CA2118371A1 - Process for the production of dialkyl pyrimidylphosphates - Google Patents
Process for the production of dialkyl pyrimidylphosphatesInfo
- Publication number
- CA2118371A1 CA2118371A1 CA 2118371 CA2118371A CA2118371A1 CA 2118371 A1 CA2118371 A1 CA 2118371A1 CA 2118371 CA2118371 CA 2118371 CA 2118371 A CA2118371 A CA 2118371A CA 2118371 A1 CA2118371 A1 CA 2118371A1
- Authority
- CA
- Canada
- Prior art keywords
- dialkyl
- hydroxypyrimidine
- amine
- tris
- organic solvent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
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Abstract
A PROCESS FOR THE PRODUCTION
OF DIALKYL PYRIMIDYLPHOSPHATES
ABSTRACT OF THE DISCLOSURE
O,O-dialkyl pyrimidylphosphates are made by reacting an O,O-dialkyl phosphorohalothioate with a 5-hydroxypyrimidine in the presence of a cation coordinating catalyst, an organic solvent and an alkali metal hydroxide at a pH of from about 8 to about 12 and a temperature of up to about 70°C. The products of this process are obtained in high yield.
These compounds are useful as pesticides and insecticides.
OF DIALKYL PYRIMIDYLPHOSPHATES
ABSTRACT OF THE DISCLOSURE
O,O-dialkyl pyrimidylphosphates are made by reacting an O,O-dialkyl phosphorohalothioate with a 5-hydroxypyrimidine in the presence of a cation coordinating catalyst, an organic solvent and an alkali metal hydroxide at a pH of from about 8 to about 12 and a temperature of up to about 70°C. The products of this process are obtained in high yield.
These compounds are useful as pesticides and insecticides.
Description
,- 21~8371 :-Mo4029 MD-93-126-AD ~ :
A PROCESS FOR THE PRODUCTiON
OF DIALKYL PYRIMIDYLPHOSPHATES
BACKGROUND OF THE INVENTION
The present invention relates to a process for the production of O,O-dialkyl pyrimidylphosphates.
Pyrimidylphosphates are known to be useful in the control of soil ;
pests or insects such as corn rootworrn, thrips, leafhoppers, and nematodes when applied to the soil of corps such as com, sorghum, cotton and sugar beets.
Processes for making these pesticides are also known. U.S. ~-Patent 4,094,873, for example, discloses a process in which an alkali metal phenoxide, pyridinoxide or pyrimidinoxide is reacted with an O,O-dialkyl phosphorochloridothioate or O-alkyl phenylphosphonochlorido-thioate or O-alkyl phenylphosphonochloridothioate in the presence of a catalyst mixture under alkaline conditions in a liquid reaction medium.
The catalyst mixture is made up of a quaternary ammonium salt and a diazole.
U.S. Patent 4,147,866 also discloses a process in which an alkali metal phenoxide, pyridinoxide or pyrimidinoxide is reacted with an O,O-dialkylphosphorochloridothioate in the presence of a catalyst mixture under alkal~ne conditions in a liquid reaction medium. The catalysts used in this process are a quatemary ammonium salt and a sterically unhindered, nucleophilic, tertiary amine. U.S. 4,147,866 also teaches that use of either the tertiary amine or the quaternary ammonium catalyst aione results in low yields, high amounts of unwanted by-products and expensive, difficult purification steps. Each of the processes disclosed in U.S. 4,094,873 and 4,147,866 is disadvantageous in that two catalysts must be employed. The cost of raw materials and product purification is therefore increased.
vj t/an4029 ~ 2118371 ~ ~
.
U.S. Patent 4,429,125 discloses a process for the production of phosphorus esters of 5-pyrimidinols in which a 5-pyrimidinol is reacted with a phosphorochloridothioate in an inert organic liquid in the presence of an acid binding agent or acceptor. The acid binding agent or acceptor is selected from alkali carbonates, alkali hydroxides, and alcoholates such as sodium carbonate, potassium carbonate, sodium or potassium methoxide, sodium or potassium ethoxide, and amines. No phase catalyst is included in the reaction mixture.
U.S. Patent 4,729,987 also discloses a process in which a 5-pyrimidinol represented by a given formula is reacted with a phosphorochloridothioate in an inert organic liquid and an acid binding agent or acceptor at a temperature of from about 0 to about 100C. No :
phase transfer catalyst is included in the reaction mixture.
Published European Patent Application 277,292 discloses a process for producing O-pyrimidinyl phosphorus compounds in which an aqueous solution of a salt of pyrimidine is reacted with a phosphorus ~ -ester in the presence of a phase transfer catalyst without added organic solvent. This disclosure teaches that low yields are to be expected when -an organic solvent such as toluene is used as the reaction medium.
None of these patents disclose a process in which a cation coordinating catalyst such as a crown ether, cryptand, or related acyclic catalyst is used.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide an improved process for the production of O,O-dialkyl pyrimidylphosphates.
It is also an object of the present invention to provide a process for the production of dialkyl pyrimidylphosphates in which only a single phase transfer catalyst is employed.
Mo4029 .' , ' ~ 211~371 :
It is another object of the present invention to provide a process for the production of dialkyl pyrimidylphosphates in which the phase ~ -transfer catalyst is effective even when the reaction is carried out in a solvent such as toluene.
These and other objects which will be apparent to those skilled in ;
the art are accomplished by reacting an O,O-dialkyl substituted phosphorohalothioate with a 5-hydroxypyrimidine in the presence of a phase transfer catalyst, an organic solvent and an alkali metal hydroxide at a pH of from about 8 to about 12 and a temperature of up to 70C.
The phase transfer catalyst must be a cation coordinating catalyst. The product O,O-dialkyl pyrimidylphosphate may be recovered from the reaction mixture by adding water to the reaction mixture with agitation to cause the formation of an aqueous and an organic phase. The organic and aqueous phases may then be separated and the organic solvent removed from the organic phase by, e.g., steam stripping. '.. ! ,, DETAILED DESCRIPTION OF THE PREFERRED
EMBODIMENTS OF THE INVENTION
The present invention relates to a process in which an O,O-alkyl 20 substituted phosphorohalothioate is reacted with a 5-hydroxypyrimidine in the presence of a cation coordinating catalyst, an organic solvent and an alkali metal hydroxide. This reaction is carried out at a pH of from about 8 to about 12 and a temperature of up to 70-C.
The O,O-alkyl substituted phosphorohalothioates useful in the 25 process of the present invention are known. Examples of such compounds include those represented by the forrnula Mo4029 ~''' ~'" ''' .
. :;, . , , "' '. ", . ~ 2118371 ' , ~
-4- ~;
~'; ~ ''`',',' S
R O P X
R'--O ~:
, , .
.
in which R and R' each represents a lower alkyl group, preferably an alkyl ~:
group having from 1 to 4 carbon atoms, and ~ ;~
10 X represents a halogen atom, preferably chloride.
Preferred O,O-alkyl phosphorohalothioates include: O-ethyl-0-(1-methyl ethyl) phosphorochloridothioate; O,O-diethyl phosphoro-chloridothioate; O,O-dimethyl phosphorochloridothioate; and 0,0-diisopropyl phosphorochloridothioate.
The 5-hydroxypyrimidines useful in the process of the present invention include any of the known 5-hydroxypyrimidines represented by the formula R"
/ N C-\ ~
R"'--C\ O /C OH
N C \
R""
in which 25 R" represents hydrogen, methyl or an alkylthio group having from 1 to 2 carbon atoms;
R"' represents hydrogen, an alkyl group having from 1 to 8 carbon atoms, an alkylthiomethyl group, an alkylsulfinylmethyl group or an Mo4029 : ~:
~ ~.
~ 211~71 alkylsulfonylmethyl group with alkyl meaning from 1 to 4 carbon atoms, a phenyl group, a phenylthio group, an alkylthio group having from 1 to 4 carbon atoms, an alkylsulfinyl group having from 1 to 4 carbon atoms, an alkylsulfonyl group having from 1 to 4 carbon atoms, or an alkylthioethylthio group having from 1 to 2 carbon atoms in the alkyl group; and R"" represents hydrogen or a methyl group.
Particularly preferred 5-hydroxypyrimidines include: 2-(1,1-dimethyl ethyl)-5-hydroxypyrimidine; 2-(1-methylethyl)-5-hydroxypyrimidine; 2-ethyl-5-hydroxypyrimidine; and 2-(1-methyl)thio)-5-hydroxypyrimidine.
The phase transfer catalyst used in the process of the present invention must be a cation coordinating catalyst. As used herein, a cation coordinating catalyst is a non-metallic molecule which will unite with a postively charged ion to form a coordination compound ~r complex. Any of the known cation coordinating catalysts may be used.
Such catalysts are represented by either of the following formulae:
R
~aA
~ ( (O~x ~R
z(O ' in which 25 A represents oxygen or nitrogen;
R" R2, R3, R4, Rs~ R6, R7, an~ R8 each represents: a proton; an alkyl group having from 1 to 16 carbon atoms which alkyl group may contain or be substituted by one or more heteroatoms (i.e. atoms Mo4029 ~ .
~ 2 1 1 8 3 7 1 .~ - ~ ,.
which are not carbon) or one or more heterocycles; an aryl group having from 6 to 7, preferably 6 carbon atoms which may be substituted by heteroatoms; a heterocycle; an aralkyl group having from 7 to 10, preferably 7 carbon atoms; or a cycloalkyl group having from 5 to 10, preferably from 5 to 7 carbon atoms;
x represents a numberfrom 0 to 1000;
y represents a numberfrom 0 to 5; ~ -z represents a number from 2 to 3; and Q represents phosphorous, nitrogen, sulfur or oxygen.
10 R" R2, R3, R4, R5, R6, R7, and/or R8 may be joined in a ring.
Suitable cation coordinating catalysts include cryptates, crown ethers, polyols which will act as a cation coordinating compound in the reaction medium and tertiary alkoxy alkyl amines.
Specific examples of suitable cation coordinating catalysts include~
18-crown-6-ether, cryptand 12-2-2], tetraethyleneglycol dimethly ether, poly(ethylene glycol)s with a molecular weight of from 200 to 10,000, tris[dioxa-3,6-octyl] amine, tris[dioxa-3,6-decyl]amine, tris[trioxa-3,6,8 decyl] amine, and tris[2-(2-methoxyethoxy)ethyll amine. Tris[2-(2-methoxyethoxy)ethyl]-amine is preferred.
The solvents useful in the process of the present invention include any of the known and commonly used organic solvents.
Specific examples of suitable solvents include: toluene, benzene, xylenes, ethylbenzene, cumene, mesitylene, chlorobenzene, and non- -aromatic solvents such as dichloromethane, ethylene dichloride, acetone and methyl ethyl ketone.
The process of the present invention is carried out at a pH of from about 8 to about 12 in the presence of an alkali metal hydroxide. Any of the alkali metal hydroxides may be used but sodium hydroxide is Mo4029 ~-~ 3 7 i particularly preferred.
The reaction which occurs in the process of the present invention is carried out at a temperature of up to 70C, preferably at a temperature of from about 30 to about 6QC, most preferably at a temperature of about 45C.
The reaction components are generally used in amounts such that at least 1 mole of 5-hydroxypyrimidine is present for each mole of O,O-dialkyl phosphorohalothioate, preferably from 1 to about 2 moles per mole of O,O-dialkyl phosphorohalothioate. The O,O-dialkyl phosphoro-halothioate may be dissolved in the solvent in an amount such that the O,O-dialkyl phosphorohalothioate is present at concentration of from 10 to 90%, preferably from about 50 to 85%. The cation coordinating catalyst is generally used in an amount of from about 10 mole % to about 20 mole % based on the O,O-dialkyl phosphorohalothioate. The alkali metal hydroxide is generally used in an amount sufficient to maintain the pH of the reaction mixture between about 8 and about 12. Generally, from about 1 to about 1.1 moles of alkali metal hydroxide per mole of S-hydroxypyrimidine are used. The alkali metal hydroxide is generally used in the form of an aqueous solution having a concentration of from about 10 to about 50% by weight. -~
Afterthe reaction betweenthe O,O-dialkyl phosphorohalothioate and the 5-hydroxypyrimidine has been substantially completed, the product O,O-dialkyl pyrimidylphosphate is recovered by, for example, a phase separation process. Water may be added to the reaction mixture with agitation. The resultant mixture is allowed to settle until two distinct r :
phases are formed. The organic phase which includes the product to be recovered is separated from the aqueous phase and then treated (e.g., steam stripped) to remove the organic solvent. The O,O-dialkyl Mo4029 ~ ~ ,""~,",~
~ 211~37~ ~
pyrimidylphosphate remains.
The process of the present invention produces the desired 0,0-dialkyl pyrimidylphosphate in yields of at least 80%, generally better than 90% in reaction times as short as 2 hours. Typical reaction Umes range 5 from about 4 to about 7 hours.
The invention is further illustrated but is not intended to be limited by the following examples in which all parts and percentages are by ~ .
weight unless otherwise specified.
EXAMPLES
10 ExamPles 1-13 A 25% sodium hydroxide solution was added dropwise to a mixture of 0-ethyl-0-(1-methylethyl) phosphorochloridothioate in toluene, 2-(1,1-dimethylethyl)-5-hydroxypyrimidine and trisl2(2-methoxy-ethoxy)ethyl] amine at 45C. The amounts of each material used in each 15 Example is reported in the following table. The sodium hydroxide was added at a rate sufficient to maintain the pH of the reaction mixture between 8 and 10. The reaction mixture was subsequently stirred at 45C until the unreacted phosphorochloridothioate was less than 0.5% as determined by gas chromatography. The mixture was then cooled to ~;;
20 25C and 50 ml of water were added. The resultant mixture was agitated for 15 minutes and allowed to stand until the organic and aqueous layers separated. The layers were separated and the organic layer was steam stripped to remove the toluene present. 0-12-(1,1-dimethylethyl)-5~
pyrimidinyl]-0-ethyl-0-(1-methylethyl) phosphorothioatewas isolated as 25 the product.
."~
Mo4029 211~371 g c~ _ o o _ _ o o o o o -o _ o~ '' O ~ O ~ 0 _ _ ___ _ 0 _ N .V/~
~:7 ~ ~ ~ ~') 0 ~D ~C) C~l O) O ~_ ) 0 ~
_ o) a) CJ~ ~ ~ ~ ~ U~ O) ~ a) ~ ~ a)O
g g ~_ _ ~q N _ ~ ~1> CJ) ~ C') U) ~ I E E
~ ~D u~ ~ ~ ~ a~ a) ~D U~ U~ ~ ~ ~ 8 8 s~i; ~ Ic~
. O O O O N N O O N N O ~ O C) ~1) ~0 o o o o o o o o o o o o o lo~
_ 6 6 6 _ 6 6 6 _ IIJ N _ 6 O O
Q _ _ _ ( ) U~ 'J ~t ~ ~ ~ U~ U~
~o _ _ _ 0 O O O O N N N ~O O N O O u~) -- ;
~Z o o o o o o o o o o o _ a~ O O ~ N 1~ ~) ~ N 1~ N U~ U~ 10 O O O O
~ g O O O O O O O O O O O N o ' a~ F ~I) N N ~ U~ O U) 1-') U~ 1~ .
~ O O O O O O O O O O O _ O ~
o _ _ _ I
Lll _ N _ ___ _ _ _ O _ N _ 6 Mo4029 : ~ :
211~71 ,. ~-.` .
i -10-Although the invention has been described in detail in the foregoing for the purpose of illustration, it is to be understood that such detail is solely for that purpose and that variations can be made therein by those skilled in the art without departing from the spirit and scope of the invention except as it may be limited by the claims. ~ : :
;
Mo4029
A PROCESS FOR THE PRODUCTiON
OF DIALKYL PYRIMIDYLPHOSPHATES
BACKGROUND OF THE INVENTION
The present invention relates to a process for the production of O,O-dialkyl pyrimidylphosphates.
Pyrimidylphosphates are known to be useful in the control of soil ;
pests or insects such as corn rootworrn, thrips, leafhoppers, and nematodes when applied to the soil of corps such as com, sorghum, cotton and sugar beets.
Processes for making these pesticides are also known. U.S. ~-Patent 4,094,873, for example, discloses a process in which an alkali metal phenoxide, pyridinoxide or pyrimidinoxide is reacted with an O,O-dialkyl phosphorochloridothioate or O-alkyl phenylphosphonochlorido-thioate or O-alkyl phenylphosphonochloridothioate in the presence of a catalyst mixture under alkaline conditions in a liquid reaction medium.
The catalyst mixture is made up of a quaternary ammonium salt and a diazole.
U.S. Patent 4,147,866 also discloses a process in which an alkali metal phenoxide, pyridinoxide or pyrimidinoxide is reacted with an O,O-dialkylphosphorochloridothioate in the presence of a catalyst mixture under alkal~ne conditions in a liquid reaction medium. The catalysts used in this process are a quatemary ammonium salt and a sterically unhindered, nucleophilic, tertiary amine. U.S. 4,147,866 also teaches that use of either the tertiary amine or the quaternary ammonium catalyst aione results in low yields, high amounts of unwanted by-products and expensive, difficult purification steps. Each of the processes disclosed in U.S. 4,094,873 and 4,147,866 is disadvantageous in that two catalysts must be employed. The cost of raw materials and product purification is therefore increased.
vj t/an4029 ~ 2118371 ~ ~
.
U.S. Patent 4,429,125 discloses a process for the production of phosphorus esters of 5-pyrimidinols in which a 5-pyrimidinol is reacted with a phosphorochloridothioate in an inert organic liquid in the presence of an acid binding agent or acceptor. The acid binding agent or acceptor is selected from alkali carbonates, alkali hydroxides, and alcoholates such as sodium carbonate, potassium carbonate, sodium or potassium methoxide, sodium or potassium ethoxide, and amines. No phase catalyst is included in the reaction mixture.
U.S. Patent 4,729,987 also discloses a process in which a 5-pyrimidinol represented by a given formula is reacted with a phosphorochloridothioate in an inert organic liquid and an acid binding agent or acceptor at a temperature of from about 0 to about 100C. No :
phase transfer catalyst is included in the reaction mixture.
Published European Patent Application 277,292 discloses a process for producing O-pyrimidinyl phosphorus compounds in which an aqueous solution of a salt of pyrimidine is reacted with a phosphorus ~ -ester in the presence of a phase transfer catalyst without added organic solvent. This disclosure teaches that low yields are to be expected when -an organic solvent such as toluene is used as the reaction medium.
None of these patents disclose a process in which a cation coordinating catalyst such as a crown ether, cryptand, or related acyclic catalyst is used.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide an improved process for the production of O,O-dialkyl pyrimidylphosphates.
It is also an object of the present invention to provide a process for the production of dialkyl pyrimidylphosphates in which only a single phase transfer catalyst is employed.
Mo4029 .' , ' ~ 211~371 :
It is another object of the present invention to provide a process for the production of dialkyl pyrimidylphosphates in which the phase ~ -transfer catalyst is effective even when the reaction is carried out in a solvent such as toluene.
These and other objects which will be apparent to those skilled in ;
the art are accomplished by reacting an O,O-dialkyl substituted phosphorohalothioate with a 5-hydroxypyrimidine in the presence of a phase transfer catalyst, an organic solvent and an alkali metal hydroxide at a pH of from about 8 to about 12 and a temperature of up to 70C.
The phase transfer catalyst must be a cation coordinating catalyst. The product O,O-dialkyl pyrimidylphosphate may be recovered from the reaction mixture by adding water to the reaction mixture with agitation to cause the formation of an aqueous and an organic phase. The organic and aqueous phases may then be separated and the organic solvent removed from the organic phase by, e.g., steam stripping. '.. ! ,, DETAILED DESCRIPTION OF THE PREFERRED
EMBODIMENTS OF THE INVENTION
The present invention relates to a process in which an O,O-alkyl 20 substituted phosphorohalothioate is reacted with a 5-hydroxypyrimidine in the presence of a cation coordinating catalyst, an organic solvent and an alkali metal hydroxide. This reaction is carried out at a pH of from about 8 to about 12 and a temperature of up to 70-C.
The O,O-alkyl substituted phosphorohalothioates useful in the 25 process of the present invention are known. Examples of such compounds include those represented by the forrnula Mo4029 ~''' ~'" ''' .
. :;, . , , "' '. ", . ~ 2118371 ' , ~
-4- ~;
~'; ~ ''`',',' S
R O P X
R'--O ~:
, , .
.
in which R and R' each represents a lower alkyl group, preferably an alkyl ~:
group having from 1 to 4 carbon atoms, and ~ ;~
10 X represents a halogen atom, preferably chloride.
Preferred O,O-alkyl phosphorohalothioates include: O-ethyl-0-(1-methyl ethyl) phosphorochloridothioate; O,O-diethyl phosphoro-chloridothioate; O,O-dimethyl phosphorochloridothioate; and 0,0-diisopropyl phosphorochloridothioate.
The 5-hydroxypyrimidines useful in the process of the present invention include any of the known 5-hydroxypyrimidines represented by the formula R"
/ N C-\ ~
R"'--C\ O /C OH
N C \
R""
in which 25 R" represents hydrogen, methyl or an alkylthio group having from 1 to 2 carbon atoms;
R"' represents hydrogen, an alkyl group having from 1 to 8 carbon atoms, an alkylthiomethyl group, an alkylsulfinylmethyl group or an Mo4029 : ~:
~ ~.
~ 211~71 alkylsulfonylmethyl group with alkyl meaning from 1 to 4 carbon atoms, a phenyl group, a phenylthio group, an alkylthio group having from 1 to 4 carbon atoms, an alkylsulfinyl group having from 1 to 4 carbon atoms, an alkylsulfonyl group having from 1 to 4 carbon atoms, or an alkylthioethylthio group having from 1 to 2 carbon atoms in the alkyl group; and R"" represents hydrogen or a methyl group.
Particularly preferred 5-hydroxypyrimidines include: 2-(1,1-dimethyl ethyl)-5-hydroxypyrimidine; 2-(1-methylethyl)-5-hydroxypyrimidine; 2-ethyl-5-hydroxypyrimidine; and 2-(1-methyl)thio)-5-hydroxypyrimidine.
The phase transfer catalyst used in the process of the present invention must be a cation coordinating catalyst. As used herein, a cation coordinating catalyst is a non-metallic molecule which will unite with a postively charged ion to form a coordination compound ~r complex. Any of the known cation coordinating catalysts may be used.
Such catalysts are represented by either of the following formulae:
R
~aA
~ ( (O~x ~R
z(O ' in which 25 A represents oxygen or nitrogen;
R" R2, R3, R4, Rs~ R6, R7, an~ R8 each represents: a proton; an alkyl group having from 1 to 16 carbon atoms which alkyl group may contain or be substituted by one or more heteroatoms (i.e. atoms Mo4029 ~ .
~ 2 1 1 8 3 7 1 .~ - ~ ,.
which are not carbon) or one or more heterocycles; an aryl group having from 6 to 7, preferably 6 carbon atoms which may be substituted by heteroatoms; a heterocycle; an aralkyl group having from 7 to 10, preferably 7 carbon atoms; or a cycloalkyl group having from 5 to 10, preferably from 5 to 7 carbon atoms;
x represents a numberfrom 0 to 1000;
y represents a numberfrom 0 to 5; ~ -z represents a number from 2 to 3; and Q represents phosphorous, nitrogen, sulfur or oxygen.
10 R" R2, R3, R4, R5, R6, R7, and/or R8 may be joined in a ring.
Suitable cation coordinating catalysts include cryptates, crown ethers, polyols which will act as a cation coordinating compound in the reaction medium and tertiary alkoxy alkyl amines.
Specific examples of suitable cation coordinating catalysts include~
18-crown-6-ether, cryptand 12-2-2], tetraethyleneglycol dimethly ether, poly(ethylene glycol)s with a molecular weight of from 200 to 10,000, tris[dioxa-3,6-octyl] amine, tris[dioxa-3,6-decyl]amine, tris[trioxa-3,6,8 decyl] amine, and tris[2-(2-methoxyethoxy)ethyll amine. Tris[2-(2-methoxyethoxy)ethyl]-amine is preferred.
The solvents useful in the process of the present invention include any of the known and commonly used organic solvents.
Specific examples of suitable solvents include: toluene, benzene, xylenes, ethylbenzene, cumene, mesitylene, chlorobenzene, and non- -aromatic solvents such as dichloromethane, ethylene dichloride, acetone and methyl ethyl ketone.
The process of the present invention is carried out at a pH of from about 8 to about 12 in the presence of an alkali metal hydroxide. Any of the alkali metal hydroxides may be used but sodium hydroxide is Mo4029 ~-~ 3 7 i particularly preferred.
The reaction which occurs in the process of the present invention is carried out at a temperature of up to 70C, preferably at a temperature of from about 30 to about 6QC, most preferably at a temperature of about 45C.
The reaction components are generally used in amounts such that at least 1 mole of 5-hydroxypyrimidine is present for each mole of O,O-dialkyl phosphorohalothioate, preferably from 1 to about 2 moles per mole of O,O-dialkyl phosphorohalothioate. The O,O-dialkyl phosphoro-halothioate may be dissolved in the solvent in an amount such that the O,O-dialkyl phosphorohalothioate is present at concentration of from 10 to 90%, preferably from about 50 to 85%. The cation coordinating catalyst is generally used in an amount of from about 10 mole % to about 20 mole % based on the O,O-dialkyl phosphorohalothioate. The alkali metal hydroxide is generally used in an amount sufficient to maintain the pH of the reaction mixture between about 8 and about 12. Generally, from about 1 to about 1.1 moles of alkali metal hydroxide per mole of S-hydroxypyrimidine are used. The alkali metal hydroxide is generally used in the form of an aqueous solution having a concentration of from about 10 to about 50% by weight. -~
Afterthe reaction betweenthe O,O-dialkyl phosphorohalothioate and the 5-hydroxypyrimidine has been substantially completed, the product O,O-dialkyl pyrimidylphosphate is recovered by, for example, a phase separation process. Water may be added to the reaction mixture with agitation. The resultant mixture is allowed to settle until two distinct r :
phases are formed. The organic phase which includes the product to be recovered is separated from the aqueous phase and then treated (e.g., steam stripped) to remove the organic solvent. The O,O-dialkyl Mo4029 ~ ~ ,""~,",~
~ 211~37~ ~
pyrimidylphosphate remains.
The process of the present invention produces the desired 0,0-dialkyl pyrimidylphosphate in yields of at least 80%, generally better than 90% in reaction times as short as 2 hours. Typical reaction Umes range 5 from about 4 to about 7 hours.
The invention is further illustrated but is not intended to be limited by the following examples in which all parts and percentages are by ~ .
weight unless otherwise specified.
EXAMPLES
10 ExamPles 1-13 A 25% sodium hydroxide solution was added dropwise to a mixture of 0-ethyl-0-(1-methylethyl) phosphorochloridothioate in toluene, 2-(1,1-dimethylethyl)-5-hydroxypyrimidine and trisl2(2-methoxy-ethoxy)ethyl] amine at 45C. The amounts of each material used in each 15 Example is reported in the following table. The sodium hydroxide was added at a rate sufficient to maintain the pH of the reaction mixture between 8 and 10. The reaction mixture was subsequently stirred at 45C until the unreacted phosphorochloridothioate was less than 0.5% as determined by gas chromatography. The mixture was then cooled to ~;;
20 25C and 50 ml of water were added. The resultant mixture was agitated for 15 minutes and allowed to stand until the organic and aqueous layers separated. The layers were separated and the organic layer was steam stripped to remove the toluene present. 0-12-(1,1-dimethylethyl)-5~
pyrimidinyl]-0-ethyl-0-(1-methylethyl) phosphorothioatewas isolated as 25 the product.
."~
Mo4029 211~371 g c~ _ o o _ _ o o o o o -o _ o~ '' O ~ O ~ 0 _ _ ___ _ 0 _ N .V/~
~:7 ~ ~ ~ ~') 0 ~D ~C) C~l O) O ~_ ) 0 ~
_ o) a) CJ~ ~ ~ ~ ~ U~ O) ~ a) ~ ~ a)O
g g ~_ _ ~q N _ ~ ~1> CJ) ~ C') U) ~ I E E
~ ~D u~ ~ ~ ~ a~ a) ~D U~ U~ ~ ~ ~ 8 8 s~i; ~ Ic~
. O O O O N N O O N N O ~ O C) ~1) ~0 o o o o o o o o o o o o o lo~
_ 6 6 6 _ 6 6 6 _ IIJ N _ 6 O O
Q _ _ _ ( ) U~ 'J ~t ~ ~ ~ U~ U~
~o _ _ _ 0 O O O O N N N ~O O N O O u~) -- ;
~Z o o o o o o o o o o o _ a~ O O ~ N 1~ ~) ~ N 1~ N U~ U~ 10 O O O O
~ g O O O O O O O O O O O N o ' a~ F ~I) N N ~ U~ O U) 1-') U~ 1~ .
~ O O O O O O O O O O O _ O ~
o _ _ _ I
Lll _ N _ ___ _ _ _ O _ N _ 6 Mo4029 : ~ :
211~71 ,. ~-.` .
i -10-Although the invention has been described in detail in the foregoing for the purpose of illustration, it is to be understood that such detail is solely for that purpose and that variations can be made therein by those skilled in the art without departing from the spirit and scope of the invention except as it may be limited by the claims. ~ : :
;
Mo4029
Claims (12)
1. A process for the production of an O,O-dialkyl pyrimidyl-phosphate comprising reacting a) an O,O-dialkyl phosphorohalothioate, with b) a 5-hydroxypyrimidine, in the presence of c) a cation coordinating catalyst, d) an organic solvent, and e) an alkali metal hydroxide, at a pH of from about 8 to about 12 and a temperature of up to about 70°C.
2. The process of Claim 1 in which the alkyl pyrimidyl-phosphate is recovered from the reaction mixture by a) adding water to the reaction mixture with agitation, b) separating the organic and aqueous layers which form in a), c) stripping the organic layer separated in b) of the organic solvent present therein and d) recovering the O,O-dialkyl pyrimidylphosphate.
3. The process of Claim 1 in which the reaction is carried out at a temperature of from about 30 to about 60°C.
4. The process of Claim 1 in which the O-alkyl-O-(alkyl)phos-phorohalothioate is O-ethyl-O-(1-methylethyl)phosphorochloridothioate.
5. The process of Claim 4 in which the 2-(1,1-dialkyl)-5-hydroxypyrimidine is 2-(1,1-dimethylethyl)-5-hydroxypyrimidine.
6. The process of Claim 1 in which the 2-(1,1-dialkyl)-5-hydroxypyrimidine is 2-(1,1-dimethylethyl)-5-hydroxypyrimidine.
7. The process of Claim 1 in which the cation coordinating compound is selected from the group consisting of 18-crown-6-ether, cryptand [2-2-2], poly(ethylene glycol)s, tetraethylene glycol dimethyl ether, tris[dioxa-3,6-octly amine, tris[dioxa-3,6-decyl] amine, tris[trioxa-3,6,8-decyl] amine, and tris[2-(2-methoxyethoxy)ethyl] amine.
8. The process of Claim 1 in which the organic solvent is selected from the group consisting of toluene, benzene, xylene, cumene, ethylbenzene, mesitylene, chlorobenzene, methylene chloride, ethylene dichloride, acetone, and methylethyl ketone.
9. The process of Claim 1 in which the alkali metal hydroxide is sodium hydroxide.
10. The process of Claim 1 in which the organic solvent is removed from the organic phase by steam stripping.
11. The process of Claim 1 in which the cation coordinating catalyst is tris[2-(2-methoxyethoxy)ethyl] amine, the organic solvent is toluene and the alkali metal hydroxide is sodium hydroxide.
12. The process of Claim 1 in which the reaction is carried out at a temperature of about 45°C.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US15133393A | 1993-11-12 | 1993-11-12 | |
| US08/151,333 | 1993-11-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2118371A1 true CA2118371A1 (en) | 1995-05-13 |
Family
ID=22538284
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2118371 Abandoned CA2118371A1 (en) | 1993-11-12 | 1994-10-18 | Process for the production of dialkyl pyrimidylphosphates |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2118371A1 (en) |
-
1994
- 1994-10-18 CA CA 2118371 patent/CA2118371A1/en not_active Abandoned
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