The nitride of the transition metal complex

 

(57) Abstract:

Usage: as a radiopharmaceutical product having cardiotonic tropism. The inventive nitride complex of the transition metal f-crystals, where M is Tc99, Re,186, Re,188:L L2the remains of ligands f-crystals, where R11and R2have the same or different values and mean alkyl, C1-C6with a straight or branched chain which may be substituted by lower alkoxygroup, m, n 0,1; W, V O, S, Se, obtained by the interaction pertechnitat or ammonium perrhenate or alkali metal with the first ligand selected from lower aliphatic or aromatic phosphine, a second reagent selected from a nitride, ammonium or alkali metal nitride, and a second nitrogen ligand selected from the corresponding S-lower alkyldithiophosphate hydrazine in the form of a hydrochloride of thiosemicarbazide. 3 table.

The invention relates to radiopharmaceutical products. More specifically, the invention relates to a new nitride complex of the transition metal, which can be used as a radiopharmaceutical product having cardiotonic tropism.

From between the substitution connection99mNl4by specifying that these complexes can be used as radiopharmaceutical products.

However, this document does not provide results showing the binding of these complexes in the body, and therefore does not say about their tropism for certain organs and, in particular, of the heart.

Among radiopharmaceutical products with cardiotonic tropism known complexes of technetium, which contain as the ligand isonitrile, replaced by a simple ester, as described in the application for the European patent EP-A-0233368 and dioxime complexes of technetium, as described in the application for the European patent EP-A-0268801. However, these complexes are formed from ligands that are difficult to synthesise.

The purpose of the invention is the development of radiopharmaceutical products that could be used as a diagnostic or therapeutic products, in particular, as radiopharmaceutical products with cardiotonic tropism, for example, for scintigraphy of the myocardium.

This goal is achieved by using the nitride complex of the transition metal of the formula:

/M N/L1L2,

in which M stands for Theablaut themselves About, S or Se, n and m are equal to 0 or 1, and R1and R2that may be the same or different values, represent an alkyl radical with a straight or branched chain having 1-6 carbon atoms which may be substituted by lower alkoxygroup.

Radiopharmaceutical products, including transition metal complexes in accordance with the above formula possess cardiotonic tropism, which makes them very useful as products for the diagnosis or treatment of heart disease.

In the complexes according to the invention the use of a transition metal, in particular, depends on the application of the radiopharmaceutical product.

So, if you want to use this product is for diagnostic purposes, used radioactive transition metal with a relatively short half-lives, for example, technetium99m.

If this radiopharmaceutical product is to be used for therapeutic purposes, applies the transition metal, which creates an effective radiation for treatment and has a longer half-life, such as rhenium, for example, Re-186 or Re-188.

Nitride complexes of technetium, use the ako preference is usually given to this complex in accordance with an easier way, which is easier to implement in a hospital laboratory and which allows to obtain a high output.

This method includes the following successive stages:

1) interaction of the oxidized compound of the transition metal:

a) a first ligand selected from the group comprising substituted or unsubstituted, aromatic and lower aliphatic phosphines

b) a second reagent selected from nitrides of ammonium and alkali metals and nitrogenous ligands with group N-N, in which the nitrogen atoms are attached to hydrogen atoms and/or monovalent organic group through a carbon atom, or in which one of the nitrogen atoms attached to the carbon atom, or in which one of the nitrogen atoms attached to the carbon atom of the divalent organic groups across the double bond and the other nitrogen atom attached to the carbon atoms and/or monovalent organic group through a carbon atom, and

2) interaction of the intermediate obtained in the first stage, with the compound of the formula:

N C pH2O(X)

in which R1, R2, V, W, n, m have the above meaning, R6represents an alkali metal ion, N+or NH+4and R equals STE oxidized transition metal compound of the transition metal may be pertechnetate ammonium or alkali metal. In that case, if the transition metal is rhenium, you can use the ammonium perrhenate or alkali metal.

Thus, in the first stage of this method are nitride complex of technetium, which then interacts with the compound of the formula (X) with the aim of replacing the first and second ligands this connection.

To perform this reaction in aseptic conditions to enter the first ligand, namely nitride ammonium or alkali metal, or nitrogen ligand in the vessel, and then add the required amount of oxidized compounds of the transition metal, for example, pertechnetate technetium99mafter bringing pH to the appropriate value by adding acid or base.

This reaction can be performed at room temperature or at an elevated temperature from 50 to 100aboutC. Temperature and pH, in particular, depend on the second nitrogen of the ligand. This process usually occurs at pH 2-7.

In the first stage, you can use the first and second ligands in the form of alcohol, giprospirtvino or aqueous solutions and simply add these solutions to the oxidized compound of the transition metal.

The second Handicap is usually when the pH is above 7 and for example, in a buffer of sodium bicarbonate-carbonate.

In the second stage, you can also use alcohol or hidroportos solution of the compound (X).

The first ligand, which allows you to get nitride complex is an organic ligand with the phosphorus atom as an electron donor, which is chosen from substituted or unsubstituted, aliphatic and aromatic phosphines.

Acceptable phosphines can have the formula

PR8,

in which R7, R8and R9that may be the same or different values, represent a hydrogen atom, alkyl radical, aryl radical, CNS radical or an alkyl or aryl radical, substituted by a group selected from amino, amido-, cyano - or sulphonate radicals.

Examples of the phosphines of this type are triphenylphosphine, trisulfonic triphenylphosphine, diethylphenylphosphine, triethylphosphine, trimethylphosphine and Tris(2-cyanoethyl)-phosphine P(CH2-CH2CN)3.

In the first stage as the second reagent can be used nitride ammonium or alkali metal, e.g. sodium nitride or nitrogen ligand with group N-N such as hydrazine and its prosand preferably used dithiocarbamate acid or its derivative.

Thus, the second nitrogenous ligand can be dithiocarbamate acid or its derivative of the formula:

H2N-

in which R10represents a hydrogen atom, an alkyl radical or aryl radical, and R14represents a hydrogen atom, alkyl radical, aryl radical, CNS radical, alkyl radical, substituted with at least one group selected from hydroxyl, carboxyl, amino, amido and mercapto radicals, and amino radicals substituted by at least one alkyl radical.

They can also be a condensation product obtained by the interaction of dithiocarbamate acid with a ketone or an aliphatic aldehyde of the formula R15-CO-R16. In this case, it has the formula:

C= N - C

in which R10represents a hydrogen atom, an alkyl radical or aryl radical; R14represents a hydrogen atom, alkyl radical, aryl radical, alkoxyalkyl radical, alkyl radical, substituted with at least one group selected from hydroxyl, carboxyl, amino, amido and mercapto radicals, or aryl radical substituted by at least one group selected from halogen atoms, alkaline radical; and R15and R16that may be the same or different values, represent a hydrogen atom, an alkyl radical or alkyl radical, substituted with at least one group chosen from hydroxyl carboxyl, amino, amido and mercapto radicals.

Derived from dithiocarbamate acid used as the second ligand may also be a product of the condensation of dithiocarbamate acid with a ketone or aromatic aldehyde. In this case, this derivative has the formula:

N< / BR>
in which R10represents a hydrogen atom, an alkyl radical or aryl radical; R14represents a hydrogen atom, alkyl radical, aryl radical, CNS radical, alkyl radical, substituted with at least one group selected from hydroxyl, carboxyl, amino, amido and mercapto radicals, or aryl radical substituted by at least one group selected from halogen atoms, CNS, hydroxyl, amino and mercapto radicals, and aminoacyl, substituted by at least one alkyl radical; R17represents a hydrogen atom, alkyl radical, alkyl radical, substituted with at least one group is hydrogen, halogen atom, CNS radical, aminoacyl or aminoacyl, substituted by at least one alkyl group, R19represents a hydrogen atom, hydroxyl radical or mercapto radical, E represents a carbon atom or a nitrogen atom, and n is an integer from 1 to 4, or in which n equals 2, and two elements of R18located next to each other to form an aromatic cycle.

As the second ligand is also possible to use a product obtained by condensation of dithiocarbamate acid with a ketone, comprising a heterocycle with five links. In this case, the second ligand has the formula:

< / BR>
in which R10represents a hydrogen atom, an alkyl radical or aryl radical; R14represents a hydrogen atom, alkyl radical, aryl radical, CNS radical, alkyl radical, substituted with at least one group chosen from hydroxyl carboxyl, amino, amido and mercapto radicals, or aryl radical substituted by at least one group chosen from halogen atoms and CNS, hydroxyl, amino and mercapto radicals, and aminoacyl, substituted by at least one alkyl radical; R17not only is from hydroxyl, carboxyl, amino, amido and mercapto radicals, R18represents a hydrogen atom, halogen atom, CNS radical, aminoacyl or aminoacyl, substituted by at least one alkyl group, G is S or 0, and p is 1, 2 or 3.

Examples of the second nitrogenous ligands, which may be used in carrying out the invention include S-methyl-beta-N - (2-hydroxyphenyl)metalinguistically - ZAT, S-methyldithiocarbamate, S-methyl-N-methyl-dithiocarbamate, alpha-N-methyl-S-methyl-beta-N-pyridylmethylamine and alpha-N-methyl-S-methyl-beta-N - (2-hydroxyphenyl)methylenedioxybenzyl.

If the radiopharmaceutical product according to the invention is to be used for diagnostic purposes, it must be obtained at the time of application.

Radiopharmaceutical products in accordance with the invention, in particular, can be used for scintigraphy of the myocardium.

In this case, the nitride complex of technetium, obtained by carrying out the method according to the invention, is injected to the patient to be examined, after which produce a scintigraphy of the heart.

When injecting this product number of different ligands have with the, depends on the ligands and their toxicity.

Generally satisfactory results are achieved in the use of the overall quantities of ligands from 0.05 to 0.40 mg/kg of body weight.

The total number of the transition metal, for example, the dose of technetium, which typically ranges from 185 to 740 Mbq (5-20 km millicurie).

After the introduction of the nitride complex of the transition metal to produce a satisfactory examination for 0.5 to 3 h to achieve good contrast, clear images and good detection of pathological changes.

Other distinctive features and advantages of the present invention will become more clear from the following illustrative and not limiting of the invention examples.

P R I m e R 1. Obtaining bis(diethyldithiocarbamate)nitride complex 99mTC(V) (NDEDC).

a) Obtaining intermediate compounds

Into a flask similar to that used to obtain penicillin injected with 0.4 ml of a solution containing 210-2moles/l (2.5 mg/ml) S-methyldithiocarbamate in ethanol, and then 0.2 ml 2 10-2moles/l (5 mg/ml) solution of triphenylphosphine in ethanol and 0.1 ml of 1 n hydrochloric acid.

aboutC for 30 min or at 100aboutC for 15 minutes

b) receipt of the final complex.

The contents of the flask obtained in stage a), add 0.1 ml of 1 n solution Paon and 0.5 ml of a solution containing 0.18 mol/l digidratirovannogo diethyldithiocarbamate sodium (40 mg/ml) in 0.5 mol/l-1buffer of bicarbonate sodium carbonate at a pH of 9.0.

This reaction is carried out for 15 min at 100aboutC, for 30 min at 80aboutWith or for 60 min at room temperature.

Radiochemical purity of the obtained complex was investigated using thin-film chromatography using silica gel and toluene as solvent.

The resulting complex was characterized by the speed of chromatographic paper (Rf) equal to 0.3 to 0.4. Radiochemical purity was equal to or exceeded 93%

P R I m m e R 2. Obtaining bis(diethyldithiocarbamate)nitride complex99mTC(V) (NDEDC)

a) Obtaining an intermediate compound.

Into a flask similar to that used to obtain penicillin, administered 0.2 ml of a solution containing 7,7 10-2moles/l (5.0 mg/ml) of sodium nitride in water, then 0.2 ml 2 10-2moles">

Then add 0.5 to 1 ml pertechnitat sodium (TC-99m) and carry out the reaction at 80aboutC for 30 min or at 100aboutC for 15 minutes

b) Obtaining the end product.

The contents of the flask obtained in stage a), add the same way as in example 1, 0.1 ml of 1 n solution Paon and 0.5 ml of a solution containing of 0.18 mol/l (40 mg/ml) digidratirovannogo of sodium diethyldithiocarbamate in 0.5 mol/l buffer of bicarbonate sodium carbonate at pH 9. This reaction is performed in the same way as in example 1.

Explore the radiochemical purity of the obtained product by thin-film chromatography, with results identical to those obtained in example 1.

P R I m e R 3.

Obtaining bis(diethyldithiocarbamate)nitride complex99mTC(V) (NDEDC).

a) Obtaining an intermediate compound.

Into a flask similar to that used to obtain penicillin, administered 0.2 ml of a solution containing 7,7 10-2moles/l (5 mg/ml) of sodium nitride in water, then 0.4 ml of a solution containing 1 to 10-2moles/l (2 mg/ml) of Tris(2-cyanoethyl)-phosphine in water and 0.1 ml of 1 n hydrochloric acid.

After that, we use the ri 100aboutC for 15 min way to get free of alcohol.

b) receipt of the final complex.

For more complex NDEDC of the previously obtained intermediate of the connections are working procedure described in example 1, stage b).

P R I m e R 4. Obtaining bis(diethyldithiocarbamate)nitride complex99mTC(V) (NDEDC).

a) Obtaining an intermediate compound.

Into a flask similar to that used to obtain penicillin, administered 0.2 ml of a solution containing 7,7 10-2moles/l (5 mg/ml) of sodium nitride in water, then 0.4 ml of a solution containing 1 to 10-2moles/l of Tris(2-cyanoethyl)-phosphine.

After that, add 0,5-5 ml pertechnitat sodium /99mTC) and carry out the reaction at 80aboutC for 30 min or at 100aboutC for 15 minutes, This process is performed at a pH close to 7.

b) Obtaining the end product.

The contents of the flask obtained in stage a), add 0.5 ml of a solution containing of 0.18 mol/l (40 mg/g) digidratirovannogo of sodium diethyldithiocarbamate in 0.5 mol/l buffer of bicarbonate sodium carbonate at pH 9. The reaction is carried out as in example 1.

P R I m e R 5. In the procedure, described in example 1, except that the final stage of the diethyldithiocarbamate replace 0.5 ml of a solution containing of 0.18 mol/l digidratirovannogo of sodium dimethyldithiocarbamate (30 mg/ml) in the same buffer. Get complex of technetium NDMDC c radiochemical purity equivalent to the same indicator as defined in example 1.

P R I m e R 6. Obtaining bis(di-n-providetournament)nitride complex 99mTC(V) (NDPDC).

Perform the operating procedure described in example 1, except that the diethyldithiocarbamate replace 0.5 ml of a solution containing of 0.18 mol/l (40,7 mg/ml) sesquipedalianism di-n-propertyliability sodium in a mixture with 0.5 mol/l buffer of bicarbonate sodium carbonate to pH 9 and ethanol with a volume ratio of 7:3.

Get complex of technetium NDPDC with radiochemical purity equivalent to the metric defined in example 1.

P R I m e R s 7-9. In these examples investigated the properties of the complexes obtained in example 1, 5 and 6, by determining their biological distribution in male rats "Spraque Daw ley" mass 200 20

In this case, rats, shot by pentobarbital sodium were injected with the 1-2,5 MX. After 5, 30 or 60 min after injection of this product, rats were killed and removed their organs. After this was determined by radioactivity, specific to each organ.

The results are shown in table.1 and shows the percentage of injected radioactivity detected in the organs, followed by sampling and counting.

The values are given in table.1 represent the average of two extreme values.

Table. 1 shows that these complexes have a good cardiotonic tropism.

P R I m e R 10. Obtaining bis(N,N-dimethoxymethylsilane)nitride complex99mTC(V) (NMeDC).

a) Obtaining an intermediate compound.

Into a flask similar to that used to obtain penicillin, administered 0.5 ml of a solution containing 0.8 10-2mol/l (1 mg/ml) S-methyl-N-methyldithiocarbamate in the water, and then 0.5 ml of solution 2 10-2moles/l (10 mg/ml) risulteranno of triphenylphosphine in water and 0.1 ml of 1 n hydrochloric acid. After that, add 0,5-5 ml pertechnitat sodium (TC99mand carry out the reaction at 80aboutC for 30 min or at 100aboutC for 15 minutes

b) to Receive Paon and 0.5 ml of solution containing 0.1 mol/l of dimethoxyphenylethylamine sodium (23 mg/ml) in 0.5 mol/l buffer of bicarbonate sodium carbonate at a pH of 9.5. This reaction is carried out for 30 min at room temperature.

Get nitride complex NMEDC or complex formulas (TC N/L1L2in which L1and L2represented the compound of the formula (Y1).

P R I m e R 11. Obtaining bis(N-ethyl-N-(2-methoxyethyl)dithiocarbamate) nitride complex99mTC(V) (NEMEC)

Perform the operating procedure described in example 10, to obtain the intermediate compounds of S-methyl-N-methyldithiocarbamate and risulteranno of triphenylphosphine. After that he received the final product in accordance with the working procedure described in example 10, but using 0.5 ml of 0.1 mol/l N-ethyl-N-(2-methoxyethyl)-dithiocarbamate sodium (20 mg/ml) instead of dimethoxyphenylethylamine sodium in example 10.

Receive bis((N-ethyl-N-(2-methoxyethyl)-dithiocarbamate)nitride complex99mTC(V), i.e. the product of the formula:

/TC N/L1L2in which L1and L2are compounds of the formula (VII).

P R I m e R 12. Obtaining bis(N-ethyl-N-(3-methoxypropyl) -dithiocarbamate) nitride completo complex of intermediate compounds, obtained in stage a) of example 10, the reagent at the stage b) using 0.5 ml of 0.1 mol/l N-ethyl-N-(3-methoxypropyl)-dithiocarbamate sodium (22 mg/ml).

Get nitride complex Testers or complex of the formula (N)L1L2in which L1and L2consist of a compound of formula (VIII).

P R I m e p 13. Obtaining bis(N-ethyl-N-(2-ethoxyethyl)-dithiocarbamate) nitride complex99mTC(V) (NEEDC).

Did the working procedure described in example 10, to obtain the intermediate and the final product except for the fact that as a reactant to obtain the final product using 0.5 ml of 0.1 mol/l N-ethyl-N-(2-ethoxyethyl)-dithiocarbamate sodium (22 mg/ml).

Get nitride complex NEEDC or complex formulas (TC N/L1L2in which L1and L2consist of a compound of the formula (1X).

P R I m e R 14. Obtaining bis(N-methoxy-N-methyldithiocarbamate) nitride complex99mTC(NMEMC).

a) Obtaining an intermediate compound.

Perform the operating procedure described in example 10, to obtain the intermediate compound using the same reagents and the creation and the military to stage a), add 0.1 ml of 1 n solution Paon and 0.5 ml of a solution containing of 0.13 mol/l N-methoxy-N-methyldithiocarbamate sodium (20 mg/ml) in 0.5 mol/l buffer of bicarbonate sodium carbonate at a pH of 9.5. This reaction is performed for 30 min at room temperature.

Get complex NME having the formula (N/L1L2in which L1and L2are:

N-C

P R I m e R 15. Obtaining bis(N-methoxy-N-metilditiocarbaminic/nitride complex99mTC/V/ /NMEEC/.

Perform the operating procedure described in example 14, to obtain this complex of technetium from the same intermediate compounds using to obtain the final product with 0.5 ml of a solution of 0.12 mol/l N-methoxy-N-ethyldiethanolamine sodium (20 mg/ml). Get complex NMEEC, in particular, the complex of formula (N/L1L2in which L1and L2have the formula:

N-C

P R I m e R 16. Obtaining bis/N-ethoxy-N-methyldithiocarbamate/nitride complex99mTC/V/ /NE/.

In this example, perform the operating procedure described in example 14, except that as a reactant to obtain the final product using 0.5 ml of a solution of 0.12 mol/l N-ethoxy-N-methyldithiocarbamate sodium (20 mg/is ormulu:

N-C

P R I m e R 17. Obtaining bis(N-ethoxy-N-metilditiocarbaminic) nitride complex99mTC(V)(NE).

Perform the operating procedure described in example 14, to obtain this complex of technetium using as a reagent in the second stage, 0.5 ml of a solution containing of 0.11 mol/l N-ethoxy-N-ethyldiethanolamine (20 mg/ml).

Get the complex of formula (TS N/L1L2in which L1and L2have the formula:

N-C

P R I m e R 18. Biological properties of the complexes obtained in accordance with examples 10-13 and 17, were investigated by determining the value retention of radioactivity by the myocardium in dogs weighing 10 to 15 kg

In this case, dogs, shot by pentobarbital sodium and undergoing mechanical ventilation, were injected with a dose equal to 2 mcmole/kg of body weight myotropic complex of technetium, which corresponds to a dose of 2-5 mCi.

The amount of retention of radioactivity in the myocardium and surrounding organs (easy and liver) were determined on the basis of the dynamic susceptibility between injection and the end of the study using the gamma camera when setting interest u.

The magnitude of the contrast of the heart and liver as well as heart and lung was measured by establishing a simple relationship between the number of beats per unit surface area (or point) in the organs. The magnitude of the ratio between the heart and the liver, as well as between the heart and lungs are given in table.2.

The correlation between the noises of the target organ and the background noises are very favorable.

P R I m e R s 19-21. In these examples, we investigate the properties of the complexes obtained in examples 15-18, by determining their biological distribution in male rats "Spraque Dawley weighing 200 20

In this case, rats, shot by pentobarbital sodium were injected with a dose of the complex corresponding to 15 mcmole/kg of body weight mechanism of ligand, which corresponds to a dose of 1-2,5 mkCi.

After 5, 30 or 60 min after injection of this product, rats were killed and removed the bodies. Determined the radioactivity characteristic of each of the bodies.

The results are shown in table.3 and presented as percent injected radioactivity detected in the body after sampling and counting. The values in table 3 represent the average SNIM tropism.

NITRIDE COMPLEX of the TRANSITION METAL General formula

/M N/ L1L2,

where M Tc99That Re186That Re188;

L1and L2the remains of ligands of General formula

< / BR>
where R1and R2the same or different, C1C6alkyl straight or branched chain which may be substituted by lower alkoxygroup;

m and n are 0, 1;

W and V 0, S, Se,

obtained by the interaction pertechnitat or ammonium perrhenate or alkali metal with the first ligand selected from lower aliphatic or aromatic phosphine, a second reagent selected from the group nitride ammonium or alkali metal nitride, and a second nitrogen ligand selected from the corresponding S-lower arkitekturmuseet, hydrazine in the form of hydrochloride, thiosemicarbazide, and then adding to the resulting intermediate compound of dithiocarbamate General formula

< / BR>
where R1, R2, V, W, n and m have the above meanings;

R3ion of an alkali metal, H+, NH+4< / BR>
p is 0 or 1 5.

 

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16 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention is related to improved method for preparation of manganese oxalate (II) by means of direct interaction of metal with acid in bead mill in presence of liquid phase, in which manganese and oxalic acid are loaded into bead mill in stoichiometric ratio in amount of 0.75-2.4 mole/kg of load at mass ratio of load and glass beads of 1:1.2, liquid phase dissolvent used is water or organic substance, or mixture of organic substances; loading is carried out in the following sequence: liquid phase dissolvent, acid, then metal; process is started at room temperature and is carried out under conditions of forced cooling in the temperature range of 18-39°C with control over procedure by sampling method to practically complete spend of loaded reagents for product making, afterwards mixing and cooling are terminated, suspension of reaction mixture is separated from glass beads and filtered, salt deposit is sent for product cleaning from traces of non-reacted metal, and filtrate is returned into repeated process.

EFFECT: method makes it possible to produce target product in absence of manganese dioxide and stimulating additive at temperatures close to room temperature.

2 cl, 13 ex, 2 tbl

FIELD: medicine.

SUBSTANCE: invention refers to chelating agents and their technetium complexes to be used as radiopharmaceuticals and characterised by formula I where X is -NR-, -CO2-, -CO-, -NR(C=S)-, -NR(C=O)-, -CONR- or Q; Y represents amino acid, -CH2-, -CH2OCH2-, -OCH2CH2O- or X; Z is an aggregation from peptides, their analogues, substrata, antagonists or enzyme inhibitors, receptor-bonding compounds, oligonucleotides, oligo-DNA- or oligo-RNA-fragments; n is a number 1 to 8; m is a number 0 to 30; R represents H, C1-4alkyl, C2-4alkoxyalkyl, C1-4hydroxyalkyl or C1-4fluoroalkyl; Q represents remains of succinimide , A is a pharmaceutically acceptable anion.

EFFECT: production of new chelating agents applicable for making the technetium complexes.

22 cl, 12 ex, 3 dwg, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to an improved method of producing manganese (II) fumarate from manganese metal and its oxide (III) through direct reaction of the metal and its oxide Mn2O3 with an acid in the presence of a liquid phase and a stimulating iodine additive in a vertical type bead mill with glass beads as grinding agent. The metal and its oxide are loaded in molar ratio (2±0.1):1 in total amount of 7.87 to 10.93% of the mass of the load. Acid is added with 15 to 25% excess of the calculated value, equal to the number of moles of metal and twice the number of moles of metal oxide in the load. The base of the liquid phase is isoamyl alcohol, in which the iodine stimulating additive is dissolved in amount of 0.02 to 0.05 mol/kg. Glass beads are loaded first, in mass ratio to the reaction mixture of 1.35:1, and then later the liquid phase solvent, acid and stimulating additive, and after brief stirring, metal oxide and metal, stirring all the while. Taking this moment as the beginning of the process, forced cooling is introduced right away. Operating temperature is stabilised in the range 33 to 45°C and in this mode, the process is carried out until virtually quantitative conversion of metal and its oxide to the target salt, after which stirring and forced cooling are stopped. The reaction mixture is separated from the glass beads, cooled to temperature 5 to 6°C and kept at that temperature for 1 to 2 hours. The solid phase of the target salt is filtered off and washed with isoamyl on a filter cooled to approximately the same temperature, after which it is taken for purification by recrystallisation. The filtrate and the cleaning solvent, containing excess acid, the bulk of the stimulating additive and a certain amount of dissolved target salt, are returned for loading in the repeated process. The process is carried out in light temperature conditions. The target substance can be easily separated.

EFFECT: design of a low-waste method, which allows for obtaining target product from available manganese oxide with an easy to implement process.

9 ex

FIELD: chemistry.

SUBSTANCE: method of synthesis of manganese (II) fumarate through direct reaction of metal with acid is presented. The process is carried out in a vertical type bead mill with mass ratio of beads to the reaction mixture equal to 1:1, and the liquid phase is a solution of fumaric acid in an organic solvent with content of acid of 0.70-1.80 mol/kg. Manganese is taken in stoichiometric amount with acid or in deficiency of up to 5%. The process is started by loading the liquid phase solvent and acid and preparation of the acid solution in a bead mill, after which metal is loaded and the process is carried out at temperature ranging from 25 to 35°C while preventing spontaneous increase of temperature through forced cooling and controlling through sample taking and determination of manganese salt in the samples and residual amount of acid until attaining values close to calculated values during quantitative conversion of the reagent in deficiency. After that stirring and cooling are stopped. The suspension of the reaction mixture is separated from the glass beads, cooled to temperature between 5.2 and 6.2°C and filtered. The filtering residue is washed with the liquid phase solvent, cooled to approximately the same temperature, and taken for purification by recrystallisation. The filtrate and the washing solvent are returned to the repeated process.

EFFECT: method is easy to implement, the end product can be easily separated and there are no auxiliary materials which contaminate the obtained product.

2 cl, 11 ex

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