SU654613A1 - Method of obtaining pyridoxylamine salts - Google Patents

Description

The invention relates to an improved process for the preparation of salts of pyridoxypamines, which can be used in the chemical and pharmaceutical industry. I A known method for the preparation of pyridoxylamines is that pyridoxal is reacted with an amine and the resulting Schiff base is hydrogenated in the presence of talizator 1. The amount of this method is multistage and the use of scarce catalysts. A known method of producing salts; pyridoxylamine by reacting pyridoxine or its alkyl ether with ammonia under pressure at a temperature of about, possibly in the presence of solvent 2. A disadvantage of the known method is the duration of the process. The aim of the invention is to intensify the process and expand the range of pyridoxyl amines with vitamin activity. This goal is achieved by the method of obtaining salts of pyridoxylamines of the general formula I HjC-N, where R is hydrogen, -dendiated alkyl, alkylindolyl; R is hydrogen or lower alkyl, in that pyridoxine or its methyl ester is reacted with an amine of the general formula HNRR, where R and R are as indicated above, when heated, usually at a temperature of 120-160 ° C, under pressure in the presence of oxides or hydrates of metal oxides of groups I-III of the periodic system of elements. As compounds accelerating. the reaction of the preparation of pyridoxylamines; it is necessary to note alumina, calcium oxide, magnesium oxide, caustic soda. The use of these catalysts makes it possible to shorten the process time, reduce the amount of by-products and in some cases increase the yield of the desired product. It is necessary to point out the high selectivity of the replacement of the hydroxy group in the position of the pyridoxine molecule: carrying out the reaction at 140–160 ° C for 4–18 h is not accompanied by the replacement of the hydroxy group in the position of the pyridoxine molecule; p.5. 3-O-isopropylidenepyridoxine does not undergo transformation under these conditions. The most suitable for practical application is moisture oxide, having sufficient catalytic activity (the yield of pyridoxyl amine in the ammonolysis of pyridoxine 17% alcoholic solution of ammonia increases from 20 to 70%; the duration of the reaction b h at). It is easily separated from the reaction solution and can be used repeatedly. The table shows the yields of pyridoxylamines by aminating 0.05 M pyridoxine {A) or its methyl ester (B) with a 50-fold excess of an aminating agent in the presence of 3 g of alumina.

Aqueous 2 to 5% solution alfadaka

Methanol 17% ammonia solution

Methanol 20% dimethyl solution Example 1, Preparation of pyridoxy silamine. A, In the presence of alumina. 1.03 g (0.005 mol) of pyridoxine hydrochloride is dissolved in 20 ml of a 17% ammonia solution in methanol, 3 g of alumina II of activity is added and the reaction mixture is kept at 140 ° C in a glass ampoule. The alumina is filtered off and washed with methanol and the filtrate is evaporated in vacuo. 1 ml of concentrated hydrochloric acid is added to the dry residue, evaporated to dryness, and the residue is crystallized from alcohol. 0.86 g (70%) of pyri doxylamine dichlorohydrate is obtained, melting point 223-225 ° C (lit. data 225-226 0 Mixed sample with a known sample of pyridoxylamine dihydrochloride does not give a melting point depression, Rf 0.47, hereinafter the chromatography was carried out t on Silufol-254 plates in the acetone: dioxang system 25% ammonia (9: 9: 2). The appearance is carried out with the Gibs reagent. Calculated,%: C 37.07; H 6.22; N 10.80; all 27.36; CgH NgO-cevH O Found%: C 37.17; H 6.14; 10.63; ce 27.32,

7

b

65 61

63 63

67

Claims (2)

70 B. With the addition of alumina. 1.03 g (0.005 mol) of pyridoxine hydrochloride are dissolved in 20 ml of a 17% ammonia-methanol solution and incubated for 18 hours at 140 ° C in a glass ampoule. The solution is evaporated in vacuo and 1 ml of concentrated hydrochloric acid is added to the dry residue, evaporated and the residue is crystallized from alcohol. 0.78 g (63%) of pyridoxylamine dichlorohydrate is obtained, melting point 223-225 ° C; R 0.47. Example 2. Preparation of pyridoxylamine from pyridoxine methyl ester, 1.1 g (0/005 mol) of pyridoxine methyl ester hydrochloride dissolved in 20 ml of a 17% aqueous solution of ammonia in methanol, 3 g of alumina II of activity was added and kept the reaction mixture for 6 h at. The alumina is filtered off, washed with methanol and the filtrate evaporated in vacuo. Further processing is carried out similarly to the previous experience. 0.89 g (72%) of pyridoxylamine dichlorohydrate is obtained, melting point 223-225 ° C; Kg 0.47. Example 3. Preparation of 2-methyl-3-hydroxy-cC-diethylaminomethyl-b-β-oxymethyl pyridine (pyridoxyl diethyl amine). 1.03 g (0.005 mol) of pyridoxine hydrochloride is dissolved in 10 ml of diethyl amine, 3 g of alumina of the second degree of activity is added and kept for 6 hours in a glass ampoule. The alumina is filtered off and the filtrate is evaporated in vacuo. To the residue is added 1 ml of concentrated hydrochloric acid and evaporated to dryness. The residue is crystallized from methanol: acetone (1: 1). 1.1 g (77%) of pyridoxydiethyl amine dichlorohydrate are obtained, melting point 115118 ° C; Rf 0.70. Calculated,%: 45.71; H 7.68; N 0.88; All 22.49; HgO. Found,%: -, C 45,52; H 7.55; N 8.93; All 21, 64. Example 4. Preparation of 2-methyl-3-hydroxy-oC-dimethylaminomethyl-cC-oxymethyl-pyridine (pyridoxydimethylamine). A. 1.03 g (0.005 mol) of pyridoxine dichlorohydropafB are dissolved in 20 ml of an aqueous solution of dimethylamine, 3 g of alumina of II degree of activity is added and suspended at 140 ° C in a steamed ampoule. The alumina oxide is filtered off, washed with methanol and the filtrate evaporated in vacuo. To the dry residue is added 1 ml of concentrated hydrochloric acid, evaporated to dryness and the residue is crystallized three times from methanol: acetone (1:10). 0.14 g (10%) of pyridoxyl dimethylamine hydrochloride is obtained, melting point 128-130 ° C; Rp 0.61. Calculated,%: C, 41.82; H 7.01; N 9.75; All 24.69; . CYO th 2 Found,%: C 41.76; H 7.04; N 9.8; se24,22. B. 1.03 g (0.005 mol) of pyridoxine hydrochloride is dissolved in 20 ml of a 20% methanol solution of dimethylamine, 3 g of aluminum oxide, degree II of activity, are added and incubated for 6 hours at a glass amp. The alumina is filtered off (taken up in methanol and the filtrate is evaporated in vacuo. 1 ml of concentrated hydrochloric acid is added to the dry residue. The residue is crystallized from methanol: acetone (1:10). 0.72 g (52%) is obtained. pyridoxydimethylamine dihydrochloride, melting point 128-130 ° C; Co 0.61. Example 5. Preparation of 2-methi-3-hydroxy-cC - (p-indolylethyl) -ct -oxyxypyridine (pyridoxyl tryptamine 1.03 g (0.005 mol) hydrochloride pyridoxine, 0.98 g (0.005 mol) chlorine tryptamine hydrate, 2.02 g (0.02 mol liter) triethylamine are dissolved in 15 ml of methanol and the solution is evaporated in vacuo, 20 ml of methanol is added to the dry residue and the resulting solution is acidified with a 10% solution of hydrogen chloride in methanol to pH 3. The solution is evaporated in vacuo and the residue is crystallized from methanol: acetone (1:10). Get 1.62 g of pyridoxyltryptamine dihydrochloride, yield 81%, melting point 238-239s. Upon acidification of the reaction solution to pH 6, pyridoxyltryptamine monochloride is formed with a melting point of 221-223 ° C (lit. data 222-223c); Rj 0.9. Vmsleno,%: C 56.26; H 6.02; N 10.93; CE 18.45; Found:% 55.84; H 5.97; N 10.64; every 18,34. Example 6. Getting pyridoxyethylamine. 1.1 g (0.005 mol) of pyridoxine methyl ester hydrochloride is dissolved in a mixture of 10 ml of diethylamine and 10 ml of methanol, 1 g of sodium hydroxide is added and kept at 150 ° C for 6 hours. The reaction mixture is evaporated in vacuo. 3 ml of concentrated hydrochloric acid is added to the residue, evaporated to dryness, and the residue is crystallized from methanol: acetone (1:10). Obtain 0.81 g (62%) of pyridoxyl diethylamine dihydrochloride. Example 7. Getting pyridoxymethylamine. 1.03 g (0.005 M) of pyridoxine hydrochloride is dissolved in 20 ml of a 20% methanol solution of dimethylamine, 3 g of calcium oxide is added and held at 140 ° C for 6 hours. The calcium oxide is filtered off, washed with methanol and the filtrate evaporated in vacuo. To the residue was added 2 ml of concentrated hydrochloric acid and evaporated to dryness. The residue is crystallized from methanol: acetone (1:10). 0.65 g (47%) of pyridoxydimethylamine dichlorohydrate is obtained. The invention The method for producing prioxylamine salts of the general formula I where R is hydrogen, lower alkyl, alkylindolyl; R is hydrogen or lower alkyl, 5 is interacting with pyridoxine or its 7 654613 methyl ester with an amine of the general formula, UNRR, where you are not k, when heated under pressure, which is different, in order to intensify the process and expand the range products, the process is carried out in the presence of 5 oxides or hydrates of metal oxides of the I – III groups of the periodic sietem of elements. eight 2. The method according to pl, which is also distinguished by the fact that the process is carried out at a temperature of 120-160 s. Information sources taken in attendees upon examination 1. D. Heyl et al. The vitamin B –group. Yii. J, Amer. Chem. Soc 1948, 70, p. 3G6§. 2, US Patent No. 2,522,407, Cl, 260-296, 1950.