RU2001112774A - CHEMICAL METHODS - Google Patents

Claims (32)

1. The method of obtaining the compounds of formula (I)

where R ¹ is C _1-4 haloalkyl, fluoro, chloro or bromo; R ² is hydrogen or C _1-4 alkoxy; comprising the interaction of the corresponding ortho-nitrogalobenzene formula (II)

where R ¹ and R ² have the above meanings; X is an atom of fluorine, chlorine or bromine, in the case where X is a fluorine atom: (a) with an alkali metal cyanide in an anhydrous solvent, optionally in the presence of a catalyst, or in the case where X is a chlorine atom: (b) with copper cyanide (I) and a source of bromide selected from bromide hydrogen, bromine and tetraalkylammonium bromide; optionally in the presence of an alkali or alkaline earth metal bromide, or (c) with an alkali metal or tetraalkylammonium cyanide in the presence of copper (I) bromide and an interphase catalyst, or (d) copper (I) cyanide and lithium iodide, or in the case where X - bromine atom: (e) with copper cyanide (I) optionally in the presence of a catalyst selected from alkali or alkaline earth metal bromide, or (f) alkali metal cyanide in the presence of a catalytic amount of copper (I) cyanide and an interphase catalyst. 2. The method according to claim 1 (a), in which the catalyst is selected from ammonium salts and guanidinium. 3. The method according to claim 1 (a) or 2, in which the alkali metal cyanide is sodium cyanide. 4. The method according to claim 1 (a), 2 or 3, in which 1-2 molar equivalents of cyanide are used. 5. The method according to claim 1 (a) or any one of claims 2 to 4, wherein the solvent is benzonitrile, acetonitrile, tetrahydrofuran or N, N-dimethylformamide. 6. The method according to claim 1 (a) or any one of claims 2-5, wherein the solvent contains less than 1 vol.% Water. 7. The method according to claim 1 (b), in which apply 0.5-2 molar equivalents of copper cyanide (I). 8. The method according to claim 1 (b) or 7, in which 0.05-1 molar equivalents of a bromide source are used. 9. The method according to claim 1 (b), 7 or 8, in which 0.01-0.5 molar equivalents of alkali or alkaline earth metal bromide are used. 10. The method according to claim 1 (c), in which potassium cyanide is used. 11. The method according to claim 1 (c) or 10, in which 0.1-2 molar equivalents of copper bromide (I) are used. 12. The method according to claim 1 (c), 10 or 11, in which the interfacial catalyst is selected from salts of tetraalkylammonium, trialkylbenzylammonium, phosphonium, guanidinium, as well as crown ethers. 13. The method according to claim 1 (b) or 1 (c), or any one of claims 7-12, wherein the concentration of the compound of formula (II) used in the reaction solvent is 0.1-2 ml / mmol. 14. The method according to claim 1 (d), in which apply 0.5-2 molar equivalents of copper cyanide (I). 15. The method according to claim 1 (d) or 14, in which the amount of lithium iodide used is 0.05-2 molar equivalents. 16. The method according to claim 1 (e), in which the catalyst is lithium bromide. 17. The method according to claim 1 (e) or 16, in which apply 0.5-2 molar equivalents of copper cyanide (I). 18. The method according to claims 1 (e), 16 or 17, in which the amount of catalyst is 0.05-2 molar equivalents. 19. The method according to claim 1 (f), in which 0.05-0.2 molar equivalents of copper cyanide (I) are used. 20. The method according to claim 1 (f) or 19, in which potassium cyanide is used. 21. The method according to claims 1 (f), 19 or 20, in which apply 0.5-2 molar equivalents of alkali metal cyanide. 22. The method according to claims 1 (f), 19, 20 or 21, in which the interfacial catalyst is selected from alkali metal or alkaline earth metal bromide, tetraalkylammonium and trialkylbenzylammonium bromides, phosphonium and guanidinium salts, as well as crown ethers. 23. The method according to claim 1 (f) or any one of claims 19-22, wherein the interfacial catalyst is lithium bromide. 24. The method according to claim 1 (e) or 1 (f), or any one of claims 16-23, wherein the concentration of the compound of formula (II) used in the reaction solvent is 0.1-2 ml / mmol. 25. A method of obtaining a compound of formula (II), where R ¹ and R ² have the meanings indicated in claim 1, and X is a bromine atom comprising a reaction of the corresponding compound of formula (II), in which X is a chlorine atom, with a source of bromide . 26. The method according A.25, in which the source of bromide is selected from bromides of alkali and alkaline earth metals, copper bromide (I), copper bromide (II), zinc bromide, hydrogen bromide and bromine, or a mixture of lithium bromide and copper bromide (I) . 27. The method according A.25 or 26, in which the source of bromide is a mixture of lithium bromide and copper bromide (I), or magnesium bromide, or copper bromide (II). 28. The method according to claims 25, 26 or 27, wherein the amount of the bromide source used is 1-5 molar equivalents. 29. A method of obtaining a compound of formula (I) according to claim 1 (e) or 1 (f), in which a compound of formula (II), where X is a bromine atom, is obtained by the method in accordance with claim 25. 30. The method according to any one of the preceding paragraphs, in which R ¹ is trifluoromethyl, fluorine or bromine, R ² is hydrogen or methoxy. 31. The method according to any one of the preceding paragraphs, in which R ¹ is trifluoromethyl, and R ² is hydrogen. 32. The method according to claims 1, 25 or 29 essentially as described above.