CA1145358A - Process for the preparation of (phenoxy- or benzyl-) -phenoxy-propionic acids and their alkali metal salts - Google Patents
Process for the preparation of (phenoxy- or benzyl-) -phenoxy-propionic acids and their alkali metal saltsInfo
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- CA1145358A CA1145358A CA000353872A CA353872A CA1145358A CA 1145358 A CA1145358 A CA 1145358A CA 000353872 A CA000353872 A CA 000353872A CA 353872 A CA353872 A CA 353872A CA 1145358 A CA1145358 A CA 1145358A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/367—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by introduction of functional groups containing oxygen only in singly bound form
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Abstract
PROCESS FOR THE PREPARATION OF (PHENOXY- OR BENZYL-)-PHENOXYPROPIONIC ACIDS AND THEIR ALKALI METAL SALTS
Abstract of the disclosure:
Process for the preparation of (phenoxy- or benzyl-)-phenoxypropionic acids and the alkali metal salts thereof by adding a double molar amount of an aqueous alkali hy-droxide to a boiling mixture of a (benzyl- or phenoxy-)-phenol and 2-chloropropionic acid (ester), with simul-taneous azeotropic distillation of the water introduced or formed in the reaction.
Abstract of the disclosure:
Process for the preparation of (phenoxy- or benzyl-)-phenoxypropionic acids and the alkali metal salts thereof by adding a double molar amount of an aqueous alkali hy-droxide to a boiling mixture of a (benzyl- or phenoxy-)-phenol and 2-chloropropionic acid (ester), with simul-taneous azeotropic distillation of the water introduced or formed in the reaction.
Description
35~3
- 2 - ~OÉ 7g/~ 27~ Y~
The present invention relates to a process for ihe preparation of (phenoxy- or benzyl-)-phenoxypropionic asids of the formula X ~ ~ -t~i-C00l~1 (I) in which Y is a radical selected from the group of halogen, preferably chlorine or bromine, CF3, N02 or CN, X is oxygen or -CH2-, W is hydrogen, sodium or potassium, and _ is 1 or 2, and the optically active D-isomers thereof.
It is kno~m that alkyl- and/or halogen-substituted phenoxy-alkanecarboxylic acids which are of great economic importance as hormone-type herbicides are obtained by reac-tion of alkali phenolates with alkali salts of correspond-ing 2-haloalkanecarboxylic acids.
The reaction is generally carried out by condensing alkali phenolate and alkali-2 haloalkanecarboxylate in a molar ratio of 1:1 in water as solvent or diluent ~see G. Erfurt et al., Chem. Technik 15 (1964), No. 4, p. 199;
GDR Patent Specifications Nos. 64,279, 64,972, 64,723).
Because of inevitable side reactions, mainly hydroly-sis of haloalkanecarboxylate to hydroxyalkanecarboxylate, the yield is not satisfactory (70-80 ~ of theory). The yield is even more reduced if the reaction is transferred from 2-chloroacetic acid to higher 2-chloroalkanecarboxylic acids such as 2-chloropropionic and 2-chlorobutyric acid (German Patent No. 1,153,762).
The yield of hormone-type herbicides can be increased by suppressing the hydrolysis to a certain extent, for example according to the following methods:
a) Use of anhydrous reactants (U.S. Patent No. 2,651,o59).
Although considerably increased yields are obtained accor-~5~3S~3
The present invention relates to a process for ihe preparation of (phenoxy- or benzyl-)-phenoxypropionic asids of the formula X ~ ~ -t~i-C00l~1 (I) in which Y is a radical selected from the group of halogen, preferably chlorine or bromine, CF3, N02 or CN, X is oxygen or -CH2-, W is hydrogen, sodium or potassium, and _ is 1 or 2, and the optically active D-isomers thereof.
It is kno~m that alkyl- and/or halogen-substituted phenoxy-alkanecarboxylic acids which are of great economic importance as hormone-type herbicides are obtained by reac-tion of alkali phenolates with alkali salts of correspond-ing 2-haloalkanecarboxylic acids.
The reaction is generally carried out by condensing alkali phenolate and alkali-2 haloalkanecarboxylate in a molar ratio of 1:1 in water as solvent or diluent ~see G. Erfurt et al., Chem. Technik 15 (1964), No. 4, p. 199;
GDR Patent Specifications Nos. 64,279, 64,972, 64,723).
Because of inevitable side reactions, mainly hydroly-sis of haloalkanecarboxylate to hydroxyalkanecarboxylate, the yield is not satisfactory (70-80 ~ of theory). The yield is even more reduced if the reaction is transferred from 2-chloroacetic acid to higher 2-chloroalkanecarboxylic acids such as 2-chloropropionic and 2-chlorobutyric acid (German Patent No. 1,153,762).
The yield of hormone-type herbicides can be increased by suppressing the hydrolysis to a certain extent, for example according to the following methods:
a) Use of anhydrous reactants (U.S. Patent No. 2,651,o59).
Although considerably increased yields are obtained accor-~5~3S~3
- 3 - ~OE 78/F 272 ding to this process, it is unfit for application on an industrial scale because - preparation of anhydrous agents, especially of alkali metal salts of 2-haloalkanecarboxylic acids sensitive to hydrolysis, is difficult and expensive, - large volumes of organic solvents are required, - solids and suspensions are difficult to dose, and - considerable amounts of lactates are formed as undesirable by-products because of side reaction of phenoxyalkanecarboxylic acid salts with haloalkane-carboxylic acid salt.
b) Partial replacement of water as solvent and diluent by high-boiling alcohols (German Patent No.
1,153,762, U.S. Patent No. 2,914,558, USSR Patent No.
187,766, Japanese Patent Application No. 48,705/65), hydro-carbons (U.S. Patent No. 2,480,817), or excess free phenol ~U.S. Patent No. 4,035,496, GDR Patent No. 50,622).
c) Use of alkali metal phenolate in an excess of up to 100 ~, relative to 2-haloalkanecarboxylic acid salt, in order to increase the speed of the main reaction as com-pared to that of the side reaction (U.S. Patents Nos.
b) Partial replacement of water as solvent and diluent by high-boiling alcohols (German Patent No.
1,153,762, U.S. Patent No. 2,914,558, USSR Patent No.
187,766, Japanese Patent Application No. 48,705/65), hydro-carbons (U.S. Patent No. 2,480,817), or excess free phenol ~U.S. Patent No. 4,035,496, GDR Patent No. 50,622).
c) Use of alkali metal phenolate in an excess of up to 100 ~, relative to 2-haloalkanecarboxylic acid salt, in order to increase the speed of the main reaction as com-pared to that of the side reaction (U.S. Patents Nos.
4,035,416 and 3,257, 453, German Patent No. 1,153,762, Japa-nese Patent Publication No. 74/24463).
d) Reduction of the water amount present in the reac-tion mixture by distilling off water during the reaction (U.S. Patent No. 4,035,416).
All processes for the preparation of hormone-type herbicides hitherto known have the following characteristic features in common:
1) The amount of phenol to be used in the reaction is introduced into the reaction vessel in the form of alkali phenolate, and 2-haloalkanecarboxylie acid salt is added in one portion, in dosed amounts or continuously. In some cases, the alkali amount required in total is introduced as excess alkali phenolate or as a mixture of alkali pheno-late and alkali hydroxide, and free 2-haloalkanecarboxylic acid is added.
2) The phenol componenl: is not reacted quantitatively.
.,
d) Reduction of the water amount present in the reac-tion mixture by distilling off water during the reaction (U.S. Patent No. 4,035,416).
All processes for the preparation of hormone-type herbicides hitherto known have the following characteristic features in common:
1) The amount of phenol to be used in the reaction is introduced into the reaction vessel in the form of alkali phenolate, and 2-haloalkanecarboxylie acid salt is added in one portion, in dosed amounts or continuously. In some cases, the alkali amount required in total is introduced as excess alkali phenolate or as a mixture of alkali pheno-late and alkali hydroxide, and free 2-haloalkanecarboxylic acid is added.
2) The phenol componenl: is not reacted quantitatively.
.,
5~3 - 4 - _~ 7g/F ~7 Separation and recovery of unreacted phenol ls requi-red after completion of the reaction.
However, (phenoxy- or benzyl-) phenox.ypropionic acids of the formula I (see below) cannot be obtained indust ial-ly in a similar manner, because the starting phenoxy- or benzyl-phenols cannot be separated from the compounds of the formula I except by complicated and time-consuming purification operations resulting in great losses.
For the preparation of the formula I compounds various 10 process variations have been described which, however, do not lead to quantitative yields either. For example, German Offenlegungsschrift No. 16,68,896 describes among others the reaction of alpha-haloalkanecarboxylic acids with phenoxyphenols in aqueous strongly alkaline solution. When 15 operating according to this method, which corresponds to the early state of hormone-type herbicide manufacture, by condensing phenoxyphenols with a 20 molar % excess of L-2-chloropropionic acid in an aqueous, strongly alkaline ~solution, a yield of only 82 % of theory is obtained. A
- 20 conversion rate of more than 95 % of the phenol component is achieved only with a considerably increased excess of L-2-chloropropionic acid (more than 40 %). Such a process is unfit for quantitatively converting phenols of the formula IT on an industrial scale.
Improvement of this reaction by replacing water as solvent or diluent by a hydrocarbon such as toluene or xylene and azeotropic distillation of water during the reaction (as described in b) and d) above) likewise does not result in quantitative yields. Thus, use of an excess 30 of 20 % of 2-chloropropionic acid (relative to the amount ~f phenol used~ yields a conversion rate of 92-93 % of the phenol component only.
The preparation of optically active D-isomers of the compounds of the formula I presents particular difficulties.
The usual racemate separa~ion of optically inactive 2-pnenoxypropionic acids by means of optically active auxi-liary bases is unfit for production on an industrial scale since fractional crystallization which is required in s~
this process necessitates complicated operations and re-sults in high losses. Moreover~the reaction yields the un-- desired L-enantiomer in stoichiometric amounts ~hich for all practical purposes is lost for further reactions since it cannot be reconverted to a cleavable racemate.
The method described in German Offenlegungsschrift No. 27,58,002, starting from 2-methane-sulfonyloxypropionic or toluenesulfonyloxypropionic acid derivatives, yields derivatives of the intended 2-phenoxypropionic acids from which the methanesulfonyl or toluenesulfonyl group has to be split off by alkaline or acidic saponification. This re~action step bears a high risk of racemization of the D-enantiomer obtained.
This, too, appliesfor the reaction of substituted phenols with optically active 2-bromopropionic acid deri-vatives in organic solvents such as acetone, methylethyl-ketone or acetonitrile in the presence of a base ~H.J. Nest-ler and H. Bieringer, Zeitschr. f. Naturforsch. 1980, in the press).
Moreover, the optically active 2-sulfonyloxvpropionic and 2-bromopropionic acid derivatives are available only to a limited extent. On the other hand, optically active startinq products easily obtainable on a larqe scale are L-2-chloropropionic acid alkyl esters, especiallY the methyl ester. However, the reaction of the latter with the phenols in or~anic solvents such as acetone, methylethylketone or acetonitrile in the presence of orqanic or inorqanic bases is incomplete and therefore unfit for practical applicationD
A nearly quantitative yield is obtained by reacting an al-kali phenolate with 2-chloropropionic acid ester in high -boiling organic solvents such as toluene, xylene or chloro-benzene and subsequent saponification to give the acid;
however, this reaction results in nearly complete race-mization when carried out with optically active esters.
~hen using alkali salts of optically active 2~chloro-propionic acid instead of esters the optical activity is substantially maintained; however, preparation of these salts by saponification of the L-2-chloropropionic acid iB
However, (phenoxy- or benzyl-) phenox.ypropionic acids of the formula I (see below) cannot be obtained indust ial-ly in a similar manner, because the starting phenoxy- or benzyl-phenols cannot be separated from the compounds of the formula I except by complicated and time-consuming purification operations resulting in great losses.
For the preparation of the formula I compounds various 10 process variations have been described which, however, do not lead to quantitative yields either. For example, German Offenlegungsschrift No. 16,68,896 describes among others the reaction of alpha-haloalkanecarboxylic acids with phenoxyphenols in aqueous strongly alkaline solution. When 15 operating according to this method, which corresponds to the early state of hormone-type herbicide manufacture, by condensing phenoxyphenols with a 20 molar % excess of L-2-chloropropionic acid in an aqueous, strongly alkaline ~solution, a yield of only 82 % of theory is obtained. A
- 20 conversion rate of more than 95 % of the phenol component is achieved only with a considerably increased excess of L-2-chloropropionic acid (more than 40 %). Such a process is unfit for quantitatively converting phenols of the formula IT on an industrial scale.
Improvement of this reaction by replacing water as solvent or diluent by a hydrocarbon such as toluene or xylene and azeotropic distillation of water during the reaction (as described in b) and d) above) likewise does not result in quantitative yields. Thus, use of an excess 30 of 20 % of 2-chloropropionic acid (relative to the amount ~f phenol used~ yields a conversion rate of 92-93 % of the phenol component only.
The preparation of optically active D-isomers of the compounds of the formula I presents particular difficulties.
The usual racemate separa~ion of optically inactive 2-pnenoxypropionic acids by means of optically active auxi-liary bases is unfit for production on an industrial scale since fractional crystallization which is required in s~
this process necessitates complicated operations and re-sults in high losses. Moreover~the reaction yields the un-- desired L-enantiomer in stoichiometric amounts ~hich for all practical purposes is lost for further reactions since it cannot be reconverted to a cleavable racemate.
The method described in German Offenlegungsschrift No. 27,58,002, starting from 2-methane-sulfonyloxypropionic or toluenesulfonyloxypropionic acid derivatives, yields derivatives of the intended 2-phenoxypropionic acids from which the methanesulfonyl or toluenesulfonyl group has to be split off by alkaline or acidic saponification. This re~action step bears a high risk of racemization of the D-enantiomer obtained.
This, too, appliesfor the reaction of substituted phenols with optically active 2-bromopropionic acid deri-vatives in organic solvents such as acetone, methylethyl-ketone or acetonitrile in the presence of a base ~H.J. Nest-ler and H. Bieringer, Zeitschr. f. Naturforsch. 1980, in the press).
Moreover, the optically active 2-sulfonyloxvpropionic and 2-bromopropionic acid derivatives are available only to a limited extent. On the other hand, optically active startinq products easily obtainable on a larqe scale are L-2-chloropropionic acid alkyl esters, especiallY the methyl ester. However, the reaction of the latter with the phenols in or~anic solvents such as acetone, methylethylketone or acetonitrile in the presence of orqanic or inorqanic bases is incomplete and therefore unfit for practical applicationD
A nearly quantitative yield is obtained by reacting an al-kali phenolate with 2-chloropropionic acid ester in high -boiling organic solvents such as toluene, xylene or chloro-benzene and subsequent saponification to give the acid;
however, this reaction results in nearly complete race-mization when carried out with optically active esters.
~hen using alkali salts of optically active 2~chloro-propionic acid instead of esters the optical activity is substantially maintained; however, preparation of these salts by saponification of the L-2-chloropropionic acid iB
- 6 - HCE 78/F 272 Y~
esters (sole s.lbstances of industrial availability~ is likewise problematic because of racemization. Moreover, in a side reaction to the ester saponification, saponifica-- tion of the chlorine atom in alpha-position occurs with ormation of lactic acid.
; In German Patent No. 1,543,841, a process for the manufacture of D-phenoxypropionic acids is described ac-cording to which allcali salts of L-2-chloropropionic acid are formed in situ and reacted with phenolates, thus pre-venting racemization. This process requires maintaining narrow temperature limits of from 5 to 35C. Due to the reactivity of the chloropropionic acid esters on the one hand and the tendency to crystallization on the other, however, these limits are inevitably exceeded with increa-sinq batch volume. Thus, there is the risk of uncontrollablespontaneous reaction with overheating. Moreover, the water remaining in the reaction mixture according to the process of the patent prevents complete conversion of the reactants, so that considerable amounts of phenol remain in the final products.
Surprisingly, the disadvantages of the above proces-ses are overcome by the process of the invention which furthermore to obtain the compounds of the formula I with yields of more than 99 ~, and the D-isomers thereof with yields of more than 95 ~ and with high op~ical purity.
The process comprises adding to a solution of a phenol of the formula II
~ X ~ 08 . .
:
in which Y and _ are as defined above, and an at least equimolar amount of 2-chloropropionic acid or 2-chloropro-pionic acid lorler alkyl ester of the formula III
C~3 Cl-C~I-COCR (III) :
~5~35~
esters (sole s.lbstances of industrial availability~ is likewise problematic because of racemization. Moreover, in a side reaction to the ester saponification, saponifica-- tion of the chlorine atom in alpha-position occurs with ormation of lactic acid.
; In German Patent No. 1,543,841, a process for the manufacture of D-phenoxypropionic acids is described ac-cording to which allcali salts of L-2-chloropropionic acid are formed in situ and reacted with phenolates, thus pre-venting racemization. This process requires maintaining narrow temperature limits of from 5 to 35C. Due to the reactivity of the chloropropionic acid esters on the one hand and the tendency to crystallization on the other, however, these limits are inevitably exceeded with increa-sinq batch volume. Thus, there is the risk of uncontrollablespontaneous reaction with overheating. Moreover, the water remaining in the reaction mixture according to the process of the patent prevents complete conversion of the reactants, so that considerable amounts of phenol remain in the final products.
Surprisingly, the disadvantages of the above proces-ses are overcome by the process of the invention which furthermore to obtain the compounds of the formula I with yields of more than 99 ~, and the D-isomers thereof with yields of more than 95 ~ and with high op~ical purity.
The process comprises adding to a solution of a phenol of the formula II
~ X ~ 08 . .
:
in which Y and _ are as defined above, and an at least equimolar amount of 2-chloropropionic acid or 2-chloropro-pionic acid lorler alkyl ester of the formula III
C~3 Cl-C~I-COCR (III) :
~5~35~
- 7 - HOE 78/F 272 K
in which R is hydrogen or (C1-C4)-alkylrin an organic sol-vent forming an azeotropic mixture with water~an about double molar amount, relative to III, or a slight excess thereover~of an aqueous alkali hydroxide, at boiling temperature, distilling off the water introduced or formed during the reaction as an azeotropic mixture, and optional-ly convertlng the alkali salts of the formula I obtained to the free acids by acidification.
For quantitative conversion 099.5 %) of the phenoxy-phenols or benzylphenols of tke formula II it is advan-tageous to add an at least 10 % excess of compound III
relative to the phenol amount used; generally, an excess of 12 to 20 % is used.
The reaction is generally carried out at temperatures 15 or from 80 to 130C, preferably 90 to 120C.
-~ The process is described in detail as follows:
The starting and 2-chloropropionic acid or its ester are dissolved in an organic solvent forming an azeotropic - mixture with water, for example toluene, xylene, chloro-20 benzene or dichlorobenzene. A 20-60 ~, preferably 30-50 %, aqueous alkali hydroxide solution is then added, if desired at a reduced pressure, to the solution while simultaneously distilling off water.
~epending on the solvent, the reaction is carried out under normal or reduced pressure. The reduced pressure to be applied furthermore depends on the reaction temperature.
It is recommended to carry out the reaction at a tempera-ture of no less than 80C, because otherwise the reaction ~ would proceed to slowly, so that generally the pressure ; 30 is not less than 200 mbar. In the case of xylene as solvent and a reaction temperature of 110C, the pressure is about 500 mbar.
For the preparation of optically active D-isomers of the formula I, L-2-chloropropionic acid or its esters are used as starting material.
Per mol of phenol~about 1.1 to 1.4 mols, preferably 1.1 to 1.2 mols, of chloropropionic acid (ester), preferably chloropropionic acid methyl esterland 2.2 to 2.g mols, pre-ferably 2.2 to 2.5 mols, of alkali hydroxide are used~
' ', .
:
~ ~5~3~
in which R is hydrogen or (C1-C4)-alkylrin an organic sol-vent forming an azeotropic mixture with water~an about double molar amount, relative to III, or a slight excess thereover~of an aqueous alkali hydroxide, at boiling temperature, distilling off the water introduced or formed during the reaction as an azeotropic mixture, and optional-ly convertlng the alkali salts of the formula I obtained to the free acids by acidification.
For quantitative conversion 099.5 %) of the phenoxy-phenols or benzylphenols of tke formula II it is advan-tageous to add an at least 10 % excess of compound III
relative to the phenol amount used; generally, an excess of 12 to 20 % is used.
The reaction is generally carried out at temperatures 15 or from 80 to 130C, preferably 90 to 120C.
-~ The process is described in detail as follows:
The starting and 2-chloropropionic acid or its ester are dissolved in an organic solvent forming an azeotropic - mixture with water, for example toluene, xylene, chloro-20 benzene or dichlorobenzene. A 20-60 ~, preferably 30-50 %, aqueous alkali hydroxide solution is then added, if desired at a reduced pressure, to the solution while simultaneously distilling off water.
~epending on the solvent, the reaction is carried out under normal or reduced pressure. The reduced pressure to be applied furthermore depends on the reaction temperature.
It is recommended to carry out the reaction at a tempera-ture of no less than 80C, because otherwise the reaction ~ would proceed to slowly, so that generally the pressure ; 30 is not less than 200 mbar. In the case of xylene as solvent and a reaction temperature of 110C, the pressure is about 500 mbar.
For the preparation of optically active D-isomers of the formula I, L-2-chloropropionic acid or its esters are used as starting material.
Per mol of phenol~about 1.1 to 1.4 mols, preferably 1.1 to 1.2 mols, of chloropropionic acid (ester), preferably chloropropionic acid methyl esterland 2.2 to 2.g mols, pre-ferably 2.2 to 2.5 mols, of alkali hydroxide are used~
' ', .
:
~ ~5~3~
- 8 - HOE 7~/F 272 preferred alkali hydroxides are NaOI~ and KOH. Feed rate and reaction temperature are adjusted in such a manner t'na~
the total amount of water introduced and formed in the reaction corresponds substantially to the amount of water removed by azeotropic distillation. The alcohol formed by saponification of the ester/preferably methanol is distilled off with the water.
The addition of alkali hydroxide solution being com-plete, stirring is continued for about 15 minutes at con-stant reaction temperature. The alkali salts of formula Ican be directly converted to acid derivatives (for example esters) or to the free acids by acidification.
The compounds of the formula I obtained according to the invention are highly active weed herbicides or interme-diates for other acid derivatives, for example esters, whichare likewise very efficient, selective weed herbicides (German Offenlegungsschriften~1os.22,23894; 24,33,067;
26,01,548, 24,17,487 and 27,58,002).
The yields are above 98 %, in many cases above 99.5 %.
The degree of optical purity of the D-enaotiomers is no~
more than 25 ~ below that of the optically active 2-chloro-propionic acid esters used. The optical purity in percent is calculated as follows: % content ~-form minus % content L-form = optical purity.
The process of the invention differs from the known process in the art in that free phenoxyphenols or benzyl-phenols are used. By the addition of sodium hydroxide so-lution only/as much phenolate is formed as can immediately react with 2-chloropropionate, thus preventing an excess of alkali in the reaction mixture. Losses of compound III
due to hydrolysis are thereby considerably reduced.
The following examples illustrate the invention. All parts are by weight unless otherwise stated.
Example 1 2~ -(2ll,4"-Dichloroph~noxy)-phenoxyJ-propionic acid 208 parts of 50 ~ sodium hydroxide solution are added portion ~ise at about 90C and at a reduced pressure of 270 mbar to a solution of 255 parts of 4-(2l,4'-dichloro-S;~5~3
the total amount of water introduced and formed in the reaction corresponds substantially to the amount of water removed by azeotropic distillation. The alcohol formed by saponification of the ester/preferably methanol is distilled off with the water.
The addition of alkali hydroxide solution being com-plete, stirring is continued for about 15 minutes at con-stant reaction temperature. The alkali salts of formula Ican be directly converted to acid derivatives (for example esters) or to the free acids by acidification.
The compounds of the formula I obtained according to the invention are highly active weed herbicides or interme-diates for other acid derivatives, for example esters, whichare likewise very efficient, selective weed herbicides (German Offenlegungsschriften~1os.22,23894; 24,33,067;
26,01,548, 24,17,487 and 27,58,002).
The yields are above 98 %, in many cases above 99.5 %.
The degree of optical purity of the D-enaotiomers is no~
more than 25 ~ below that of the optically active 2-chloro-propionic acid esters used. The optical purity in percent is calculated as follows: % content ~-form minus % content L-form = optical purity.
The process of the invention differs from the known process in the art in that free phenoxyphenols or benzyl-phenols are used. By the addition of sodium hydroxide so-lution only/as much phenolate is formed as can immediately react with 2-chloropropionate, thus preventing an excess of alkali in the reaction mixture. Losses of compound III
due to hydrolysis are thereby considerably reduced.
The following examples illustrate the invention. All parts are by weight unless otherwise stated.
Example 1 2~ -(2ll,4"-Dichloroph~noxy)-phenoxyJ-propionic acid 208 parts of 50 ~ sodium hydroxide solution are added portion ~ise at about 90C and at a reduced pressure of 270 mbar to a solution of 255 parts of 4-(2l,4'-dichloro-S;~5~3
- 9 - HOE 78/F 272 ~.
phenoxy)-phenol and 132 parts of 2-chloropropionic acid in 1,200 parts of xylene. By distilling off the water present in the reaction mixture, the reaction temperature is maintained at 90C. The addition being complete, stirring is continued for 15 minutes at this temperature, subsequent-ly the batch is brought to normal pressure~400 Parts of water are then added, and stirring is continued for 10 minutes at 85C. The batch is subsequently acidified at this tem-: perature with 120 parts of phosphoric acid, and stirriny is continued for 10 minutes. After elimination of the waterphase via a separating funnel, xylene is distilled off under a pressure of 80 mbar, and the solids are dried at 60C and 250 mbar. 327 Parts of 2-/4'-(2,4-dichloro-phenoxy)-phenox~7-propionic acid are obtained. The content of pure final product is 99.5 %, corresponding to a yield of 99.5 % of theory. The residual amount of 4-(2',4'-dichlorophenoxy)-phenol is 0.3 %.
Example 2 2-~4'-(2",4"-Dichlorophenoxy)-phenoxy.7-propionic acid To a stirred solution of 127.5 parts of 4-(2',4'-di-chlorophenoxy)-phenol and 69.2 parts of 2-chloropropionic acid methyl ester in 650 parts of xylene, 1GO parts of 50 %
sodium hydroxide solution are added dropwise at about 110C
and 500 mbar while simultaneously distilling off the azeotropic mixture of water and methanol. The addition being complete, stirring is continued for 15 minutes at 110C.
Work-up is as described in Example 1. 163.3 Parts of 2-/4'-(2",4"-dichlorophenoxy)-phenox_7propionic acid are ob-tained. The content of pure final product is 99.8 %, corres-ponding to 99.6 % of theory. The residual amount of 4 (2',4 ! -dichlorphenoxy)-phenol is 0.15 %.
Example ~
D-2- ~-(2,4-dichlorophenoxy)-phenoxyJ-propionic acid Within about 1 nour, 77,7 g of 51.5 % sodium hydroxide solution (1.0 mol) are added at 110C and SOO mbar and with vigorous stirring to a solution of 102 g (0.4 mol) of 4-(2,4-dichlorophenoxy)-phenol an~ 56.35 g (0.46 mol) of L-2-chloropropi.onic acid s~
phenoxy)-phenol and 132 parts of 2-chloropropionic acid in 1,200 parts of xylene. By distilling off the water present in the reaction mixture, the reaction temperature is maintained at 90C. The addition being complete, stirring is continued for 15 minutes at this temperature, subsequent-ly the batch is brought to normal pressure~400 Parts of water are then added, and stirring is continued for 10 minutes at 85C. The batch is subsequently acidified at this tem-: perature with 120 parts of phosphoric acid, and stirriny is continued for 10 minutes. After elimination of the waterphase via a separating funnel, xylene is distilled off under a pressure of 80 mbar, and the solids are dried at 60C and 250 mbar. 327 Parts of 2-/4'-(2,4-dichloro-phenoxy)-phenox~7-propionic acid are obtained. The content of pure final product is 99.5 %, corresponding to a yield of 99.5 % of theory. The residual amount of 4-(2',4'-dichlorophenoxy)-phenol is 0.3 %.
Example 2 2-~4'-(2",4"-Dichlorophenoxy)-phenoxy.7-propionic acid To a stirred solution of 127.5 parts of 4-(2',4'-di-chlorophenoxy)-phenol and 69.2 parts of 2-chloropropionic acid methyl ester in 650 parts of xylene, 1GO parts of 50 %
sodium hydroxide solution are added dropwise at about 110C
and 500 mbar while simultaneously distilling off the azeotropic mixture of water and methanol. The addition being complete, stirring is continued for 15 minutes at 110C.
Work-up is as described in Example 1. 163.3 Parts of 2-/4'-(2",4"-dichlorophenoxy)-phenox_7propionic acid are ob-tained. The content of pure final product is 99.8 %, corres-ponding to 99.6 % of theory. The residual amount of 4 (2',4 ! -dichlorphenoxy)-phenol is 0.15 %.
Example ~
D-2- ~-(2,4-dichlorophenoxy)-phenoxyJ-propionic acid Within about 1 nour, 77,7 g of 51.5 % sodium hydroxide solution (1.0 mol) are added at 110C and SOO mbar and with vigorous stirring to a solution of 102 g (0.4 mol) of 4-(2,4-dichlorophenoxy)-phenol an~ 56.35 g (0.46 mol) of L-2-chloropropi.onic acid s~
- 10 - H0~ 7~/F 772 K
methyl ester in 450 ml of xylene. The azeotropie mixtur~
of methanol formed and water introduced or ~ormed is con-- tinuously distilled off.
The addition being complete, stirring is continued for 15 minutes at 110C and 500 mbar and the reactor is brought to normal pressure. At 90C first 100 rnl of water are added and then the D-2-/4-(2,4-dichlorophenoxy)-phen-oxy7-propionic acid is set free with dilute sulfuric acid.
After separation of the water phase and distillation of xylene under reduced pressure, 129.8 g (99 % of th.) of D--2-/4-(2,4-dichlorophenoxy)-phenox_7-propionic acid are ob`tained with a purity of 98.8 % according to gas chromato-graphy. The residual amount of 4-(2,4-d~chlorophenoxy)-phenol is 0.~ %.
The optical purity is evaluated after conversion to the methyl ester. The optical rotation of the product ob-tained is _c~ 7D2 = 21.14, corresponding to an optical purity of 76 %.
When using an L-chloropropionic acid ester having an optical purity of 95 % (corresponding to 97.5 % of L-form), - the following compounds are obtained with optical purity degrees of more than 70 % (corresponding ~o 85 % of D-form3:
D-2-/4-(4-chlorophenoxy)-phenoxy7-propionic acid D-2-/4-(2,4-dichlorophenoxy)-phenoxy7-propionic acid D-2-/4-(4-trifluoromethylphenoxy)-phenox~7-propionic acid D-2-/4-(2,4-dichlorobenzyl)-phenox~7-propionic acid D-2-/2-ehloro-4-trifluoromethylphenoxy)-phenox~7-propionic acid D-2-/4-(4-bromo-2-chlorophenoxy)-phenox~7-propionic aeidland the Na and K salts.
; ' ` ' .
methyl ester in 450 ml of xylene. The azeotropie mixtur~
of methanol formed and water introduced or ~ormed is con-- tinuously distilled off.
The addition being complete, stirring is continued for 15 minutes at 110C and 500 mbar and the reactor is brought to normal pressure. At 90C first 100 rnl of water are added and then the D-2-/4-(2,4-dichlorophenoxy)-phen-oxy7-propionic acid is set free with dilute sulfuric acid.
After separation of the water phase and distillation of xylene under reduced pressure, 129.8 g (99 % of th.) of D--2-/4-(2,4-dichlorophenoxy)-phenox_7-propionic acid are ob`tained with a purity of 98.8 % according to gas chromato-graphy. The residual amount of 4-(2,4-d~chlorophenoxy)-phenol is 0.~ %.
The optical purity is evaluated after conversion to the methyl ester. The optical rotation of the product ob-tained is _c~ 7D2 = 21.14, corresponding to an optical purity of 76 %.
When using an L-chloropropionic acid ester having an optical purity of 95 % (corresponding to 97.5 % of L-form), - the following compounds are obtained with optical purity degrees of more than 70 % (corresponding ~o 85 % of D-form3:
D-2-/4-(4-chlorophenoxy)-phenoxy7-propionic acid D-2-/4-(2,4-dichlorophenoxy)-phenoxy7-propionic acid D-2-/4-(4-trifluoromethylphenoxy)-phenox~7-propionic acid D-2-/4-(2,4-dichlorobenzyl)-phenox~7-propionic acid D-2-/2-ehloro-4-trifluoromethylphenoxy)-phenox~7-propionic acid D-2-/4-(4-bromo-2-chlorophenoxy)-phenox~7-propionic aeidland the Na and K salts.
; ' ` ' .
Claims
What is claimed is:
1) A process for the preparation of (phenoxy- or benzyl-)-phenoxypropionic acids and the alkali metal salts thereof corresponding to the formula I
(I) in which Y is a radical selected from the group of halogen, preferab-ly chlorine or bromine, CF3, NO2 or CN, X is oxygen or -CH2-, W is hydrogen, sodium or potassium, and m is 1 or 2, and the optically active D-isomers thereof, by adding to a solution of a phenol of the formula II
(II) in which Y and m are as defined above, and an at least equimolar amount of 2-chloropropionie acid or 2-chloro-propionic acid lower alkyl ester of the formula III
(III) in which R is hydrogen or (C1-C4)-alkyl, in an organic solvent forming an azeotropic mixture with water, an about double molar amount, relative to III, or a slight excess thereover, of an aqueous alkali hydroxide, at boiling temperature, distilling off the water introduced or formed during the reaction as an azeotropic mixture, and optionally converting the alkali salts of the formula I obtained to the free acids by acidification.
2) The process as claimed in Claim 1, which comprises operating at temperatures of from 80 to 130°C, preferably 90-120°C, and under a pressure of from 200 mbar to normal pressure.
1) A process for the preparation of (phenoxy- or benzyl-)-phenoxypropionic acids and the alkali metal salts thereof corresponding to the formula I
(I) in which Y is a radical selected from the group of halogen, preferab-ly chlorine or bromine, CF3, NO2 or CN, X is oxygen or -CH2-, W is hydrogen, sodium or potassium, and m is 1 or 2, and the optically active D-isomers thereof, by adding to a solution of a phenol of the formula II
(II) in which Y and m are as defined above, and an at least equimolar amount of 2-chloropropionie acid or 2-chloro-propionic acid lower alkyl ester of the formula III
(III) in which R is hydrogen or (C1-C4)-alkyl, in an organic solvent forming an azeotropic mixture with water, an about double molar amount, relative to III, or a slight excess thereover, of an aqueous alkali hydroxide, at boiling temperature, distilling off the water introduced or formed during the reaction as an azeotropic mixture, and optionally converting the alkali salts of the formula I obtained to the free acids by acidification.
2) The process as claimed in Claim 1, which comprises operating at temperatures of from 80 to 130°C, preferably 90-120°C, and under a pressure of from 200 mbar to normal pressure.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEP2949681.9 | 1979-12-11 | ||
| DE19792949681 DE2949681A1 (en) | 1979-12-11 | 1979-12-11 | METHOD FOR PRODUCING OPTICALLY ACTIVE D- (PHENOXY, OR BENZYL) -PHENOXYPROPIONIC ACIDS AND THEIR ALKALINE SALTS |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1145358A true CA1145358A (en) | 1983-04-26 |
Family
ID=6088084
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000353872A Expired CA1145358A (en) | 1979-12-11 | 1980-06-12 | Process for the preparation of (phenoxy- or benzyl-) -phenoxy-propionic acids and their alkali metal salts |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP0030251B1 (en) |
| JP (1) | JPS5683441A (en) |
| CA (1) | CA1145358A (en) |
| DE (2) | DE2949681A1 (en) |
| IL (1) | IL60281A (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2460286A1 (en) * | 1979-06-29 | 1981-01-23 | Rhone Poulenc Agrochimie | PROCESS FOR PREPARING OPTICALLY ACTIVE PHENOXY-2 PROPIONIC ACID |
| FR2577924B1 (en) * | 1985-02-28 | 1987-03-06 | Cortial | NOVEL METHOD OF MANUFACTURING P-CHLOROPHENOL ESTER OF P-CHLOROPHENOXYISOBUTYRIC ACID |
| FR2602228A1 (en) * | 1986-07-30 | 1988-02-05 | Kirkiacharian Serge | New phenoxyisobutyric acids, their derivatives and processes for producing them |
| DE19755598A1 (en) * | 1997-12-15 | 1999-06-17 | Huels Chemische Werke Ag | Process for the preparation of aryloxyacetic acid esters |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3113965A (en) * | 1961-06-23 | 1963-12-10 | Dow Chemical Co | Bromophenoxyaliphatic acid |
| US3493604A (en) * | 1967-03-15 | 1970-02-03 | Upjohn Co | 3,5-dihalo-4-(4-alkoxyphenoxy) phenoxy acetic acids and derivatives |
| BE786644A (en) * | 1971-07-23 | 1973-01-24 | Hoechst Ag | PHENOXY-4 PHENOXY-ALKANE-CARBOXYL ACID DERIVATIVES THEIR PREPARATION AND THE MEDICINAL PRODUCTS CONTAINING THEM |
| DE2223894C3 (en) * | 1972-05-17 | 1981-07-23 | Hoechst Ag, 6000 Frankfurt | Herbicidal agents based on phenoxycarboxylic acid derivatives |
| US4035416A (en) * | 1972-11-02 | 1977-07-12 | The Dow Chemical Company | Process for making phenoxyalkanoic acids |
| GB1422679A (en) * | 1972-11-16 | 1976-01-28 | Funai Pharmaceutical Ind Ltd | Substituted phenoxy-a-methylpropionic acid derivatives and a process for producing the same |
| CS185694B2 (en) * | 1974-07-17 | 1978-10-31 | Ishihara Sangyo Kaisha | Herbicidal agent |
| JPS5283640A (en) * | 1976-01-01 | 1977-07-12 | Hoechst Ag | Benzyllphenoxyalkane carboxylate and derivatives thereof |
| DE2601548C2 (en) * | 1976-01-16 | 1984-01-26 | Hoechst Ag, 6230 Frankfurt | 2- [4- (2'-chloro-4'-bromophenoxy) phenoxy] propionic acid and derivatives and herbicidal agents containing them |
| JPS5287129A (en) * | 1976-01-16 | 1977-07-20 | Ishihara Sangyo Kaisha Ltd | 4-trifluoromethyl phenoxy phenoxyankane carboxylic acid |
| DE2715319A1 (en) * | 1976-04-13 | 1977-11-03 | Ishihara Mining & Chemical Co | HERBICIDE COMPOUNDS, HERBICIDE COMPOSITIONS, CONTAINING THESE COMPOUNDS, AND METHODS OF USE |
| DE2725590A1 (en) * | 1977-06-07 | 1978-12-21 | Bayer Ag | (4)-Phenoxy-phenoxy-alkanoic acid and ester derivs. - used as plant growth regulators esp. herbicides |
-
1979
- 1979-12-11 DE DE19792949681 patent/DE2949681A1/en not_active Withdrawn
-
1980
- 1980-06-10 JP JP7727080A patent/JPS5683441A/en active Granted
- 1980-06-10 IL IL60281A patent/IL60281A/en unknown
- 1980-06-10 EP EP80103215A patent/EP0030251B1/en not_active Expired
- 1980-06-10 DE DE8080103215T patent/DE3065764D1/en not_active Expired
- 1980-06-12 CA CA000353872A patent/CA1145358A/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| DE2949681A1 (en) | 1981-07-02 |
| JPH0565500B2 (en) | 1993-09-17 |
| DE3065764D1 (en) | 1984-01-05 |
| IL60281A0 (en) | 1980-09-16 |
| JPS5683441A (en) | 1981-07-08 |
| EP0030251B1 (en) | 1983-11-30 |
| EP0030251A1 (en) | 1981-06-17 |
| IL60281A (en) | 1985-05-31 |
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