MXPA00012744A - Process for the manufacture of substituted triazolinones - Google Patents

Abstract

The present invention relates to a process for manufacturing substituted triazolinones, which are intermediates in the preparation of herbicidally active compounds. In particular, this invention relates to the alkylation of a non-alkylated triazoline intermediate product, wherein the improvement comprises conducting the alkylation reaction under pH controlled conditions. In a preferred embodiment, the invention relates to the preparation of a 5-alkoxy(or aryloxy)-2,4-dihydro-3H-1,2,4-triazol-3-one, and the alkylation of this non-alkylated triazolinone intermediate product, to produce a 5-alkoxy(or aryloxy)-4-alkyl-2,4-dihydro-3H-1,2,4-triazol-3-one.

Description

A PROCEDURE FOR THE MANUFACTURE OF SUBSTITUTE TRIAZOLINONES TECHNICAL FIELD OF THE INVENTION The present invention relates to a process for the manufacture of substituted triazolinones, which are intermediates in the preparation of active compounds from the herbicidal point of view. Specifically, this invention relates to the alkylation of a non-alkylated triazolinone intermediate product, where the improvement consists in carrying out the alkylation reaction under conditions of controlled pH. In this context, the term "alkylation" represents a generic term and, therefore, includes the use of alkylating agents having an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, a cycloalkylalkyl group, an aryl group or an arylalkyl group. In a preferred embodiment, the invention relates to the preparation of a 5-alkoxy (or aryloxy) -2,4-dihydro-3H-1, 2,4-triazol-3-one and with the alkylation of this intermediate product triazolinone not alkylated to produce a 5-alkoxy (or aryloxy) -4-alkyl-2,4-dihydro-3H-1,2,4-triazol-3-one.

BACKGROUND OF THE INVENTION Triazolinones are well known in the art, as are the processes for their preparation and their use as herbicides. U.S. Pat. 5,708,183 discloses a process for the preparation of triazolinones substituted by reaction of triazolinateas with methyl iodide in the presence of an acid-binding agent and subsequent heating of the alkylthiodiazole derivative with hydrogen peroxide in the presence of acetic acid. U.S. Pat. No. 5,912,354 discloses a process for the preparation of substituted aminotriazolines, which includes the reaction of an oxadia-zolinone with hydrazine hydrate in the absence of a solvent. The US patent No. 5,917,050 describes a process for the preparation of alkoxytriazolinones by reacting thioimidodicarboxylic diesters with hydrazine, hydrazine hydrate or an acid adduct of hydrazine, in the presence of a diluent and a basic reaction auxiliary agent. Moreover, US Patents 5,606,070, 5,599,945 and 5,594,148 each describe a process for the preparation of alkoxytriazolinones including the reaction of iminothiocarbon diesters with carbazinic esters, then subjecting the resulting semicarbazide derivatives to a condensation reaction by cyclization. However, prior art processes produce triazolinones with unsatisfactory yield and purity. Therefore, a process for the manufacture of substituted triazolinones with a high yield and purity is needed in the art.

BRIEF COMPENDI OF THE INVENTION The present invention relates to a process for the preparation of a substituted triazolinone. The process includes the reaction of a thionocarbamate of the following general formula (I) wherein R 1 represents an unsubstituted or substituted alkyl, arylalkyl or aryl and R 2 represents an unsubstituted or substituted, unsubstituted or substituted alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl or arylalkyl, with hydrazine, hydrazine hydrate or an acid hydrazine adduct to produce a triazolinone intermediate product of the following general formula (II) where R2 is as defined previously. The intermediate product of general formula (II) then reacts under controlled pH reaction conditions with an alkylating agent of the following general formula (III) R3-X (III) where X represents a halogen, -0-S02-0-R u -0-CO-OR and RJ represents an unsubstituted or substituted alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl or arylalkyl, in the presence of a solvent and a base, to produce a substituted triazolinone of the following general formula (IV) where R2 and R3 are as defined above, DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a process for the preparation of a triazolinone substituted by alkylation of a non-alkylated triazolinone intermediate product. In this context, the term "alkylation" is used as a generic term and, therefore, expressly includes the definition of R3 which is included below. The process includes the reaction of a thionocarbamate of the following general formula (I) wherein R 1 represents an unsubstituted or substituted alkyl, arylalkyl or aryl and R 2 represents an unsubstituted or substituted, unsubstituted or substituted alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl or arylalkyl, with hydrazine, hydrazine hydrate or an acid hydrazine adduct to produce a triazolinone intermediate product of the following general formula (II) where R2 is as defined previously. The intermediate product of general formula (II) then reacts under controlled pH reaction conditions with an alkylating agent of the following general formula (III) R3-X (III) where X represents a halogen, -0-S02-0-R3 or -0-CO-O-R3 and R3 represents an unsubstituted or substituted alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl or arylalkyl, in the presence of a solvent and a base, to produce a substituted triazolinone of the following general formula (IV) where R and R are as defined above. In a preferred embodiment of the invention, Rx represents an alkyl group of 1 to 4 carbon atoms, a benzyl group or a phenyl group and R represents an alkyl group, an alkenyl group or an alkynyl group each having up to 6 atoms of carbon and each of which is unsubstituted or substituted by cyano, halogen or C1-C4 alkoxy, represents a cycloalkyl group of 3 to 6 carbon atoms or a cycloalkylalkyl group of 3 to 6 carbon atoms in the cycloalkyl moiety and 1 to 4 carbon atoms in the alkyl moiety, each of which is unsubstituted or substituted by halogen or C- alkyl represents an aryl group having 6 or 10 carbon atoms or an arylalkyl group having 6 or 10 carbon atoms in the aryl moiety and 1 to 4 carbon atoms in the alkyl moiety, each of which is unsubstituted or substituted by carboxyl, nitro, cyano, halogen, C 1 -C 4 alkyl, C 1 -Chaloalkyl, C 4 -C 4 alkoxy, C 1 -C 4 haloalkoxy or C 1 -C 4 alkoxycarbonyl, and RJ represents a alkyl, alkenyl or alkynyl, each of which has up to 6 carbon atoms and each of which is unsubstituted or substituted by cyano, halogen or C? -C4 alkoxy, represents a cycloalkyl of 3 to 6 carbon atoms or a cycloalkylalkyl of 3 to 6 carbon atoms in the cycloalkyl moiety and of 1 to 4 carbon atoms in the alkyl moiety, each of which is unsubstituted or substituted by halogen or C 1 -C 4 alkyl, or represents an aryl of 6 to 10 carbon atoms or an arylalkyl of 6 or 10 carbon atoms in the aryl moiety and of 1 to 4 carbon atoms in the alkyl moiety, each of which is unsubstituted or substituted by carboxyl, cyano, nitro, halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl C 4 -C 4 alkoxy, C 1 -C 4 haloalkoxy or C 1 -C 4 alkoxycarbonyl. More preferably, R 2 represents methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl, each of which is unsubstituted or substituted by cyano, fluoro, chloro or bromo, methoxy or etoxi, represents propenyl, butenyl, propynyl or butynyl, each of which is unsubstituted or substituted by cyano, fluoro, chloro or bromo, or represents cyclopropyl or cyclopropylmethyl, each of which is unsubstituted or substituted by fluorine, chlorine , bromine, methyl or ethyl, or represents phenyl or benzyl, each of which is unsubstituted or substituted by cyano, fluoro, chloro, bromo, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, methoxycarbonyl or ethoxycarbonyl, and represents methyl, ethyl, n- or i-propyl or n-, i-, s- or t-butyl, each of which is unsubstituted or substituted by cyano, fluoro, chloro or bromo, methoxy or ethoxy, or represents propenyl, butenyl, propynyl or butynyl, each of which is unsubstituted or substituted by cyano, fluoro, chloro or bromo, or represents cyclopropyl, cyclobutyl or cyclopropylmethyl, each of which is unsubstituted or substituted by fluorine, chlorine, bromine, methyl or ethyl, or represents phenyl or benzyl, each of which is unsubstituted or substituted by cyano, fluoro, chloro, bromo, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, methoxycarbonyl or ethoxycarbonyl. More preferably, R1 and R2 each represent methyl or n- or i-propyl and R3 represents methyl. The process of the invention can be carried out as a one-pot process, without isolation of the intermediate product of formula (II). The process according to the invention is generally carried out at atmospheric pressure. However, it is also possible to carry out the process at elevated or reduced pressure. The reaction of a thionocarbamate with hydrazine, hydrazine hydrate or an acid hydrazine adduct is conducted at a temperature from about -10 ° C to about 95 ° C and, preferably, at a temperature from about 0 ° C to about 60 ° C . Examples of suitable acidic hydrazine adducts include hydrazine acetate, hydrazine hydrochloride, and hydrazine sulfate. In one embodiment of the invention, the reaction of the thio-nocarbamate with hydrazine, hydrazine hydrate or an acid adduct of hydrazine is carried out in the presence of a base, a solvent or mixtures thereof. Suitable bases include customary inorganic or organic bases or acid acceptors. Included herein are acetates, amides, carbonates, bicarbonates, hydrides, hydroxides or alkoxides of alkali metals or alkaline earth metals, such as, for example, sodium acetate, potassium acetate or calcium acetate, lithium amide, sodium amide, potassium amide or calcium amide, sodium carbonate, potassium carbonate or calcium carbonate, sodium bicarbonate, potassium bicarbonate or calcium bicarbonate, lithium hydride, sodium hydride, potassium hydride or calcium hydride, lithium hydroxide, sodium hydroxide, potassium hydroxide or calcium hydroxide, sodium methoxide or methoxy-do potassium, sodium ethoxide or potassium ethoxide, sodium n- or i-propoxide or potassium n- or i-propoxide, n- sodium, sodium t-butoxide or n-, i-, s- or potassium t-butoxide and also basic organic nitrogenous compounds, such as trimethylamine, triethylamine, tripropylamine, tributylamine, ethyldiisopropylamine, N, N-dimethylcyl- clohexylamine, dicyclo- hexylamine, ethyldicyclohexylamine, N, N-dimethylaniline, N, N-dimethylbenzylamine, pyridine, 2-methyl-, 3-methyl-, 4-methyl-, 2,4-dimethyl-, 2,6-dimethyl-, 3,4 -dimethyl- and 3,5-dimethyl-pyridine, 5-ethyl-2-methylpyridine, 4-dimethylaminopyridine, N-methylpiperidine, 1,4-di-azabicyclo [2.2.2] octane (DABCO), 1,5 -diazabicyclo [4.3.0] -non-5-ene (DBN) or 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU). Suitable solvents include aliphatic, alicyclic or aromatic, non-halogenated or halogenated hydrocarbons, such as, for example, benzene, toluene, xylene, chlorobenzene, dichlorobenzene, petroleum ether, hexane, cyclohexane, dichloromethane, chloroform, carbon tetrachloride.; ethers, such as diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran or ethylene glycol dimethyl ether or ethylene glycol diethyl ether; ketones, such as acetone, butanone or methyl isobutyl ketone; nitriles, such as acetonitrile, propionitrile or butyronitrile; amides, such as N, N-dimethylformamide, N, N-dimethylacetamide, N-methylformanilide, N-methylpyrrolidone or hexamethylphosphoric triamide; esters, such as methyl acetate or ethyl acetate; sulfoxides, such as dimethyl sulfoxide; alcohols, such as methanol, ethanol, n- or i-propanol, n-, i-, s- or t-butanol, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether; water, and its mixtures. Preferred solvents include water, methanol, propanol and a commercial mixture of xylenes containing ethylbenzene, ortho-xylene, para-xylene and meta-xylene. In one embodiment of the invention, the reaction of a thionocarbamate with hydrazine hydrate is carried out in a mixture of water and methanol, or a mixture of water, propanol and xylenes. In another embodiment, a flow of nitrogen is maintained through the reaction mixture in order to remove the H2S formed in the reaction. In addition, in another embodiment of the invention, benzyl chloride is added to the reaction mixture containing the thionocarbamate and hydrazine, hydrazine hydrate or hydrazine acid adduct to improve the purity of the alkylated triazolinone product of formula (IV). The benzyl chloride is added to the reaction mixture at a temperature of from about -10 ° C to about 95 ° C, in an amount such that the benzyl chloride is from about 0.1% to about 10 mol% of the mixture and, preferably, from about 3% to about 5 mol%. In one embodiment of the invention, a base is added to the reaction mixture upon completion of the reaction between the thionocarbamate and the hydrazine, the hydrazine hydrate or the hydrazine acid adduct. The base is added in an amount such that the pH of the resulting mixture is from about 8.0 to about 12.0. Suitable bases include alkali metal or alkaline earth metal salts of an acid having a pKa value of 5 or higher. Examples of such bases include hydroxides, carbonates, bicarbonates and alkoxides of alkali metals or alkaline earth metals. In a preferred embodiment, the base is potassium hydroxide.

In the process of the invention, after completion of the reaction between the thionocarbamate and the hydrazine, the hydrazine hydrate or the hydrazine acid adduct, an alkylating agent is added to the reaction mixture. The alkylation of the intermediate compound of formula (II) proceeds with a high selectivity on the N atom at position 4. In this context, the terms "alkylation" and "alkylating agent" (formula (III) are used as generic terms and , therefore, expressly include the above definition of R3 The alkylation reaction is carried out at a temperature of about -10 ° C to about 95 ° C and, preferably, at a temperature of about 20 ° C to about 70 C. As a result of the addition of the alkylating agent, the pH of the reaction mixture decreases to a value of about 7.0 to about 9.0 The reaction mixture is then maintained at a pH of about 7, 0 to about 9.0, preferably from about 7.5 to about 8.5 and, more preferably, from about 7.9 to about 8.1 by adding a base to the mixture as needed. The reaction for the alkylation step corresponds to the time necessary for the pH of the reaction mixture to remain stable between 7.0 and 9.0, and preferably between 7.5 and 8.5, without the addition of a base. The base for use in the alkylation step of the present invention includes conventional inorganic or organic bases. These include, for example, hydrides, hydroxides, amides, alcoholates, acetates, carbonates or hydrogen carbonates of alkaline earth metals or alkaline metals, such as, for example, sodium hydride, sodium amide, sodium methylate. , sodium ethylate, potassium tert-butylate, sodium hydroxide, potassium hydroxide, ammonium hydroxide, sodium acetate, potassium acetate, calcium acetate, ammonium acetate, sodium carbonate, potassium carbonate, hydrogen potassium carbonate, sodium hydrogen carbonate or ammonium carbonate, and also basic organic nitrogen compounds, such as trimethylamine, triethylamine, tributylamine, N, N-dimethylaniline, N, N-dimethylbenzylamine, pyridine, 1,4-diazabicyclo [ 2.2.2] octane (DABCO), 1, 5-diazabicyclo [4.3.0] non-5-ene (DBN) or 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU). Suitable alkylating agents for use in the process of the present invention include compounds of general formula (III) as defined above. A preferred alkylating agent is dimethyl sulfate. The alkylation reaction is carried out in the presence of a solvent. Suitable solvents for use in the alkylation reaction of the present invention include aliphatic, alicyclic or optionally halogenated aromatic hydrocarbons, such as, for example, benzene, toluene, xylene, chlorobenzene, dichlorobenzene, petroleum ether, hexane, cyclohexane. , dichloromethane, chloroform or tetrachloromethane; ethers, such as diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran or ethylene glycol dimethyl ether or ethylene glycol diethyl ether; ketones, such as acetone, butanone or methylisobutyl ketone; nitriles, such as acetonitrile, propionitrile or benzonitrile; amides, such as N, N-dimethylformamide, N, N-dimethylacetamide, N-methylformanilide, N-methylpyrrolidone or hexamethylphosphoric triamide; esters, such as methyl acetate or ethyl acetate; sulfoxides, such as dimethyl sulfoxide; alcohols, such as methanol, ethanol, n- or i-propanol, n-, i-, s- or t-butanol, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, diethylene glycol monomethyl ether or diethylene glycol monoethyl ether; water, and its mixtures. Preferred solvents include methyl isobutyl ketone, methanol, propanol, water and a commercial mixture of xylenes containing ethylbenzene, ortho-xylene, para-xylene and meta-xylene. In an embodiment of the invention, the alkylation reaction is carried out in the presence of a mixture of water, methanol and methyl isobutyl ketone, or a mixture of water, propanol and xylenes. In another embodiment of the invention, the substituted triazolinone product of general formula (IV) is isolated as a hydrate at the end of the alkylation reaction. Further, in a preferred embodiment, 5-methoxy-4-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (MMT) is produced by methylating 5-methoxy-2,4- dihydro-3H-1,2,4-triazol-3-one (HMT) in a mixture of MIBC, methanol and water. The molar ratio of HMT to MIBC is from about 1.0: 2.0 to about 1.0: 3.5 and, preferably, from about 1.0: 2.8. The molar ratio of HMT to methanol is from about 1.0: 5.0 to about 1.0: 15.0 and, preferably, from about 1.0: 9.5. The molar ratio of HMT to water is from about 1.0: 3.0 to about 1.0: 6.0 and, preferably, about 1.0: 4.8. Moreover, in a preferred embodiment, 5-propoxy-4-methyl-2,4-dihydro-3H-1, 2,4-triazol-3-one (PMT) is produced by 5-propoxy-2, 4-methylation. -dihydro-3H-1,2,4-triazol-3-one (HPT) in a mixture of xylenes, propanol and water. The reaction mixture contains an aqueous phase and an organic phase. The aqueous phase is discarded (lower phase) and the PMT is recovered from the organic phase (upper phase) at a temperature of 60 ° C, in the presence of propanol and methanol. The mole ratio of HPT to xylenes is from about 1.0: 2.0 to about 1.0: 4.0 and, preferably, about 1.0: 3.0. The molar ratio of HPT to propanol is from about 1.0: 2.0 to about 1.0: 6.0 and, preferably, about 1.0: 4.0. The molar ratio of HPT to water is from about 1.0: 3.0 to about 1.0: 9.0 and, preferably, about 1.0: 6.1.

The invention is further illustrated, but without intending to limit it, by the following examples, where all parts and percentages are by weight, unless otherwise specified. EXAMPLES Example 1 - Preparation of HMT To a cold solution (i.e., about 0 ° C) containing 399.0 grams (2.68 moles) of N-methoxycarbonyl-O-methylthiocarbamate (MTC) and 710 grams of methanol were added. 17.8 grams (0.143 moles) of 45% aqueous potassium hydroxide and 40.0 grams of water. At a temperature of about 0 ° C, 133.8 grams (2.65 moles) of 64% hydrazine hydrate were added to the reaction mixture over a period of about 2 hours at a uniform rate. A flow of net nitrogen below the surface (to help remove the HS formed in the reaction) was maintained through the reaction mixture. The reaction mixture was stirred at a temperature of about 0 ° C for about 4 hours. The mixture was then heated to a temperature of about 40 ° C over a period of time of about 2 hours. At a temperature of about 40 ° C, 17.1 grams (0.135 moles) of benzyl chloride was added to the reaction mixture and the mixture was kept at this temperature for about 1 hour. The reaction mixture was then heated to a temperature of about 50 ° C over a period of about 1 hour and the mixture was kept at this temperature for about 2 hours. The reaction mixture contained approximately 262 grams (2.28 moles, 85% yield based on MTC) of 5-methoxy-2,4-dihydro-3H-1, 2,4-triazol-3-one (HMT) in a mixture of methanol (MeOH) and water. At this point, either the HMT suspension was reacted to produce a 5-alkoxy-4-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (e.g., Example 3). ), or pure HMT was isolated from the reaction mixture. To isolate the pure HMT, the reaction mixture was cooled to a temperature of about 0 ° C, filtered under vacuum and the filter cake was washed with 2 x 50 ml of cold methanol (about 0 ° C). The filter cake was then dried in a vacuum oven at a temperature of about 50 ° C for about 16 hours to obtain 223.6 grams of HMT (96.5% purity and 70.0% yield based on MTC ). Example 2 - Preparation of HPT To a solution containing 587.0 grams (2.86 moles) of N-propoxycarbonyl-O-propylthiocarbamate (PTC) and 240 grams of propanol were added 280 grams of xylenes (ie, a commercial mixture). of ethylbenzene, ortho-xylene, para-xylene and meta-xylene), 70.0 grams of water and 4.2 grams (0.03 mole) of 45% aqueous potassium hydroxide. The reaction mixture was then cooled to a temperature of about 0 ° C. At a temperature of about 0 ° C, 146.0 grams (2.95 moles) of 64% hydrazine hydrate was added to the reaction mixture over a period of about 2 hours at a uniform rate. A flow of net nitrogen below the surface (to help remove the H2S formed in the reaction) was maintained through the reaction mixture. After the addition of the hydrazine hydrate, the reaction mixture was heated to a temperature of about 20 ° C and stirred for about 3 hours. The mixture was then heated to a temperature of about 50 ° C over a period of time of about 2 hours. The reaction mixture was cooked at a temperature of about 50 ° C for about 1 hour. The reaction mixture was then diluted with 525 grams of xylenes. This suspension contained approximately 348 grams (2.43 moles, 85% yield based on PTC) of 5-propoxy-2,4-dihydro-3H-1,2,4-triazol-3-one (HPT) in one suspension. mixture of xylenes, propanol and water.

At this point, the HPT still reacted to produce 5-propoxy-4-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (e.g., Example 4). Example 3 - Preparation of MMT hydrate from a suspension of HMT To a suspension of HMT (e.g., as prepared in Example 1), which contained 262 grams (2.28 moles) of HMT in a mixture of methanol and water, a 45% strength aqueous solution of potassium hydroxide (KOH) was added at a temperature of of approximately 50 ° C and over a period of approximately 30 minutes. The KOH solution was added in an amount such that the pH of the reaction mixture increased to about 10.0. Approximately 650 grams of methyl isobutyl ketone (MIBC) was then added to the reaction mixture and the mixture was cooled to room temperature (i.e., about 25 ° C). About 446 grams (3.54 moles) of dimethyl sulfate were then added to the mixture over a period of about 2 hours, while maintaining the temperature of the mixture between about 25 ° C and about 30 ° C. C. Upon adding the dimethyl sulfate, the pH of the reaction mixture decreased. The pH of the mixture was maintained between about 7.9 and about 8.1 by the simultaneous addition of a 45% aqueous solution of KOH. After the addition of the dimethyl sulfate, the temperature of the reaction mixture increased to about 60 ° C over a period of time of about 4 hours, while maintaining the pH between about 7.9 and about 8, 1. The reaction mixture was baked at about 60 ° C until the pH remained stable, i.e., to the point where the addition of aqueous KOH was not necessary to maintain the pH between about 7.9 and about 8.1 . A fractional distillation of the reaction mixture was then carried out under reduced pressure to remove methanol and isolate 5-methoxy-4-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (MMT) product as hydrate. Approximately 680 grams of water was added to the residue and heated to a temperature of about 75 ° C to dissolve the MMT. The mixture was then cooled to a temperature of about 0 ° C over a period of about 4 hours and stirred for about 1 hour. The resulting two-phase suspension was filtered and washed with 280 grams of hot MIBC and 280 grams of ice water. The filter cake was dried at room temperature for about 8 hours under 200 mm vacuum, to obtain 261 grams of MMT hydrate (1.74 moles, 98% purity as a hydrate and 76% yield based on HMT) . Example 4 - Preparation of a solution of PMT in xylenes from a suspension of HPT in xylenes / propanol / -water To a suspension of HPT (eg, as prepared in Example 2), containing 348 grams (2 , 43 moles) of HPT in a mixture of xylenes, propanol and water, a 45% aqueous solution of potassium hydroxide (KOH) was added at a temperature of about 30 ° C and over a period of about 30 minutes. minutes The KOH solution was added in an amount such that the pH of the reaction mixture increased to about 10.0. Approximately 480 grams (3.77 moles) of dimethyl sulfate was then added to the mixture over a period of about 2 hours, while maintaining the temperature of the mixture between about 25 ° C and about 30 ° C. C. Upon addition of dimethyl sulfate, the pH of the reaction mixture decreased. The pH of the mixture was maintained between about 7.9 and about 8.1 by the simultaneous addition of a 45% aqueous solution of KOH. After adding the dimethyl sulfate, the temperature of the reaction mixture was increased to about 60 ° C over a period of time of about 4 hours, while maintaining the pH between about 7.9 and about 8, 1. The reaction mixture was baked at about 60 ° C until the pH remained stable, i.e., to the point where it was not necessary to add aqueous KOH to maintain the pH between about 7.9 and about 8.,1. The stirring of the reaction mixture was stopped and the mixture was separated in two phases. The aqueous phase was discarded (lower phase) and the organic phase (upper phase) was subjected to distillation under reduced pressure to remove methanol, dipropyl ether, propanol and water. The residue, consisting of crude 5-propoxy-4-methyl-2,4-dihydro-3H-l, 2,4-triazol-3-one (PMT) in xylenes, was diluted with fresh anhydrous xylenes to adjust its concentration to approximately 13% with respect to the PMT. At this point, the PMT solution contained 319 grams (2.03 moles) of PMT in 2.455 grams of total solution. The solvent-free purity of the PMT was 82% and the yield was 83.5% based on the HPT. Although the invention has been described in detail in the foregoing for purposes of illustration, it is to be understood that such detail has only such purposes and that those skilled in the art will be able to make variations therein without deviating from the spirit and scope of the invention, except in what may be limited by the claims.

Claims (29)

Claims

1. A process for preparing a substituted triazolinone, consisting of the following steps: a) reacting a thionocarbamate of the following general formula (I) wherein R 1 represents an unsubstituted or substituted alkyl, arylalkyl or aryl and R 2 represents an unsubstituted or substituted, unsubstituted or substituted alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl or arylalkyl, with hydrazine, hydrazine hydrate or an acid hydrazine adduct to produce a triazolinone intermediate product of the following general formula (II) where R2 is as defined above, and b) reacting the intermediate product of formula (II) of step a) under controlled pH conditions with an alkylating agent of the following general formula (III) R3-X (III) where X represents a halogen, -0-S02-0-R3 or -O-CO -O-R3 and R represents an unsubstituted or substituted alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl or arylalkyl, in the presence of a solvent and a base, to produce a substituted triazolinone of the following general formula (IV) where R2 and R3 are as defined above.

2. The process of Claim 1, wherein the reaction of step a) is carried out at a temperature of about -10 ° C to about 95 ° C.

3. The method of Claim 1, wherein the reaction of step a) is carried out at a temperature from about 0 ° C to about 60 ° C.

4. The method of Claim 1, wherein the re-action of step a) is carried out in the presence of a compound selected from the group consisting of a base, a solvent and mixtures thereof.

5. The process of Claim 4, wherein the ba-se is selected from the group consisting of alkali metals, alkaline earth metals and basic organic nitrogenous compounds, amides, carbonates, bicarbonates, hydrides, hydroxides and alkoxides.

6. The process of Claim 4, wherein the solvent is selected from the group consisting of aliphatic, alicyclic and halogenated and non-halogenated aromatics, ethers, ketones, nitriles, esters, sulphoxy, amides, alcohols, water and mixtures thereof.

7. The process of Claim 1, wherein the reaction of step a) is carried out in the presence of water, methanol and potassium hydroxide.

8. The process of Claim 1, wherein the reaction of step a) is carried out in the presence of water, propanol, xylenes and potassium hydroxide.

9. The process of Claim 1, wherein a flow of nitrogen is maintained through the reaction mixture.

10. The process of Claim 1, wherein benzyl chloride is added to the reaction mixture of step a).

11. The method of Claim 10, wherein the benzyl chloride is added in an amount such that the benzyl chloride constitutes from about 0.1% to about 10 mol% of the reaction mixture.

12. The method of Claim 1, wherein the reaction of step b) is carried out at a temperature of about -10 ° C to about 95 ° C.

13. The method of Claim 1, wherein the reaction of step b) is carried out at a temperature of about 20 ° C to about 70 ° C.

14. The process of Claim 1, wherein the alkylating agent is added in an amount such that the pH of the reaction mixture of step b) is from about 7.0 to about 9.0.

15. The method of Claim 1, wherein the base mentioned in step b) is selected from the group consisting of aliphatic, alicyclic and halogenated and non-halogenated aromatic hydrocarbons, ethers, ketones, nitriles, esters, sulfoxides, amides, alcohols, water and its mixtures

16. the process of Claim 1, wherein the base mentioned in step b) is potassium hydroxide.

17. The process of Claim 1, wherein the alkylating agent is dimethyl sulfate.

18. The process of Claim 1, wherein the solvent mentioned in step b) is selected from the group consisting of aliphatic, alicyclic and halogenated or non-halogenated aromatic hydrocarbons, ethers, ketones, nitriles, esters, sulfoxides, amides, alcohols, water and its mixtures

19. The process of Claim 1, wherein the solvent is a mixture of methyl isobutyl ketone, methanol and water.

20. The process of Claim 1, wherein the solvent is a mixture of xylenes, propanol and water.

21. The method of Claim 1, wherein steps a) and b) are carried out through a single container process without separation of the intermediate product of formula (II).

22. The method of Claim 1, wherein the triazolinone product of formula (IV) is 5-methoxy-4-methyl-2,4-dihydro-3H-1, 2,4-triazoi-3-one (MMT).

23. The method of Claim 22, further comprising the step of isolating 5-methoxy-4-methyl-2,4-dihydro-3H-1, 2,4-triazol-3-one (MMT) as monohydrate.

24. The process of Claim 1, wherein the triazolinone product of formula (IV) is 5-propoxy-4-methyl-2,4-dihydro-3H-1, 2,4-triazol-3-one (PMT).

25. The method of Claim 1, wherein, in step b), the base is added to the reaction mixture in an amount such that the pH of the reaction mixture is maintained at a pH of between about 7.0 and about 9. , 0.

26. The method of Claim 25, wherein the pH of the reaction mixture is from about 7.5 to about 8.5.

27. The method of Claim 25, wherein the pH of the reaction mixture is from about 7.9 to about 8.1.

28. The method of Claim 24, which further includes the step of recovering the PMT by separating it from an organic phase of the reaction mixture at a temperature of 60 ° C, in the presence of propanol and methanol.

29. The method of Claim 1, further including the step of adding a base to the reaction mixture of step a) before adding the alkylating agent in step b), in an amount such that the pH of the mixture of reaction is between about 8.0 and about 12.0.