CA1070696A - Process for the production of 3-hydroxy-1,2,4-triazole derivatives - Google Patents
Process for the production of 3-hydroxy-1,2,4-triazole derivativesInfo
- Publication number
- CA1070696A CA1070696A CA234,232A CA234232A CA1070696A CA 1070696 A CA1070696 A CA 1070696A CA 234232 A CA234232 A CA 234232A CA 1070696 A CA1070696 A CA 1070696A
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- carbon atoms
- group
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Classifications
-
- 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
- C07D249/12—Oxygen or sulfur atoms
Abstract
ABSTRACT OF THE DISCLOSURE
Process for the production of 3-hydroxy-1,2,4-triazole derivatives of the formula I
wherein R1 represents an alkyl or cycloalkyl group, R2 denotes an alkyl, cyclo-alkyl, alkenyl, alkynyl or an optionally substituted benzyl group and X stands for oxygen, sulphur or a group
Process for the production of 3-hydroxy-1,2,4-triazole derivatives of the formula I
wherein R1 represents an alkyl or cycloalkyl group, R2 denotes an alkyl, cyclo-alkyl, alkenyl, alkynyl or an optionally substituted benzyl group and X stands for oxygen, sulphur or a group
Description
- ~()7(~696 ; The present invention relates to a process for the production of 3-hydroxy-1,2,4-triazole deriva~ives of the formula 1 R~
.~ R2 X C C - OH ~I) N
. . .
wherein Rl represents an alkyl group having 1 to 6 carbon atoms or a cycloalkyl group having 3 to 8 carbon atoms, R2 represents an alkyl group having 1 to 6 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, an alkenyl group having 3 to 6 carbon atoms, an alkynyl group having 3 to 6 carbon atoms, or a benzyl group optionally mono- or di-substituted by alkyl alkoxy or alkylthio each having 1 to 4 carbon atoms, or by halogen, trifluoromethyl or nitro, and X represents oxygen, sulphur or a group ~N-R3, wherein R3 denotes an alkyl group having 1 to 6 carbon atoms, an alkenyl group having 3 to 6 carbon atoms or an alkynyl group having 3 to 6 carbon atoms.
The 3-hydroxy-1,2,4-triazole derivatives of the above . .
:
, . .
., .
,.
, :~
: .~
-1 ~
~ B -2-, . - . . , : . ' : ' .,, , . , . . . , ~ , .
' ' ' , ' ' " ' ' : , , , formula I are valuable intermediates for the production :~ of phosphoric acid esters which can be used as pest-: ~ control agents, eo~cci~l ~ as insecticides. Such phosphoric acid esters are described, for example, in the German 5 'Offenlegungsschriften' Nos. 2,259,960, 2,259,974 and
.~ R2 X C C - OH ~I) N
. . .
wherein Rl represents an alkyl group having 1 to 6 carbon atoms or a cycloalkyl group having 3 to 8 carbon atoms, R2 represents an alkyl group having 1 to 6 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, an alkenyl group having 3 to 6 carbon atoms, an alkynyl group having 3 to 6 carbon atoms, or a benzyl group optionally mono- or di-substituted by alkyl alkoxy or alkylthio each having 1 to 4 carbon atoms, or by halogen, trifluoromethyl or nitro, and X represents oxygen, sulphur or a group ~N-R3, wherein R3 denotes an alkyl group having 1 to 6 carbon atoms, an alkenyl group having 3 to 6 carbon atoms or an alkynyl group having 3 to 6 carbon atoms.
The 3-hydroxy-1,2,4-triazole derivatives of the above . .
:
, . .
., .
,.
, :~
: .~
-1 ~
~ B -2-, . - . . , : . ' : ' .,, , . , . . . , ~ , .
' ' ' , ' ' " ' ' : , , , formula I are valuable intermediates for the production :~ of phosphoric acid esters which can be used as pest-: ~ control agents, eo~cci~l ~ as insecticides. Such phosphoric acid esters are described, for example, in the German 5 'Offenlegungsschriften' Nos. 2,259,960, 2,259,974 and
2,330,089.
It is known that 1,5-disubstituted 3-hydroxy-1,2,4-triazoles of the above formula I can be produced by ~: reaction of a sèmicarbazide, substituted by the radical Rl according to the aforementioned definition, with orthoformic acid ester, subsequent chlorination in the 5-position of the initially resulting 3-hydroxy-1,2,4-triazole substituted in the l-position, and replacement of ~' the chlorine atom by the radical R2-X-, wherein R2 and X
~: 15 have the meanings given under the formula I. This known : process requires a large number of reaction steps and, in ~ addition, is unsatisfactory with regard to the attainable "~7 yields. The losses in yield occur mainly on carrying out chlorination of the 3-hydroxy-1,2;`4-triazole occurring as an intermediate and on replacement of the introduced chlorine by the group R2X-.
. It has now been found that the 3-hydroxy-1,2,4-triazolederivative of the formula I can be produced in a simple .
. . .
. .
. . .
..... , . ~ . . . . . .
. . . :- , ~ ~ .
. ', .
1070~96 manner by a process in which a hydraæinecarboxylic acid ester of the formula II
Rl-NH-NH~COOR (II) wherein Rl has the meaning given under formula I, and R represents an alkyl radical having 1 to 4 carbon atoms, is firstly reacted with cyanogen chloride to the corresponding 2-substituted 2-cyanohydrazinecarboxylic acid ester of the formula III
Rl - N - NH - COOR
C - N (III), ; 10 wher~in Rl and R have the meanings given under the formulae I and II, and thîs is subsequently cyclised under alkaline conditions in the presence of a compound R2-X-H.
The process of the invention is advantageously performed , in an inert solvent. For the reaction of a hydrazine-carboxylic acid ester of the formula II with cyanogen chloride, suitable solvents are, in particular, halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, chlorobenzene, or aromatic hydrocarbons such as benzene and toluene, or ketones, especially methyl ethyl ketone, or esters, particularly ethyl acetate, or . - ~
':
.' ' , ' ' . ~ ' .
, ' ' . ', ~ ~ :
~070696 ethers and ethereal liquids such as diethyl ether, tetrahydrofuran and dioxane. For the concluding cyclisation reation, suitable solvents are, in particular, alcohols and water, with suitable alcohols being lower alkanols having 1 to 4 carbon atoms. The cyclisation reaction can however be performed also in the absence of solvents.
The reaction o a hydrazine carboxylic acid ester of the formula II with cyanogen chloride is carried out i~` advantageously in the presence of an acid-binding agent at a temperature of between 0 and 30C. Suitable acid-binding agents are, in particular, alkali metal hydroxides, alkali . ~ .
metal carbonates and especially alkali metal hydrogen carbonates. It is furthermore advantageous to perform the reaction of a hydrazine carboxylic acid ester of the formula II
with cyanogen chloride in a two-phase reaction medi~
consisting of water and one of the above mentioned solvents immiscible with water.
The cyclisation reaction is performed at a temperature of between 0 and 140C, preferably at 40 to 80C. The reaction can be carried out at normal pressure or, if necessary, at excess pressure up to 50 atm. in an auto-clave. Where the cyclisation reaction is performed in a lower alkanol, it is advantageous to operate in the presence _ 5 _ .
. ~ j .
i , , . .
.. ..
, .. . , ~
~f the corresponding sodiu~ or potassium alcoholate. The cyclisation reaction in a lower alkanol can rnoreover by carried out also in the presence of sodium hydroxide or potassium hydroxide. In the case where the cyclisation S reaction is performed in water, it is preferable to operate in the presence of sodium hydroxide or potassium hydroxide.
The radicals Rl and R2 comprise as alkyl groups straight-chain and branched-chain alkyl radicals having 1 to 6 carbon atoms. As cycloalkyl groups having 3 to carbon atoms, the radicals Rl and R2 comprise also cycloalkyl radicals substituted in the ring by lower alkyl groups. In addition, these cycloalkyl radicals can be bound by way of 1 to 3 methylene groups to the nitrogen atom or to X. The radical R2 as a ben~yl group can be mono- to di-substituted in the benzene nucleus by alkyl, alkoxy, or alkylthio groups each having 1 to 4 carbon atoms, halogen, especially chlorine or bromine, nitro or trifluoromethyl.
The process according to the invention is further illustrated by the following Examples.
.
, ' :
., - :
, f ,' . ' . ' ' : ' ' ' ' .
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Example 1 73.0 g of 2-isopropylhydrazinecarboxylic acid ethyl ; ester and 42.0 g of sodium bicarbonate are stirred into 200 ml of methylene chloride and 400 ml of water. There is then introduced at room temperature in the course of 20 minutes, wi~h continuous stirring, 30.8 g of gaseous cyanogen chloride. After an hour's stirring, the methylene chloride base is separated, dried over sodium sulphate and the solvent is distilled off in vacuo. There is obtained as residue 75.0 g (87.5% of theory) of 2-isopropyl-2 cyanohydrazinecarboxylic acid ethyl ester as co]ourless oil.
1370 g of 2-isopropyl-2-cyanohydrazinecarboxylic acid ` ethyl ester is placed into an autoclave, and 423 g of methyl is injected. The temperature is held for 24 hours at 40C. Yhe resulting crystal mass is afterwards transferred to a 2.5 litre sulphonating flask, and heated i~ an oil bath for 2 1/2 hours at 120C. There is then added to the - reactiorL mixture cooled to 90C 1.2 litres of wa~er, whereupon the the reaction product precipitates in crystalline form. Crude l-isopropyl-S-methylthio-3-hydroxy-1,2,4-~hiazole is filtered off, and recrystallised from one litre of acetonitrile~ There is obtained 730 g (52% of theory) of pure l-isopropyl-5~methylthio-3-hydroxy-1,2,4-triazole, m.p. 88-93C _ 7 .
, .~ , ,,. , - :
' .
,, ' . -'"'`''''' ~ ;. .. .
.. ~ ' - .
~:
Example 2 960 g of methyl mercaptan is lntroduced into a solution of 800 g of sodium hydroxide in 5000 ml of water, and 3024 g of 2-isopropyl-2-cyanohydrazinecarboxylic acid ethyl ester is subsequently added dropwise. During the dropwise addition, the temperature rises to 80C and is then maintained for 2 hours at 80C. Stirring is afterwards continued for 15 hours at 20C. After the addition of 1200 g of glacial acetic acid, 2872 g of l-isopropyL-S-methylthio-3-hydroxy-1,2,4-triazole, m.p. 93-96C, precipitates. From the filtrate there is obtained, by extraction with ethyl acetate, a further 175 g if 1-isopropyl-5-methylthio-3-hydroxy-1,2,4-triazole.
; The total yield is therefore 3047 g (87.5% of theory).
'. .. ' . .
: . , : ' ' ,' . . - - . .
. . ', . .:
Example 3 66.0 g of 2-ethylhydrazinecarboxylic acid ethyl ester and 42.0 g of sodium bicarbonate are stirred into 200 ml - of methylene chloride and 400 ml of wa~er. There is then introduced at room temperature in the course of 20 minutes, with continuous stirring, 30.~ g of gaseous cyanogen chloride. After one hour's subsequent stirring, the methylene ch]oride phase is separated and dried over sodium sulphate, and the solvent is distilled off in vacuo.
There is obtained as residue 69.0 g ~88% of theory) of 2-ethyl-2-hydraæinecarboxylic acid ethyl ester as colourless oil.
To a solution of 4.6 g of sodium in 150 ml of absolute ethanol there is added dropwise at 60C 31.4 g of 2-ethyl-2-cyanohydrazinecarboxylic acid ethyl ester. The solution is subsequently refluxed for 4 hours. ~rom the cooled solution there precipitates, after the adfiition of 12 g of glacial acetic acid, sodium acetate, which is separated by filtration. The filtrate is concentr&ted in vacuo to dryness, and the residue is extracted with 200 ml of chloroform. The extract is again concentrated to dryness and the residue is recrystallised from cyclohexane. There is obtained 18.8 g (60% of theory) of 1-ethyl-5-ethoxy-3-hydroxy-1,2,4-triazole, m.p. 64 to 6~C.
'.
~.
Example 4 35.0 g of 2-isopropyl-2-cyanohydrazinecarboxylic acid ethyl ester is added dropwise to a solution of 100 ml of 33% dimethylamine in absolute e~hanol. The solu~ion is maintained firstly for lS hours at room temperature S and afterwards for 1 1/2 hours a~ reflux temperature (65C). After concentration by evaporation ~o dryness there remains an oily residue, which slowl.y crystal]ises on standing. The semisolid product is washed with e~hyl acetate. There is obtained 15.5 g (44% of theory) of l-isopropyl 5-dimethylamino-3-hydroxy-1,2,4-triazole, m,p. 111-112C.
. , ' .
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. ~; .
. . .
.
...... ~ . . . ~ - -:, . . ' - , , ' . ", , , i - ~ ' . ,:
.
Example 5 48 g of methyl mercaptan is introduced into a solution of 40 g of sodium hydroxide in 300 ml of water, and 185 g of 2-sec.butyl-2-cyanohydrazinecarboxylic acid ethyl ester is subsequently added dropwise. The temperature rises to 90C during the dropwise addition. The mixture is then allowed to cool to room temperature. After the addition of 60 g of glacial acetic acid, there precipitates 148.9 g (79.5% of theory) of 1-sec.butyl-5-methylthio-3-hydroxy-1,2,4-triazole, m.p. 104-106C.
The 2-sec-butyl-2-cyanohydrazinecarboxylic acid ethyl ester used as starting material is produced by methods analogous to those given in Examples 1 and 3 by reaction of 2-sec.butylhydrazinecarboxylic acid ethyl ester with . cyanogen chloride.
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i '' .
, , - 11 -., . ~ ~ .
~070696 Example 6 905 g of methyl mercaptan is introduced into an ethanolic solution of sodium ethylate produced from 361 g of sodium and 9 litres of absolute ethanol, and an addition is subsequently made of 2470 g of 2-ethyl-2-cyanohydrazinecarboxylic acid ethyl ester. The soLution obtained is kept firstly for lS hours at room temperature and then for 3 hours at reflux temperature (80C). After ~he addition of 942 g of glacial acetic acid, there precipitates from the cooled solution sodium acetate, which is separated by filtration. The filtrate is concentrated in vacuo to dryness; the residue is taken up in 7 litres of chloroform and filtratlon is performed.
The filtrate is concentrated by evaporation at normal pressure and toluene is added; ~iltration is carried out , and 1 litre of cyclohexane is added to the filtrate. There is obtained 1890 g (75.5% of theory) of 1-ethyl-5-methyl thio-3-hydroxy-1,2,4-triazole, m.p. 83-87C.
.
,, ~
~, ' .
. , '. " ~ ' ,. ,. ' ~,, "', ,~ ;.'' . ', , ~070696 , Rxample 7 To an ethanolic solution of sodium ethylate produced from 4.6 g of sodium and 100 ml of absolute ethanol there is firstly added dropwise 14.9 g of ethyl mercaptan and subsequently 31.4 g of 2-e~hyl-2-cyanohydrazine-S carboxylic acid ethyl ester is added dropwise. There isformed a crystalline precipitate, which is refluxed for
It is known that 1,5-disubstituted 3-hydroxy-1,2,4-triazoles of the above formula I can be produced by ~: reaction of a sèmicarbazide, substituted by the radical Rl according to the aforementioned definition, with orthoformic acid ester, subsequent chlorination in the 5-position of the initially resulting 3-hydroxy-1,2,4-triazole substituted in the l-position, and replacement of ~' the chlorine atom by the radical R2-X-, wherein R2 and X
~: 15 have the meanings given under the formula I. This known : process requires a large number of reaction steps and, in ~ addition, is unsatisfactory with regard to the attainable "~7 yields. The losses in yield occur mainly on carrying out chlorination of the 3-hydroxy-1,2;`4-triazole occurring as an intermediate and on replacement of the introduced chlorine by the group R2X-.
. It has now been found that the 3-hydroxy-1,2,4-triazolederivative of the formula I can be produced in a simple .
. . .
. .
. . .
..... , . ~ . . . . . .
. . . :- , ~ ~ .
. ', .
1070~96 manner by a process in which a hydraæinecarboxylic acid ester of the formula II
Rl-NH-NH~COOR (II) wherein Rl has the meaning given under formula I, and R represents an alkyl radical having 1 to 4 carbon atoms, is firstly reacted with cyanogen chloride to the corresponding 2-substituted 2-cyanohydrazinecarboxylic acid ester of the formula III
Rl - N - NH - COOR
C - N (III), ; 10 wher~in Rl and R have the meanings given under the formulae I and II, and thîs is subsequently cyclised under alkaline conditions in the presence of a compound R2-X-H.
The process of the invention is advantageously performed , in an inert solvent. For the reaction of a hydrazine-carboxylic acid ester of the formula II with cyanogen chloride, suitable solvents are, in particular, halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, chlorobenzene, or aromatic hydrocarbons such as benzene and toluene, or ketones, especially methyl ethyl ketone, or esters, particularly ethyl acetate, or . - ~
':
.' ' , ' ' . ~ ' .
, ' ' . ', ~ ~ :
~070696 ethers and ethereal liquids such as diethyl ether, tetrahydrofuran and dioxane. For the concluding cyclisation reation, suitable solvents are, in particular, alcohols and water, with suitable alcohols being lower alkanols having 1 to 4 carbon atoms. The cyclisation reaction can however be performed also in the absence of solvents.
The reaction o a hydrazine carboxylic acid ester of the formula II with cyanogen chloride is carried out i~` advantageously in the presence of an acid-binding agent at a temperature of between 0 and 30C. Suitable acid-binding agents are, in particular, alkali metal hydroxides, alkali . ~ .
metal carbonates and especially alkali metal hydrogen carbonates. It is furthermore advantageous to perform the reaction of a hydrazine carboxylic acid ester of the formula II
with cyanogen chloride in a two-phase reaction medi~
consisting of water and one of the above mentioned solvents immiscible with water.
The cyclisation reaction is performed at a temperature of between 0 and 140C, preferably at 40 to 80C. The reaction can be carried out at normal pressure or, if necessary, at excess pressure up to 50 atm. in an auto-clave. Where the cyclisation reaction is performed in a lower alkanol, it is advantageous to operate in the presence _ 5 _ .
. ~ j .
i , , . .
.. ..
, .. . , ~
~f the corresponding sodiu~ or potassium alcoholate. The cyclisation reaction in a lower alkanol can rnoreover by carried out also in the presence of sodium hydroxide or potassium hydroxide. In the case where the cyclisation S reaction is performed in water, it is preferable to operate in the presence of sodium hydroxide or potassium hydroxide.
The radicals Rl and R2 comprise as alkyl groups straight-chain and branched-chain alkyl radicals having 1 to 6 carbon atoms. As cycloalkyl groups having 3 to carbon atoms, the radicals Rl and R2 comprise also cycloalkyl radicals substituted in the ring by lower alkyl groups. In addition, these cycloalkyl radicals can be bound by way of 1 to 3 methylene groups to the nitrogen atom or to X. The radical R2 as a ben~yl group can be mono- to di-substituted in the benzene nucleus by alkyl, alkoxy, or alkylthio groups each having 1 to 4 carbon atoms, halogen, especially chlorine or bromine, nitro or trifluoromethyl.
The process according to the invention is further illustrated by the following Examples.
.
, ' :
., - :
, f ,' . ' . ' ' : ' ' ' ' .
' ' ' , , ' ` " ' , ' ' ' ' ~ ' , ' , ~ , , .
'' ' ' ' ' ` , ' . ` ' ' ' . ' ' " '' ~ ' ~ . ' ' ~"
' ' ' ' ' ' ";
Example 1 73.0 g of 2-isopropylhydrazinecarboxylic acid ethyl ; ester and 42.0 g of sodium bicarbonate are stirred into 200 ml of methylene chloride and 400 ml of water. There is then introduced at room temperature in the course of 20 minutes, wi~h continuous stirring, 30.8 g of gaseous cyanogen chloride. After an hour's stirring, the methylene chloride base is separated, dried over sodium sulphate and the solvent is distilled off in vacuo. There is obtained as residue 75.0 g (87.5% of theory) of 2-isopropyl-2 cyanohydrazinecarboxylic acid ethyl ester as co]ourless oil.
1370 g of 2-isopropyl-2-cyanohydrazinecarboxylic acid ` ethyl ester is placed into an autoclave, and 423 g of methyl is injected. The temperature is held for 24 hours at 40C. Yhe resulting crystal mass is afterwards transferred to a 2.5 litre sulphonating flask, and heated i~ an oil bath for 2 1/2 hours at 120C. There is then added to the - reactiorL mixture cooled to 90C 1.2 litres of wa~er, whereupon the the reaction product precipitates in crystalline form. Crude l-isopropyl-S-methylthio-3-hydroxy-1,2,4-~hiazole is filtered off, and recrystallised from one litre of acetonitrile~ There is obtained 730 g (52% of theory) of pure l-isopropyl-5~methylthio-3-hydroxy-1,2,4-triazole, m.p. 88-93C _ 7 .
, .~ , ,,. , - :
' .
,, ' . -'"'`''''' ~ ;. .. .
.. ~ ' - .
~:
Example 2 960 g of methyl mercaptan is lntroduced into a solution of 800 g of sodium hydroxide in 5000 ml of water, and 3024 g of 2-isopropyl-2-cyanohydrazinecarboxylic acid ethyl ester is subsequently added dropwise. During the dropwise addition, the temperature rises to 80C and is then maintained for 2 hours at 80C. Stirring is afterwards continued for 15 hours at 20C. After the addition of 1200 g of glacial acetic acid, 2872 g of l-isopropyL-S-methylthio-3-hydroxy-1,2,4-triazole, m.p. 93-96C, precipitates. From the filtrate there is obtained, by extraction with ethyl acetate, a further 175 g if 1-isopropyl-5-methylthio-3-hydroxy-1,2,4-triazole.
; The total yield is therefore 3047 g (87.5% of theory).
'. .. ' . .
: . , : ' ' ,' . . - - . .
. . ', . .:
Example 3 66.0 g of 2-ethylhydrazinecarboxylic acid ethyl ester and 42.0 g of sodium bicarbonate are stirred into 200 ml - of methylene chloride and 400 ml of wa~er. There is then introduced at room temperature in the course of 20 minutes, with continuous stirring, 30.~ g of gaseous cyanogen chloride. After one hour's subsequent stirring, the methylene ch]oride phase is separated and dried over sodium sulphate, and the solvent is distilled off in vacuo.
There is obtained as residue 69.0 g ~88% of theory) of 2-ethyl-2-hydraæinecarboxylic acid ethyl ester as colourless oil.
To a solution of 4.6 g of sodium in 150 ml of absolute ethanol there is added dropwise at 60C 31.4 g of 2-ethyl-2-cyanohydrazinecarboxylic acid ethyl ester. The solution is subsequently refluxed for 4 hours. ~rom the cooled solution there precipitates, after the adfiition of 12 g of glacial acetic acid, sodium acetate, which is separated by filtration. The filtrate is concentr&ted in vacuo to dryness, and the residue is extracted with 200 ml of chloroform. The extract is again concentrated to dryness and the residue is recrystallised from cyclohexane. There is obtained 18.8 g (60% of theory) of 1-ethyl-5-ethoxy-3-hydroxy-1,2,4-triazole, m.p. 64 to 6~C.
'.
~.
Example 4 35.0 g of 2-isopropyl-2-cyanohydrazinecarboxylic acid ethyl ester is added dropwise to a solution of 100 ml of 33% dimethylamine in absolute e~hanol. The solu~ion is maintained firstly for lS hours at room temperature S and afterwards for 1 1/2 hours a~ reflux temperature (65C). After concentration by evaporation ~o dryness there remains an oily residue, which slowl.y crystal]ises on standing. The semisolid product is washed with e~hyl acetate. There is obtained 15.5 g (44% of theory) of l-isopropyl 5-dimethylamino-3-hydroxy-1,2,4-triazole, m,p. 111-112C.
. , ' .
,., .. .
:'...
. . .
,~ .
. ~; .
. . .
.
...... ~ . . . ~ - -:, . . ' - , , ' . ", , , i - ~ ' . ,:
.
Example 5 48 g of methyl mercaptan is introduced into a solution of 40 g of sodium hydroxide in 300 ml of water, and 185 g of 2-sec.butyl-2-cyanohydrazinecarboxylic acid ethyl ester is subsequently added dropwise. The temperature rises to 90C during the dropwise addition. The mixture is then allowed to cool to room temperature. After the addition of 60 g of glacial acetic acid, there precipitates 148.9 g (79.5% of theory) of 1-sec.butyl-5-methylthio-3-hydroxy-1,2,4-triazole, m.p. 104-106C.
The 2-sec-butyl-2-cyanohydrazinecarboxylic acid ethyl ester used as starting material is produced by methods analogous to those given in Examples 1 and 3 by reaction of 2-sec.butylhydrazinecarboxylic acid ethyl ester with . cyanogen chloride.
`:
i '' .
, , - 11 -., . ~ ~ .
~070696 Example 6 905 g of methyl mercaptan is introduced into an ethanolic solution of sodium ethylate produced from 361 g of sodium and 9 litres of absolute ethanol, and an addition is subsequently made of 2470 g of 2-ethyl-2-cyanohydrazinecarboxylic acid ethyl ester. The soLution obtained is kept firstly for lS hours at room temperature and then for 3 hours at reflux temperature (80C). After ~he addition of 942 g of glacial acetic acid, there precipitates from the cooled solution sodium acetate, which is separated by filtration. The filtrate is concentrated in vacuo to dryness; the residue is taken up in 7 litres of chloroform and filtratlon is performed.
The filtrate is concentrated by evaporation at normal pressure and toluene is added; ~iltration is carried out , and 1 litre of cyclohexane is added to the filtrate. There is obtained 1890 g (75.5% of theory) of 1-ethyl-5-methyl thio-3-hydroxy-1,2,4-triazole, m.p. 83-87C.
.
,, ~
~, ' .
. , '. " ~ ' ,. ,. ' ~,, "', ,~ ;.'' . ', , ~070696 , Rxample 7 To an ethanolic solution of sodium ethylate produced from 4.6 g of sodium and 100 ml of absolute ethanol there is firstly added dropwise 14.9 g of ethyl mercaptan and subsequently 31.4 g of 2-e~hyl-2-cyanohydrazine-S carboxylic acid ethyl ester is added dropwise. There isformed a crystalline precipitate, which is refluxed for
3 hours. The cooled suspension is freed, after the addition of 12 g of glacial acetic acid, by filtration from the - precipitated sodium acetate, and the filtrate is concentrated in vacuo to dryness~ 200 ml of chloroform is added to the residue and filtration is performed. The filtrate is again concentrated to dryness. The residue is recrystalli~ed with cyclohexane. There is obtained 26 g (75~/O of theory) of l-ethyl-5-ethylthio-3-hydroxy-1,2,4-triazole, m.p. 65-68C~
,, .
.
... .
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:' ' J' ' :~ ~
~070696 ExamPle 8 51.5 g of ethyl mercaptan and subsequently 163 g of 2-cyclopentyl-2-cyanohydrazinecarboxylic acid ethyl ester are added dropwise to a solution of 33~2 g of sodium hydroxide in 190 ml of water at room temperature. The S solution is subsequently refluxed for 1 hour. From the cooled solution there precipitates, after the addition : of 50 g of glacial acetic acid~ 167 g (94% of theory) of l-cyclopentyl-5-methylthio-3-hydroxy-1~2~4-triazole, m-p~ 93-95C.
. lO The 2-cyclopentyl-2~cyanohydrazinecarboxylic acid ethyl ester used as starting material i9 produced by a method analogous to that described in the Examples l and 3 by ~: reaction of 2-cyclopentylhydrazinecarboxylic acid ethyl ester with cyanogen chloride.
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~0706g6 ~ Exam~ 9 .
244 g of allyl mercaptan is added to a solution of 132 g of sodium hydroxide in 750 ml of water, and - subsequently at room temperature 514 g of 2-ethyl-2-cyanohydrazinecarboxylic acid ethyl ester is added dropwise. After one hour's refluxing, there is added to the cooled solution 198 g of glacial acetic acid.
i'.
.- The oily phase is separated and concentrated in vacuo to dryness. There is obtained 260 g (43% of theory) of l-ethyl-5-allylthio-3-hydroxy-1,2,4-triazole, m.p~ 74-76C.
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.`'' ' .. .. . .
i~ :
Example 10 31.7 g of 4-chlorobenzyl mercaptan is added -~o a solution of 8 g of sodium hydroxide in 100 ml of water and 50 ml of alcohol, and subsequent]y 34.2 g of 2-isopropyl-2 cyanohydrazinecarboxylic acid ethyl ester ~, 5 is added dropwise. The temperature rises to 38C during the dropwise addition. The temperature is then maintained for 2 hours at 85C. After cooling of the mixture to 20C, 12 g of glacial acetic acid is added dropwise, whereupon white crystals of l-isopropyl 3-hydroxy-5 (4-chlorobenzyl-` 10 thio) 1,2,4-triazole precipitate. These are recrystallised in 400 ml of methanol and yield 42 g of product, m.p.
140--141C (74% of theory).
.
. .
. i , .
. .
, j. .
.
: .
.
; - 16 -. .
, :
. ,, .: . - , . .' . .
'' ' ' : ' ~ ' - '~
~o706s6 F.xample Ll To a solution o 8 g of sodium hydroxide in 100 ml of water and 50 ml of alcohol there is firstly added 24.8 g of benzyl mercapta,n, and subsequently 34.2. g of 2-isopropyl-2-cyanohydrazinecarboxylic acid ethyl ester '~ 5 is added dropwise. The temperature rises to 38C during the dropwise addition. The temperature is then held for 2 hours at 85C. After cooling to 20C, there is added dropwise 12 g o~ glacial acetic acid, whereupon white crystals of 31 g of 1-isopropyl-3-hydroxy-S-benzylthio-1~2,4-triazole, m.p. 134-135C, precipitate (62% of theory).
.~
;
. .
.
1~70696 . .
Example 12 24.05 g of methyl mercaptan is introduced into a solution of sodium ethylate produce~ by dissolving 11.5 g of sodium in 300 ml of absolute ethanol. There . . .
is then added dropwise at 60C 71.5 g of 2-cyano-2-methyl-hydrazinecaxboxylic acid ester, whereupon the temperature rises to 75C. After completion of the addition, the reaction mixture is refluxed for 5 hours.
30 g of glacial acetic acid is subsequently added dropwise to the solution cooled to room temperature. After separation of the resulting precipitate by filtration, the solvent is removed in vacuo from the iiltrateO With dry-ice cooling, the residue is recrystallised from 140 ml of methanol. Thexe is obtained 21.8 g of 1-methyl-5-methyl thio-3-hydroxy-1,2,4-triazole (30% of theory) having a melting point of 128-130C.
The 2-cyano-2-methylhydrazinecarboxylic acid ethyl ester required as starting material is produced by a method analogous to that described in Examples 1 and 3 by reaction of 2~methylhydrazinecarboxylic acid ethyl ester with cyanogen chloride.
:' -.. . .
,, .
.
... .
'~ .
:' ' J' ' :~ ~
~070696 ExamPle 8 51.5 g of ethyl mercaptan and subsequently 163 g of 2-cyclopentyl-2-cyanohydrazinecarboxylic acid ethyl ester are added dropwise to a solution of 33~2 g of sodium hydroxide in 190 ml of water at room temperature. The S solution is subsequently refluxed for 1 hour. From the cooled solution there precipitates, after the addition : of 50 g of glacial acetic acid~ 167 g (94% of theory) of l-cyclopentyl-5-methylthio-3-hydroxy-1~2~4-triazole, m-p~ 93-95C.
. lO The 2-cyclopentyl-2~cyanohydrazinecarboxylic acid ethyl ester used as starting material i9 produced by a method analogous to that described in the Examples l and 3 by ~: reaction of 2-cyclopentylhydrazinecarboxylic acid ethyl ester with cyanogen chloride.
;'. .
.
P.
''..~
...
.
..:
.~ , ~; . . : :
, . , ~ ' .
~0706g6 ~ Exam~ 9 .
244 g of allyl mercaptan is added to a solution of 132 g of sodium hydroxide in 750 ml of water, and - subsequently at room temperature 514 g of 2-ethyl-2-cyanohydrazinecarboxylic acid ethyl ester is added dropwise. After one hour's refluxing, there is added to the cooled solution 198 g of glacial acetic acid.
i'.
.- The oily phase is separated and concentrated in vacuo to dryness. There is obtained 260 g (43% of theory) of l-ethyl-5-allylthio-3-hydroxy-1,2,4-triazole, m.p~ 74-76C.
,, .
~.' . ~ .
.
".' ~;' ;
~ - 15 -.' .
,~ .
.
.`'' ' .. .. . .
i~ :
Example 10 31.7 g of 4-chlorobenzyl mercaptan is added -~o a solution of 8 g of sodium hydroxide in 100 ml of water and 50 ml of alcohol, and subsequent]y 34.2 g of 2-isopropyl-2 cyanohydrazinecarboxylic acid ethyl ester ~, 5 is added dropwise. The temperature rises to 38C during the dropwise addition. The temperature is then maintained for 2 hours at 85C. After cooling of the mixture to 20C, 12 g of glacial acetic acid is added dropwise, whereupon white crystals of l-isopropyl 3-hydroxy-5 (4-chlorobenzyl-` 10 thio) 1,2,4-triazole precipitate. These are recrystallised in 400 ml of methanol and yield 42 g of product, m.p.
140--141C (74% of theory).
.
. .
. i , .
. .
, j. .
.
: .
.
; - 16 -. .
, :
. ,, .: . - , . .' . .
'' ' ' : ' ~ ' - '~
~o706s6 F.xample Ll To a solution o 8 g of sodium hydroxide in 100 ml of water and 50 ml of alcohol there is firstly added 24.8 g of benzyl mercapta,n, and subsequently 34.2. g of 2-isopropyl-2-cyanohydrazinecarboxylic acid ethyl ester '~ 5 is added dropwise. The temperature rises to 38C during the dropwise addition. The temperature is then held for 2 hours at 85C. After cooling to 20C, there is added dropwise 12 g o~ glacial acetic acid, whereupon white crystals of 31 g of 1-isopropyl-3-hydroxy-S-benzylthio-1~2,4-triazole, m.p. 134-135C, precipitate (62% of theory).
.~
;
. .
.
1~70696 . .
Example 12 24.05 g of methyl mercaptan is introduced into a solution of sodium ethylate produce~ by dissolving 11.5 g of sodium in 300 ml of absolute ethanol. There . . .
is then added dropwise at 60C 71.5 g of 2-cyano-2-methyl-hydrazinecaxboxylic acid ester, whereupon the temperature rises to 75C. After completion of the addition, the reaction mixture is refluxed for 5 hours.
30 g of glacial acetic acid is subsequently added dropwise to the solution cooled to room temperature. After separation of the resulting precipitate by filtration, the solvent is removed in vacuo from the iiltrateO With dry-ice cooling, the residue is recrystallised from 140 ml of methanol. Thexe is obtained 21.8 g of 1-methyl-5-methyl thio-3-hydroxy-1,2,4-triazole (30% of theory) having a melting point of 128-130C.
The 2-cyano-2-methylhydrazinecarboxylic acid ethyl ester required as starting material is produced by a method analogous to that described in Examples 1 and 3 by reaction of 2~methylhydrazinecarboxylic acid ethyl ester with cyanogen chloride.
:' -.. . .
Claims (9)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. Process for the production of 3-hydroxy-1,2,4-triazole derivatives of the formula I
(I) wherein R1 represents an alkyl group having 1 to 6 carbon atoms or a cycloalkyl group having 3 to 8 carbon atoms, R2 represents an alkyl group having 1 to 6 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, an alkenyl group having 3 to 6 carbon atoms, an alkynyl group having 3 to 6 carbon atoms, or a benzyl group optionally mono- to disubstituted by alkyl, alkoxy or alkylthio groups each having 1 to 4 carbon atoms, halogen, trifluoromethyl or nitro, and X represents oxygen, sulphur or a group , wherein R3 denotes an alkyl group having 1 to 6 carbon atoms, an alkenyl group having 3 to 6 carbon atoms or an alkynyl group having 3 to 6 carbon atoms, in which process a hydr-azinecarboxylic acid ester of the formula II
R1 - NH - NH - COOR (II), wherein R1 has the meaning given under formula I, and R represents an alkyl radical having 1 to 4 carbon atoms, is firstly reacted with cyanogen chloride to the corresponding 2-substituted 2-cyanohydrazinecarboxylic acid ester of the formula III
(III) wherein R1 and R have the meanings given under the formulae I and II, and the resulting intermediate product is subsequently cyclised under alkaline condi-tions in the presence of a compound R2XH.
(I) wherein R1 represents an alkyl group having 1 to 6 carbon atoms or a cycloalkyl group having 3 to 8 carbon atoms, R2 represents an alkyl group having 1 to 6 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, an alkenyl group having 3 to 6 carbon atoms, an alkynyl group having 3 to 6 carbon atoms, or a benzyl group optionally mono- to disubstituted by alkyl, alkoxy or alkylthio groups each having 1 to 4 carbon atoms, halogen, trifluoromethyl or nitro, and X represents oxygen, sulphur or a group , wherein R3 denotes an alkyl group having 1 to 6 carbon atoms, an alkenyl group having 3 to 6 carbon atoms or an alkynyl group having 3 to 6 carbon atoms, in which process a hydr-azinecarboxylic acid ester of the formula II
R1 - NH - NH - COOR (II), wherein R1 has the meaning given under formula I, and R represents an alkyl radical having 1 to 4 carbon atoms, is firstly reacted with cyanogen chloride to the corresponding 2-substituted 2-cyanohydrazinecarboxylic acid ester of the formula III
(III) wherein R1 and R have the meanings given under the formulae I and II, and the resulting intermediate product is subsequently cyclised under alkaline condi-tions in the presence of a compound R2XH.
2, Process according to claim 1, wherein the reaction of the hydrazine-carboxylic acid ester of the formula II with cyanogen chloride is performed at a temperature of between 0 and 30°C in an inert solvent in the presence of an acid-binding agent.
3. Process aecording to Claim 1 wherein the reaction of a hydrazinecarboxylic acid ester of the formula II
with cyanogen chloride is performed in a two-phase reaction medium consisting of water and a solvent immiscible with water.
with cyanogen chloride is performed in a two-phase reaction medium consisting of water and a solvent immiscible with water.
4. Process according to Claim 1 wherein the cyclisation reaction is performed at a temperature of between 0 and 140°C.
5. Process according to Claim 1 wherein the cyclisation reaction is performed at a temperature of between 40 and 120°C.
6. Process according to Claim 1 wherein the cyclisation reaction is performed in a lower alkanol.
7. Process according to Claim 1 wherein the cyclisation reaction is performed in water.
8. Process according to Claim 1 wherein the cyclisation reaction is performed in a lower alkanol in the presence of the corresponding sodium or potassium alcoholate.
9. Process according to Claim 1 wherein the cyclisation reaction is performed in water in the presence of sodium hydroxide or potassium hydroxide.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1177174A CH601266A5 (en) | 1974-08-29 | 1974-08-29 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1070696A true CA1070696A (en) | 1980-01-29 |
Family
ID=4376715
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA234,232A Expired CA1070696A (en) | 1974-08-29 | 1975-08-27 | Process for the production of 3-hydroxy-1,2,4-triazole derivatives |
Country Status (18)
| Country | Link |
|---|---|
| JP (1) | JPS5910351B2 (en) |
| AT (1) | AT342587B (en) |
| AU (1) | AU499371B2 (en) |
| BE (1) | BE832830A (en) |
| CA (1) | CA1070696A (en) |
| CH (1) | CH601266A5 (en) |
| CS (1) | CS193522B2 (en) |
| DD (1) | DD122535A5 (en) |
| DE (1) | DE2537973A1 (en) |
| ES (1) | ES440532A1 (en) |
| FR (1) | FR2283132A1 (en) |
| GB (1) | GB1512456A (en) |
| HU (1) | HU172771B (en) |
| IL (1) | IL48008A (en) |
| NL (1) | NL7510012A (en) |
| NZ (1) | NZ178271A (en) |
| SU (1) | SU577989A3 (en) |
| ZA (1) | ZA755512B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3070073D1 (en) * | 1979-10-22 | 1985-03-14 | Glaxo Group Ltd | 1,2,4-triazole derivatives, processes for their production and pharmaceutical compositions containing them |
| DE3068712D1 (en) * | 1979-10-23 | 1984-08-30 | Glaxo Group Ltd | Aminoalkyl compounds, their production and pharmaceutical compositions containing them |
| DE3267240D1 (en) * | 1981-04-09 | 1985-12-12 | Hoechst Ag | Process for the preparation of substituted 3-hydroxy-1,2,4-triazoles |
| DE3939952A1 (en) * | 1989-12-02 | 1991-06-06 | Bayer Ag | SUBSTITUTED TRIAZOLINONES |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE792451A (en) * | 1971-12-10 | 1973-06-08 | Ciba Geigy | TRIAZOLYL ESTERS OF PHOSPHORIC ACIDS AND PESTICIDE PRODUCTS WHICH CONTAIN |
| BE792449A (en) * | 1971-12-10 | 1973-06-08 | Ciba Geigy | TRIAZOLYL ESTERS OF OXYGENIC ACIDS OF PHOSPHORUS AND PESTICIDE PRODUCTS THAT CONTAIN |
| IL42316A (en) * | 1972-06-16 | 1976-02-29 | Ciba Geigy Ag | Triazolyl organophosphorus derivatives,their manufacture and their use as pesticides |
| DE2250572A1 (en) * | 1972-10-14 | 1974-04-18 | Bayer Ag | N, N-DIMETHYL-O-TRIAZOLYL-CARBAMIC ACID ESTER, METHOD FOR THEIR MANUFACTURING AND USE AS INSECTICIDES AND ACARICIDES |
| NL7316469A (en) * | 1972-12-08 | 1974-06-11 | ||
| DE2301400C2 (en) * | 1973-01-12 | 1984-12-13 | Bayer Ag, 5090 Leverkusen | 0-Triazolyl-thionophosphorus (phosphonic) acid esters and ester amides, process for their preparation and their use as insecticides and acaricides |
-
1974
- 1974-08-29 CH CH1177174A patent/CH601266A5/xx not_active IP Right Cessation
-
1975
- 1975-07-31 NZ NZ178271A patent/NZ178271A/en unknown
- 1975-08-15 CS CS755621A patent/CS193522B2/en unknown
- 1975-08-18 SU SU7502163216A patent/SU577989A3/en active
- 1975-08-25 NL NL7510012A patent/NL7510012A/en not_active Application Discontinuation
- 1975-08-26 DE DE19752537973 patent/DE2537973A1/en active Granted
- 1975-08-27 HU HU75CI00001600A patent/HU172771B/en unknown
- 1975-08-27 CA CA234,232A patent/CA1070696A/en not_active Expired
- 1975-08-27 GB GB35411/75A patent/GB1512456A/en not_active Expired
- 1975-08-27 DD DD188052A patent/DD122535A5/xx unknown
- 1975-08-28 AU AU84345/75A patent/AU499371B2/en not_active Expired
- 1975-08-28 AT AT664775A patent/AT342587B/en active
- 1975-08-28 IL IL48008A patent/IL48008A/en unknown
- 1975-08-28 FR FR7526487A patent/FR2283132A1/en active Granted
- 1975-08-28 BE BE159531A patent/BE832830A/en not_active IP Right Cessation
- 1975-08-28 ZA ZA00755512A patent/ZA755512B/en unknown
- 1975-08-28 ES ES440532A patent/ES440532A1/en not_active Expired
- 1975-08-29 JP JP50104879A patent/JPS5910351B2/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| DE2537973C2 (en) | 1989-04-06 |
| ZA755512B (en) | 1976-07-28 |
| FR2283132B1 (en) | 1978-04-07 |
| JPS5148668A (en) | 1976-04-26 |
| HU172771B (en) | 1978-12-28 |
| DE2537973A1 (en) | 1976-03-11 |
| IL48008A0 (en) | 1975-11-25 |
| JPS5910351B2 (en) | 1984-03-08 |
| ES440532A1 (en) | 1977-03-01 |
| BE832830A (en) | 1976-03-01 |
| GB1512456A (en) | 1978-06-01 |
| ATA664775A (en) | 1977-08-15 |
| AU8434575A (en) | 1977-03-03 |
| NZ178271A (en) | 1978-04-03 |
| FR2283132A1 (en) | 1976-03-26 |
| CH601266A5 (en) | 1978-06-30 |
| SU577989A3 (en) | 1977-10-25 |
| IL48008A (en) | 1979-07-25 |
| NL7510012A (en) | 1976-03-02 |
| CS193522B2 (en) | 1979-10-31 |
| DD122535A5 (en) | 1976-10-12 |
| AU499371B2 (en) | 1979-04-12 |
| AT342587B (en) | 1978-04-10 |
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