SU739076A1 - Method of preparing beta-aminoethylidenediphosphonic acids - Google Patents

Description

(54) METHOD FOR OBTAINING p-AMINOETHILIDENDIFOS 1ZONE

NO SLOT

This invention relates to the chemistry of organophosphorus compounds with a C — P bond, and specifically to a method for producing new p) aminoethylidene diphosphonic acids of the general formula p, .uC, Npo, where R and R are hydrogen, alkyl oxyalkyl, aryl Cj, or R and R - together represent a chain having the structure - (CH) or 7- (CH2) 2-O- (CH2) 2.-. These compounds can be used as complex-forming cells for multiply charged ions, medical preparations or flotation agents to enrich non-ferrous metal ores. A known method for the production of lipophosphonic acid CL-a by the interaction of carboxylic acid nitriles with phosphorus trihalides, followed by hydrolysis of the obtained product 1. There is also known a method for the preparation of ji-aminoalkylphosphonates attached to amines to vinylphosphonate 2, However, p) -amine oe tylidene and background acids are not described in the literature and are new. The aim of the invention is to develop a process for the preparation of L-aminoethylidene diphosphonic acids. The aim is to ensure that in the process for the preparation of p -aminoethylidene diphosphonic acids, which consists in reacting vinylidene diphosphonic acid or its salt with primary N1L or secondary amine or its salt with water. aqueous organic or organic medium at 50-150 ° C; lower carboxylic acids, alcohols or glycols are used as the organic medium. To shorten the reaction time, the process is carried out at a temperature higher than the boiling point of the reaction mixture at atmospheric pressure, the process is carried out at elevated pressure in a closed system. The process is carried out at 100-120, since at higher temperatures the reaction rate is small high pressure develops, making reactions difficult. The acidity of the medium varies over a wide range (from pH 1 to pFI 11) depending on the nature of the amine. Thus, aliphatic primary amines react best of all in weakly acidic and neutral environments, secondary ones in neutral and weakly alkaline, and aromatic in acidic environments. Cyclic amines (morpholine) react quickly enough in a wide range of acidity (from pH 2 to pH 9). The reaction time is determined in different cases from 0.5 hours to several tens of hours. The structure of the compounds obtained is proved by elemental analysis, pH by metric titration, their ability to complex formation and NMR spectra. Titration curves in the coordinates of NotOH PH are common d of polybasic acids, which have e and ionization constants. Thus, the titration curves of all p-aminoethylidene diphosphonic acids with aliphatic substituents have two fairly sharp inflection points at pH 7.3, corresponding to cleavage of one and two protons. The equivalent volumes of alkali found at the inflection points are 1: 2, and the acid equivalents at the first point correspond to the molecular weight, and at the second point, half the molecular weight. Alkaline equivalents of a tape are determined by the formula KB M N NaOH NaOH where m is the weight of the titrated acid, mg; mzon equivalent slit volume 1ll; waoM normality of alkali titrating solution. The titration curves of fb-aminoethyls of dendiphosphonic acids with aromatic substituents also have two inflection points at pHCii3.5 and a ratio of equivalent volumes of alkali 1: 3, i.e. the first point corresponds to the removal of one proton and the second to three protons and the equivalents found from these two inflection points are equal, respectively, to the molecular weight and 1/3 of the molecular weight. This is consistent with the lower basicity of aromatic amines compared to aliphatic. . The NMR spectra of the obtained compounds (on the cores) contain, as follows from the doublet triplet theory, which is the result of splitting the P signal into one ° C and two (L-protons. Suppressing spin-spin interaction with protons gives a singlet showing the equivalence of phosphorus atoms, and chemical motions of the signals lie in the everyday region of the POjH group. The proposed method of obtaining L-aminoethylidene diphosphonic acids is new, since it is possible to react the aminophosphonic acids and salts with amines. Example 1. 2- (N-morpholino) ethylidene-1,1-diphosphonic acid (1) 3.0 g of anhydrous salt trisodium salt of vinylidene diphosphonic acid are dissolved in 12 ml of glacial acetic acid; (7.9 mol) and 3 ml (3.35 g, 38.5 mol) of morpholine are added. The reaction mixture is heated for 2 hours in a boiling water bath, then diluted with water and passed through a column with KU-2 cationate in H-form. Eluted with water until neutral, the eluate is evaporated in vacuo to a syrupy state and crystallized by addition of methanol. After the crystallization is complete, the precipitate is filtered off and washed with methanol. 2.2 g (1) are obtained, yield about 100%. For final purification, the product is precipitated with methanol from hot water. Results of pH-metric titration (1). Found: Equivalent to 278; Equivalent to 138.0. Calculated: Equivalent to -275.1; Equivalent2 137.6. The results of elemental analysis. Found,%: C 25.89; 2b, 01; C 5.45; 5.55. . ,,,. Calculated,%: C 26.19; And 5.50 NMR () -spectrum 1: 3 -14.3 ppm (relative to 85%), J rts (triplet) 13 Hz, JPH (doublet) 17.5 Hz. Example 2. 2- (S, L-diethyl) aminoethylidene-1,1-diphosphonic acid (P). 4.0 g of the hydrate of trisodium salt of vinylidene diphosphonic acid containing 2.6 g (10.2 mol) of the anhydrous salt are dissolved in 10 ml of water, 8 ml (5.65 g of 77.5 mol) are added | diethylamine and. are heated in a sealed ampoule for h with periodic shaking. Then it is passed through a cation exchanger, the etoate is evaporated to a syrup and ethanol is added. After a long time it is crystallized. (P). The crystals are filtered off and run with ethanol. Obtain 2.05 g of almost pure product, yield 74%. For final purification, dissolve the product in a minimum amount of water and precipitate with ethanol. The results of pH-metric titration (P). Found: Equivalent to 264.3; Equivalent: 132.5. Calculated; Equivalent, 261.2 Equivalent / j, 130.6. Results of elemental analysis (Found,%: C 27.68; 27.39; H 6.90 6.90; R 22.03; 22.23. Cf, H,; Calculated,%: C 27.59; H 6.56; P 23.72. Example 3. 2- (N-Piperidino) ethylidene-1,1-diphosphonic acid (III) 3.0 g of disodium salt of vinylidene diphosphonic acid, containing 2.4 g ( 10.3 mol) of anhydrous salt, 15 ml of glacial acetic acid and 3.4 g of piperidine were heated to a boil and refluxed for 40 hours and then passed through a cation resin, ethanol was evaporated to a syrup, and after 2 days one hundred times crystallized (III). The crystals are filtered and washed with 2.37 g of an almost pure product is obtained, yield 84%, which is treated with activated carbon for final purification of the solution in hot water and precipitated with ethanol. Results of pH-metric titration (III)., Found: Equivalent 278 , 0; 138.0 Equivalent, Calculated: Equivalent to 273.3; Equivalent. 136.6. Results of elemental analysis (III) Found,%: C 31.26; 31.07; H 6.73 6.63, C t H NOePz- Calculated: С 30.98; H 6.27i. Example 4. 2- (Nl-bis-2-oxyethyl) aminoethylidene-1, 1-DIFOS-. background acid (IV). In a mixture of 2 ml of water and 1.35 ml (15., Vmolj of concentrated HCE, 1.0 g of the disodium salt of vinylidene diphosphonic acid disodium salt containing 0.77 g (3.3 mol) of anhydrous salt is dissolved and neutralized with diethanolamine (about 1 in total, 5 g, 14 mol) to pH 4 on universal indicator paper. The reaction mixture is heated in a sealed ampoule for 5 hours at 120 °, then passed through cations, and the eluate is evaporated to dryness and the residue is heated in a vacuum water jet for 1 hour in a boiling water bath. to remove HCE. The residue is dissolved in a minimum amount of water and diluted ethanol., A syrup-like product precipitates which crystallizes on standing, the crystals are filtered and washed with ethanol to obtain 0.50 g (IV), yield 52%, which is re-precipitated with ethanol from the minimum amount of water for purification and dried in vacuum at 100. Results pH Metric titration (IV) Found: Equivalent to 294.0 Equivalent to 147.0 Calculated: Equivalent, 293.3 Equivalent to 146.6 Elemental analysis results (IV) Found,%: C 24.65; 24.55; H 6.07; 6.22 ,, .NOgP. ,, Calculated,%: C 24, 5.85 Example 5. 2- (N-2-hydroxyethyl) aminoethylidene-1,1-diphosphonic acid (V). 0.5 g of the disodium salt hydrate of vinylidene diphosphonic acid, containing 0.38 g (1.65 mol) of anhydrous substance, dissolved in 0.6 ml of water, 0.65 ml (0.67 g, 11 mol) of monoethanolamine and acid is added A mixture of acetic acid (about 0.7 ml in total. 0-, 73 g 12 mol) to pH 4 (according to universal indicator paper). The mixture is heated in a sealed ampoule for 14 hours at .120 °, then passed through cationite, eluate evaporated to dryness, the residue is dissolved in 5 ml of water and 6 ml of ethanol are added. After standing, (V) is crystallized. An excess of ethanol is added to more fully crystallize The precipitated crystals are filtered off and washed with ethanol to give 0.35 g (V), 35% yield, which is reprecipitated from water for final purification. The results of pH – metric titration (V) 250.0 Found: Equivalent, Equivalent 126, 2. 249.2 Calculated: Equivalent to 124.6. Equivalent Tg Results of elemental analysis Found,%: C 18.61; 18.78; H 5.39; 5.55 Cx H. ,, NO-; P2. Calculated,%: C 19.29; H 5.26. Example 6. 2- (N-Ethyl) aminoethylidene-1, 1-diphosphonic acid (VI) In 8 ml of water, 2.0 g of trisodium salt of vinylidene diphosphonic acid containing 1.4 g (5.5 mol) of anhydrous substance is dissolved and, 6 g of ethylamine hydrochloride and heated in a sealed ampoule for 4 hours while they are then passed through a cationite, the lute is evaporated to dryness and the chlorine is removed. hydrogen, heating the residue in a boiling water bath for about 1 hour. Then, 0 ml of 90% aqueous methanol is added to the residue. The mixture is wiped with a stick until crystallization begins. When the syrupy product is crystallized completely, another 20 ml of methanol is added and left to stand for a few hours, then the crystals are filtered off and washed with methAnol. 0.91 g, VI is obtained, yield 71%. The product is finally cleaned, re-precipitating it from a hot water ethanol.

Results pH - Metric Titration (VI).

Found: Equivalent to 241;

Equivalent to 2 118.5,

 233.2g

Calculated: Equivalent

H Equivalent to 116.6

Elemental Analysis Results (V

Found,%: C 20.80; 21.02; H 5.97; 5.98.

 .

Calculated,%: C 20.61; H 5.62

Example 7, 2- (L-phenyl) aminoethylidene-1; 1-diphesphonic acid (VII),

A mixture of 2.0 g (8.6 mol) of anhydrous vinylidene diphosphonic acid disodium salt, 2.0 ml of aniline (2.04 g, 2.2 mol) and 5.0 ml of water was acidified with concentrated hydrochloric acid to pH 1 ( universal indicator paper), only 2.5 ml of conc., HC The mixture is heated to reflux for 7 hours. The mixture is then diluted with 15 ml of water, 2.0 g of sodium hydroxide are added and the mixture is carefully extracted with ether to remove unreacted aniline. the layer after extraction is passed through cationite, the eluate is evaporated in vacuo and the residue is heated for 2 hours in vacuum e-BOS at 50 to remove hydrogen chloride and then dissolved in 5 ml of water. After a few minutes, the basic mass (VII) crystallizes. The crystalline porridge is diluted with ethanol and left to stand for several hours, then the crystals are filtered off and proglutted with ethanol. 1.0 g (VII) is obtained, the yield is 80%; / o for final purification is recrystallized from 3% hydrochloric acid.

Results pH - metric titration (VII).

Found: Equivalent. 288; The equivalent of 95.6.

Calculated: Equivalent to 281.1. Equivalent to 93.7.

Results of elemental analysis (VII).

Found,%: C 33.60; 33.32; H 5.32 5.15

Sbts. (

Calculated,%: C 34.18; H 4.66

The NMR spectrum (VII) on the core P is in accordance with its structure.

Example 8, The reaction mixture prepared according to example 1, is heated at 50 °, then treated in the same way as described in example 1 poluchhot 1.3 g (1), Yield 60%.

Example 9: The reaction mixture prepared as in example 1 was sealed in a glass flask and heated for 15 minutes in an oil bath heated to 150 °. After cooling, the ampoule was opened and the reaction mixture was treated as in example 1. 1.7 g acid (I), Yield 78%

Example 10. 2- (N-ct-naphthyl) aminoethylidene-1,1-diphosphonic acid (VIII). .

In a flask equipped with a stirrer and reflux condenser were placed 7 MJ: water, 7 ml of ethylene glycol, 2.0 g (8.6 mol) of anhydrous vinylidene diphosphonic acid disodium salt, and 4.0 g (22 mol) of c-naphtylamine hydrochloride. The reaction mixture is heated to a gentle boil with vigorous stirring, avoiding strong foaming for 4.5 hours. After cooling, the reaction mixture is diluted with 20 ml of water and alkalinized with 1.6 g of sodium hydroxide. The excess of c-naphthylamine is removed by extraction with ether, the aqueous layer is boiled with activated carbon, filtered and quickly poured in a hot state in 35 ml of concentrated hydrochloric acid. After cooling to room temperature, it crystallizes out (VIII in the form of small, slightly pinkish crystals. It is filtered off, washed with water, methanol and acetone. After drying in vacuum, 2.3 g (VIII) is obtained. Yield 82%.

Results pH - metric titration (VIII).

 110.3.

Equivalent,

Found:

Included: Equivalent to 110.33.

The results of elemental analysis. (Viii).

Found,%: C 43.49; 43.75; H 5.24; 5.16

calculated,%: C 43.51; P. 4.57. Example 11,2-N-Nonyl aminoslidene-1, 1-diphosphonic acid (IX). In a flask equipped with a Reverse chiller, 5.0 g of the disodium salt of the vinylidene diphosphonose acid disodium salt containing 4.1 g (17.7 mol) of anhydrous salt, 9 ml of glacial acetic acid and 6.5 g of nonylamine are placed. The reaction mixture is heated on a glycerin bath to a boil for 10 hours, then dissolved by heating in 30% aqueous acidic acid, placed on a column with cation exchange resin KU-2 in the form, eluted first with a hot 30% acetic acidic drink and then hot water until neutral. The eluate is evaporated and (IX) crystallizes out. The crystalline porridge is diluted with ethanol, filtered (IX), washed with ethanol and acetone. 5.1 g (IX) are obtained. Output 86, For additional purification of recrystallization from 9% aqueous hydrochloric acid

Results pH - metric titration (IX).

Claims (3)

Claim 1. A method of producing β-aminoethylidene diphosphonic acids of the general formula where R and R ¹ are hydrogen, alkyl Cg — C ^, hydroxyalkyl, aryl _Cb — C ^ _o or R and R ^f together represent a chain having the structure - (CH ₂ ) ₅ ~ or - (CH _Z ) ₂ O- (CH ₂ ) ₂ consisting in the fact that vinylidene diphosphonic acid or its salt is reacted with a primary or secondary amine or its salt in an aqueous, aqueous organo or organic medium at 50-150 C. 2. The method of pop. 1, which consists in the fact that as the organic medium using lower carboxylic acids, alcohols or glycols. 3. The method according to PP, 1 and 2, which consists in the fact that the process is conducted in a closed volume.