{[1-(ammonio)-3,5,7-triazaadamantyl]-methylcarbonyloxypoly-(alkyleneoxy)}propane chloride possessing bactericidal and fungicide activity and method for their preparing

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention describes {[1-(ammonio)-3,5,7-triazaadamantyl]methylcarbonyloxypoly-(alkyleneoxy)}-propane chlorides of the general formula: wherein at X+ = Y+ means ; R1 means aliphatic unsaturated hydrocarbon C17-radical; a + c + e = 49; b + d + f = 9; at X+ = Y+ means ; R1 means aliphatic unsaturated hydrocarbon C17-radical; a + c + e = 55; b + d + f = 10; at X+ = Y+ means ; a + c + e = 49; b + d + f = 9; at X+ = Y+ means ; a + c + e = 55; b + d + f = 10; at X+ = Y+ means ; R1 means aliphatic unsaturated hydrocarbon C17-radical; a + c + e = 49; b + d + f = 0; at X+ = Y+ means ; R1 means aliphatic unsaturated hydrocarbon C17-radical; a + c + e = 55; b + d + f = 0; at X+ = Y+ means -RNH2+-; R means aliphatic hydrocarbon (C10-C16)-radical; a + c + e = 49; b + d + f = 9; at X+ = Y+ means -RNH2+-; R means aliphatic hydrocarbon (C10-C16)-radical; a + c + e = 55; b + d + f = 10. Also, invention describes a method for synthesis of abovementioned compounds that possess antibactericidal and fungicide activity and can be used for control of bacterial and fungal damages in medicine, veterinary science and agriculture.

EFFECT: improved method of synthesis, valuable properties of compounds.

7 cl, 2 tbl, 8 ex

 

The invention relates to organic chemistry, namely the synthesis of previously unknown {[1-(ammonia)-3,5,7-triathalete]methylcarbazole(alkylene)}propane chloride with a bactericidal and fungicidal activity, which can be used to combat bacterial and fungal lesions in medicine, veterinary medicine and agriculture.

A special feature of this series of compounds is the presence in their structure of {[1-(ammonia)-3,5,7-trazadoneelavil]} fragment of the formula:

as well as ester and polyoxyalkylene groups.

Known Quaternary ammonium compounds containing ester groups, and represents a N,N-dimethyl-N-alkyl-N-[ethoxycarbonylmethyl]ammonium chloride, of the formula:

[Shelton R.S., M.J. Van Campen et al. Quaternary Ammonium Salts as Germicides. II Acetoxy at Carbethoxy Derivates of Aliphatic Quaternary Ammonium Salts // j. Chem. Soc., 1946, v.68, No. 5, p.755-757].

Also known Quaternary ammonium compound comprising the structure of one or more polyoxyethylene fragments. Such, for example, are Quaternary ammonium compounds with three polyoxyethylene fragments having the General formula:

[M. Pletnev Cosmetics and hygienic detergents. - M.: Chemistry, 1990, 272 S.; Kroke . // Cosmet. Perfum. 1975. V.90. No. 11. R.31-34.]

The most similar structure to the proposed compounds containing both ester groups and polyoxyethylene fragments are N-[isononylphenol(ethylenoxy)carbonylmethyl]ammonium chlorides, of General formula:

where:

R1=R2=CH3; alkyl fraction C7-C9;

R3=alkyl fraction C7-C9, alkyl fraction10-C16, alkyl fraction C15-C18;

n=3, 10.

[Pat. 1531416 of the Russian Federation. IPC C 07 C 87/30. Publ. 1995.04.10. Fakhretdinov PS, Novels, GV, etc. a Method of producing corrosion inhibitors for carbon steel in hydrogen sulfide-containing saline water environments, showing fungistatic, bacteriostatic and disinfectant action].

The technical result of the present invention is a new synthesis of {[1-(ammonia)-3,5,7-triathalete]methylcarbazole(alkylene)}propane chloride with a bactericidal and fungicidal activity, and the way they are received.

Offers {[1-(ammonia)-3,5,7-triathalete]methylcarbamyl-actipole(alkylene)}propane chloride containing both ester, polyoxyalkylene group and 1-(ammonia)-3,5,7-trazadoneelavil fragment of General formula:

where:

R' = aliphatic unsaturated hydrocarbon radical containing 17 carbon atoms;

a+C+e = total oxypropylation, equal to 49;

b+d+f = total degree of oksietilirovannye equal to 9;

R' = aliphatic unsaturated hydrocarbon radical containing 17 carbon atoms;

a+C+e = total oxypropylation equal to 55;

b+d+f = total degree of oksietilirovannye equal to 10;

a+C+e = total oxypropylation, equal to 49;

b+d+f = total degree of oksietilirovannye equal to 9;

a+C+e = total oxypropylation equal to 55;

b+d+f = total degree of oksietilirovannye equal to 10;

R' = aliphatic unsaturated hydrocarbon radical containing 17 carbon atoms;

a+C+e = total oxypropylation, equal to 49;

b+d+f = total degree of oksietilirovannye 0;

R' = aliphatic unsaturated hydrocarbon radical containing 17 carbon atoms;

a+C+e = total oxypropylation equal to 55;

b+d+f = total degree of oksietilirovannye 0;

when: X+=Y+=RNH2+-;

R = aliphatic hydrocarbon radical containing 10 to 16 carbon atoms;

a+C+e = is BSA degree oxypropylation, is 49;

b+d+f = total degree of oksietilirovannye equal to 9;

when: X+=Y+=RNH2+-;

R = aliphatic hydrocarbon radical containing 10 to 16 carbon atoms;

a+C+e = total oxypropylation equal to 55;

b+d+f = total degree of oksietilirovannye equal to 10.

Declare {[1-(ammonia)-3,5,7-triathalete]methylcarbamyl-actipole(alkylene)}propane chlorides are new, not previously known compounds having bactericidal and fungicidal activity.

A method of obtaining Quaternary ammonium compounds containing ester and polyoxyethylene groups, for example N-[isononylphenol(ethylenoxy)carbonylmethyl]ammonium chloride, the General formula:

where:

R1=R2=CH3, alkyl fraction7-C9;

R3= alkyl fraction C7-C9, alkyl fraction10-C16, alkyl fraction C15-C18;

n=3, 10;

by interacting monochloracetic acid with an alcohol component, which are economicpolitical, of General formula:

where: n=3, 10;

and subsequent treatment of the amines, the General formula:

where:

R1=R2=CH3, alkyl fraction C7-C9

R3= alkyl fraction C7-C9, alkyl fraction10-C16, alkyl fraction C15-C18;

[Patent 1531416 of the Russian Federation. IPC C 07 C 87/30. Publ. 1995.04.10.] (Prototype)

To declare us {[1-(ammonia)-3,5,7-triathalete]methylcarbazole(alkylene)}propane chloride serves the retrieval method by reacting 1,2,3-Tris[hydroxypoly(alkylene)]propanol, of the formula:

where:

a+C+e = total oxypropylation equal 49-55;

b+d+f = total degree of oksietilirovannye equal 9-10,

with monochloracetic acid in the presence of an acid catalyst, in the medium boiling solvent, with azeotropic removal of water formed and the subsequent processing when heated in the polar solvent of the obtained reaction product of the amino compounds selected from the set:

primary amines of the formula:

RNH2,

where: R is an aliphatic hydrocarbon radical containing 10 to 16 carbon atoms;

pyridines of the formula:

the alkylimidazolines, of the formula:

where:

R' = aliphatic unsaturated hydrocarbon radical containing 17 carbon atoms;

and/or 1,3,5,7-tetraazacyclooctane, of the formula:

in molar ratios of reagents - hydro is a strong derivative of propane: monochloracetic acid : aminosidine : tetrathionate = 1,0:3,0-3,2:0-2,1:1,0-2,1 respectively.

For the proposed method as the acid catalyst used N+-form cation-exchange resin KU-2-8, which is a solid, partially swellable macromolecular polysulphonate copolymer of styrene with divinylbenzene General formula:

and is available in different versions, differing in the amount of divinylbenzene in the copolymer. For example, the brand of the cation exchange resin KU-2-8 and KU-2-10 contain 8% and 10% divinylbenzene, respectively. [Saldadze K.M., Pashkov A.B., Titov, V.S. Ion-exchange high-molecular compounds. Edited Saldadze K.M. Moscow: GOS. ).technology. ed. chem. lit., 1960, s.112-114]. Cation-exchange resin KU-2-8 produced according to GOST 20298-74.

As the organic solvent for the reaction between hydroxyl derivative of propane with monochloracetic acid using an aromatic hydrocarbon solvent, for example toluene, xylene, nefras-120/200.

Under the symbol Nefras-120/200 petrochemical industry produces heavy oil solvent on THE 38-101809-90 obtained from the products of catalytic reforming and containing a mixture of aromatic hydrocarbons, C8-C9(xylenes, propylbenzene, methylethylbenzene, mesitylene, pseudotumor and others)

The proposed method of obtaining new, not known to the wound is {[1-(ammonia)-3,5,7-triathalete]methylcarbazole(alkylene)}propane chloride has some similarities with the way other series of Quaternary ammonium compounds, for example, N-[isononyl-phenoxypoly(ethyleneoxy)carbonylmethyl]ammonium chloride [U.S. Pat. 1531416 of the Russian Federation. Publ. 1995.04.10.] But the differences between these two methods are significant. In a known way as alcohol components use economicpolitical, of General formula:

but as amino compounds - long-chain aliphatic tertiary amines of the type N,N,N-dialkylamino fraction C7-C9N,N-dimethyl-N-alkylamines followed fraction10-C16or fraction C15-C18.

In the proposed method as alcohol components use 1,2,3-Tris[hydroxypoly(ethylenoxy)]propane, of General formula:

where:

a+C+e = total oxypropylation equal 49-55;

b+d+f = total degree of oksietilirovannye equal 9-10;

and processing of the reaction product of hydroxyl derivative of propane with monochloracetic acid are amino compounds selected from a range of primary amines, of the formula:

RNH2,

where: R is an aliphatic hydrocarbon radical containing 10 to 16 carbon atoms;

pyridines of the formula:

the alkylimidazolines, of the formula:

where:

R' = aliphatic unsaturated hydrocarbon radical containing 17 carbon atoms;

or 1,3,5,7-tetraazacyclooctane, formula:

In the proposed method used the molar ratio of the reactant - hydroxyl derivative of propane : monochloracetic acid : aminosidine : tetrathionate = 1,0:3,0-3,2:0-2,1:1,0-2,1 respectively.

In connection with the foregoing it can be concluded that the proposed method for {[1-(ammonia)-3,5,7-triathalete]methylcarbazole(alkylene)}propane chloride is significantly different from the existing methods of obtaining well-known series of Quaternary ammonium compounds.

The proposed method allows to obtain {[1-(ammonia)-3,5,7-triathalete]methylcarbazole(alkylene)}propane chlorides, which have bactericidal and fungicidal activity.

Thus, the claimed {[1-(ammonia)-3,5,7-triathalete]methylcarbazole(alkylene)}propane chlorides are new, and the retrieval method is new.

Cited specific examples of carrying out the invention.

Example 1

{[1-(Ammonia)-3,5,7-triathalete]methylcarbazole(ethylenoxy)poly(2-methylethylidene)}bis{2|-(hexadecynyl)imidazolinium]}methylcarbazole(ethylenoxy)poly(2-methylethylidene)propane trichloride with a total degree of oxypropylation, equal to 49, and the total degree of oksietilirovannye equal to 9.

A mixture of 50.0 (1,5·10-2g-mol) of 1,2,3-t is IP[hydroxypoly(ethylenoxy)poly(2 |-methylethylidene)]propane with a total degree of oxypropylation, equal to 49, and the total degree of oksietilirovannye equal to 9; 4.3 g (4,5·10-2g-mole) monochloracetic acid and 100 ml of toluene, 1.5 g of H+-form cation-exchange acid KU-2-8 (as acid catalyst) is boiled with trap Dean-stark and reflux until complete cessation of water excretion and reducing the acid number of the reaction mass to values less than or equal to 2 mg KOH/g acid Value of the number in the sample is determined by titration with alcoholic KOH solution. The reaction time of 14 hours. Filtered the reaction mass of the catalyst and vacuum to remove the organic solvent (toluene) and unreacted monochloracetic acid.

The resulting reaction product is mixed with 8.8 g (3,0·10-2g-mole) (2-hexadecanol)imidazoline and 2.1 g (1.5·10-2g-mol) of 1,3,5,7 - tetraazacyclooctane in 70 ml of isopropanol and 5 ml of water and heated under stirring and the temperature of 60-85°C for 10 hours. Control reactions are titrimetrically, determining the content of free amines potentiometric titration with alcoholic solution of hydrochloric acid. The reaction is stopped at a residual content of free amines is less than 0.2%. The solvent is removed in vacuum. The output of 63.6 g (99,0% of theoretical.) viscous liquid light yellow color.

The K-range: ν (C=On)=1753 cm-1; ν(C-O)acicl=1109 cm-1; ν(C-O)acetate=1263 cm-1.

Example 2

{[1-(Ammonia)-3,5,7-triathalete]methylcarbazole(ethylenoxy)poly(2-methylethylidene)}bis{2|-(hexadecynyl)imidazolinium]}methylcarbazole(ethylenoxy)poly(2-methylethylidene) propane trichloride with a total degree of oxypropylation equal to 55, and the total degree of oksietilirovannye equal to 10.

Is obtained analogously to example 1 from 75.0 g (2.0·10-2g-mol) of 1,2,3-Tris[hydroxypoly(ethylenoxy)poly(2-methylethylidene)] propane with a total degree of oxypropylation equal to 55, and the total degree of oksietilirovannye equal to 10; 6.1 g (6.4·10-2g-mole) monochloracetic acid; 150 ml of xylene; 3.8 g H+-form cation-exchange resin KU-2-8 (as acid catalyst); 4 ml of water; ethanol 100 ml; 3.1 g (2.2·10-2g-mol) of 1,3,5,7-tetraazacyclooctane and 12.4 g (4.2·10-2g-mole) (2-hexadecanol)imidazoline. Output 93.5 g (99.5% of theory.) viscous liquid red color.

IR-spectrum: ν(C=On)=1754 cm-1; ν(C-O)acicl=1109 cm-1; ν(C-O)acetate=1263 cm-1.

Example 3

{[1-(Ammonia)-3,5,7-triathalete]methylcarbazole(ethylenoxy)poly(2-methylethylidene)}-bis[(pyridinio)methylcarbazole(ethylenoxy)poly(2-methylethylidene)]propane trichloride with total step the new oxypropylation, is 49, and the total degree of oksietilirovannye equal to 9.

Is obtained analogously to example 1 from 65.0 g (2.0·10-2g-mol) of 1,2,3-Tris [hydroxypoly(ethylenoxy)poly(2-methylethylidene)]propane with a total degree of oxypropylation, equal to 49, and the total degree of oksietilirovannye equal to 9; 5.5 g (5.9·10-2g-mole) monochloracetic acid; 130 ml of xylene; 2.0 g of N+-form cation-exchange resin KU-2-8 (as acid catalyst); 6 ml of water, 90 ml of isopropanol; 2.7 g (2.0·10-2g-mol) of 1,3,5,7-tetraazacyclooctane and 3.0 g (3.9·10-2g-mol) of pyridine. Output 74.7 g (99.8% of theory.) viscous liquid red color.

IR-spectrum: ν(C=On)=1754 cm-1; ν(C-O)acicl=1110 cm-1; ν(C-O)acetate=1260 cm-1.

Example 4

{[1-(Ammonia)-3,5,7-triathalete]methylcarbazole(ethylenoxy)poly(2-methylethylidene)}-bis[(pyridinio)methylcarbazole(ethylenoxy)poly(2-methylethylidene)]propane trichloride with a total degree of oxypropylation equal to 55, and the total degree of oksietilirovannye equal to 10.

Is obtained analogously to example 1 from 68.0 g (1.8·10-2g-mol) of 1,2,3-Tris[hydroxypoly(ethylenoxy)poly(2-methylethylidene)] propane with a total degree of oxypropylation equal to 55, and the total degree of oksietilirovannye equal to 10; 5.5 g (5.8·10-2g-mole) monochloracetic acid; 136 ml of xylene; 3.4 g H+ -form cation-exchange resin KU-2-8 (as acid catalyst); 4 ml of water; 92 ml isopropanol; 2.8 g (2.0·10-2g-mol) of 1,3,5,7-tetraazacyclooctane and 3.0 g (3.8·10-2g-mol) of pyridine. Output 77.2 g (99.6% of theory.) viscous liquid red color.

IR-spectrum: ν(C=On)=1755 cm-1; ν(C-O)acicl=1108 cm-1; ν(C-O)acetate=1262 cm-1.

Example 5

{[1-(Ammonia)-3,5,7-triathalete]methylcarbonate(2 methylethylidene)}bis{[2'-(hexadecynyl)imidazolinium]}methylcarbonate(2 methylethylidene)propane trichloride with a total degree of oxypropylation, equal to 49.

Is obtained analogously to example 1 from 72.0 g (2.5·10-2g-mol) of 1,2,3-Tris[hydroxypoly(ethylenoxy)]propane with a total degree of oxypropylation, equal to 49; 7.0 g (7.4·10-2g-mole) monochloracetic acid; 150 ml of xylene; 2.2 g of N+-form cation-exchange resin KU-2-8 (as acid catalyst); 7 ml water; 100 ml isopropanol; 3.4 g (2.5·10-2g-mol) of 1,3,5,7-tetraazacyclooctane and 14.4 g (4.9·10-2g-mole) (2-hexadecanol)imidazoline. Output 95.5 g (99.7% of theory.) viscous liquid red color.

IR-spectrum: ν(C=On)=1754 cm-1; ν(C-O)acicl=1108 cm-1; ν(C-O)acetate=1264 cm-1.

Example 6

{[1-(Ammonia)-3,5,7-triathalete]methylcarbonate(2 methylethylidene)}bis{['-(hexadecynyl)imidazolinium]}methylcarbonate(2 methylethylidene)propane trichloride with a total degree of oxypropylation, equal to 55.

Is obtained analogously to example 1 from 74.0 g (2.3·10-2g-mol) of 1,2,3-Tris[hydroxypoly(ethylenoxy)]propane with a total degree of oxypropylation equal to 55; 6.8 g (7.2·10-2g-mole) monochloracetic acid; 150 ml of xylene; 3.7 g of N+-form cation-exchange resin KU-2-8 (as acid catalyst); 4 ml water; 100 ml isopropanol; 3.5 g (2.5·10-2g-mol) of 1,3,5,7-tetraazacyclooctane and 13.9 g (4.7·10-2g-mole) (2-hexadecanol)imidazoline. Output 95.6 g (99.4% of theory.) viscous liquid red color.

IR-spectrum: ν(C=On)=1754 cm-1; ν(C-O)acicl=1110 cm-1; ν(C-O)acetate=1261 cm-1.

Example 7

{[1-(Ammonia)-3,5,7-triathalete]methylcarbazole(ethylenoxy)poly(2-methylethylidene)}-bis[(alkylamino)methylcarbazole(ethylenoxy)poly(2-methylethylidene)]propane trichloride fraction10-C16with a total degree of oxypropylation, equal to 49, and the total degree of oksietilirovannye equal to 9.

Is obtained analogously to example 1 from 73.0 g (2.2·10-2g-mol) of 1,2,3-Tris[hydroxypoly(ethylenoxy)poly(2-methylethylidene)] propane with a total degree of oxypropylation, equal to 49, and the total degree of oksietilirovannye equal to 9; 6.2 g (6.6·10-2g-mole) monochloracetic acid; 150 ml of xylene; 2.2 g of N+-form cation-exchange resin KU-2-8 (as acid ka is Aligator); of 6.6 ml of water; 99 ml isopropanol; 3.1 g (2.2·10-2g-mol) of 1,3,5,7-tetraazacyclooctane and 8.7 g (4.4·10-2g-mole) alkylamines followed fraction C10-C16. Output 89.8 g (99.9% of theory.) viscous liquid red color.

IR-spectrum: ν(C=On)=1752 cm-1; ν(C-O)acicl=1110 cm-1; ν(C-O)acetate=1261 cm-1.

Example 8

{[1-(Ammonia)-3,5,7-triathalete]methylcarbazole(ethylenoxy)poly(2-methylethylidene)}-bis[(alkylamino)methylcarbazole(ethylenoxy)poly(2-methylethylidene)]propane trichloride fraction10-C16with a total degree of oxypropylation equal to 55, and the total degree of oksietilirovannye equal to 10.

Is obtained analogously to example 1 from 76.0 g (2.0·10-2g-mol) of 1,2,3-Tris [hydroxypoly(ethylenoxy)poly(2-methylethylidene)] propane with a total degree of oxypropylation equal to 55, and the total degree of oksietilirovannye equal to 10; 6.2 g (6.5·10-2g-mole) monochloracetic acid; 152 ml of xylene; 3.8 g of N+-form cation-exchange resin KU-2-8 (as acid catalyst); 4 ml water; 100 ml isopropanol; 3.1 g (2.2·10-2g-mol) of 1,3,5,7-tetraazacyclooctane and 6.2 g (3.5·10-2g-mol) of pyridine. Output 93.4 g (91.7% of theory.) viscous liquid red color.

IR-spectrum: ν(C=On)=1752 cm-1; ν(C-O)acicl=1111 cm-1; ν(C-O)acetate=1264 cm-1 .

Determination of the bactericidal activity of the compounds.

The bactericidal activity of the proposed compounds were studied against representative gram-positive group of bacteria - Staphylococcus aureus Staphylococcus aureus strain R-209 and gram-negative groups Escherichia coli Escherichia coli strain 7904 is logged on generally accepted in bacteriology methods [Methods of experimental chemotherapy / Edited. ed G. Pershina. M.: Medicine, 1973, s-320; witches E.A., purer NM Guide for Microbiology, clinic and epidemiology, clinical picture and epidemiology of infectious diseases. M.: Medicine, 1964, s-610]. Using the optical method of the turbidity standard was prepared a suspension of microorganisms in saline solution with bacterial load 500000 microbial cells in 1 ml of Bacterial suspension was poured in test tubes containing certain concentrations of these substances. Control tubes contained the same amount of sterile saline. Exposure at this amounted to 0,5; 1,0; 1,5; 2,0 and 3,0 hours. Upon expiry of the exposure experienced and control materials were sown on selective nutrient media: E. coli - Wednesday Endo; St.aureus - salt agar. Incubation was performed in a thermostat at 37°C. monitoring the crops were carried out over 7 days.

The bactericidal activity of the proposed compounds against wysokosci ivih to disinfectants bacteria was studied on the example of M. tuberculosis Micobacterium bovis strain 14 method Batiste tests. [Methods of experimental chemotherapy / edited by G. Pershina. M.: Medicine, 1973]. Sterile cambric test size 1 cm2inspired suspension culture at a concentration of 2 mltm/ml. Then in bottles with a water solution of the investigated compounds were made by two cambric test. Exposure time in all cases was 2 hours. Upon expiry of the exposure experienced and control materials were subjected to three washing with sterile distilled water from the test preparation by centrifugation at 5 Tyson./min for 30 minutes. Then spent sowing on Lowenstein - Jensen medium. Incubation was carried out in a thermostat at 37°C for one month. Analysis conducted in the presence or absence of growth of colonies in the experimental tubes compared to the control. The results are given in table 1.

As a benchmark comparison of bactericidal activity used a structural analogue of "Drug f-761", which is a N,N-dimethyl-N-alkyl-N-[isononylphenol(ethylenoxy)carbonylmethyl]ammonium chloride fraction C10-C16formula:

where:

R1=R2=CH3;

R3- aliphatic hydrocarbon radical containing 10 to 16 carbon atoms;

n=10.

[Patent 1531416 of the Russian Federation. MCI C 07 C 87/30. Fakhretdinov PS, Romanov is V and other way to obtain the corrosion inhibitors of carbon steel in hydrogen sulfide-containing saline water environments, showing fungistatic, bacteriostatic and disinfectant action].

"The drug f-761" along with the fact that is a structural analogue of the proposed in the present invention compounds, possesses the same activity (antibacterial and antifungal action).

The data in table 1 indicate the bactericidal activity of the claimed {[1-(ammonia)-3,5,7-triathalete]methylcarbazole(alkylene)}propane chloride. So, against a representative group of gram-positive bacteria Staphylococcus aureus minimum bactericidal concentration (MBC) for the proposed compounds are 0,25-2,0%, while for structural analogue - Drug f-761" (Pat. 1531416) MBCC is 0.5% (at the same exposure time). Against representative gram-negative bacteria - Eschrechia coli MBCK the claimed compounds is 0.5 to 1.0%, and MBC for structural analogue is 1.0% for the same exposure in 2 hours.

Note the high bactericidal activity of the claimed compounds against highly resistant to disinfectants M. tuberculosis Micobacterium bovis strain 14, MBC which is 0,063-1,0%, while structural analogue of the Drug f-761" against the AI M. bovis bactericidal activity is not.

The data obtained show that {[1-(ammonia)-3,5,7-triathalete]methylcarbazole(alkylene)}propane chloride on the bactericidal activity of superior structural analogue of the Drug f-761" and can be used for preventive and disinfection treatment in the foci of infection causative agents of tuberculosis in veterinary medicine and agriculture.

Determination of the fungicidal activity.

The fungicidal activity of the proposed compounds were investigated on the example of the pathogen ascosphaerosis (brood disease of bees) - Ascosphaera apis, the strain VG-8. The tests were carried out on generally accepted in Microbiology methods of serial dilutions [Methods of experimental chemotherapy / edited by G. Pershina. M.: Medicine, 1973, s-320; witches E.A., purer NM Guide for Microbiology, clinic and epidemiology, clinical picture and epidemiology of infectious diseases. M.: Medicine, 1964, s-610].

For the experiments used a suspension of fungi the fungal load 200000 fungal bodies in 1 ml of physiological solution. Fungal suspension was poured in test tubes containing certain concentrations of the studied drugs in the proportion of 1 part of a fungal suspension of 1 part of solution of the drug. As the standard of comparison used a structural analogue of N,N-dimethyl-N-alkyl-N-[isononylphenol(ethylenoxy)carbonylmethyl]ammonium chloride - Drug f-61", with antibacterial and antifungal action (Patent RF №1531416). As control using the same amount of sterile saline. Exposure is 5, 10, 30, 60 and 120 minutes After exposure carry out sowing of the test and control materials on selective nutrient medium - wort-agar. Incubation is carried out in a thermostat at a temperature of 37°and observation are within 14 days.

Research results fungicidal activity of the proposed compounds and the standard of comparison is presented in table 2.

The data of table 2 indicate the fungicidal activity of the claimed {[1-(ammonia)-3,5,7-triathalete]methylcarbazole(alkylene)}propane chloride. So, against the pathogen of ascosphaerosis (brood disease of bees) Ascosphaera apis, the minimum fungicidal concentration (MCFC) these drugs are 0,25-2,0% at exposure of 2 hours, while a structural analogue of the Drug f-761" fungicidal activity is not.

The proposed connection can be used as antifungal funds against the pathogen of ascosphaerosis (brood disease of bees), for example, in agriculture the apiary (amenyah, hives).

Thus, the claimed {[1-(ammonia)-3,5,7-triathalete]methylcarbazole(alkylene)}propane chlorides are new, and how they are p the receipt is also new.

The presented data confirm the bactericidal and fungicidal activity of the inventive compounds which can be used as an active Foundation bactericidal and fungicidal tools in medicine, veterinary medicine and agriculture.

The proposed method for {[1-(ammonia)-3,5,7-triathalete]methylcarbazole(alkylene)}propane chloride is simple, does not require special conditions and special equipment and can be performed on virtually any chemical production.

Table 1.

The results of the study of bactericidal activity of drugs.
Connection

for example
Exposure time, hThe minimum bactericidal concentration %
St.aurerusE.coliM. bovis
12,00,250,50,125
22,00,250,50,125
32,01,00,51,0
42,01,00,51,0
52,00,250,50,125
62,00,250,50,125
72,02,01,00,063
82,02,01,00,063
Structural similar - Drug f-761"Pat. 15314162,00,51,0not active

Table 2.

The results of the study fungicidal activity.
ConnectionExposure time, hMinimum fungicidal concentration %
123
120,5
220,5
322,0
422,0
520,5
620,5
721,0
821,0
A structural analogue of the Drug f-761" Pat. Of the Russian Federation No. 1531416Does not possess fungicidal activity

1. {[1-(Ammonia)-3,5,7-triathalete]methylcarbamyl csepeli(alkylene)}propane chloride, the General formula

where

R'= aliphatic unsaturated hydrocarbon radical containing 17 carbon atoms;

a+C+e=total oxypropylation, equal to 49;

b+d+f=total degree of oksietilirovannye equal to 9;

R'= aliphatic unsaturated hydrocarbon radical containing 17 carbon atoms;

a+C+e=total oxypropylation equal to 55;

b+d+f=total degree of oksietilirovannye equal to 10;

a+C+e=total oxypropylation, equal to 49;

b+d+f=total degree of oksietilirovannye equal to 9;

a+C+e=total oxypropylation equal to 55;

b+d+f=total degree of oksietilirovannye equal to 10;

R'= aliphatic unsaturated hydrocarbon radical containing 17 carbon atoms;

a+C+e=total oxypropylation, equal to 49;

b+d+f=total degree of oksietilirovannye 0;

R'= aliphatic unsaturated hydrocarbon radical containing 17 carbon atoms;

a+C+e=o is based on the degree of oxypropylation, equal to 55;

b+d+f=total degree of oksietilirovannye 0;

when X+=Y+=RNH2+-;

R = aliphatic hydrocarbon radical containing 10 to 16 carbon atoms;

a+C+e=total oxypropylation, equal to 49;

b+d+f=total degree of oksietilirovannye equal to 9;

when X+=Y+=RNH2+-;

R = aliphatic hydrocarbon radical containing 10 to 16 carbon atoms;

a+C+e=total oxypropylation equal to 55;

b+d+f=total degree of oksietilirovannye equal to 10.

2. Compounds according to claim 1, having bactericidal and fungicidal activity.

3. Method of preparing compounds according to claim 1, which consists in the interaction of 1,2,3-Tris[hydroxypoly(alkylene)]propanol, the General formula

where a+C+e=total oxypropylation equal 49-55;

b+d+f=total degree of oksietilirovannye equal to 0-10;

with monochloracetic acid in the presence of acid catalyst in the medium boiling organic solvent, with azeotropic removal of water formed and the subsequent processing in the environment of the polar solvent by heating, the obtained reaction product of the amino compounds selected from the set:

primary amines of the formula

RNH2,

where R is an aliphatic hydrocarbon radical containing 10 to 16 carbon atoms,

pyridines of the formula

the alkylimidazolines, the formula

where:

R'= aliphatic unsaturated hydrocarbon radical containing 17 carbon atoms;

and/or 1,3,5,7-tetraazacyclooctane, of the formula:

in molar ratios of reagents - hydroxyl derivative of propane : monochloracetic acid : aminosidine : tetrathionate = 1:3,0-3,2:0-2,1:1,0-2,1 respectively.

4. The method according to claim 3, namely, that as the acid catalyst used N+-form cation-exchange resin KU-2-8, taken in an amount of 3-5% of the weight of the original hydroxyl derivative of propane.

5. The method according to claim 3, which consists in the fact that as an organic solvent using an aromatic hydrocarbon solvent, for example toluene, xylene, nefras-120/200.

6. The method according to claim 3, which consists in the fact that during the processing of a reaction product of hydroxyl derivative of propane with monochloracetic acid with amino compounds and/or 1,3,5,7-tetraazacyclooctane as polar solvents, a mixture of low molecular weight alcohol, such as ethanol or isopropanol, is water with a volumetric ratio of alcohol : water=15-25:1,0.

7. The method according to claim 3, which consists in the fact that the processing aminoguanidinium and/or 1,3,5,7-tetraazacyclooctane of the reaction product of hydroxyl derivative of propane with monochloracetic acid is conducted at a temperature of 60-85°C.



 

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FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for synthesis of novel addition agents used as regulators of viscoelastic properties of associated multicomponent petroleum systems that can be used in petroleum and petroleum chemical industry. Method involves interaction of monochloroacetic acid with alcoholic component in the presence of acidic catalysts, for example, with H+-form of cation-exchange resin KU-2-8, in boiling organic solvent medium and azeotropic removing formed water and the following treatment of the synthesized reaction substance with amines. As a alcoholic component methods involves using 1,2,3-tris-[(hydroxypoly(alkyleneoxy)]propanes of the general formula: wherein a + c + e (the total degree of oxypropylation) = 48-78, b + d + f (the total degree of oxyethylation) = 0-20, and 1,3,5,7-tetraazaadamantane of the formula: is used as amines in the molar ratio of reagents - propane hydroxyl derivative : monochloroacetic acid : tetraazaadamantane = 1.0:(3.0-3.2):(0.75-3.2), respectively. As a rule, as organic solvents in interaction of propane hydroxyl derivative with monochloroacetic acid method involves using aromatic hydrocarbon solvents, for example, toluene, xylene, nefras A-120/200. Usually, treatment of the reaction product of monochloroacetic acid with propane hydroxyl derivative with 1,3,5,7-tetraazaadamantane is carried out in polar solvents medium at temperature 40-85°C. As a rule, mixtures of water with low-molecular alcohols, for example, ethanol, isopropanol are used as polar solvents in the volume ratio water : alcohol = 1.0:(15-25).

EFFECT: improved method of synthesis.

5 cl, 1 tbl, 6 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for synthesis of 1,8-dimethyl-3,6-diazadihomoadmantane-9,10-dione. Compounds of class 3,6-diazadihomoadamantane-9,10-dione possess an antiviral effect comparable with antiviral effect of aminoadamantane, elicit strychnine-like activity and show bactericidal, fungicide and algicidic properties also. Proposed method for preparing 1,8-dimethyl-3,6-diazadihomoadamantane-9,10-dione involves interaction of 1,8-dimethyl-3,6,10,13-tetraazatetracyclo[8,4,1,18,1302,7]hexadeca-2,6-diene with water in the presence of hydrochloric acid and sodium nitrite at room temperature. The parent 1,8-dimethyl-3,6,10,13-tetraazatetracyclo[8,4,1,18,1302,7]hexadeca-2,6-diene is prepared in the condensation reaction of tetramethylenediethylenetetramine and 3,4-hexanedione in the presence of acetic acid in isopropyl alcohol medium at room temperature. Then the reaction mixture is neutralized with potash aqueous solution, water is evaporated under vacuum and solid residue is extracted with heptane. After recrystallization from heptane 1,8-dimethyl-3,5-diazadihomoadamantane-9,10-dione is prepared. The yield of the compound is 78%. Invention provides the development of available method of synthesis of 1,8-dimethyl-3,6-diazadihomoadamantane-9,10-dione.

EFFECT: improved method of synthesis.

1 ex

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4 cl, 1 ex, 2 tbl

FIELD: medicine, veterinary science, biotechnology.

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1 cl, 1 ex, 12 tbl

FIELD: medicine, disinfecting and washing agents.

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3 tbl, 3 ex

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3 cl, 7 tbl, 8 ex

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EFFECT: improved and valuable properties of agent.

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