MXPA99011481A - Process for preparing 4-amino-1,2,4-triazolin-5-ones - Google Patents

Abstract

The present invention is related to an improved process for the commercial preparation of substituted aminotriazolinones, which are known intermediates in the preparation of herbicidal active compounds. In particular, this invention relates to the preparation of 4-amino-1,2,4-triazolin-5-ones, and more particularly to the preparation of 3-isopropyl-4-aminotriazolinone. The process of the invention includes reacting an oxadiazolinone with hydrazine hydrate in the absence of a solvent. In a preferred embodiment, the hydrazinehydrate is mixed with a basic compound, preferably aqueous sodium hydroxide.

Description

AN IMPROVED PROCEDURE FOR PREPARING 4-AMINO-1, 2, -TRIAZOLIN-5-ONAS FIELD OF THE INVENTION The present invention relates to an improved process for the commercial preparation of substituted amino triazolinones, which are known intermediates in the preparation of active herbicidal compounds. In particular, this invention relates to the preparation of 4-amino-1,2,4-triazolin-5-ones and, more specifically, to the preparation of 3-isopropyl-4-aminotriazolinone. BACKGROUND OF THE INVENTION It is known that substituted aminotriazolinones are obtained when the corresponding oxadiazolino acids react with hydrazine hydrate in water. In U.S. Pat. No. 4,952,701, oxadiazolinone is initially introduced into water and an excess of hydrazine hydrate is added to the reaction mixture at room temperature. The mixture is then heated and cooked. The excess of hydrazine is removed by distillation and the desired aminotriazolinones are obtained. Due to the solubility of the aminotriazolinones in water, the resulting product is obtained in low yields and low purity and, therefore, an additional purification step is required. Furthermore, it is also known in the art that substituted aminotriazolinones are obtained when the corresponding oxadiazolinones react with hydrazine hydrate in the presence of a basic compound and in the presence of a polar organic solvent. Suitable basic compounds are, in general, inorganic or organic bases or acid acceptors. Said basic compounds include acetates of alkali metals or alkali metal metals, amides, carbonates, hydrogen carbonates, hydrides, hydroxides or alkoxides. Suitable polar organic solvents include dialkyl ethers, dialkyl ketones, nitriles, amides, esters, alcohols and sulfoxides. In the U.S. Patent Application 08 / 696,013, the hydrazine hydrate is initially introduced into the basic compound and the polar organic solvent. The mixture is then heated to the required reaction temperature. As the mixture is cooked, oxadiazolinone is added slowly until the reaction is complete. The desired amy-notriazolinones are obtained by adjusting the pH of the mixture to about 7 by addition of an acid and the organic solvent used in the initial stage of the process. The solvent and water are separated by distillation and the desired product is left as a residue, which is isolated by filtration. However, due to the solubility of the product in water, part of the desired product remains in the water and can not be recovered. The handling and isolation of the resulting product are extensive and the product is obtained in low yields. In these known processes, the use of water or a solvent in the reaction mixture introduces an excess of water in the reaction and requires extensive purification procedures, with low resulting yields. Therefore, an efficient process is needed to prepare substituted aminotriazolinones and, in particular, 4-amino-1,2,4-triazolin-5-ones, which produces a high net yield and a high purity. SUMMARY OF THE INVENTION It is an object of the present invention to provide an improved process for the preparation of 4-amino-1,2,4-triazolin-5-ones of the general formula (I): wherein R represents a radical selected from the group consisting of an alkyl, alkoxy, alkylthio, alkylamino and dialkylamino, each of which is optionally substituted; by reaction of an oxadiazolinone of general formula (II): where R has the meaning indicated above, with hydrazine hydrate in the absence of solvent. In a preferred embodiment, R represents an isopropyl group. In addition, the reaction is preferably carried out in the presence of a basic compound. The reaction mixture is heated and cooked. The desired product is then isolated and purified using a mixture of a small amount of water in combination with an organic solvent. A preferred organic solvent is toluene. DETAILED DESCRIPTION OF THE INVENTION The process according to the invention is related to the preparation of 4-amino-1,2,4-triazolin-5-ones of the general formula (I): where R represents a radical selected from the group consisting of an alkyl, alkoxy, alkylthio, alkylamino and dialkylamino, each of which is optionally substituted; by reaction of an oxadiazolinone of general formula (II): where R has the meaning indicated above, with hydrazine hydrate in the absence of solvent. In a preferred embodiment, R represents an alkyl; the alkyl is preferably isopropyl. In addition, in a preferred embodiment of the process, the hydrazine hydrate is mixed with a basic compound. Suitable basic compounds are, in general, inorganic or organic bases or acid acceptors. Said basic compounds include acetates of alkali metals or alkaline earth metals, amides, carbonates, hydrogen carbonates, hydrides, hydroxides or alkoxides. A preferred basic compound for the present invention is aqueous sodium hydroxide. The molar ratio of hydrazine hydrate to oxa-diazolinone is from about 1: 1 to about 1.5: 1 and, preferably, from about 1: 1 to about 1.1: 1. The molar ratio of the basic compound to the oxadiazolinone is from about 0.05: 1 to about 0.5: 1 and, preferably, from about 0.075: 1 to about 0.25: 1. The mixture of hydrazine hydrate and basic compound is heated to a temperature of from about 100 ° C to about 110 ° C and, preferably, from about 102 ° C to about 105 ° C. The oxadiazolinone of general formula (II) is then slowly added to the mixture of hydrazine hydrate and basic compound. The oxadiazolinone is added over a period of time from about 20 to about 60 minutes and, preferably, from about 30 to 40 minutes. This mixture is stirred for about 3 to about 5 hours at a temperature of about 90 ° C to about 110 ° C and, preferably, about 100 ° C to about 105 ° C, until the reaction is complete. After stirring and completing the reaction, the mixture is cooled to a temperature of about 80 ° C to about 100 ° C and, preferably, from about 85 ° C to about 90 ° C. After cooling the mixture, water and a solvent are added to the mixture. In a preferred embodiment, the water is added before the addition of the solvent. Preferably, the solvent is an aprotic organic solvent. Such solvents are well known in the art. Such suitable solvents include toluene, methyl acetate, t-butyl methyl ether, methyl isobuyl ketone and ethyl acetate. Toluene is a preferred solvent for the process of the present invention.

The amount of solvent used can vary over a wide range, as can be easily determined by one skilled in the art. The precise amount of solvent will depend on the particular solvent used. When the solvent is toluene, it is present in a molar ratio of toluene to oxadia-zolone from about 1: 1 to about 8: 1 and, preferably, from about 3: 1 to about 4: 1. The molar ratio of water to oxadiazolone is from about 1: 1 to about 6: 1 and, preferably, from about 1: 1 to about 3: 1. The mixture is then cooled to a temperature of about 5 ° C to about 20 ° C and, preferably, 5 ° C to about 10 ° C. A pH adjusting agent is added to the mixture to adjust the pH to from about 5.0 to about 8.0 and, preferably, from about 6.0 to about 7.0. Suitable pH adjusting agents include hydrochloric acid, sulfuric acid, phosphoric acid and acetic acid. In a preferred embodiment, concentrated hydrochloric acid or aqueous sulfuric acid is used as the pH adjusting agent. The molar ratio of acid buffering agent to oxadiazolone is from about 0.05: 1 to 0.5: 1. The desired aminotriazolinone is isolated by distilling the water from the reaction mixture. The resulting residue is dissolved in water at approximately 75 ° C, cooled to a temperature of about 10 ° C to about 20 ° C and filtered. The filter cake is washed with ice water and subsequently dried at about 60 ° C. In addition, the solvent phase is separated from the aqueous phase and the solvent is recovered by distillation. The following Examples illustrate preferred embodiments of the present invention and are not limiting of the description or the claims in any way. EXAMPLES Example 1 - Preparation of 3-isopropyl-4-aminotriazolino-na using a mixture of toluene and 20 ml of water Approximately 53 g (1.05 mol) of hydrazine hydrate was charged into a flask. The hydrazine hydrate was stirred and then approximately 15.6 g (0.195 mole) of a 50% sodium hydroxide solution (NaOH) was added. This mixture was heated to reflux and then approximately 132 g (1.0 mol) of isopropyloxadia-zolinone was added through a funnel. The total time for the addition of the isopropyloxadiazolinone was about 40 minutes. The reaction mixture was cooked at a temperature of about 105 ° C for about 5 hours. After completion of the reaction, the mixture was cooled to about 85 ° C. About 300 g (3.26 moles) of toluene and about 20 ml of fresh water were added to the mixture. The mixture was then cooled to approximately 10 ° C. The pH of the mixture was adjusted to approximately 7.0 by the addition of approximately 15 g (0.076 moles) of 50% sulfuric acid. The solids were recovered by filtration. The solids were then washed with approximately 100 ml of toluene and then with 2 x 20 ml of ice water. The solids were dried at a temperature of about 60 C in vacuo. The toluene phase was then separated from the mother liquor and the toluene was recovered by distillation. Table I shows the active component (C.A.) of the product and the net yield. Example 2 - Preparation of 3-isopropyl-4-aminotriazoline using a mixture of toluene and 40 ml of water The procedure described in Example 1 was repeated, except that, after completion of the reaction and cooling to About 85 ° C, about 40 ml (instead of 20 ml) of fresh water with about 300 g (3.26 mol) of toluene was added to the reaction mixture. The results are shown in Table I. Example 3 - Preparation of 3-isopropyl-4-aminotriazoline using a mixture of toluene and 60 ml of water The procedure described in Example 1 was repeated, with the exception that after After the reaction was completed and cooled to approximately 85 ° C, approximately 60 ml (instead of 20 ml) of fresh water with approximately 300 g (3.26 mol) of toluene was added to the reaction mixture. In Table I the results are shown. Example 4 - Preparation of 3-isopropyl-4-aminotriazoline using a mixture of toluene and 50 ml of water The procedure described in Example 1 was repeated, with the exception that, after completion of the reaction and of cooling to approximately 85 ° C, approximately 50 ml (instead of 20 ml) of fresh water with approximately 280 ml (instead of 300 g) of toluene was added to the reaction mixture. In Table I the results are shown. TABLE I V Vuueellttaa T Teemmpp .. dclee Time of C.A. performance No. reaction (° C) reaction (h) (%) net (%) 1 103 4 96 93 2 103 3.5 91 91 3 103 4 98.3 89 4 4 1 10033 4 98 90 Although the invention has been described with detail in the foregoing for purposes of illustration, it is to be understood that said detail has only that purpose and that those skilled in the art can make variations therein without departing from the spirit and scope of the invention, except as may be limited for the claims.

Claims (12)

1. A process for preparing 4-amino-1,2,4-triazolin-5-ones of the formula: where R represents a radical selected from the group consisting of an alkyl, alkoxy, alkylthio, alkylamino and dialkylamino, each of which is optionally substituted, consisting of: a) reacting an oxadiazolinone of the formula: where R has the meaning indicated above, with hydrazine hydrate in the absence of solvent; b) adding water and a solvent to the reaction product of step a) after completion of the reaction in step a); c) adjusting the pH of the mixture of step b) to a value of from about 5.0 to about 8.0 by adding an acidic material to allow the 4-amino-1,2,4-triazolin-5 -one precipitate, and d) recover the precipitate.

2. The method of Claim 1, wherein R represents isopropyl.

3. The process of Claim 1, wherein step a) is carried out in the presence of a basic compound selected from the group consisting of aqueous sodium hydroxide, acetates of alkali metals and alkaline earth metals, amides, carbonates, hydrogen carbonates, hydrides, hydroxides and alkoxides.

4. The method of Claim 1, wherein the solvent used in step b) is an aprotic organic solvent selected from the group consisting of toluene, methyl acetate, t-butyl methyl ether, methyl isobutyl ketone and ethyl acetate. . The method of Claim 1, wherein, in step c), the pH of the mixture is adjusted to a value of from about 6.0 to about 7.0. The method of Claim 1, wherein the acidic material used in step c) is selected from the group consisting of hydrochloric acid, sulfuric acid, phosphoric acid and acetic acid. The method of Claim 1, wherein the temperature in step a) is from about 90 ° C to about 110 ° C, in step b) from about 80 ° C to about 100 ° C and in step c) of Approximately 5 ° C to about 20 ° C. The method of Claim 1, wherein, in step a), the molar ratio of hydrazine hydrate to oxadiazolinone is from about 1: 1 to about 1.5: 1. 9. The process of Claim 3, wherein the molar ratio of basic compound to oxadiazolinone is from about 0.05: 1 to about 0.5: 1. The process of Claim 4, wherein the molar ratio of toluene to oxadiazolinone is from about 1: 1 to about 8: 1. 11. The process of Claim 1 step b), wherein the molar ratio of water to oxadiazolinone is from about 1: 1 to about 6: 1. 12. The process of Claim 1 step c), wherein the molar ratio of acidic material to oxadiazolinone is from about 0.05: 1 to about 0.5: 1.