A method of obtaining a condensed 2-getreleasedate
The invention relates to a method for producing a condensed 2-getreleasedate General formula
using the diamine of General formula
R=2-furyl, 2-thienyl, 2-(1-methyl)pyrrolyl, 3-(1-methyl)indolyl, and aldehydes in the presence of acetate or copper sulfate, characterized in that the interaction takes place by boiling in 50% acetic acid, followed by decomposition of the copper salt, the effect on its suspension in 50% acetic acid sodium thiosulfate at 100C. The technical result is an increase in technological process. table 2.
The invention can find application in pharmacology and for new photoluminescent products.
A method of obtaining 2-(2'-thienyl)benzimidazole (Perry R., Wilson D. // J. Org. Chem 1993. Vol. 58. P. 7016-7021).
In the reaction vessel, pressure is placed 967 mg (to 8.94 mmol) of o-phenylenediamine, 1877,4 mg (8,94 pitch) 2-idioten, 94 mg (0.13 mmol) PdCl2and 27 ml of dimethylacetamide. Then out of the reactor with argon to remove oxygen, and then fill it with carbon monoxide under a pressure of 35 inches/m2and maintained at a temperature of 120 C to dissolve all the components again create pressure and CO contents of the stand 19 h at 145 C. Then from the reaction mixture to separate the catalyst, and the filtrate was concentrated in vacuo, the residue is dissolved in 25 ml of hot ethanol, add 2 ml of NH4OH and 25 ml of water, and leave overnight. The precipitated crystals are separated, washed with a cold aqueous solution of ethanol and dried. Output 588 mg (32%). From the filtrate by chromatography was carried out through a layer of silicagel, eluent toluene:ethyl acetate (1:1), obtained 104 mg (6%) of product.
The closest is a method of obtaining 2-(2'-furyl)-, 2-(2'-thienyl) and 2-(1'-methyl-2-pyrrolyl)benzimidazole (Elchaninov M. M., Oleinikov L. Y. Simonov, A. M. // CHC. 1979. No. 8. S. 1047-1049, and Elchaninov M. M., Simonov, A. M., Oleinikov L. I. // CHC. 1980. No. 1. S. 71-73).
The mixture 4,32 g (40 mmol) of o-phenylenediamine in 75 ml of isopropyl alcohol, 16 g (80 mmol) of copper acetate in 200 ml of water and 40 mmol of the corresponding aldehyde are heated at 80-90 With 2 hours the Reaction mass is then cooled, the precipitated copper salt is separated, suspended it in 150 ml of isopropyl alcohol and passed through the suspension of the sulfide in an hour. Filtered copper sulfide, the filtrate is evaporated twice, the residue is diluted with 250 ml of water, the precipitated product is filtered and dried. Output up 67-90%.
However, these methods are not General enough, prodoljitel redlagaemyi, from the viewpoint of processability and clarity.
The objective of the invention is the expansion of the range of whole foods while simplifying and environmental purification process of getting known and new 2-getreleasedate.
The problem is solved so that the condensed 2-getreleasedate General formula
unlike structural analogue, is obtained by using a diamine of General formula
R=2-furyl, 2-thienyl, 2-(1-metl)pyrrolyl 3-(1-methyl)indolyl,
and aldehydes in the presence of acetate or copper sulfate by boiling in 50% acetic acid, followed by decomposition of the copper salt, the effect on its suspension in 50% acetic acid sodium thiosulfate at 100 C.
These conditions significantly increase environmental cleanliness and manufacturability of the process due to the fact that earlier for the decomposition of copper salt was used for a long bubbling hydrogen sulfide through its suspension in alcohol (Elchaninov M. M., Oleinikov L. Y. Simonov, A. M. // CHC, 1979. No. 8. S. 1047-1049).
Hydrogen, as is well known, high-risk substance 2 class with very low (0.008 mg/m3) maximum allowable concentration, was thrown into the air.
Example. Obtaining condensed 2 the red acid are added 16 g (80 mmol) acetate ((CH3SOO)2Cu N2O) or 20 g (80 mmol) sulfate (CuSO45H2O) copper in 200 ml of water and 40 mmol of the corresponding aldehyde in 50 ml of 50% acetic acid. The resulting mixture is heated to boiling for 1-2 hours Then the reaction mass is then cooled, the precipitated copper salt of the desired product is separated and suspended in 150 ml of 50% aqueous solution of acetic acid. The suspension is heated to boiling and portions over 0.5 h made of 20 g (80 mmol) of sodium thiosulfate (Na2S2O35H2On and after the addition of all of the thiosulfate and the mixture was kept at a low boil for another 0.5 h, after which the precipitated copper sulfide is separated. The crude reaction product falls from the mother liquor by neutralizing the latter concentrated ammonia solution. The output of 60-90%.
The proposed method allows to synthesize compounds with biological activity. So, for example, 2-(2'-furyl)- (1A) and 2-(2'-thienyl)benzimidazole (1B) have fungicidal activity (Preston P. N. // Chem Rews. 1974. Vol. 74. No. 3. P. 311; Elchaninov M M etc. // ABT. mon. No. 1032755, 1983).
Furthermore, they are synthons for obtaining a large series of products with antifungal and antibacterial activity (Elchaninov M M etc. // ABT. mon. No. 614630, 1978;723853, 1979) and phosphors (Pechkin A. A. // Diss. K. H. N., Novocherkassk, 2000, S. 92.).
Physico-chemical constants of the compounds shown in tables 1 and 2.
A method of obtaining a condensed 2-getreleasedate General formula
using the diamine of General formula
R=2-furyl, 2-thienyl, 2-(1-methyl)pyrrolyl, 3-(1-methyl)indolyl, and aldehydes in the presence of acetate or copper sulfate, characterized in that the interaction takes place by boiling in 50% acetic acid, followed by decomposition of the copper salt, the effect on its suspension in 50% acetic acid sodium thiosulfate at 100C.
< / BR>or their pharmaceutically acceptable salts, in which the dotted lines indicate optional double bonds; A is-CR7or N; - - NR1R2, -CR1R2R11, -C(= CR2R12R1, -NHCHR1R2, -ОСHR1R2, -SCHR1R2, -CHR2OR12,
-CHR2SR12, -C(S)R2or-C(O)R2N-ethyl-2,2,2-triptorelin; G is oxygen, sulfur, NH, NH3hydrogen, methoxy, ethoxy, triptoreline, methyl, ethyl, dimethoxy, NH2, NHCH3N(CH3)2or trifluoromethyl; Y Is N; Z is NH, O, S, -N(C1-C2alkyl) or-C(R13R14), where R13and R14independently of one another represent hydrogen, trifluoromethyl or methyl, or one of the elements of R13and R14is cyano and the other is hydrogen or stands; R1- C1-C6alkyl which may be optionally substituted by one or two substituents R8independently from each other selected from the group comprising hydroxy, fluorine, chlorine, bromine, iodine, CF3C1-C4alkoxy, -O-CO-(C1-C4alkyl), where (C1-C2- C1-C12alkyl, aryl or -(C1-C4alkylene)aryl, where aryl is phenyl, naphthyl; R3is methyl, ethyl, fluorine, chlorine, bromine, iodine, cyano, methoxy, OCF3, methylthio, methylsulphonyl, CH2HE or CH2OCH3; R4is hydrogen, C1-C4alkyl, fluorine, chlorine, bromine, iodine, C1-C4alkoxy, triptoreline, -CH2OCH3, -CH2OCH2CH3, -CH2CH2OCH3, -CF3, amino, nitro, -NH(C1-C4alkyl), -N(CH3)2, -NHCOCH3, -NHCONHCH3, hydroxy, -CO(C1-C4alkyl), -Cho, COOH, cyano, or-COO(C1-C4alkyl), where C1-C4the alkyl may be substituted by one Deputy chosen from the group comprising hydroxy, amino, -NHCOCH3, -NH(C1-C2alkyl), -N(C1-C2alkyl)2, fluorine, chlorine, cyano, nitro; R5is phenyl, naphthyl, pyridyl, pyrimidyl, where each of the above groups R5substituted with one to three substituents that are independently from each other selected from fluorine, chlorine, C1-C6the alkyl or C1-C6alkoxyl, or one Deputy chosen from the group comprising hydroxy, iodine, bromine, formyl, cyano, nitro, trifluoromethyl, amino, -(C1-C6these groups of R5may be optionally substituted with one hydroxy-group; R6is hydrogen or C1-C6alkyl; R7is hydrogen, methyl; R11is hydrogen, hydroxy, fluorine or methoxy; R12is hydrogen or C1-C4alkyl, and R16and R17independently of one another represent hydrogen, hydroxy, methyl, ethyl, methoxy or ethoxy, except that both R16and R17cannot both be methoxy or ethoxy; or R16and R17together form oxo (=O) group; provided that if G is an atom of oxygen, sulfur, NH or NCH3he is joined by a double bond to a five-membered ring of the formula III, and further provided that R6is absent when the nitrogen atom to which it is linked, is attached by a double bond to an adjacent carbon atom in the ring
< / BR>and/or their stereoisomeric forms and/or physiologically acceptable salts, where R1means phenyl, phenyl, one or twice substituted by a group WITH1-C6-alkyl-Oh, halogen, trifluoromethyl, a group WITH1-C6-alkyl-O-C(O)-, methylenedioxy-, R4-(R5)N-; triazole, thiophene, pyridine; R2means H, C1-C6alkyl; R4and R5are adnikowymi or different and denote H, C1-C6-alkyl; R3means H, C1-C10-alkyl, where alkyl unsubstituted and/or one hydrogen atom of the alkyl residue substituted by hydroxyl,2-C10alkenyl, R2-S(O)n-C1-C6-alkyl, where n means 0, 1, 2; R2-S(O)(=NH)-(C1-C6)-alkyl and the other, or R2and R3together form a cycle with a carboxyl group as a substituent cycle of partial formula II:
< / BR>where r is 0, 1, 2, 3 and/or one of the carbon atoms in the cycle replaced by-O-, and/or the carbon atom in the cycle part of the formula II substituted once by phenyl; a represents a covalent bond, -O-;