boiling at 222225 C under a pressure of 3 mmHg are obtained. Analysis results (, 39) Calculated,%: N14.23. Found,%: N14, 30. White crystalline N- (pyridyl- (2) -acetyl-N-benzylpiperazine dihydrochloride after perekristisshadadia from ethanol melts at 190-192 ° C with decomposition. Analysis results (M 368f32) Calculated: N11, 41, SC 19.25. Found: N11.16, CE 18.80 951271 Formula of inven tion A method of obtaining 1,4-disubstituted piperaeins of the general formula I .. 5 | j. L. chal-C-M K-B 1 I V- / where is a hydrogen atom, methyl, Yu K is a hydrogen atom, an alkali metal atom, alkyl with 1-3 carbon atoms, which can be replaced by a hydroxyl group, benzyl, benzyl, is replaced by a halogen atom, A represents t is a group - (SCPSP ,, or their salts, a tl and h "and ft with the fact that the compound of the general formula P x RN i O is where and A has the indicated values, K is a hydrogen atom, halogen, a hydroxy, amino, straight-chained or branched alkoxy group containing from 1 to 4 carbon atoms is reacted with a compound of the general formula VZ H-ii i c, where "has the above value" ° followed by isolation of the desired product in in free form or in the form of its salt.