SU349688A1 - METHOD FOR PRODUCING ALKYLACETHYLENE ETHIROBANABAZA - Google Patents

Description

The invention relates to the field of the preparation of novel aminoether acetyl.enov derivatives, as physiologically active substances. The proposed method is based on the known reaction of reacting paraform and propargyl ester of carboxylic acids with amines in an organic solvent medium when heated in the presence of a catalyst.

The use of a known reaction to produce compounds of the aiabazine series led to the production of anabazine alkyl acetylene esters, which are valuable products with high biological activity. The proposed method for the preparation of anabasine alkyl acetylene esters is that anabasia is reacted with the paraform and fatty acid propargyl ester of the composition C-Cis in an organic solvent medium in the presence of copper salts as a catalyst. The process is conducted at a temperature of 95-97 ° C.

The synthesized compounds are purified by chromatography on a column (the ratio of the substance to be divided and the sorbent is 1:50), filling with alumina, eluting with a mixture of ether and petroleum ether (3: 1). Separation is monitored by thin layer chromatography on ABOZ. The yield of the desired products is 50-62%.

The resulting hexa-, hepta-, octadecaiacido-6yTHH-2, 4-Na- (| 3-pyridyl) -piperidyls are light yellow oils that turn into a white amorphous mass upon standing, and tetradecananacide-butin-2,4-N-sb (p-pyridyl) -Piideidyl does not harden.

The synthesized alkyl acetylene ethers of a- (| 3-pyridyl) -piperidyl are characterized by the preparation of crystalline derivatives; chlorohydrates and tetrabro. which are white or yellowish. crystalline substances.

To characterize and prove the structure of the synthesized alkyl acetylene esters of a- (p-pyridyl) -piperidyls and their tetrabromo derivatives, they remove the UV, IR, and NMR spectra.

Example 1. Hexadecanacid and H-2,4-N-a- (p-p and p and d and l) -n and p and p and d and l.

In a round bottom flask equipped with a reflux condenser and a calcium chloride tube, the mixture consisting of 2.3 ml (0.015 g-mol) of a- (p-pyridyl) -piperidyl, 0 is heated at 95-97 ° C , 54 g (0.018 g-mol) paraform, 3.6 g (0.012 g-mol) 3- (hexadecanacido) -propium-1, 0.3 g copper acetate in 60 ml of dioxane. Every 6 hours after the start of heating, 0.1 g of paraform is added. The reacted mixture is poured into a glass containing a mixture of ice with 10% hydrochloric acid and extracted with ether. The aqueous acidic layer is made alkaline with a 25% ammonia solution until alkaline and the mixture is again extracted with ether. The ether extracts are combined to form over calcined potash, the solvent is distilled off. The residue is a dark thick oil, which is purified by chromatography on a column (the ratio of the substance and sorbent is 1:50), filled with alumina, eluting with a mixture of ether and petroleum ether (3: 1). Completeness is controlled by thin layer chromatography on ABOZ.

3.45 g (60.2% of theoretical) of hexadecanane-cac-butin-2,4-N-a - (p-pyridyl) piperidyl, which is a light-yellow oil, is converted to a white amorphous mass with a m.p. 25 to 26.5 ° C; -98.01 °, 84 (paper chromatography — butanol: hydrochloric acid: water — 50: 7.5: 13.5).

Found,%: C 76.75, 76.81; H 10.21, 10.30; N 6.23, 6.12.

C3H4802N2.

Calculated,%: C, 76.87; H 10.32; N 5.98. Estimated structure of hexadecananacidobutin-2, 4-M-a- (p-pyridyl) -piperidyl

N | ii

CH-C-C-CH2-0-C-C, 5Nm

confirmed by IR and NMR spectroscopy.

A white crystalline iodomethyl was obtained by pouring out an acetone solution of the synthesized compound and methyl iodide with m.p. 156-158 ° C.

The hydrochloride was also obtained by adding a saturated methanolic solution of hydrogen chloride to the pH4 amino acid solution of the acetylene ether to pH 4. The product has a melting point of 20 ml. 109-110 ° С (from acetone). . Found%: C1 13.23, 13.19.

СзоН5оО2Н2С12.

Calculated,%: C1 13,32.

Example 2. Heptadecanacid and H-2,4-N-a- (p-iridyl) -piperidnl.

Under the conditions of example 1, from 0.45 g (0.015 g-mol) paraform, 1.85 ml (0.012 g-mol) a- (p-pyridyl) -piperidyl, 3.12 (0.01 g-mol) 3 - (heptadecano) -propin-1 in 60 ml of dioxane, in the presence of 0.24 g of copper acetate by heating for 18-20 hours at a temperature of 95-97 ° C, adding 2.07 g of paraforme twice, 2, 95 g of heptadecanecidobutin2, 4-Na- (p-pyridyl) -piperidyl.

Yield 61.4%.

(3: 1). The purified product is a light yellow oil that hardens on standing with t. Pl. 29-30 ° C; a 2f -95,93 °; , 81 (t.s.x., sorbent, system - ether: petroleum

ether with a ratio of 3: 1, iodine producer). , 89-0.90 (paper chromatography, the system is butanol: acetic acid: water with a ratio of 5: 1: 4).

Found,%: C 77.03, 76.97; H 10.37, 10.21;

N 5.39, 5.41.

C3lH5oO2N2.

Calculated,%: C 77.18; H 10.39; N 5.80. The proposed structure of heptadecanacidobutin-2, 4-M-a- (p-pyridyl) -piperidyl

II

CH.2- .H7 0-C-CiyH 3

confirmed by UV, IR and NMR spectra.

Heptadecanacidobutin-2,4-M iodomethyl (p-pyridyl) -piperidyl iodomethyl is a white powder with mp. 161-163 ° C (from acetone). The hydrochloride substance has a mp. 112-114 ° C (from acetone).

Found,%: C1 12.82, 12.78.

C3lH5202N2Cl2.

Calculated,%: C1 12.88.

Example 3. Octadecanacid and H-2,4-N-a- (rn iridyl) -piperidyl.

Under similar conditions of examples 1 and 2, heating for 18-20 hours at 95-

97 ° C mixture consisting of 0.84 g (0, Q28 g - mol) paraform, 2.62 ml (0.017 g-mol) a- (p-pyridyl) -piperidyl, 4.4 g (0.014 g - mol), 3- (octadecanacido) -propin-1, 0.35 g of copper acetate in 100 ml of dioxane obtained 4.05 g (50.3% of theoretical) octadecananacobutin-2, 4-N-a- (p-pyridyl ) -piperidil with m. pl. 33-35 ° C, which is a yellowish amorphous mass with a -94.65 °;

Rf 0.81 (tsx,, ether: petroleum ether 3: 1, iodine). Rf 0.89-0.90 (paper chromatography — butanol: acetic acid: water 5: 1: 4).

Found,%: C 77.02, 77.19; H 10.43, 10.29;

N5,77,5,69.

C32H52O2N2.

Calculated,%: C 77.40; H 10.48; N 5.64. The proposed structure of octadecanacidobutin-2, 4-N-a- (p-pyridyl) -piperidyl

О CH.2-C C-CH2-0-C-Ci7H55

Found%: Cl 12.41, 12.38.

C32H5402N2C12.

Calculated,%: Cl 12.47.

Example 4. Tetradecanicide and H-2,4-N-a- (p-iridyl) -piperidyl.

Under the conditions of examples 1, 2 and 3, from a mixture of 0.6 g of paraform, 2.31 ml of a- (p-pyridyl) -piperidyl, 2.66 g of H- (tetradecanacido) propyl-1, 0.21 g of acetate copper in 60 ml of dioxane received 2.55 g (60.8% of theoretical) of tetradecane-cac-butin-2, (p-pyridyl) -piperidyl.

The purified product is yellow thick oil with m. Bale. 183-185 ° C, - a - 100.72 °; Rf, 80-0,81 (t. C.H., ABOz, ether: petroleum ether 3: 1, iodine); , 89 (paper chromatography, butanol: acetic acid:: water 5: 1: 4).

Found,%: N 7.02.

C28H44O2N2.

Calculated,%: N 6.70.

Estimated chemical structure of tetradecanacidobutin-2, 4-M-a- (p-pyridyl) - piperidyl

СН2-С С-СНс-0-С-С ,,, Н

confirmed by IR spectroscopy.

Yodmetidat with t. Pl. 152-154 ° С (from acetone).

Hydrochloride with t. PL. 104-106 ° C (from acetone).

Found,%: C1 13.51, 13.47.

C28H46O2N2C12.

Calculated,%: C1 13.79.

Subject invention

The method of producing alkyl acetylene esters of anabazine, characterized in that the anabazine is reacted, when heated, with the paraform and fatty acid propargyl ester of the composition Cu-Cig in the medium of an organic solvent in the presence of copper salts as a catalyst, with

the subsequent selection of the target product in a known manner.