DE1670807A1 - Process for the preparation of cyclic guanidines - Google Patents

Description

Process for the production of @v @ lischen guanidines The coccidiosis is still a significant veterinary problem. These are around intestinal infections, more rarely liver or kidney infections, especially in the Poultry and other small animal husbandry lead to major economic losses can. Coc @ idiosis also plays a role in cattle, sheep and other large animals to an increasing extent a role. Erreg @ r are unicellular organisms (protozoa) that develop in the tissue of the affected organs and cause severe organ damage being able to lead. At the end of the Vermehru @ diesel parasite the opposite environmental influences relatively resistant permanent infectious stages (oocysts) from the host animals divorced. The main pets can each be from several species of Coooidia be infested. So are z. B. nine different species of the genus Eimeria in the chicken known. The respective Eimeria species often prefer certain sections of the intestine or also different ages of the host animals. In many cases - so in the Poultry farming is the possibility of spreading as a result of modern, rational husbandry methods of coccidia Infections strongly favored and with it the use particularly urgent before effective coccidiostats. None of the known ones Coccidiostatica is effective against all important coccidia species. Therefore be new compounds with coccidiostatic properties are needed, especially if they are supposed to influence infections with coccidia species, which so far have been difficult to treat could be influenced.

It has now been found that cyclic guanidines of the general formula in which R stands for an aromatic radical substituted by halogen, cyano, alkyl, haloalkyl and / or alkoxy, R ′ and R ″ stand for hydrogen, alkyl with 1 to 4 carbon atoms and / or acyl, n stands for 0, 1 and 2 and m stand for 1 and 2, have strong coccidiostatic properties.These new cyclic guanidines are highly effective against various coccidial infections in poultry, e.g.

@@@ enia tenella u. e., but also from Säugeti @@@@, like inderTierj'.edisinsur'Pekämj'l'ungderCor'cidiosvbrwer'.d '. i ~ r ~ ai. '. ; v; rd ~; ~; ir.: z't: e::. : r ~ W eza e. :: z Cccvta ~ r: v : WG: i. ": T; [: I. i, ~., Will.

With the compound mentioned in Example 1, for. B. by one to four doses of 25 to 50 mg / kg each of experimental and natural infections of the rabbit with t Eimeria stiedae (liver coccidiosis) Clinically z. T. also parasitological heal. This means a step forward over all previously tested for the same indication certain commercial preparations, especially since the compounds z. Belly against small intestinal coccidia of the rabbit and against coccidia of the Hunes, e.g. B. E. tenella, are highly effective.

In the Belgian patent 632 578, the implementation is already from phenyl isocyanide dichloride with N, N'-dimethylethylenediamine to 2-phenylimino - N, N'-dinethylimide. 33olidine et al. described. However, these compounds are ineffective against coccidiosis.

The new compounds are obtained in a manner known per se either a) by reacting aromatic @: yanamides with aliphatic diamines, e.g. B. bb); I: t Y? I1 t. '.,: T, "Uu'f.' IC: E ',. E! ~ I. I. f? 111?.''I: 13? Grl;:: 1? S: 0'TI J'7. L; Ei (- '): L-' wart of heavy metal oxides or salts @@ sets, e.g. or c) by reacting aromatic amines with O-alkylisoureas or S-alkylisothioureas, optionally in the presence of metal salts, e.g. B. R ' I. zN-CaL ", R- o-1 i, 'N-CR'"" - 110-Alkvl "-HS-alkyl -HS-. : i. lyl or d) by cyclizing aminoalkyl-substituted S-alkyl-isothioureas, see B. 4th R-; -C -``.-; '.- (CR ", -C'r.-Ru! ......... ..-.-.. L ; ti '' -ti.-i t "} LL or e) by adding aminoalkyl-substituted thioureas by treatment with inorganic acid chlorides, e.g. B. SOCl2, CoCl2, PCl5 etc., cyclized via the corresponding chloroformamidines, z. B. or f) by nan reacting aromatic guanidines with aliphatic diamines in the melt flow, e.g. B. or g) by reacting aromatic amines with Isoharnatoffchloriden, z. B. or h) by reacting aromatic halogenated hydrocarbons with halogen with a sufficient amount of plus activation, e.g. hexalobenzene, with cyclic guanidines, e.g. B. or i) by reacting aromatic isocyanide halides with aliphatic diamines, e.g. B. or k) by adding compounds of the general formula i: .s? ~ .ij- ~ L ~; .1 ', si.Jj..iaf ~~ .4 -'. sW.t ~ iZLy-'F .. (?: [.- '~' J '.c; .l B. of pentachlorophenyl isocyanide dichloride and N, N'-dimethyl-Pen'tacMorphpnylisocye-n.iddichloric! UdN, N'-Diüetb.yl "N, N'-dimethylimidazolidine according to the following formula: lJ.:Ll A solution of 346.5 g of pentachlorophenyl isocyanide dichloride in 300 cc of toluene is added dropwise to a mixture of 88 g of NN'-dimethylethylenedismine, 202 g of triethylamine and 300 cc of toluene under external cooling. The reaction mixture is then left to react at 70 to 800 for some time.

The salt formed is filtered off with suction while hot and the filtrate is concentrated, or but @au shakes out with water, separates and dries the organic phase and a.

In both cases you get a solid residue that is used for cleaning is recrystallized from petroleum ether or ethanol.

Working on the product of the above formula: 89% of theory, mp 146 to 147 ° C.

Example 2: 277.5 g of 2,4,6-trichlorophenyl isocyanide dichloride, dissolved in 200 cc of acetone, are added dropwise with external cooling to a vin solution of 88 g of N'-dimethylethylenediamine and 80 g of sodium hydroxide in 300 cc of water. The reaction mixture is a few more Zei. t stirred at 50 ° C and then taken up in benzene. After the solvent has been distilled off, a residue remains which is recrystallized from white spirit for cleaning.

Yield of the product of the above formula: 81% of theory, melting point 99 to 100.degree.

The compounds of the following constitution are prepared under reaction conditions analogous to those in Examples 1 and 2: M.p. 63 to 64 ° C bp 143 to 145 ° C / 0.1 mm F. 209 to 211 ° C F. 187 to 188 ° C 149-150 ° C F. 191-198 ° C / 15 mm F. 228-230 ° C / 15 mm F. 214-223 ° C / 46 mm F. 216-225 ° C / 15 mm F. 230 - 238 ° C / 17 mm F. 71-75 ° C F. 79 - 81 ° C F. 146 - 148 ° C Oil F. 99 - 101 ° C F. 99-102 "C / 0.08mm F. 44 - 46 ° C F. 83 - 87 ° C F. 190 to 192 ° C F. 166 to 168 ° C F. 245 to 247 ° C F. 108bir.; 1100 F. 169 to 170 ° C F. 235 to 237 ° C 149 to 151 ° C. 209 to 211 ° C F. 196 to 198 ° C. 245 to 246 ° C F. 339 to 341 ° C F. 244 to 245 ° C F. 193 to 195 ° C Example 3: 33 g of 2-pentachlorophenylimino-imidazolidine are refluxed in 150 cc of acetic anhydride. After concentration ex, a residue remains which is recrystallized from xylene.

Yield of the product of the above formula: 94% of theory, F.

224 to 225 ° C. Under reaction conditions analogous to those in Example 3, the compounds of the following constitution are prepared.

M.p. 150 to 152 ° C M.p. 305 to 307 ° C

Claims (2)

Claims 1. Process for the preparation of cyclic guanidines, characterized in that either a) arom: @tische cyanamides with aliphatic Reacting diamines or by b) aromatic amines with thioureas in the presence of heavy metal oxides or salts or by c) aromatic amines with O-alkylisoureas or S-alkyl-isothioureas, optionally in the presence of metal salts, or by d) aminoalkyl-substituted S-alkyl-isothioureas cyclized or by e) aminoalkyl-substituted thioureas by treatment cyclized with inorganic acid chlorides via the corresponding chloroformamidines or by f) aromatic guanidines or aliphatic diamines in melt flow converts or by g) aromatic amines with isourea chlorides u @ sets or by adding h) aromatic halocarbons j. ws. sserstc. ffe With sufficient activated Reacts halogen with cyclic guanidines or index one i) aromatic Reacts isocyanide dihalides with aliphatic diamines. 2) Cyclic guanidines of the formula