GB2077718A

GB2077718A - Process for the production of 1-substituted-3-hydroxy-5-chloro- 1,2,4-triazoles

Info

Publication number: GB2077718A
Application number: GB8019529A
Authority: GB
Original assignee: Ciba Geigy AG
Current assignee: Novartis AG
Priority date: 1980-06-14
Filing date: 1980-06-14
Publication date: 1981-12-23
Also published as: GB2077718B

Abstract

A process for the production of 1-substituted-3-hydroxy-5-chloro- 1,2,4-triazoles comprises reacting in dilute solution a 1-substituted-1- cyanohydrazine with phosgene in tetrahydrofuran as the specific inert solvent at - 10 to + 50 DEG C, treating the reaction mixture with anhydrous ammonia to form a novel ammonium salt of the 1,2,4-triazole, said ammonium salt being insoluble in tetrahydrofuran, and liberating from said isolated salt the 1,2,4-triazole by treating said salt with an acid. The 1,2,4-triazoles are valuable intermediates in the manufacture of pesticides.

Description

SPECIFICATION Process for the production of 1-substituted 3-hydroxy-5-chloro-1 ,2,4-triazoles The present invention relates to a process for the production of 1 -su bstituted-3-hyd roxy-5- chIoro-1 2,4-triazoles of formula I

wherein R represents an alkyl group having 1 to 5 carbon atoms, a cycloalkyl group having 3 to 7 carbon atoms or an aryl group selected from the group consisting of phenyl, 1-naphthyl and 2-naphthyl which aryl groups are unsubstituted or substituted by alkyl groups having 1 to 4 carbon atoms, alkoxy groups having 1 to 4 carbon atoms, halogen, nitro or cyano groups, by reaction of a compound of formula II

wherein R has the meaning given above, with phosgene in an inert solvent.

In the above definition R as an alkyl group having 1 to 5 carbon atoms can be straight chain or branched and is, for instance, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec.-butyl, n-pentyl, iso-pentyl or neo-pentyl.

The alkyl groups as substituents of the above mentioned aryl groups can also be straight chain or branched and are, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec.butyl, tert.-butyl or isobutyl. Alkoxy groups as substituents of the above-mentioned aryl groups are, for instance, methoxy, ethoxy, npropoxy, isopropoxy, n-butoxy, isobutoxy, sec.-butoxy and tert.-butoxy. Halogen denotes chlorine, fluorine, or bromine and particularly chlorine. R as aryl group can carry up to 3 of the afore-mentioned substituents.

The 1 -substituted-3-hydroxy-5-chloro- 1 ,2,4- triazoles of formula I are valuable intermediates in the manufacture of pesticides. They can be converted by reaction with phosphoric acid ester halides or thiophosphoric acid ester halides into phosphoric or thiophosphoric acid esters, respectively, which have excellent insecticidal and nematicidal action. Such compounds are disclosed, for example, in U.S.

Patents Nos. 3,867,396 and 3,932, 629.

According to a process disclosed in U.S.

Patent No. 3.992,398 l-alkyl-3-hyd 1-alkyl-3-hydroxy-5- chloro-1,2,4-triazoles of the formula

wherein alkyl represents a straight-chain or branched alkyl group having 1 to 5 carbon atoms, are produced by reacting a compound of the formula

wherein alkyl has the meaning given above, with phosgene in an inert solvent, e.g. aliphatic, aromatic or halogenated hydrocarbons, ethers or etheral compounds, dialkylated amides, sulphoxides, nitriles and ketones, with methylene chloride and dioxane being preferred, at a temperature of between 0" and 1 80 C, preferably between 20 and 1 30 C, and a 1 -alkyl-3-hydroxy-5-chloro-1 ,2,4-triazole of the formula as defined above is isolated, preferably in the form of a hydrochloride, with the yields varying in the range of between 53,2% and 79,5% of theory.

The improved process according to the invention comprises reacting a compound of formula 11, as defined above, with phosgene in tetrahydrofuran as solvent at a temperature of between - 10 and 50"C, treating the reaction mixture with anhydrous ammonia to form an insoluble ammonium salt of a 1su bstituted-3-hydroxy-5-chloro- 1 , 2, 4-triazole of formula I, isolating said salt and liberating from said salt a compound of formula I with a mineral acid.

According to a preferred mode of the improved process a 4-10 percent (weight by volume) solution of a compound of formula ll in tetrahydrofuran is reacted with phosgene.

More specifically, a 6-8 percent solution of a compound of formula II in tetrahydrofuran is employed.

Within the above-stated temperature range of between - 1 0 and 50"C temperatures between - 5 and 40"C are preferred and most preferably a temperature between 0 and 30"C is employed.

After the reaction of a compound of formula II with phosgene the reaction mixture is treated with ammonia to form an ammonium salt of a compound of formula I.

The ammonia is preferably employed in gaseous and anhydrous form but can also be in anhydrous liquid form. By introducing anhydrous ammonia into the tetrahydrofuran solution containing the reaction mixture, the novel ammonium salt of a compound of the formula (I) precipitates. This can be isolated in pure state by filtering, washing the precipitate with tetrahydrofuran or other suitable solvent and drying the product. From such a salt of a compound of the formula (I) the compound itself-is liberated in high yield and very pure state by treating an aqueous solution of the salt with an acid, such as a mineral acid, e.g., hydrochloric acid, sulfuric acid, or phosphoric acid, in excess. Preferably, hydrochloric acid is used.

The ammonium salts of the compounds of formula I are not only novel but are particularly useful and advantageous in the present process in conjunction with the use of tetrahydrofuran as specific solvent. Of particular importance is the fact that isolation of compounds of formula I as their ammonium salts allows recycle of the dry tetrahydrofuran solvent to the reaction with minimum cleanup.

Use of other bases to accomplish this either leaves large quantities of the product salt in the tetrahydrofuran solution or contaminates the tetrahydrofuran with water. Wet tetrahy dtofuran cannot be recycled to the reactor; it must first go through a complicated double distillation under pressure which requires special equipment and significantly increases costs. The use of tetrahydrofuran under the very specific, relatively low temperature and high dilution conditions to achieve superior yields, especially in conjunction with the ammonium salt isolation technique, is also a significant feature of the subject process.

According to the improved process of the present invention a compound of the formula (I) may be obtained in yields ranging from about 85-92% of theory and in very pure state, such as for instance, of 98% assay.

A preferred embodiment of the improved process according to the present invention comprises reacting 1 -isopropyl- 1 -cyanohydrazine in the form of a 6-8 percent solution in tetrahydrofuran with phosgene at a temperature of between 0-30"C, treating the reaction mixture with anhydrous ammonia to form the ammonium salt of 1-isopropyl-3-hydroxy-5 chloro- 1 , 2,4-triazole, which precipitates al most totally from the tetrahydrofuran reaction mass, and liberating from said isolated salt 1 isopropyl-3-hydroxy-5-ch loro- 1 , 2,4-triazole in a yield ranging from 85, 8-92%,1% of theory and in a very pure state, such as of 98% assay, by treating it with 32-37% hydrochioric acid.

The following examples will serve to illustrate the improved process. The temperatures are given in degrees centigrade.

Example 1: A 300-gallon, glass-lined, jacketed and agitated reactor is charged with 800 pounds of dry tetrahydrofuran (THF) and cooled below 0 , Liquid phosgene weighing 230 pounds is then transferred to the reactor with appropriate safety precautions and dis-- solved in the THF. To a 50-gallon, stainless steel, agitated hold tank is charged 74 pounds of dry THF (874 pounds total) and 178 pounds of 1-isoprnpyl-1-cyanohydrazine (IPCH), calculated as 100% material (this is an equivalent 16,9% IPCH in the total THF).

The main reactor is further cooled to 15 and then the IPCH solution is slowly charged.

The temperature is allowed to rise to 12-14" where it is maintained by regulating the IPCH solution feed rate. After the IPCH feed is complete, the temperature is allowed to rise to 20-25" and is maintained by regulating the IPCH solution feed rate. After the IPCH feed is complete, the temperature is allowed to rise to 20-25" and is maintained for four hours.

Next, 110 pounds of anhydrous ammonia is slowly sparged in with good agitation to destroy the phosgene and precipitate the ammonium salt of 1-isopropyl-3-hydroxy-5 chloro- 1 , 2,4-triazole (I HCT. NH3). The entire reaction mass is then pressure-filtered, and the wet cake is washed with 100 pounds of fresh THF and dried under vacuum to recover THF. The dry solid is dissolved in 11 5 gallons of water, to which is then added 93 gallons of ethylene dichloride (EDC). Next, about 143 pounds of 32% HCI is slowly charged to drop the pH to 1 to 2. The EDC layer containing the product is removed and analyzed for use in the next step. Yield: about 75% of IHCT assaying 98-99,5% on a solventfree basis.

Example 2: A jacketed resin kettle is charged with 800 g of dry tetrahydrofuran (THF) and cooled to 0" with circulating brine.

Then 76,6 g of phosgene is sparged into the the THF and dissolved. A mixture of 67,57 g of 87,2% 1 -isopropyl-1 -cyanohydrazine (IPCH) in 53 g of dry THF is slowly dropped into the reactor over 1 7 minutes. A maximum temperature of 3" is allowed. After IPCH addition, the reactor is held one hour at 0" and then three hours at 20 . Anhydrous ammonia weighing about 36,4 9 is then sparged slowly into the reactor holding 25 maximum. The resulting slurry is filtered in a Gelman pressure filter and dried, in vacuo on the filter with gentle heating. The cake is dissolved in about 200 ml of water, to which 400 ml of ethylene dichloride (EDC) is then added. Next, 37% HCI is added to release 1-isopropyl-3 hydroxy-5-chloro-1 ,2,4-triazole (IHCT) into the EDC layer at pH 1-2. The EDC is stripped off under vacuum, leaving IHCT in 86,7% yield with an assay of 99,2%. (This was an equiva lent 6,4% IPCH in THF).

Example 3: A jacketed reactor is charged with 3,1 37 ml of tetrahydrofuran and the mass is chilled to - 5'. Gaseous phosgene (263,5 g) is sparged into the stirred solvent.

Following this, a solution of 232,7 g of 87,2% 1 -isopropyl-1 -cyanohydrazine in 209 ml of tetrahydrofuran (THF) is added over 35 minutes. After three hours at 20 the reaction mixture is quenched by the addition of anhy drous ammonia in excess, whereafter 1-isopro pyl-3-hydroxy-5-chloro- 1,2,4-triazole ammonium salt precipitates. The resulting slurry of said ammonium salt in THF is filtered and washed with fresh tetrahydrofuran. The wet filter cake is dissolved in 2 liters of water followed by stripping out the THF in form of its azeotrope with 1 mol water.The remaining solution is rendered acid to pH 1,0 with 37% hydrochloric acid, whereafter 1-isopropyl-3-hy droxy-5-chloro-1 2,4-triazole is obtained which is isolated by extraction with ethylene dichloride and evaporation of the resulting solution yielding 306,6 g (92,1 % of theory) of the product of 99,4% purity). (This was an equivalent 6,8% IPCH in THF).

Example 4: A jacketed resin kettle is charged with 974 ml of tetrahydrofuran (THF) and cooled to - 5'. Gaseous phosgene (81,8 g) is sparged in over 30 minutes. Immediately after this a solution of 72,5 g of 87,2% 1isopropyl-1-cyano-hydrazine in 65 ml of THF is charged to the reactor in 65 seconds. (This is 6,8% IPCH in the total THF present). The temperature is controlled at 10 maximum.

The reactor is maintained at 10 for one hour followed by quenching with gaseous anhydrous ammonia, whereafter 1-isopropyl-3-hy- droxy-5-chloro-1,2,4-triazole ammonium salt precipitates. The slurry is filtered and the filter cake is washed with three portions of ethylene dichloride (EDCach 1 50 ml) to displace tetrahydrofuran in the filter. The filter cake is dissolved in 500 ml of water, and the pH of the solution is lowered to 1,0 by adding 37% hydrochloric acid. The mixture is treated with ethylene dichloride. Two more extractions using 50 ml of EDC are employed. The combined organic layers are stripped, leaving 1isopropyl-3-hydroxy-5-chloro- 1 , 2, 4-triazole of 98% assay, the yield being 92,5 g (88,2% of theory).The dry THF filtrate and EDC washings can be fractionally distilled to recover the anhydrous solvents.

Example 5: A jacketed resin kettle is charged with 717 g of dry tetrahydrofuran (THF) and 14 g of ethylene dichloride (EDC) and cooled to 0'. Then 68,6 g phosgene is sparged in and dissolved in the solvent. A solution of 60,5 g of 87,2% 1-isopropyí-1- cyanohydrazine (IPCH) in 48 g of dry THF is then charged to the reactor over 25 minutes while holding 0 . After charging IPCH, the reactor is held 35 minutes at 0" and three hours at 20 . Then 32,6 g of anhydrous ammonia is sparged into the reactor. The resulting slurry contains the ammonium salt of 1 -isopropyl-3-hydroxy-5-chloro- 1 2, 4-triazole (IHCT.NH3). Workup as in Example 2 produces an 87,9% yield of 99% assay IHCT.

Claims

1. In a process for the production of a 1 substituted-3-hydroxy-5-chloro-1,2,4-triazole compound of the formula

wherein R represents lower alkyl, cycloalkyl or aryl, which comprises reacting a compound of the formula

wherein R has the meaning given under formula (I), with phosgene in an inert solvent, the improvement which consists in reacting a compound of the formula (II) with phosgene as a dilute solution in tetrahydrofuran, at a temperatur of between - 1 0 and 50"C, treating the reaction mixture with anhydrous ammonia to form an insoluble ammonium salt of a compound of the formula (I) isolating said salt and liberating from said salt a compound of the formula (I) with a mineral acid.

2. A process as claimed in claim 1 which comprises reacting a 4-10 percent solution of a compound of the formula (II) in tetrahydrofuran.

3. A process as claimed in claim 1 which comprises reacting a 6-8 percent solution of a compound of the formula (II) in tetrahydrofuran.

4. A process as claimed in claim 1 which comprises liberating from such ammonium salt a compound of the formula (I) in very pure state by treating such salt with excess hydrochloric acid, sulfuric acid or phosphoric acid, preferably with excess hydrochloric acid.

5. A process as claimed in claim 1 which comprises reacting a compound of the formula (II) with phosgene in tetrahydrofuran at a temperature of between - 5 and 40"C.

6. A process as claimed in claim 1 which comprises reacting a compound of the formula (II) with phosgene in tetrahydrofuran at a temperature of between 0 and 30"C.

7. A process as claimed in claim 1 which comprises reacting a compound of the formula (II), wherein R represents lower alkyl, in the form of a 6-8 percent solution in tetrahydrofuran, with phosgene at a temperature of between - 5 and 40"C, treating the reaction mixture with anhydrous ammonia to form an insoluble ammonium salt of a compound of the formula (I) wherein R represents lower alkyl isolating said salt, and liberating from said salt a compound of the formula (I), wherein R represents lower alkyl, with a mineral acid.

8. A process as claimed in claim 1 which comprises reacting 1 -isopropyl- 1 -cyanohydrazine in the form of a 6-8 percent solution in tetrahydrofuran with phosgene at a temperature of between O-30 C, treating the reaction mixture with anhydrous ammonia to form the ammonium salt of 1 -isopropyl-3-hydroxy-5chloro-1,2,4-triazole, isolating said salt, and liberating from said salt pure 1-isopropyl-3- hydroxy-5-chloro-1,2,4-triazole with hydrochloric acid.

9. 9. A compound of the formula

where R represents lower alkyl, cycloalkyl or aryl in the form of its ammonium salt.

10. A compound of the formula (I) as defined in claim 10 wherein R represents lower alkyl in the form of its ammonium salt.

11. The ammonium salt of 1-isopropyl-3 hydroxy-5-chloro-1,2,4-triazole.

1 2. A process as claimed in Claim 1, substantially as hereinbefore described with reference to any of the foregoing Examples.

13. A compound as claimed in Claim 9, substantially as hereinbefore described with reference to any of the foregoing Examples.