DE2910330A1 - 1-Phenyl-3-amino-5-hydroxy-1,2,4-triazole derivs. - useful as antiinflammatory, diuretic, analgesic and antipyretic agents - Google Patents

1-Phenyl-3-amino-5-hydroxy-1,2,4-triazole derivs. - useful as antiinflammatory, diuretic, analgesic and antipyretic agents

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DE2910330A1
DE2910330A1 DE19792910330 DE2910330A DE2910330A1 DE 2910330 A1 DE2910330 A1 DE 2910330A1 DE 19792910330 DE19792910330 DE 19792910330 DE 2910330 A DE2910330 A DE 2910330A DE 2910330 A1 DE2910330 A1 DE 2910330A1
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triazole
hydroxy
phenyl
formula
methyl
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Georg Dr Alpermann
Heinz Dipl Chem Dr Loewe
Josef Urbanietz
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Hoechst AG
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Hoechst AG
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D249/14—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
    • C07C275/70—Compounds containing any of the groups, e.g. isoureas

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  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Triazole derivs. of formula (I) are new. In (I) R1-R3 are 1-4C alkyl, 1-4C alkoxy, halogen or CF3, or 2 adjacent alkyl gps. can form a 4C ring, or R3 can be opt. substd. phenoxy when R1 and/or R2 is H. (I) have antiinflammatory, diuretic, analgesic and antipyretic activity and can be used to treat inflammations, rheumatic disorders or multiple sclerosis.

Description

1-Phenyl-3-amino-5-hydroxy-1,2,4-triazolderivate,1-phenyl-3-amino-5-hydroxy-1,2,4-triazole derivatives,

Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel Es ist bekannt, daß man durch Umsetzen von Phenylhydrazin mit S-Methyl-mono-methoxycarbonyl-isothioharnstoff unter Abspaltung von Methylmercaptan und Methanol 1-Phenyl-3-amino-5-hydroxy-1,2,4-triazol erhält (K.Mohan, K. Bhramaramba und R.V.Venkataratnam, Chemind. 1978, 125). Ferner ist bekannt, daß man das nämliche Produkt auch durch Verseifung von 1-Phenyl-3-acetamido-5-hydroxy-1,2,4-triazol oder 1-Phenyl-3-benzamido-5-hydroxy-1,2,4-triazol erhält, das seinerseits aus 5-Methyl-3- (N-phenyl-ureido) -1,2,4-oxdiazol bzw. 5-Phenyl-3- (N-phenyl-ureido) -1,2 ,4-oxdiazol durch Ringschluß im alkalischen Medium zugänglich ist (M.Ruccia und N.Vivona, J.chem.Soc. D 1970, 866).Process for their manufacture and their use as pharmaceuticals It is known that by reacting phenylhydrazine with S-methyl-mono-methoxycarbonyl-isothiourea with elimination of methyl mercaptan and methanol, 1-phenyl-3-amino-5-hydroxy-1,2,4-triazole (K.Mohan, K. Bhramaramba and R.V.Venkataratnam, Chemind. 1978, 125). Further it is known that the same product can also be obtained by saponifying 1-phenyl-3-acetamido-5-hydroxy-1,2,4-triazole or 1-phenyl-3-benzamido-5-hydroxy-1,2,4-triazole, which in turn is obtained from 5-methyl-3- (N-phenyl-ureido) -1,2,4-oxdiazole or 5-phenyl-3- (N-phenyl-ureido) -1,2,4-oxdiazole is accessible by ring closure in an alkaline medium (M.Ruccia and N.Vivona, J.chem.Soc. D 1970, 866).

Gegenstand der Erfindung sind 1-Phenyl-3-amino-5-hydroxy-1,2,4-triazolderivate der Formel (1) in der R1, R2 und R3 gleich oder verschieden sein können und Alkyl mit 1 - 4 C-Atomen, wobei im Falle der Substitution durch 2 Alkylgruppen in ortho-position zueinander die beiden Alkyle mit zusammen 4 C-Atomen einen Ring bilden können, Alkoxy mit 1 - 4 C-Atomen, Halogen oder Trifluormethyl in der R1 und/oder R2 auch Wasserstoff und unabhängig davon R3 auch gegebenenfalls substituiertes Phenoxy bedeuten.The invention relates to 1-phenyl-3-amino-5-hydroxy-1,2,4-triazole derivatives of the formula (1) in which R1, R2 and R3 can be identical or different and alkyl with 1-4 carbon atoms, whereby in the case of substitution by 2 alkyl groups in the ortho position to one another, the two alkyls with 4 carbon atoms together can form a ring, alkoxy with 1-4 carbon atoms, halogen or trifluoromethyl in which R1 and / or R2 also denote hydrogen and, independently thereof, denote R3 also optionally substituted phenoxy.

Gegenstand der Erfindung ist auch ein Verfahren zur Herstellung der Verbindung der Formel (1) , das dadurch gekennzeichnet ist, daß man ein a) Phenylhydrazinderivat der Formel (2) in der R1, R2 und R3 die für Formel (1) angegebenen Bedeutungen haben, mit S-Methyl-bis-methoxycarbonylisothioharnstoff umsetzt und das erhaltene 1,2,4-Triazol- in der R1, R2 und R3 die für Formel (1) angegebenen Bedeutungen haben, im alkalischen Medium verseift, b) ein Phenylhydrazinderivat der Formel (2), in der R1, R2 und R3 die für Formel (1) angegebenen Bedeutungen haben, mit S-Methyl-mono-methoxycarbonyl-isothioharnstoff bei erhöhter Temperatur umsetzt, c) ein Phenylhydrazinderivat der Formel (2), in welcher R1, R2 und R3 die für Formel (1) angegebenen Bedeutungen haben- mit O-Methyl-mono-methoxycarbonyl-isoharnstoff oder S-Methyl-mono-methoxycarbonyl- isothioharnstoff umsetzt und die erhaltenen Guanidinderivate der Formel (4) in welcher R1 R2 und R3 die für Formel (1) angegebenen Bedeutungen haben, mit Alkali behandelt, d) ein 1,2,4-Oxdiazolderivat der Formel (5) in der R1, R2 und R3 die für in Formel (1) angegebenen Bedeutungen haben und R4 für Methyl oder Phenyl steht, mit Alkali zu einem 1,2,4-Triazolderivat der Formel (6) umsetzt, in der die Substituenten die für Formel (5) angegebenen Bedeutungen haben, besitzen, und diese Verbindung im sauren Medium verseift.The invention also relates to a process for the preparation of the compound of the formula (1), which is characterized in that a) phenylhydrazine derivative of the formula (2) in which R1, R2 and R3 have the meanings given for formula (1), with S-methyl-bis-methoxycarbonylisothiourea and the resulting 1,2,4-triazole in which R1, R2 and R3 have the meanings given for formula (1), saponified in an alkaline medium, b) a phenylhydrazine derivative of the formula (2) in which R1, R2 and R3 have the meanings given for formula (1), with S-methyl-mono-methoxycarbonyl-isothiourea reacts at elevated temperature, c) a phenylhydrazine derivative of the formula (2), in which R1, R2 and R3 have the meanings given for formula (1) - with O-methyl-mono-methoxycarbonyl- isourea or S-methyl-mono-methoxycarbonyl-isothiourea and the resulting guanidine derivatives of the formula (4) in which R1, R2 and R3 have the meanings given for formula (1), treated with alkali, d) a 1,2,4-oxdiazole derivative of the formula (5) in which R1, R2 and R3 have the meanings given in formula (1) and R4 represents methyl or phenyl, with alkali to form a 1,2,4-triazole derivative of the formula (6), in which the substituents have the meanings given for formula (5), and this compound is saponified in an acidic medium.

Als Bedeutungen für die Substituenten R1, R2 und R3 in den Formeln (1) bis (6) seien R1, R2 und R3 beispielhaft genannt: Alkyl wie Methyl, Äthyl, n- und i-Propyl, n-, iso- und tert. Butyl, vorzugsweise Methyl; Alkoxy wie Methoxy, Äthoxy, n- und i-Propoxy sowie n-, iso- und tert. Butoxy, vorzugsweise Methoxy; und Halogen wie Fluor, Chlor, Brom und Jod, vorzugsweise Chlor.As meanings for the substituents R1, R2 and R3 in the formulas (1) to (6) R1, R2 and R3 are mentioned by way of example: alkyl such as methyl, ethyl, n- and i-propyl, n-, iso- and tert. Butyl, preferably methyl; Alkoxy such as methoxy, Ethoxy, n- and i-propoxy and n-, iso- and tert. Butoxy, preferably methoxy; and halogen such as fluorine, chlorine, bromine and iodine, preferably chlorine.

Die Phenoxygruppe kann ein- oder zweimal durch Halogen, vorzugsweise Chlor, oder A-lkyl mit 1 - 4 C-Atomen, vorzugsweise Methyl, substituiert sein.The phenoxy group can be substituted once or twice by halogen, preferably Chlorine or alkyl having 1-4 carbon atoms, preferably methyl, may be substituted.

Zur Durchführung der Reaktion nach a) erhitzt man ein 1,2,4-Triazolderivat der Formel (3) in wäßrigem Alkali, wie Natron- oder Kalilauge, je nach Reaktivität des vorliegenden speziellen Derivates eine halbe bis zu fünf Stunden am Rückfluß und neutralisiert sodann mit einer anorganischen oder organischen Säure, beispielsweise mit Salzsäure, Schwefelsäure, Essigsäure oder Milchsäure.To carry out the reaction according to a), a 1,2,4-triazole derivative is heated of formula (3) in aqueous alkali, such as sodium or potassium hydroxide, depending on the reactivity of the present particular derivative from half an hour to five hours at reflux and then neutralized with an inorganic or organic acid, for example with hydrochloric acid, sulfuric acid, acetic acid or lactic acid.

Als Triazolderivate der Formel (3) kommen hierfür infrage 1 - (4-Methyl-phenyl) -3-methoxycarbonylamino-5-hydroxy-?,2,4-triazol 1-(3-Methyl-phenyll-3-methoxycarbonylamino-5-hydroxy-1,2,4-triazol 1-(2-Methyl-phenyl)-3-methoxycarbonylamino-5-hydroxy-1,2,4-triazol 1 - (3-Äthyl-phenyl) -3-methoxycarbonylamino-5-hydroxy-1,2,4-triazol F(3-PrOpyl-phenyl)-3-methoxycarbonylamino-5-hydroxy-1,2,4-triazol t-(3-tert. Butyl-phenyl) -3-methoxycarbonylamino-5-hydroxy-1,2,4-triazol 1-(4-Chlor-phenyl)-3-methoxycarbonylamino-5-hydroxy-1,2,4-triazol 1-(3-Chlor-phenyl)-3-methoxyearbonylamino-5-hydroxy-1,2,3-triazol 1-(2-Chlor-phenyl)-3-methoxycarbonylamino-5-hydroxy-1,2,4-triazol 1- (4-Brom-phenyl) -3-methoxycarbonylamino-5-hydroxy-1,2,4-triazol 1-(4-Jod-phenyl)-3-methoxyearbonylamino-5-hydroxy-1,2,4-triazol 1-(4-Fluor-phenyl)-3-methoxyearbonylamino-5-hydroxy-1,2,4-triazol 1 - (4-Methoxy-phenyl) -3-methoxycarbonylamino-5-hydroxy-1,2,4-triazol 1-(3-Methoxy-phenyl)-3-methoxycarbonylamino-5-hydroxy-1,2,4-triazol 1 - (2-Methoxy-phenyl) -3-methoxycarbonylamino-5-hydroxy-1,2,4-trazol 1 - (4-Äthoxy-phenyl) - 3-methoxycarbonylamino-5-hydroxy-1,2,4-triazol 1-(4-Propoxy-phenyl)-3-methoxyearbonylamíno-5-hydroxy-1,2,4-triazol 1 - (4-Isopropoxy-phenyl) -3-methoxycarbonylamino-5hydroxy-1,2,4-triazol 1-(4-n-Butoxy-phenyl)-3-methoxyzarbonylamino-5-hydroxy-1,2,4-triazol 1-{2,3-Dimethyl-phenyl)-3-methoxyzarbonylamino-5-hyaroxy-1,2,4-triazol 1 - (2, 4-Dimethyl-phenyl) -3-methoxycarbonylamino-5-hydroxy-1;2,4-triazol 1-(2,5-Dimethyl-phenyl}-3-methoxyzarbonylamino-5-hydroxy-1,2,4-triazol 1- (2, 6-Dimethyl-phenyl) -3-methoxycarboflylamino-5-hydroxy-1,2,4-triazol 1-(3,4-Dimethyl-phenyl9-3-methoxycarbonylamino-5-hydroxy-1,2,4-triazol 1-(3,5-Dimethyl-phenyl)-3-methoxycarbonylamino-5-hydroxy-1,2,4-triazol 1-(2,3-Dichlor-phenyl)-3-methoxycarbonylamino-5-hydroxy-1,2,4-triazol 1-(2,4-Dichlor-phenyl)-3-metoxycarbonylamino-5-hydroxy-1,2,4-triazol 1-(2,5-Dichlor-phenyl)-3-methoxycarbonylamino-5-hydroxy-1,2,4-triazol 1-(2,6-Dichlor-phenyl)-3-methoxycarbonylamino-5-hydroxy-1,2,4-triazol 1-(3 r 4-Dichlor-phenyl)-3-methoxyzarbonylamino-5-hydroxy-1,2,4-triazol 1-(3,5-Dichlor-phenyl)-3-methoxycarbonylamino-5-hydroxy-1,2,4-triazol 1 - (3-Trifluormethyl-phenyl) -3-methoxycarbonylamino-5-hydroxy- 1,2 4-triazol 1- ( 3,5-Bis-trifluormethyl-phenyl)-3-methoxycarbonylamino-5-hydroxy-1,2 r 4-triazol 1- (2 3-Tetramethylen-p-henyl) -3-methoxycarbonylamino-5-hydroxy- 1 2 , 4-triazol 1-(3,4-Tetramethylen-phenyl}-3-methoxycarbonylamino-5-hydroxy-1,2,4-triazol, welche gemäß dem Verfahren nach a) folgende 1,2,4-Triazolderivate der Formel (1) liefern: 1-(4-Methyl-phenyl)-3-amino-5-hydroxy-1,2,4-triazol 1- (3-Methyl-phenyl) -3-amino-5-hydroxy-1-,2 4-triazol 1-(2-Methyl-phenyl)-3-amino-5-hydroxy-1,2,4-triazol 1-(3-Xthyl-phenyl}-3-amino-5-hydroxy-1,2,4-triazol 1-(3-Propyl-phenyl)-3-amino-5-hydroxy-1,2,4-triazol 1-(3-tert.Butyl-phenyl)-3-amino-5-hydroxy-1,2,4-triazol 1-(4-Chlor-phenyl)-3-amino-5-hydroxy-1,2,4-triazol 1-(3-Chlor-phenyl)-3-amino-5-hydroxy-1,2,4-triazol 1- (2-Chlor-phenyl)-3-amino-5-hydroxy-1 2,4-triazol 1-(4-Brom-phenyl)-3-amino-5-hydroxy-1,2,4-triazol 1-(4-Jod-phenyl)-3-amino-5-hydroxy-1,2,4-triazol 1-(4-Fluor-phenyl)-3-mino-5-hydroxy-1,2,4-triazol 1-(4-Methoxy-phenyl)-3-amino-5-hydroxy-1,2,4-triazol 1-(3-Methoxy-phenyl)-3-amino-5-hydroxy-1,2,4-triazol 1-(2-Methoxy-phenyl)-3-amino-5-hydroxy-1,2,4-triazol 1-(4-Xthoxy-phenyl)-3-amino-5-hydroxy-1,2,4-triazol 1-(4-Propoxy-phenyl)-3-amino-5-hydroxy-1,2,4-triazol 1-(4-Isopropoxy-phenyl)-3-amino-5-hydroxy-1,2,4-triazol 1-(4-n-Butoxy-phenyl)-3-amino-5-hydroxy-1,2,4-triazol 1-(2,3-Dimethyl-phenyl9-3-amino-5-hydroxy-1,2,4-triazol 1-(2,4-Dimethyl-phenyl)-3-amino-5-hydroxy-1,2,4-triazol 1-(2,5-Dimethyl-phenyl)-3-amino-5-hydroxy-1 7 2,4-triazol 1-(2,6-Dimethyl-phenyl)-3-amino-5-hydroxy-1 t 2,4-triazol 1-(3,4-Dimethyl-phenyl)-3-amino-5-hydroxy-1,2,4-triazol 1-(3,5-Dimethyl-phenyl)-3-amino-5-hydroxy-1,2,4-triazol 1-(2,3-Dichlor-phenyl)-3-amino-5-hydroxy-1,2^4-triazol 1-(2,4-Dichlor-phenyl}-3-amino-5-hydroxy-1,2,4-triazol 1-(2,5-Dichlor-phenyl}-3-amino-5-hydroxy-1,2,4-triazol l-{2,6-Dichlor-phenyl)-3-amino-5-hydroxy-t,2,4-tria20l 1-{3,4-Dichlor-phenyl)-3-amino-5-hydroxy-t,2,4-triazol 1-{3,5-Dichlor-phenyl)-3-amino-5-hydroxy-1,2,4-triazol 1-{3-Trifluormethyl-phenyl)-3-amino-5-hydroxy-1,2,4-triazol 1 - (3, 5-Bis-trifluormethyl-phenyl) -3-amino-5-hydroxy-112,4-triazol 1-12,3-Tetramethylen-phenyl)-3-amino-5-hydroxy-1,2,4-hydroxy 1-(3,4-Tetramethylen-phenyl)-3-amino-5-hydroxy-1,2,4-triazol.Possible triazole derivatives of the formula (3) for this purpose are 1 - (4-methyl-phenyl) -3-methoxycarbonylamino-5-hydroxy- ?, 2,4-triazole 1- (3-methyl-phenyl-3-methoxycarbonylamino-5-hydroxy-1,2,4-triazole 1- (2-methyl-phenyl) -3-methoxycarbonylamino-5-hydroxy-1,2,4-triazole 1 - (3-ethyl-phenyl) -3-methoxycarbonylamino-5-hydroxy-1,2,4-triazole F (3-propyl-phenyl) -3-methoxycarbonylamino-5-hydroxy-1,2,4-triazole t- (3-tert-butyl-phenyl) -3-methoxycarbonylamino-5-hydroxy-1,2,4-triazole 1- (4-chloro-phenyl) -3-methoxycarbonylamino-5-hydroxy-1,2,4 -triazole 1- (3-chloro-phenyl) -3-methoxy-carbonylamino-5-hydroxy-1,2,3-triazole 1- (2-chloro-phenyl) -3-methoxycarbonylamino-5-hydroxy-1,2,4-triazole 1- (4-Bromo-phenyl) -3-methoxycarbonylamino-5-hydroxy-1,2,4-triazole 1- (4-iodo-phenyl) -3-methoxy-carbonylamino-5-hydroxy-1,2,4-triazole 1- (4-fluoro-phenyl) -3-methoxy-carbonylamino-5-hydroxy-1,2,4-triazole 1 - (4-Methoxyphenyl) -3-methoxycarbonylamino-5-hydroxy-1,2,4-triazole 1- (3-methoxyphenyl) -3-methoxycarbonylamino-5-hydroxy-1,2,4-triazole 1 - (2-methoxyphenyl) -3-methoxycarbonylamino-5-hydroxy-1,2,4-trazol 1 - (4-ethoxyphenyl) 3-methoxycarbonylamino-5-hydroxy-1,2,4-triazole 1- (4-propoxyphenyl) -3-methoxy-carbonylamino-5-hydroxy-1,2,4-triazole 1 - (4-Isopropoxyphenyl) -3-methoxycarbonylamino-5-hydroxy-1,2,4-triazole 1- (4-n-Butoxyphenyl) -3-methoxycarbonylamino-5-hydroxy-1,2,4-triazole 1- {2,3-Dimethyl-phenyl) -3-methoxycarbonylamino-5-hyaroxy-1,2,4-triazole 1 - (2,4-Dimethyl-phenyl) -3-methoxycarbonylamino-5-hydroxy-1; 2,4-triazole 1- (2,5-dimethyl-phenyl} -3-methoxycarbonylamino-5-hydroxy-1,2,4-triazole 1- (2,6-Dimethyl-phenyl) -3-methoxycarboflylamino-5-hydroxy-1,2,4-triazole 1- (3,4-Dimethyl-phenyl9-3-methoxycarbonylamino-5-hydroxy-1,2, 4-triazole 1- (3,5-Dimethyl-phenyl) -3-methoxycarbonylamino-5-hydroxy-1,2,4-triazole 1- (2,3-dichloro-phenyl) -3-methoxycarbonylamino-5-hydroxy-1,2 , 4-triazole 1- (2,4-dichloro-phenyl) -3-metoxycarbonylamino-5-hydroxy-1,2,4-triazole 1- (2,5-dichloro-phenyl) -3-methoxycarbonylamino-5-hydroxy-1,2 , 4-triazole 1- (2,6-dichloro-phenyl) -3-methoxycarbonylamino-5-hydroxy-1,2,4-triazole 1- (3 r 4-dichloro-phenyl) -3-methoxycarbonylamino-5-hydroxy-1,2 , 4-triazole 1- (3,5-dichloro-phenyl) -3-methoxycarbonylamino-5-hydroxy-1,2,4-triazole 1 - (3-Trifluoromethyl-phenyl) -3-methoxycarbonylamino-5-hydroxy-1,2 4-triazole 1- (3,5-Bis-trifluoromethyl-phenyl) -3-methoxycarbonylamino-5-hydroxy-1,2r 4-triazole 1- (2 3-Tetramethylene-p-henyl) -3-methoxycarbonylamino-5-hydroxy-1 2, 4-triazole 1- (3,4-Tetramethylene-phenyl} -3-methoxycarbonylamino-5-hydroxy-1,2,4-triazole, which according to the process according to a) provide the following 1,2,4-triazole derivatives of the formula (1): 1- (4-methyl-phenyl) -3-amino-5-hydroxy-1,2,4-triazole 1- (3-methyl-phenyl) -3-amino-5-hydroxy-1-, 2 4-triazole 1- (2-methyl-phenyl) -3-amino-5-hydroxy-1,2,4-triazole 1- (3-ethylphenyl} -3-amino-5-hydroxy-1,2, 4-triazole 1- (3-propyl-phenyl) -3-amino-5-hydroxy-1,2,4-triazole 1- (3-tert-butyl-phenyl) -3-amino-5-hydroxy-1,2,4 -triazole 1- (4-chloro-phenyl) -3-amino-5-hydroxy-1,2,4-triazole 1- (3-chloro-phenyl) -3-amino-5-hydroxy-1,2,4-triazole 1- (2-chloro-phenyl) -3-amino-5-hydroxy-1,2,4-triazole 1- (4-bromo-phenyl) -3-amino-5-hydroxy-1,2,4-triazole 1- (4-iodo-phenyl) -3-amino-5-hydroxy-1,2,4-triazole 1- (4-fluoro-phenyl) -3-mino-5-hydroxy-1,2,4-triazole 1- (4-methoxyphenyl) -3-amino-5-hydroxy-1,2,4-triazole 1- (3-methoxyphenyl) -3-amino-5-hydroxy-1,2,4-triazole 1- (2-methoxyphenyl) -3-amino-5-hydroxy-1,2,4-triazole 1- (4-xthoxyphenyl) -3-amino-5-hydroxy-1,2,4-triazole 1- (4-propoxyphenyl) -3-amino-5-hydroxy-1,2,4-triazole 1- (4-isopropoxyphenyl) -3-amino-5-hydroxy-1,2,4-triazole 1- (4-n-butoxyphenyl) -3-amino-5-hydroxy-1,2,4-triazole 1- (2,3-dimethyl-phenyl9-3-amino-5-hydroxy-1,2, 4-triazole 1- (2,4-dimethyl-phenyl) -3-amino-5-hydroxy-1,2,4-triazole 1- (2,5-dimethyl-phenyl) -3-amino-5-hydroxy-1 7 2,4-triazole 1- (2,6-dimethyl-phenyl) -3-amino-5-hydroxy-1 t 2,4-triazole 1- (3,4-dimethyl-phenyl) -3-amino-5 -hydroxy-1,2,4-triazole 1- (3,5-Dimethyl-phenyl) -3-amino-5-hydroxy-1,2,4-triazole 1- (2,3-dichlorophenyl) -3-amino-5-hydroxy-1,2 ^ 4-triazole 1- (2,4-dichloro-phenyl} -3-amino-5-hydroxy-1,2,4-triazole 1- (2,5-dichloro-phenyl} -3-amino-5-hydroxy-1,2,4-triazole 1- {2,6-dichloro-phenyl) -3-amino-5-hydroxy-t, 2 , 4-tria20l 1- {3,4-dichloro-phenyl) -3-amino-5-hydroxy-t, 2,4-triazole 1- {3,5-dichloro-phenyl) -3-amino-5-hydroxy-1,2 , 4-triazole 1- {3-trifluoromethyl-phenyl) -3-amino-5-hydroxy-1,2,4-triazole 1 - (3, 5-bis-trifluoromethyl-phenyl) -3-amino-5-hydroxy-112,4-triazole 1-12,3-tetramethylene-phenyl) -3-amino-5-hydroxy-1,2,4-hydroxy 1- (3,4-Tetramethylene-phenyl) -3-amino-5-hydroxy-1,2,4-triazole.

Zur Durchführung der Reaktion nach b) erhitzt man ein Phenylhydrazin-Derivat der Formel (2) in einem hochsiedenden alkoholischen Lösungsmittel wie Methylglykol mit S-Methyl-mono-methoxycarbonyl- isothioharnstoff zwechSEig in Gegenwart katalytischer Mengen einer starken organischen Säure wie p-Toluol-sulfonsäure, mehrere Stunden (je nach Reaktivität des eingesetzten Phenylhydrazinderivates) auf eine erhöhte Temperatur zwischen 60 und 1400C, vorzugsweise bis zum Sieden des eingesetzten Lösungsmittels.To carry out the reaction according to b), a phenylhydrazine derivative is heated of formula (2) in a high-boiling alcoholic solvent such as methyl glycol with S-methyl-mono-methoxycarbonyl-isothiourea two-fold in the presence of catalytic Amounts of a strong organic acid such as p-toluenesulfonic acid, several hours (depending on the reactivity of the phenylhydrazine derivative used) to an increased Temperature between 60 and 1400C, preferably up to the boiling of the solvent used.

Die Isolierung der Reaktionsprodukte der Formel (1) geschieht vornehmlich durch Eindampfen des Reaktionsgemisches, vorzugsweise unter vermindertem Druck, und Verrühren des Rückstandes mit einem geeigneten Lösungsmittel, vorzugsweise einem Alkohol, insbesondere Methanol, und Absaugen des ausgefallenen Kristallisats.The reaction products of the formula (1) are mainly isolated by evaporating the reaction mixture, preferably under reduced pressure, and stirring the residue with a suitable solvent, preferably one Alcohol, especially methanol, and filtering off the precipitated crystals.

Die hierfür infrage kommenden Phenylhydrazinderivate der Formel (2) sind die nämlichen, wie sie für das Verfahren nach a) beschrieben wurden. Ebenso entsprechen die erhaltenen Reaktionsprodukte denjenigen, wie sie nach Verfahren a) erhalten werden.The phenylhydrazine derivatives of the formula (2) that are suitable for this purpose are the same as described for the method according to a). as well the reaction products obtained correspond to those according to the process a) can be obtained.

Zur Durchführung der Reaktion nach c) verf-ährt man analog dem Verfahren a), indem man ein Guanidinderivat der Formel 4) mit wäßrig-alkoholischem Alkali behandelt. Hierzu eignen sich Mischungen von wäßrigen Lösungen anorganischer und starker organischer Basen, wie Natrium- oder Kaliumhydroxid und alkoholischen Lösungsmitteln wie Methanol, Äthanol oder Propanol.To carry out the reaction according to c) one proceeds analogously to the process a) by adding a guanidine derivative of the formula 4) with aqueous-alcoholic alkali treated. Mixtures of aqueous solutions of inorganic and are suitable for this purpose strong organic bases such as sodium or potassium hydroxide and alcoholic solvents such as methanol, ethanol or propanol.

Als geeignete Ausgangsmaterialien seien folgende Guanidinderivate der Formel (4) genannt N-(4-Methyl-phenylaminol-N'-methoxycarbonyl-guanidin N-(3-Methyl-phenylamino)-N'-methoxyearbonyl-guanidin N- (2-Methyl-phenylamino) -N' -methoxycarbonyl-guanidin N- (3-Äthyl-phenylamino) -N' -methoxycarbonyl-guanidin N-(3-Propyl-phenylamino)-N'-methoxycarbonyl-guanidin N-(3-tert.Butyl-phenylamino}-N'-methoxycarbonyl-guanidin N- (4-Chlor-phenylamino) -N' -methoxycarbonyl-guanidin N-(3-Chlor-phenylamino)-N'-methoxycarbonyl-guanidin N-(2-Chlor-phenylamino9-N'-methoxycarbonyl-guanidin N-(4-Brom-phenylamino)-N'-methoxycarbonyl)-guanidin N-(4-Jod-phenylamino)-N'-methoxycarbonyl-guanidin N- (4-Fluor-phenylamino) -N' methoxycarbonyl) -guanidin N- (4-Methoxy-phenylamino) -N' -methoxycarbonyl-guanidin N-(3-Methoxy-phenylamino)-N'-methoxycarbonyl-guanidin N- (2-Methoxy-phenylamino) -N' -methoxycarbonyl-guanidin N- (4-Äthoxy-phenylamino) -N'-methoxycarbonyl-guanidin N- (4-Propoxy-phenylamino) -N' -methoxycarbonyl-guanidin N- (4-Isopropoxy-phenylamino) rN' -methoxycarbonyl-guanidin N- (4-n-Butoxy-phenylamino) -N -methoxycarbonyl-guanidin N-(2,3-Dimethyl-phenylamino)-N'-methoxycarbonyl-guanidin N-(2,4-Dimethyl-phenylamino)-N'-methoxycarbonyl-guanidin N-(2,5-Dimethyl-phenylamino}-N'-methoxyearbonyl-guanidin N- (2, 6-Dimethyl-phenylamino) -N' -methoxycarbonyl-guanidin N-(3,4-Dimethyl-phenylamino)-N'-methoxycarbonyl-guanidin N- (3 5-Dimethyl-phenylamino) -N'-methoxycarbonyl-guanidin N-(2,3-Dichlor-phenylamino)-N'-methoxycarbonyl-guanidin N-(2,4-Dichlor-phenylamino)-NI-methoxycarbonyl-guanidin N-{2,5-Dichlor-phenylamino)-N'-methoxycarbonyl-guanidin N-(2,6-Dichlor-phenylamino9-N'-methoxycarbonyl-guanidin N-(3,4-Dichlor-phenylamino)-Nt-methoxyearbonyl-guanidin Ç N- (3, 5-Dichlor-phenylamino) -N' -methoxycarbonyl-guanidin N- (3-Trifluormethyl-phenylamino) -N methoxycarbonyl-guanidin N-(3,5-Bis-trifluormethyl-phenylamino)-N'-methxycarbonylguanidin N-{2,3-Tetramethylen-phenylamino)-N'-methoxyzarbonylguanidin N-{3,4-Tetramethylen-phenylamino}-N'-methoxycarbonylguanidin.The following guanidine derivatives are suitable starting materials of formula (4) called N- (4-methyl-phenylaminol-N'-methoxycarbonyl-guanidine N- (3-methyl-phenylamino) -N'-methoxy-carbonyl-guanidine N- (2-methyl-phenylamino) -N'-methoxycarbonyl-guanidine N- (3-ethyl-phenylamino) -N'-methoxycarbonyl-guanidine N- (3-propyl-phenylamino) -N'-methoxycarbonyl-guanidine N- (3-tert-butyl-phenylamino} -N'-methoxycarbonyl-guanidine N- (4-chloro-phenylamino) -N'-methoxycarbonyl-guanidine N- (3-chloro-phenylamino) -N'-methoxycarbonyl-guanidine N- (2-chloro-phenylamino9-N'-methoxycarbonyl-guanidine, N- (4-bromo-phenylamino) -N'-methoxycarbonyl) -guanidine N- (4-iodo-phenylamino) -N'-methoxycarbonyl-guanidine N- (4-fluorophenylamino) -N 'methoxycarbonyl) -guanidine N- (4-methoxyphenylamino) -N '-methoxycarbonyl-guanidine N- (3-methoxyphenylamino) -N'-methoxycarbonyl-guanidine N- (2-methoxyphenylamino) -N '-methoxycarbonyl-guanidine N- (4-ethoxyphenylamino) -N'-methoxycarbonyl-guanidine N- (4-propoxyphenylamino) -N'-methoxycarbonyl-guanidine N- (4-isopropoxyphenylamino) rN'-methoxycarbonyl-guanidine N- (4-n-butoxyphenylamino) -N-methoxycarbonyl-guanidine N- (2,3-dimethyl-phenylamino) -N'-methoxycarbonyl-guanidine N- (2,4-Dimethyl-phenylamino) -N'-methoxycarbonyl-guanidine N- (2,5-Dimethyl-phenylamino} -N'-methoxy-carbonyl-guanidine N- (2,6-Dimethyl-phenylamino) -N'-methoxycarbonyl-guanidine N- (3,4-Dimethyl-phenylamino) -N'-methoxycarbonyl-guanidine N- (3 5-Dimethyl-phenylamino) -N'-methoxycarbonyl-guanidine N- (2,3-dichloro-phenylamino) -N'-methoxycarbonyl-guanidine N- (2,4-dichloro-phenylamino) -NI-methoxycarbonyl-guanidine N- {2,5-dichloro-phenylamino) -N'-methoxycarbonyl-guanidine N- (2,6-dichloro-phenylamino 9-N'-methoxycarbonyl-guanidine N- (3,4-dichloro-phenylamino) -Nt-methoxy-carbonyl-guanidine Ç N- (3, 5-dichloro-phenylamino) -N'-methoxycarbonyl-guanidine N- (3-trifluoromethyl-phenylamino) -N methoxycarbonyl-guanidine N- (3,5-bis-trifluoromethyl-phenylamino) -N'-methxycarbonylguanidine, N- {2,3-tetramethylene-phenylamino) -N'-methoxycarbonylguanidine N- {3,4-tetramethylene-phenylamino} -N'-methoxycarbonylguanidine.

Zur Durchführung der Reaktion nach d) wird ein 1-Phenyl-3-acylamino-5-hydroxy-1,2,4-triazol-derivat der Formel (6) mit einem verseifenden Agens vorzugsweise einer starken anorganischen Säure wie Salzsäure, am Rückfluß erhitzt.A 1-phenyl-3-acylamino-5-hydroxy-1,2,4-triazole derivative is used to carry out the reaction according to d) of formula (6) with a saponifying agent, preferably a strong inorganic one Acid such as hydrochloric acid, heated to reflux.

Die Reaktionsdauer richtet sich nach der Reaktivität der eingesetzten Ausgangsmaterialien und kann zwischen einer und zehn Stunden liegen. Die Isolierung erfolgt durch Neutralisieren des Reaktionsgemisches, vorzugsweise mit einer anorganischen Base wie Natron- oder Kalilauge.The reaction time depends on the reactivity of the used Starting materials and can be anywhere from one to ten hours. The isolation takes place by neutralizing the reaction mixture, preferably with an inorganic one Base such as sodium or potassium hydroxide.

Für das Verfahren d) geeignete 1,2,4-Triazol-derivate sind insbesondere 1-(4-Methyl-phenyl)-3-acetamido-5-hydroxy-1,2,4-triazol 1-l3-Methyl-phenyl)-3-acetamido-5-hydroxy-1,2,4-triazol 1-(2-Methyl-phenyl)-3-acetamido-5-hydroxy-1,2,*-triazol 1-(3-Xthylen-phenyl)-3-acetamido-5-hydroxy-1,2,4-triazol 1-(3-Propyl-phenyl)-3-acetamido-5-hydroxy-1,2,4-triazol 1-(3-tert.Butyl-phenyl)-3-acetamido-5-hydroxy-1,2,4-triazol 1-(4-Chlor-phenyl)-3-acetamido-5-hydroxy-1,2,4-triazol 1-(3-Chlor-phenyl)-3-acetamido-5-hydroxy-1,2,4-triazol 1-(2-Chlor-phenyl)-3-acetamido-5-hydroxy-1,2,4-triazol 1-(4-Erom-phenyl)-3-acetamido-5-hydroxy-1,2,4-triåzol 1-(4-Jod-phenyl)-3-acetamido-5-hydroxy-1,2,4-triazol 1- (4-Fluor-phenyl) -3-acetamido-5-hydroxy-1 2) 4-triazol 1-(4-Methoxy-phenyl)-3-acetamido-5-hydroxy-1,2,4-triazol 1-(3-Methoxy-phenyl}-3-acetamido-5-hydroxy-1,2,4-triazol 1-(2-Methoxy-phenyl)-3-acetamido-i-hydroxy-1,2,4-triazol 1-(4-LthOxy-phenyl)-3-acetamxdo-F-hydroxy-1,2,4-triazol 1-(4-Propoxy-phenyl)-3-acetamido-5-hydroxy-1,2,4-triazol 1-(4-Isopropoxy-phenyl)-3-acetamido-5-hydroxy-1,2,4-triazol 1-(4-n-Butoxy-phenyl)-3-acetamino-5-hydroxy-1,2,4-triazol 1-(2,3-Dimethyl-phenyl)-3-acetamido-5-hydroxy-1,2,4-triazol 1-{2,4-Dimethyl-phenyl)-3-acetamido-5-hydroxy-1,2,4-triazol 1-(2,5-Dimethyl-phenyl)-3-acetamido-5-hydroxy-1,2 t 4~ triazol 1-(2,6-Dimethyl-phenyl)-3-acetamido-5-hydroxy-~1,2,4-triazol 1-(3,4-Dimethyl-phenyl)-3-acetamido-5-hydroxy-1,2, 4~ triazol.1,2,4-triazole derivatives suitable for process d) are in particular 1- (4-methyl-phenyl) -3-acetamido-5-hydroxy-1,2,4-triazole (1-3-methyl-phenyl) -3-acetamido-5-hydroxy-1,2,4-triazole 1- (2-methyl-phenyl) -3-acetamido-5-hydroxy-1,2, * -triazole 1- (3-xthylenephenyl) -3-acetamido-5-hydroxy-1,2,4-triazole 1- (3-propyl-phenyl) -3-acetamido-5-hydroxy-1,2,4-triazole 1- (3-tert-butyl-phenyl) -3-acetamido-5-hydroxy-1,2,4 -triazole 1- (4-chloro-phenyl) -3-acetamido-5-hydroxy-1,2,4-triazole 1- (3-chloro-phenyl) -3-acetamido-5-hydroxy-1,2,4-triazole 1- (2-chloro-phenyl) -3-acetamido-5-hydroxy-1,2,4-triazole 1- (4-erom-phenyl) -3-acetamido-5-hydroxy-1,2,4-triazole 1- (4-iodo-phenyl) -3-acetamido-5-hydroxy-1,2,4-triazole 1- (4-fluoro-phenyl) -3-acetamido-5-hydroxy-1 2) 4-triazole 1- (4-methoxyphenyl) -3-acetamido-5-hydroxy-1,2,4-triazole 1- (3-methoxyphenyl} -3-acetamido-5-hydroxy-1,2,4-triazole 1- (2-methoxyphenyl) -3-acetamido-i-hydroxy-1,2,4-triazole 1- (4-Lthoxy-phenyl) -3-acetamxdo-F-hydroxy-1,2,4-triazole 1- (4-propoxyphenyl) -3-acetamido-5-hydroxy-1,2,4-triazole 1- (4-Isopropoxyphenyl) -3-acetamido-5-hydroxy-1,2,4-triazole 1- (4-n-Butoxyphenyl) -3-acetamino-5-hydroxy-1,2,4 -triazole 1- (2,3-Dimethyl-phenyl) -3-acetamido-5-hydroxy-1,2,4-triazole 1- {2,4-dimethyl-phenyl) -3-acetamido-5-hydroxy-1,2 , 4-triazole 1- (2,5-dimethyl-phenyl) -3-acetamido-5-hydroxy-1,2 t 4-triazole 1- (2,6-dimethyl-phenyl) -3-acetamido-5-hydroxy-1, 2,4-triazole 1- (3,4-Dimethyl-phenyl) -3-acetamido-5-hydroxy-1,2,4-triazole.

1-(3,5-Dimethyl-phenyl)-3-acetamido-5-hydroxy-1,2,4-triazol 1-(2,3-Dichlor-phenyl)-3-acetamino-5-hydroxy-1,2,4-triazol 1-(2,4-Dichlor-phenyl)-3-acetamido-5-hydroxy-1,2,4-triazol 1-(2,5-Dichlor-phenyl)-3-acetamido-5-hydroxy-1,2,4-triazol 1-(2,6-Dichlor-pheny)-3-acetamido-5-hydroxy-1,2,4-triazol 1-(3,4-Dichlor-phenyl)-3-acetåmido-5-hydroxy-1,2,4-triazol 1-(3,5-Dichlor-phenyl)-3-acetamido-5-hydroxy-1,2,4-triazol 1-(Trifluormethyl-phenyl)-3-acetamido-5-hydroxy-1,2,4-triazol 1-(3,5-Bis-trifloormethyl-phenyl)-3-acetamido-5-hydroxy-1,2,4-triazol 1-l2,3-Tetramethylen-phenyl)-3-acetamido-5-hydroxy-1,2,4-triazol 1 - (3 4-Tetramethylen-phenyl) -3-acetamido-5-hydroxy-1 2 r4 triazol 1-(4-Methyl-phenyl)-3-benzamido-5-hydroxy-1,2,4-triazol 1-{3-Methyl-pher,yl)-3-benzamido-5-hydroxy-1,2,-4-triazol 1-(2-Methyl-phenyl)-3-benzamido-5-hydroxy-1,2,4-triazol 1- (3-Äthyl-phenyl)-3-benzamido-5-hydroxy-1 2,4-triazol 1-(3-Propyl-phenyl)-3-benzamid-5-hydroxy-1,2,4-triazol 1-(3-tert.Butyl-phenyl)-3-b2nzamido-5-hydroxy-1,2,4-triazol 1-14-Chlasphenyl)-3-benzamido-5-hydroxy-1,2,4-triazol 1-(3-Chlor-phenyl)-3-benzamido--5-hydroxy-1,2,4-triazol 1-(2-Chlor-phenyl)-3-bensamido-5-hydroxy-1,2,4-triazol 1-(4-Brom-phenyl)-3-benzamido-5-hydroxy-1,2,4-triazol 1-(4-Jod-phenyl)-3-benzamido-5-hydroxy-1,2,4-triazol 1-(4-Fluor-phenyl)-3-benzamido-5-hydroxy-1,2,4-triazol 1-(4-Methoxy-phenyl3-3-benzamido-5-hydroxy-1,2,4-triazol 1-(3-MethOxy-phenylJ-3-benzamido-5-hydroxy-1,2,4-triazol 1-(2-MethOxy-phenyl)-3-benzamido-5-hydroxy-1,2,4-triazol 1-(4-0thOxy-phenyl)-3-benzamido-5-hydroxy-1,2,4-triazol 1-(4-PropOxy-phenyl)-3-benzamido-5-hydroxy-1,2,4-triazol 1-(4-Isopropoxy-phenyl)-3-benzamido-5-hydroxy-1,2,4-triazol 1-(4-n-Butoxy-phenyl)-3-benzamido-5-hydroxy-1,2,4-triazol 1(2, 3-Dimethyl-phenyl)-3-benzamido-5-hydroxy-1 2,4-triazol 1-(2,4-Dimethyl-phenyl)-3-benzamido-5-hydroxy-1,2,4-triazol 1-(2,5-Dimethyl-phenyl)-3-benzamido-5-hydroxy-1,2,4-1-(2,6-Dimethyl-phenyl)-3-benzamido-5-hydroxy-1,2,4-triazol 1-(3,4-Dimethyl-phenyl)-3-benzamido-5-hydroxy-1,2,4-1-(3,5-Dimethy1-phenyl)-3-ben2amido-5-hydroxy-1t2,4-triazol 1-(2,3-Dichlor-phenyl9-3-benzoamino-5-hydroxy-1,2,4-triazol 1-(2,4-Dichlor-phenyl)-3-benzamido-5-hydroxy-1,2,4-triazol 1-(2,5-Dichlor-pheny5)-3-benzamido-5-hydroxy-1,2,4-triazol 1-(2,6-Dichlor-phenyl)-3-benzamido-5-hydroxy-1,2,4-triazol 1-(3,4-Dichlor-phenyl}-3-benzamido-5-hydroxy-1,2,4-triazol 1-(3,5-Dichlor-phenyl}-3-benzamido-5-hydroxy-1,2,4-triazol 1-(3-Trifluormethyl-phenyl)-3-benzamido-5-hydroxy-1,2,4-triazol 1-{3,5-Bis-trifluormethyl-phenyl)-3-benzamido-5-hydroxy-1,2,4-triazol 1-(2,3-Tetramethylen-phenyli-3-benzamido-5-hydroxy-12,4-triazol 1-t3,4-Tetramethylen-phenyl)-3-benzamidq-5-hydroxy-1,2,4-triazol.1- (3,5-Dimethyl-phenyl) -3-acetamido-5-hydroxy-1,2,4-triazole 1- (2,3-dichlorophenyl) -3-acetamino-5-hydroxy-1,2 , 4-triazole 1- (2,4-dichloro-phenyl) -3-acetamido-5-hydroxy-1,2,4-triazole 1- (2,5-dichloro-phenyl) -3-acetamido-5-hydroxy-1,2 , 4-triazole 1- (2,6-dichloro-pheny) -3-acetamido-5-hydroxy-1,2,4-triazole 1- (3,4-dichloro-phenyl) -3-acetamido-5-hydroxy-1,2 , 4-triazole 1- (3,5-dichloro-phenyl) -3-acetamido-5-hydroxy-1,2,4-triazole 1- (trifluoromethyl-phenyl) -3-acetamido-5-hydroxy-1,2,4-triazole 1- (3,5-bis-trifluoromethyl-phenyl) -3-acetamido-5-hydroxy-1,2,4-triazole 1-l2,3-tetramethylene-phenyl) -3-acetamido-5-hydroxy-1,2,4-triazole 1 - (3 4-Tetramethylene-phenyl) -3-acetamido-5-hydroxy-1 2 r4 triazole 1- (4-methyl-phenyl) -3-benzamido-5-hydroxy-1,2,4-triazole 1- {3-methyl-pher, yl) -3-benzamido-5-hydroxy-1,2, -4-triazole 1- (2-methyl-phenyl) -3-benzamido-5-hydroxy-1,2, 4-triazole 1- (3-Ethyl-phenyl) -3-benzamido-5-hydroxy-1 2,4-triazole 1- (3-propyl-phenyl) -3-benzamide-5-hydroxy-1,2,4-triazole 1- (3-tert-butyl-phenyl) -3-b2nzamido-5-hydroxy-1,2,4-triazole (1-14-chlasphenyl) -3-benzamido-5-hydroxy-1,2,4-triazole 1- (3-chloro-phenyl) -3-benzamido - 5-hydroxy-1,2,4-triazole 1- (2-chloro-phenyl) -3-bensamido-5-hydroxy-1,2,4- triazole 1- (4-Bromo-phenyl) -3-benzamido-5-hydroxy-1,2,4-triazole 1- (4-iodo-phenyl) -3-benzamido-5-hydroxy-1,2,4-triazole 1- (4-fluoro-phenyl) -3-benzamido-5-hydroxy-1,2,4-triazole 1- (4-methoxyphenyl3-3-benzamido-5-hydroxy-1,2,4-triazole 1- (3-Methoxy-phenyl I-3-benzamido-5-hydroxy-1,2,4-triazole 1- (2-Methoxy-phenyl) -3-benzamido-5-hydroxy-1,2,4-triazole 1- (4-0thoxy-phenyl) -3-benzamido-5-hydroxy-1,2,4-triazole 1- (4-propoxy-phenyl) -3-benzamido-5-hydroxy-1,2,4-triazole 1- (4-Isopropoxyphenyl) -3-benzamido-5-hydroxy-1,2,4-triazole 1- (4-n-Butoxyphenyl) -3-benzamido-5-hydroxy-1,2,4 -triazole 1 (2,3-Dimethyl-phenyl) -3-benzamido-5-hydroxy-1 2,4-triazole 1- (2,4-dimethyl-phenyl) -3-benzamido-5-hydroxy-1,2,4 -triazole 1- (2,5-dimethyl-phenyl) -3-benzamido-5-hydroxy-1,2,4-1- (2,6-dimethyl-phenyl) -3-benzamido-5-hydroxy-1,2, 4-triazole 1- (3,4-Dimethyl-phenyl) -3-benzamido-5-hydroxy-1,2,4-1- (3,5-Dimethyl-phenyl) -3-ben2amido-5-hydroxy-1t2,4- triazole 1- (2,3-dichloro-phenyl9-3-benzoamino-5-hydroxy-1,2,4-triazole 1- (2,4-dichloro-phenyl) -3-benzamido-5-hydroxy-1,2,4-triazole 1- (2,5-dichloro-pheny5) -3-benzamido-5-hydroxy-1,2,4-triazole 1- (2,6-dichloro-phenyl) -3-benzamido-5-hydroxy-1,2 , 4-triazole 1- (3,4-dichloro-phenyl} -3-benzamido-5-hydroxy-1,2,4-triazole 1- (3,5-dichloro-phenyl} -3-benzamido-5-hydroxy-1,2 , 4-triazole 1- (3-trifluoromethyl-phenyl) -3-benzamido-5-hydroxy-1,2,4-triazole 1- {3,5-bis-trifluoromethyl-phenyl) -3-benzamido-5-hydroxy-1,2 , 4-triazole 1- (2,3-Tetramethylene-phenyli-3-benzamido-5-hydroxy-12,4-triazole 1-t3,4-tetramethylene-phenyl) -3-benzamidq-5-hydroxy-1,2,4-triazole .

Die als Zwischenprodukte benötigten 1,2,4-Triazolderivate der Formel (3) stellt man durch Umsetzen von Phenylhydrazinderivaten der Formel (2), in denen R und n die für Formel (1) angegebene Bedeutung haben, mit S-Methyl-bismethoxycarbonyl-isothioharnstoff in Lösungsmitteln wie niedrigen Alkoholen oder Estern organischer Säuren dar, wie beispielsweise Methanol oder Essigester. Die Isolierung geschieht durch Absaugen des bereits in der Hitze ausfallenden Rohproduktes, das durch Umfällen mit verdünnter Lauge und einer Säure, wie beispielsweise Essigsäure, gegebenenfalls unter Zusatz eines Absorptionsmittels wie Aktivkohle gereinigt wird und erforderlichenfalls aus einem Lösungsmittel wie Methylglykol umkristallisiert wird.The 1,2,4-triazole derivatives of the formula required as intermediates (3) is produced by reacting phenylhydrazine derivatives of the formula (2) in which R and n have the meaning given for formula (1), with S-methyl-bismethoxycarbonyl-isothiourea in solvents such as lower alcohols or esters of organic acids, such as for example methanol or ethyl acetate. The isolation is done by suction of the crude product, which precipitates out in the heat and which has been precipitated with dilute Lye and an acid such as acetic acid, optionally with addition an absorbent such as activated carbon is cleaned and removed if necessary is recrystallized from a solvent such as methyl glycol.

Die Guanidinderivate der Formel (4), in denen R und n die für Formel (1) angegebenen Bedeutungen haben werden erhalten, indem man Phenylhydrazinderivate der Formel (2) mit S-Methyl-mono-methoxycarbonyl- isothioharnstoff in einem niedrig siedenden Alkohol wie Methanol umsetzt oder aber die Umsetzung mit O-Methyl-mono-methoxycarbonyl-isoharnstoff vornimmt, wobei eine katalytische Menge einer starken vorzugsweise organischen Säure zugesetzt werden muß; genannt sei hier die p-Toluol-sulfonsäure. Das Reaktionsprodukt scheidet sich bereits in der Hitze ab und ist nach dem Absaugen des erkaltenen Reaktionsgemisches für die-weitere Verarbeitung genügend rein.The guanidine derivatives of the formula (4) in which R and n represent the formula (1) given meanings are obtained by using phenylhydrazine derivatives of formula (2) with S-methyl-mono-methoxycarbonyl-isothiourea in one low Reacts boiling alcohol such as methanol or the reaction with O-methyl-mono-methoxycarbonyl-isourea undertakes, using a catalytic amount of a strong preferably organic acid must be added; p-toluenesulfonic acid should be mentioned here. That Reaction product already separates in the heat and is after suctioning off the cooled reaction mixture Sufficiently pure for further processing.

Die Guanidinderivate der Formel (4) brauchen zur Darstellung der Verfahrensprodukte nicht isoliert zu werden.The guanidine derivatives of the formula (4) need to represent the process products not to be isolated.

Man kann die Reaktion auch so führen, daß man aus den Phenylhydrazinderivaten der Formel (2) zuerst im sauren Medium die Guanidinderivate der Formel (4) entstehen läßt und zum Reaktionsgemisch alsdann Alka-li im Überschuß fügt, wobei sich die Verfahrensprodukte der Formel (1) bilden.The reaction can also be carried out in such a way that one of the phenylhydrazine derivatives of formula (2) first form the guanidine derivatives of formula (4) in an acidic medium and then add excess alkali to the reaction mixture, the Form process products of the formula (1).

Die 3-Acylaminotriazolderivate der Formel (6) erhält man durch Umsetzung von 1,2,4-Oxdiazolderivaten der Formel (5) mit wäßrig alkoholischen Alkalien wie einer Lösung von Kaliumhydroxid in einem Gemisch aus Äthanol und Wasser bei erhöhter Temperatur.The 3-acylaminotriazole derivatives of the formula (6) are obtained by reaction of 1,2,4-oxdiazole derivatives of the formula (5) with aqueous alcoholic alkalis such as a solution of potassium hydroxide in a mixture of ethanol and water at increased Temperature.

Die 1 ,2,4-Oxdiazolderivate der Formel (5)' schließlichentstehen durch Reaktion von 5-Methyl- oder 5-Phenyl-3-amino-1,2,4-oxdiazol mit im Ring entsprechend substituierten Phenylisocyanaten.The 1, 2,4-oxdiazole derivatives of the formula (5) 'finally arise through Reaction of 5-methyl- or 5-phenyl-3-amino-1,2,4-oxdiazole with in the ring accordingly substituted phenyl isocyanates.

Die Verfahrensprodukte sind wertvolle Pharmazeutica mit ausgeprägten antiinflammatorischen und diuretischen, sowie auch analgetischen und fiebersenkenden Eigenschaften.The process products are valuable pharmaceuticals with pronounced anti-inflammatory and diuretic, as well as analgesic and antipyretic Properties.

Beispiel 1 Man erhitzt 70 g 1-(3-Methyl-phenyl)-3-methoxycarbonylamino-5-hydroxv-1,2,4-triazol in 700 ml 2 n Natronlauge, eine halbe Stunde am Rückfluß. Anschließend wird mit Eisessig neutralisiert, der Niederschlag abgesaugt mit Wasser gewaschen und unter vermindertem Druck getrocknet.Example 1 70 g of 1- (3-methylphenyl) -3-methoxycarbonylamino-5-hydroxv-1,2,4-triazole are heated in 700 ml of 2N sodium hydroxide solution, refluxed for half an hour. Then with Glacial acetic acid neutralized, the precipitate filtered off with suction and washed with water dried under reduced pressure.

Man erhält 1- ( 3-Methyl-phenyl) - 3-amino-5-hydroxy- 1 ,2,4 -triazol in einer Ausbeute von 48 g mit F.P. 212°C.1- (3-methylphenyl) -3-amino-5-hydroxy-1,2,4-triazole is obtained in a yield of 48 g with F.P. 212 ° C.

Zur Darstellung des als Ausgangsmaterial benötigten 1- (3-Methyl-phenyl) -3-methoxycarbonylamino-5-hydroxy-1'2'4-triazols werden 32 g 3-Methyl-phenylhydrazin in 150 ml Methanol mit 53,2 g S-Methyl-bis methoxycarbonyl-isothioharnstoff 3 Stunden am Rückfluß erhitzt. Man läßt erkalten und saugt nach Stehen über Nachtdas ausgefallene 1 - (3-Methyl-phenyl) -3-methoxycarbonylamino-5-hydroxy-1,2,4-triazol ab. Zur Reinigung wird es in 11 n Natronlauge kalt verrührt, Kohle dazugefügt und über einen beschichteten Filter filtriert. Das Filtrat wird mit Essigsäure angesäuert und der Niederschlag nach zwischenzeitlichem Erhitzen und Wiederabkühlen abgesaugt.For the preparation of the 1- (3-methyl-phenyl) required as starting material -3-methoxycarbonylamino-5-hydroxy-1'2'4-triazoles are 32 g of 3-methylphenylhydrazine in 150 ml of methanol with 53.2 g of S-methylbis methoxycarbonyl-isothiourea for 3 hours heated to reflux. It is allowed to cool and the precipitated product is sucked up after standing overnight 1 - (3-methyl-phenyl) -3-methoxycarbonylamino-5-hydroxy-1,2,4-triazole. For cleaning it is stirred cold in 11 N sodium hydroxide solution, charcoal is added and coated over a Filter filtered. The filtrate is acidified with acetic acid and the precipitate sucked off after intermediate heating and cooling again.

Durch Umkristallisieren aus Methylglykol erhält man das Ausgangsmaterial in reiner Form, Ausbeute 53 g, F.P. 1970C.The starting material is obtained by recrystallization from methyl glycol in pure form, yield 53 g, F.P. 1970C.

Nach analoger Arbeitsweise werden dargestellt a) aus 1-(4-Methyl-phenyl)-3-methoxycarbonylamino-5-hydroxy-1,2,4-triazol vom F.P.2 43 OC das 1-(4-Methyl-phenyll-3-amino-5-hydroxy-1,2,4-triazol vom F.P. 2480C b) aus 1-(4-Chlor-phenyl)-3-methoxycarbonylamino-5-hydroxy-1,2,4-triazol vom F.P. 2600C das 1-(4-Chlor-phenyl)-3-amino-5-hydroxy-1,2,4-triazol vom F.P. 2700C c) aus 1 - (3-Chlor-phenyl) -3-methoxycarbonylamino-5-hydroxy-1,2,4-triazol vom F.P. 2300C das 1-(3-Chlor-phenyl)-3-amino-5-hydroxy-1,2,4-triazol vom F.P.238°C d) ans 1-(3,5-Dichlor-phenyl)-3-methoxycarbonylamino-5-hydroxy-1,2,4-triazol vom F.P. 2530C das 1-(3,5-Dichlor-phenyl)-3-amino-5-hydroxy-1,2,4-triazol vom F.P. 2750C e) aus 1-(3,5-Dimetryl-phenyl)-3-carbomethoxyamino-5-hydroxy-1,2,4-triazol vom F.P. 2750C das 1-(3,5-Dimethyl-phenyl3-3-amino-5-hydroxy-1,2,4-triazol vom F.P. 2570C f) aus 1-(4-Methoxy-phenyl)-3-methoxycarbonylamino-5-hydroxy-1'2'4-triazol vom F.P. 2250C das 1-(4-Methoxy-phenyl)-3-amino-5-hydroxy-1,2,4-tr-iazolvom F.P. 2300C g) aus 1-(3-Methoxy-phenyl)-3-methoxycarbonylamino-5-hydroxy-1,2,4-triazol vom F.P. 22500-das 1-(3-Methoxy-phenyl?-3-amino-5-hydroxy-1,2,4-triazol vom F.P. 21700 h) aus 1 - (3-Trifluormethyl-phenyl) -3-methoxycarbonylamino-5-hydroxy-1,2,4-triazol vom F.P. 2430C das 1-(3-Trifluorme.thyl-pheny3-3-amino-5-hydroxy-1r2,4-triazol vom F.P. 2290C i) aus 1-(4-Phenoxy-phenyl)-3-methoxycarbonylamino-5-hydroxy-1,2'4-triazol vom F.P. 2000C das 1-(4-Phenoxy-phenyl3-3--amino-5-hydroxy-1,2,4-triazol vom F.P. 2030C j) aus 1 (3-Methoxy- 4-chlor-pheny 1) - 3-methoxycarbonylamino-5-hydroxy-1,2,4-triazol vom F.P. 2600C das 1-(3-Methoxy-4-chlor-phenyl3-amino-5-hydroxy-1,2,4-triazol vom F.P. 2680C k) aus 1-(3-Chlor-5-methyl-phenyl)-3-methoxycarbonylamino-5-hydroxy-1,2,4-triazol vom F.P. 2540C das 1-83-Chlor-5-methyl-phenyl)-3-amino-5-hydroxy-1,2,4-triazol vom F.P. 2530C 1) aus 1-(3-Methyl-4-phenoxy-phenyl)-3-methoxycarbonylamino-5-hyduoxy-1,2,4-triazol vom F.P. 2780C das 1-(3-Methyl-4-phenoxyl)-3-amino-5-hydroxy- 1,2,4-triazol vom F.P. 2000C m) aus 1-(2,3-Tetramethylen-phenyl)-3-methoxycarbonylamino-5-hydroxy-1,2'4-triazol vom F.P. 1910C das 1-(2,3-Tetramethylen-phenyl)-3-amino-5-hydroxy-1,2,4-triazol vom F.P. 2150C n) aus 1-(3,4-Tetramethylen-phenyl}-3-methoxycarbonylamino-5-hydroxy-1,2,4-triazol vom F.P. 2480C das 1-(3,4-Tetramethylen-phenyl9-3-amino-5-hydroxyt,2,4-triazol vom F.P. 2510C.Using an analogous procedure, a) are prepared from 1- (4-methylphenyl) -3-methoxycarbonylamino-5-hydroxy-1,2,4-triazole from F.P. 2 43 OC the 1- (4-methyl-phenyl-3-amino-5-hydroxy-1,2,4-triazole from F.P. 2480C b) from 1- (4-chloro-phenyl) -3-methoxycarbonylamino-5-hydroxy-1,2,4-triazole from F.P. 2600C 1- (4-chloro-phenyl) -3-amino-5-hydroxy-1,2,4-triazole from F.P. 2700C c) from 1 - (3-chloro-phenyl) -3-methoxycarbonylamino-5-hydroxy-1,2,4-triazole from F.P. 2300C 1- (3-chloro-phenyl) -3-amino-5-hydroxy-1,2,4-triazole from mp 238 ° C d) to 1- (3,5-dichlorophenyl) -3-methoxycarbonylamino-5-hydroxy-1,2,4-triazole from F.P. 2530C 1- (3,5-dichloro-phenyl) -3-amino-5-hydroxy-1,2,4-triazole from F.P. 2750C e) from 1- (3,5-dimetryl-phenyl) -3-carbomethoxyamino-5-hydroxy-1,2,4-triazole from F.P. 2750C the 1- (3,5-dimethyl-phenyl3-3-amino-5-hydroxy-1,2,4-triazole from F.P. 2570C f) from 1- (4-methoxyphenyl) -3-methoxycarbonylamino-5-hydroxy-1'2'4-triazole from F.P. 2250C 1- (4-methoxyphenyl) -3-amino-5-hydroxy-1,2,4-tr-iazole from F.P. 2300C g) from 1- (3-methoxyphenyl) -3-methoxycarbonylamino-5-hydroxy-1,2,4-triazole from F.P. 22500-the 1- (3-methoxyphenyl? -3-amino-5-hydroxy-1,2,4-triazole from F.P. 21,700 h) from 1 - (3-trifluoromethyl-phenyl) -3-methoxycarbonylamino-5-hydroxy-1,2,4-triazole from F.P. 2430C 1- (3-trifluoromethyl-pheny3-3-amino-5-hydroxy-1r2,4-triazole from F.P. 2290C i) from 1- (4-phenoxyphenyl) -3-methoxycarbonylamino-5-hydroxy-1,2'4-triazole from F.P. 2000C 1- (4-phenoxyphenyl3-3-amino-5-hydroxy-1,2,4-triazole from F.P. 2030C j) from 1 (3-methoxy-4-chloro-pheny 1) -3-methoxycarbonylamino-5-hydroxy-1,2,4-triazole from F.P. 2600C 1- (3-methoxy-4-chloro-phenyl3-amino-5-hydroxy-1,2,4-triazole from F.P. 2680C k) from 1- (3-chloro-5-methyl-phenyl) -3-methoxycarbonylamino-5-hydroxy-1,2,4-triazole from F.P. 2540C 1-83-chloro-5-methyl-phenyl) -3-amino-5-hydroxy-1,2,4-triazole from F.P. 2530C 1) from 1- (3-methyl-4-phenoxyphenyl) -3-methoxycarbonylamino-5-hydroxy-1,2,4-triazole from F.P. 2780C the 1- (3-methyl-4-phenoxyl) -3-amino-5-hydroxy- 1,2,4-triazole from F.P. 2000C m) from 1- (2,3-tetramethylene-phenyl) -3-methoxycarbonylamino-5-hydroxy-1,2'4-triazole from F.P. 1910C 1- (2,3-tetramethylene-phenyl) -3-amino-5-hydroxy-1,2,4-triazole from F.P. 2150C n) from 1- (3,4-tetramethylene-phenyl} -3-methoxycarbonylamino-5-hydroxy-1,2,4-triazole from F.P. 2480C 1- (3,4-tetramethylene-phenyl9-3-amino-5-hydroxyt, 2,4-triazole from F.P. 2510C.

Beispiel 2 Man erhitzt 12,2 g 3-Methyl-phenylhydrazin in 25 ml Methylglykol mit 14,8 g S-Methyl-mono-methoxycarbonyl-isothioharnstoff in Gegenwart von 100 mg p-Toluol-sulfonsåure 4 Stunden am Rückfluß. Man engt die Lösung/s. vorstehende Seiten7ein und verrührt den Rückstand mit,100 ml Methanol.Example 2 12.2 g of 3-methylphenylhydrazine are heated in 25 ml of methylglycol with 14.8 g of S-methyl-mono-methoxycarbonyl-isothiourea in the presence of 100 mg p-toluenesulfonic acid under reflux for 4 hours. The solution / s is narrowed. protruding pages 7a and stir the residue with 100 ml of methanol.

Nach einer Stunde saugt man den gekthlten Kristallbrei ab und wäscht ihn zweimal mit Methanol. Ausbeute 7 g F.P.After an hour, the cooled crystal pulp is suctioned off and washed him twice with methanol. Yield 7 g of F.P.

2120C. Das Reaktionsprodukt ist identisch mit dem nach Beispiel 1 gewonnenen 1-(3-Methyl-phenyl)-3-amino-5-hydroxy-1,2,4-triazol Beispiel 3 Man erhitzt ein Gemisch aus 10 g N-(3-Methyl-phenylamino)-N'-methoxycarbonyl-guanidin, 25 ml Methanol und 50 ml 2 n Natronlauge 10 Minuten am Rückfluß und neutralisiert die Lösung mit 60 ml 2 n Essigsäure, wobei ein Brei von 1-(3-Methyl-phenyl9-3-amino-5-hydroxy-1,2,4-triazol ausfälit.2120C. The reaction product is identical to that of Example 1 1- (3-methylphenyl) -3-amino-5-hydroxy-1,2,4-triazole obtained. Example 3 The mixture is heated a mixture of 10 g of N- (3-methyl-phenylamino) -N'-methoxycarbonyl-guanidine, 25 ml Methanol and 50 ml of 2N sodium hydroxide solution under reflux for 10 minutes and neutralized Solution with 60 ml of 2N acetic acid, whereby a slurry of 1- (3-methyl-phenyl9-3-amino-5-hydroxy-1,2,4-triazole fails.

Es wird abgesaugt und mit Wasser gewaschen. Ausbeute 8,5 g mit einem F.P. von 2120C. Das Reaktionsprodukt ist identisch mit dem nach Beispiel, 1 erhaltenen.It is suctioned off and washed with water. Yield 8.5g with a F.P. from 2120C. The reaction product is identical to that obtained according to Example 1.

Zur Darstellung des als Ausgangsmaterial benötigten N- (3-Methyl-phenylamino) -N' -methoxycarbonyl-guanidin werden 12,1 g 3-Methyl-phenylhydrazin in 25 ml Methanol mit 15,5 g O-Methyl-mono-methoxyzarbonyl-isoharnstoff und 50 mg p-Toluol-sulfonsäure 6 Stunden am Rückfluß erhitzt, wobei sich nach einer halben Stunde das Reaktionsprodukt abzuscheiden beginnt.For the preparation of the N- (3-methyl-phenylamino) required as starting material -N'-methoxycarbonyl-guanidine are 12.1 g of 3-methylphenylhydrazine in 25 ml of methanol with 15.5 g of O-methyl-mono-methoxycarbonyl-isourea and 50 mg of p-toluene-sulfonic acid Heated under reflux for 6 hours, the reaction product after half an hour begins to deposit.

Es wird am nächsten Tag abgesaugt und mit Methanol gewaschen. Nach dem Trocknen auf dem Dampfbad Ausbeute 10,2 g, F.P. 198°C.It is suctioned off the next day and washed with methanol. To drying on the steam bath, yield 10.2 g, F.P. 198 ° C.

An Stelle von O-Methyl-mono-methoxycarbonyl-isoharnstoff kann man auch S-Methyl-mono-methoxycarbonyl-isothioharnstoff verwenden, wenn man bei der Reaktion mit 3-Methylphenylhydrazin nicht, wie in Beispiel 2 beschrieben,Methylglykol, sondern Methanol verwendet. Nach einstündigem Kochen und analoger Aufarbeitung erhält man 8,2 g N- (3-Methyl-phenylamino) -N' -methoxycarbonyl-guanidin vom F.P. 1980C.Instead of O-methyl-mono-methoxycarbonyl-isourea you can also use S-methyl-mono-methoxycarbonyl-isothiourea if you are at the Reaction with 3-methylphenylhydrazine not as described in Example 2, methylglycol, but methanol is used. Obtained after one hour of boiling and analogous work-up 8.2 g of N- (3-methyl-phenylamino) -N'-methoxycarbonyl-guanidine from F.P. 1980C.

O-Methyl-mono-methoxycarbonyl-isoharnstoff seinerseits wird erhalten, wenn man ein Gemisch aus 246 g O-Methylisoharnstoffsulfat und 325 ml Wasser bei 100 nacheinander mit 198,5 g Chlorameisensäuremethylester-und dann 680 g 25%iger Natronlauge unter Rühren versetzt. Am nächsten Tag wird das Reaktionsgemisch dreimal mit je 500 ml Essigester ausgeschüttelt und die Extrakte nach dem Trocknen mit Natriumsulfat eingedampft.O-methyl-mono-methoxycarbonyl-isourea in turn is obtained, if a mixture of 246 g of O-methyl isourea sulfate and 325 ml of water is used 100 in succession with 198.5 g of methyl chloroformate and then 680 g of 25% strength Sodium hydroxide solution is added while stirring. The next day the reaction mixture is used three times shaken with 500 ml of ethyl acetate and the extracts after drying with sodium sulfate evaporated.

Man erhält 139 g O-Methyl-mono-methoxycarbonyl-isoharnstoff vom F.P. 420C.One receives 139 g of O-methyl-mono-methoxycarbonyl-isourea from F.P. 420C.

Beispiel 4 Man erhitzt ein Gemisch aus 12,2 g 3-Methyl-phenylhydrazin in 25 ml Methanol mit 13,5 g O-Methyl-methoxycarbonylisoharnstoff und 6 ml Eisessig eine halbe Stunde am Rückfluß. Zu dem entstandenen Brei fügt man 50 ml Wasser und 15ml-konz.Natronlauge und erhitzt weitere 20 Minuten am Rückfluß, wobei eine rötliche Lösung entsteht. Diese wird noch heiß mit Eisessig neutralisiert, wobei sich das 1(3-Methyl-phenyl)-3-amino-5-hyãroxy-1,2,4-triazol abscheidet.Example 4 A mixture of 12.2 g of 3-methylphenylhydrazine is heated in 25 ml of methanol with 13.5 g of O-methyl-methoxycarbonylisourea and 6 ml of glacial acetic acid half an hour at reflux. 50 ml of water are added to the resulting paste 15ml concentrated sodium hydroxide solution and refluxed for a further 20 minutes, with a reddish Solution emerges. This is neutralized while still hot with glacial acetic acid, whereby the 1 (3-methylphenyl) -3-amino-5-hydroxy-1,2,4-triazole separates.

Nach Stehen bei Zimmertemperatur saugt man es ab und wäscht mit Wasser neutral. Nach dem Trocknen auf dem Dampfbad erhält man 15,4 g reines Reaktionsprodukt vom F.P. 2120C, das identisch mit dem nach Beispiel. 1 gewonnenen Verfahrensprodukt ist.After standing at room temperature, it is suctioned off and washed with water neutral. After drying on the steam bath, 15.4 g of pure reaction product are obtained from F.P. 2120C, which is identical to the one in the example. 1 obtained process product is.

Beispiel 5 Man erhitzt ein Gemisch aus 7 g 1-(3-Methyl-phenyl)-3-acetylamino-5-hydroxy-1,2,4-triazc.l in 70 ml. 2 n Salzsäure 6 Stunden am Rückfluß, neutralisiert anschließend mit Natronlauge und saugt das ausgefallene 1-(3-Methylphenyl)-3-amino-5-hydroxy-1,2,4-triazol ab, das nach dem Waschen mit Wasser und Trocknen auf dem-Dampfbad identisch mit dem nach Beispiel 1 gewonnenen Verfahrensprodukt ist.Example 5 A mixture of 7 g of 1- (3-methylphenyl) -3-acetylamino-5-hydroxy-1,2,4-triazc.l is heated in 70 ml. 2N hydrochloric acid under reflux for 6 hours, then neutralized with sodium hydroxide solution and sucks off the precipitated 1- (3-methylphenyl) -3-amino-5-hydroxy-1,2,4-triazole, that after washing with water and drying on the steam bath is identical to that according to Example 1 obtained process product.

Das als Ausgangsmaterial benötigte 1-(3-Methyl-phenyl)-3-acetylamino-5-hydroxy-1,2,4-triazol wird erhalten, indem man 10,3 g 5-Methyl-3-(N-(3-methyl-phenyl)-ureido)-1,2,4-oxadiazol mit 4,0 gKOH in einem Gemisch aus 240 ml Äthanol und 60 ml Wasser 1,5 Stunden langem Rückfluß erhitzt und das Reaktionsprodukt nach dem Erkalten durch Absaugen isoliert.The 1- (3-methyl-phenyl) -3-acetylamino-5-hydroxy-1,2,4-triazole required as starting material is obtained by adding 10.3 g of 5-methyl-3- (N- (3-methyl-phenyl) -ureido) -1,2,4-oxadiazole with 4.0 g of KOH in a mixture of 240 ml of ethanol and 60 ml of water for 1.5 hours Heated to reflux and the reaction product isolated by suction after cooling.

Claims (4)

Patentansprüche: 1. 1-Phenyl-3-amino-5-hydroxy-1,2,4-triazolderivate der Formel (1) in der R1, R2 und R3 gleich oder verschieden sein können und Alkyl mit 1 - 4 C-Atomen, wobei im Falle der Substitution durch 2 Alkylgruppen.in ortho-position zueinander die beiden Alkyle mit zusammen 4 C-Atomen einen Ring bilden können, Alkoxy mit 1 - 4 C-Atomen, Halogen oder Trifluormethyl in der R1 und/oder R2 auch Wasserstoff und unabhängig davon R3 auch gegebenenfalls substituiertes Phenoxy bedeuten.Claims: 1. 1-Phenyl-3-amino-5-hydroxy-1,2,4-triazole derivatives of the formula (1) in which R1, R2 and R3 can be identical or different and alkyl with 1 - 4 carbon atoms, whereby in the case of substitution by 2 alkyl groups in ortho-position to each other the two alkyls with 4 carbon atoms together can form a ring, Alkoxy with 1-4 carbon atoms, halogen or trifluoromethyl in which R1 and / or R2 also denote hydrogen and, independently thereof, R3 also denote optionally substituted phenoxy. 2.Verfahren zur Herstellung der Verbindung der Formel (1), dadruch gekennzeichnet, daß man ein a) Phenylhydrazinderivat der Formel (2) in der R1J R2 und R3 die für Formel (1) angegebenen Bedeutungen haben, mit S-Methyl-bis-methoxyzarbonylisothioharnstoff umsetzt und das erhaltene 1,2,4-Triazol- in der R1, R2 und R3 die für Formel (1> angegebenen Bedeutungen haben, im alkalischen Medium verseift, b) ein Phenylhydrazinderivat der Formel (2), in der R1 R2 und R3 die für Formel (1) angegebenen Bedeutungen haben, mit S-Methyl-mono-methoxycarbonyl-isothioharnstoff bei erhöhter Temperatur umsetzt, c) ein Phenylhydrazinderivat der Formel (2), in welcher Rr, R2 und R3 die für Formel (1) angegebenen Bedeutungen haben- mit 0-Methyl-mono-methoxyearbonyl-isoharnstoff oder S-Methyl-mono-methoxycarbonyl-isothioharnstoff umsetzt und die erhaltenen Guanidinderivate der Formel (4) in welcher R1, R2 und R3 die für Formel (1) angegebenen Bedeutungen haben, mit Alkali behandelt, d) ein 1,2,4-Oxdiazolderivat der Formel (5) in der R1, R2 und R3 die für in Formel (1) angegebenen Bedeutungen haben und R4 für Methyl oder Phenyl steht, mit Alkali zu einem 1,2,4-Triazolderivat der Formel (6) umsetzt, in der die Substituenten die für Formel (5) angegebenen Bedeutungen haben, besitzen, und diese Verbindung im sauren Medium verseift.2. Process for the preparation of the compound of the formula (1), characterized in that a) phenylhydrazine derivative of the formula (2) in which R1J R2 and R3 have the meanings given for formula (1), with S-methyl-bis-methoxyzarbonylisothiourea and the 1,2,4-triazole obtained in which R1, R2 and R3 have the meanings given for formula (1>, saponified in an alkaline medium, b) a phenylhydrazine derivative of the formula (2) in which R1, R2 and R3 have the meanings given for formula (1), with S. -Methyl-mono-methoxycarbonyl-isothiourea reacted at elevated temperature, c) a phenylhydrazine derivative of the formula (2), in which Rr, R2 and R3 have the meanings given for formula (1) - with 0-methyl-mono-methoxyearbonyl-isourea or S-methyl-mono-methoxycarbonyl-isothiourea and the resulting guanidine derivatives of the formula (4) in which R1, R2 and R3 have the meanings given for formula (1), treated with alkali, d) a 1,2,4-oxdiazole derivative of the formula (5) in which R1, R2 and R3 have the meanings given in formula (1) and R4 represents methyl or phenyl, with alkali to form a 1,2,4-triazole derivative of the formula (6), in which the substituents have the meanings given for formula (5), and this compound is saponified in an acidic medium. Als Bedeutungen für die Substituenten R1, R2 und R3 in den Formeln (1) bis (6) seien R1, R2 und R3 beispielhaft genannt: Alkyl wie Methyl, äthyl, n- und i-Propyl, n-, iso- und tert. Butyl, vorzugsweise Methyl; Alkoxy wie Methoxy, Äthoxy, n- und i-Propoxy sowie n-, iso- und tert. Butoxy, vorzugsweise Methoxy; und Halogen wie Fluor, Chlor, Brom und Jod, vorzugsweise Chlor. As meanings for the substituents R1, R2 and R3 in the formulas (1) to (6) R1, R2 and R3 are mentioned by way of example: alkyl such as methyl, ethyl, n- and i-propyl, n-, iso- and tert. Butyl, preferably methyl; Alkoxy such as methoxy, Ethoxy, n- and i-propoxy and n-, iso- and tert. Butoxy, preferably methoxy; and halogen such as fluorine, chlorine, bromine and iodine, preferably chlorine. 3. Arzneimittel, gekennzeichnet durch den Gehalt an - oder bestehend aus - der Verbindung nach Anspruch 1.3. Medicines, characterized by the content of - or existing from - the connection according to claim 1. 4. Verwendung der Verbindung nach Anspruch 1 zur Behandlung von Entzündungen, rheumatischen Beschwerden oder der multiplen Sklerose.4. Use of the compound according to claim 1 for the treatment of inflammation, rheumatic complaints or multiple sclerosis.
DE19792910330 1979-03-16 1979-03-16 1-Phenyl-3-amino-5-hydroxy-1,2,4-triazole derivs. - useful as antiinflammatory, diuretic, analgesic and antipyretic agents Withdrawn DE2910330A1 (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0610733A1 (en) * 1993-02-09 1994-08-17 Bayer Ag 1-Aryltriazolinones and thiones
US6919363B2 (en) 2000-03-24 2005-07-19 Euro-Celtique S.A. Aryl substituted pyrazoles, triazoles and tetrazoles, and the use thereof

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0610733A1 (en) * 1993-02-09 1994-08-17 Bayer Ag 1-Aryltriazolinones and thiones
US5476946A (en) * 1993-02-09 1995-12-19 Bayer Aktiengesellschaft 1-aryltriazolin(ethi)ones
US6919363B2 (en) 2000-03-24 2005-07-19 Euro-Celtique S.A. Aryl substituted pyrazoles, triazoles and tetrazoles, and the use thereof
US7078426B2 (en) 2000-03-24 2006-07-18 Euro-Celtique S.A. Aryl substituted pyrazoles, triazoles, and tetrazoles, and the use thereof

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