CA1159468A - Stereospecific isomers of phenoxyalkanoic acid derivatives - Google Patents
Stereospecific isomers of phenoxyalkanoic acid derivativesInfo
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- CA1159468A CA1159468A CA000282664A CA282664A CA1159468A CA 1159468 A CA1159468 A CA 1159468A CA 000282664 A CA000282664 A CA 000282664A CA 282664 A CA282664 A CA 282664A CA 1159468 A CA1159468 A CA 1159468A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
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Abstract
A B S T R A C T
Stereo-specific isomers of phenoxy-alkanoic acid derivatives, especially phenoxy-propionic acid derivatives, can be prepared by re-acting a substituted phenol, e.g., 4-chloro-2-methyl phenol or 2,4-dichlorophenol with a lactic acid derivative of formula:
Stereo-specific isomers of phenoxy-alkanoic acid derivatives, especially phenoxy-propionic acid derivatives, can be prepared by re-acting a substituted phenol, e.g., 4-chloro-2-methyl phenol or 2,4-dichlorophenol with a lactic acid derivative of formula:
Description
~L~S~4~8 The present invention relates to a process for the preparation of herbicidally active compounds. Some of the compounds are believed to be novel and the present invention therefore also relates to those compounds per se as well as to compositions containing them. The in-vention relates further to a method of eradicating or controlling weedsby applying the compounds according to the present invention or the compositions containing them to a crop or a locus infested with weeds.
It is known that phenoxy-propionic acids and derivatives thereof, such as 2-(4-chloro-2-methylphenoxy)propionic acid and 2-~2,4-dichloro-phenoxy)propionic acid and their respective alkali- and dimethylamine salts can be successfully applied to combat broad-leaved weeds. It is also known that one of the optical isomers of substituted phenoxy propionic acids exerts a higher physiological activity than the other isomer. The most active isomer is normally obtained by applying optical resolution techniques on the corresponding racemate but these techniques are laborious and have also the drawback of producing the less active isomer which is of considerable less use and has to be converted into the more active isomer in a subsequent process step.
The Applicants have now found a stereospecific route towards specific isomers of the phenoxy-alkanoic acid derivatives which avoids the need to employ lengthy resolution techniques. The process according to the invention is in particular suitable for the preparation of esters of phenoxy-propionic acid derivatives which apparently cannot be selectively prepared via the stereospecific route towards dextra-rotatory 2-(2,4-dichlorophenoxy)propionic acid described in British Patent Specification No. 1,114,040.
~r, q~
5~4b8 Thus, the present invention provides a process for the preparation of phenoxy-alkanoic acid derivatives having the following general formula and possessing the R- or S-configuration at the carbon atom marked x:
(Hal) nr~ 2 R O
~ - O - C C 0 R (I) (R)n wherein R represents an alkyl group of up to 4 carbon atoms; n is 0 or an integer up to 4; Hal represents a halogen atom; m is O or an integer up to 5; the total of n and m being zero or an integer from 1 to 5; Rl represents a hydrogen atom, a metal-salt forming or an optionally alkyl substituted ammonium ion, or an optionally substituted alkyl, cycloalkyl, alkenyl, aryl or aralkyl group; and R represents an alkyl group of up to 4 carbon atom, which comprises reacting a derivative of lactic acid of formula II possessing the S-or R-configuration at the carbon atom marked x:
COOR
X _ O Xc -H (II) with a phenol of formula III:
(Hal) m HO ~ (III) (R)n ., ,.~
~5~4i,8 (wherein the group X-O- is a eroup which will leave the molecule and be replaced by a deprotonated phenol of formula III, and Hal, R, m and n have their meaning hereinbefore specified) in the presence of a base and under conditions of elevated temperature to produce a compound of for~ula I with the required configuration.
The process according to the present invention is particularly suitable ~or the preparation of phenoxy-propionic acid derivatives of the general formula I, i.e., compounds wherein R represents a methyl group.
The leaving group X-O- in formula II must, as stated above, be capable of being replaced by a deprotonated phenol of formula III
and suitable examples of such groups are the following: -O.S02.Q, -O.CO.Q and -O.CH(OH).CV3, wherein Q represents a hydrocarbyl group, suitably an alkyl or aryl group containing up to 10 carbon atoms, and V represents a halogen atom, e.g., chlorine, fluorine or bromine.
Preferably, the leaving group X-O- is an alkylsulphonyl or aryl-sulphonyl group, e.g. methane-sulphonyl or para-toluenesulphonyl.
It has been found that the presence of one of~these leaving groups in the lactic acid derivative II enables the desired optically-active isomer of formula I to be obtained during the reaction of II
with the phenol III. Not only is the desired optically-active isomer produced by this process but the yields are in excess of 70% and often as high as 80% or more.
Reaction between the lactic acid derivative II and the phenol III
may be carried out at temperatures between 50C and 200C, preferably between 130 C and 170C.
~5S~ 8 As with all st~reospecific processes the reaction conditions must be carefully selected and tested for each particular case to ensure that the optical integrity of the required product is un-affected by these conditions. One such condition is the nature of the base present in the reaction between the lactic acid derivative II
and the phenol III; the base may be organic or inorganic and particular examples are N-ethyl-morpholine or an alkali metal carbonate or bi-carbonate. Especially good results have been obtained with anhydrous sodium carbonate.
The phenol III may be employed as the solvent for the reaction but an (additional) solvent such as tetrahydrofuran or a higher ether may be employed.
The lactic acid derivative II used as starting materi~l in the process for the preparation of R-(+)-phenoxy propionic acid derivatives according to the invention may be readily prepared by reaction of an acid halide of formula X-halide or the corresponding acid anhydride or halogenated aldehyde with a derivative of lactic acid of formula IV
possessing the S- or R-configuration at the carbon atom marked ~:
COOR
HO ~ H (IV) wherein X and R1 have the meanings hereinbefore specified. Preferably, the reaction is carried out in the presence of a base, for example an organic nitrogenous base, e.g. pyridine or a trialkylamine, such as triethylamine. Generally, reaction takes 94~8 place at room temperature but, if desired, cemperatures in the range -5 C to +80 C may be employed. The acid halide or corresponding acid anhydride or halogenated aldehyde may be selected from one of the following: V.S02.Q, V.CO.Q, (C.Q)2 and H.CO.CV3, wherein Q and V
have the meaning hereinbefore specified. Preferably an alkylsulphonyl or arylsulphonyl halide is employed, for example, methanesulphonyl chloride or para-toluenesulphonyl chloride.
Compound IV is a cheap readily available material where R
represents a hydrogen atom, i.e., it is S-(+)-lactic acid. The remsining compounds embraced by formula IV, the esters, may con-veniently be prepared from S-(+)-lactic acid by an esterification reaction with the appropriate alcohol. Alternatively, since S-(-)-ethyl lactate is also a readily available compound this can be converted into the desired lactic acid derivative IV by a trans-esterification procedure.
It will be appreciated that in the production of compounds ofgeneral formula I, wherein R is other than hydrogen, it may ac-cording to the circumstances be convenient to introduce the R
substituent into the starting material IV or, alternatively, it may be desirable to start wibh the acid (II; R1=H) and introduce the R substituent at a later stage or at the final stage in the process.
For instance, in the preparation of long-chain esters of the phenoxy-propionic acids, it is very convenient to start with S-(+)-lactic acid, or preferably with S-(-)-ethyl lactate (II; R=H
or ethyl) and then to transesterify the R-(+)-phenoxy propionic acid ethyl ester obtained under normal transesterification conditions.
~ 1 59~
It was foulld that good yields could also be obtained starting from S~ linevyl lac-tate by reacting that compound (which can be prepared from S-~)-lactic acid and linevol) with methane sulphonyl chloride followed by reaction of the product with 4-chloro-2-methyl phenol.
Equally it may be convenient in the production of compounds of formula I, wherein R is hydrogen, to start with an ester and re-move the ester grouping at an intermediate or during the last stage in the process and to convert the acid obtained into the corre-sponding salt by reacting it with an appropriate base.
Preferably, in the general formula I the alkyl, alkenyl and alkylene groups contain up to 6 carbon atoms, the aryl, aralkyl, and alkaryl groups up to 10 carbon atoms, the halogen atom unless other-wise specified is a chlorine or fluorine atom and the hetero atoms are oxygen and nitrogen.
The phenoxy propionic acid derivatives of formula I (in particular the R-(+)-isomers), wherein R, n, Hal, m and R are as defined hereinabove and R represents an optionPlly alkyl sub-stituted a~monium ion, or an optionally substituted alkyl, cyclo-alkyl, alkenyl, aryl or aralkyl group are believed to be novel compounds.
The process according to the invention produces selective herbicides for cereal crops, which are active against broad-leaved weeds. It is advantageous to use long-chain esters of phenoxy propionic acids since these compounds appear to be oil-soluble which facilitate their handling, in that they can easily be mixed with commercial wild oat herbicides.
In order to denote the absolute configuration of the products, starting materials and intermediates used in the process according to the invention and R- and S-notation has been employed as stated in Experientia, Volume 12, pages 81-94, 1956.
The process according to the invention will now be illustrated by the following Examples.
EXAMPLE I - Preparation of R-(+)-2-(4-chloro-2-methylphenoxy)-propionic acid potassium salt (a) S-(-)-ethyl lactate mesylate (C ~ ]D5= -64.89 ) was prepared in 79% yield from S-(-)-ethyl lactate, methanesulphonyl chloride and pyridine using a molar ratio of 1:1:1.05.
The mesylate (6.o mol.) was stirred with 6.o moles of 4-chloro-
It is known that phenoxy-propionic acids and derivatives thereof, such as 2-(4-chloro-2-methylphenoxy)propionic acid and 2-~2,4-dichloro-phenoxy)propionic acid and their respective alkali- and dimethylamine salts can be successfully applied to combat broad-leaved weeds. It is also known that one of the optical isomers of substituted phenoxy propionic acids exerts a higher physiological activity than the other isomer. The most active isomer is normally obtained by applying optical resolution techniques on the corresponding racemate but these techniques are laborious and have also the drawback of producing the less active isomer which is of considerable less use and has to be converted into the more active isomer in a subsequent process step.
The Applicants have now found a stereospecific route towards specific isomers of the phenoxy-alkanoic acid derivatives which avoids the need to employ lengthy resolution techniques. The process according to the invention is in particular suitable for the preparation of esters of phenoxy-propionic acid derivatives which apparently cannot be selectively prepared via the stereospecific route towards dextra-rotatory 2-(2,4-dichlorophenoxy)propionic acid described in British Patent Specification No. 1,114,040.
~r, q~
5~4b8 Thus, the present invention provides a process for the preparation of phenoxy-alkanoic acid derivatives having the following general formula and possessing the R- or S-configuration at the carbon atom marked x:
(Hal) nr~ 2 R O
~ - O - C C 0 R (I) (R)n wherein R represents an alkyl group of up to 4 carbon atoms; n is 0 or an integer up to 4; Hal represents a halogen atom; m is O or an integer up to 5; the total of n and m being zero or an integer from 1 to 5; Rl represents a hydrogen atom, a metal-salt forming or an optionally alkyl substituted ammonium ion, or an optionally substituted alkyl, cycloalkyl, alkenyl, aryl or aralkyl group; and R represents an alkyl group of up to 4 carbon atom, which comprises reacting a derivative of lactic acid of formula II possessing the S-or R-configuration at the carbon atom marked x:
COOR
X _ O Xc -H (II) with a phenol of formula III:
(Hal) m HO ~ (III) (R)n ., ,.~
~5~4i,8 (wherein the group X-O- is a eroup which will leave the molecule and be replaced by a deprotonated phenol of formula III, and Hal, R, m and n have their meaning hereinbefore specified) in the presence of a base and under conditions of elevated temperature to produce a compound of for~ula I with the required configuration.
The process according to the present invention is particularly suitable ~or the preparation of phenoxy-propionic acid derivatives of the general formula I, i.e., compounds wherein R represents a methyl group.
The leaving group X-O- in formula II must, as stated above, be capable of being replaced by a deprotonated phenol of formula III
and suitable examples of such groups are the following: -O.S02.Q, -O.CO.Q and -O.CH(OH).CV3, wherein Q represents a hydrocarbyl group, suitably an alkyl or aryl group containing up to 10 carbon atoms, and V represents a halogen atom, e.g., chlorine, fluorine or bromine.
Preferably, the leaving group X-O- is an alkylsulphonyl or aryl-sulphonyl group, e.g. methane-sulphonyl or para-toluenesulphonyl.
It has been found that the presence of one of~these leaving groups in the lactic acid derivative II enables the desired optically-active isomer of formula I to be obtained during the reaction of II
with the phenol III. Not only is the desired optically-active isomer produced by this process but the yields are in excess of 70% and often as high as 80% or more.
Reaction between the lactic acid derivative II and the phenol III
may be carried out at temperatures between 50C and 200C, preferably between 130 C and 170C.
~5S~ 8 As with all st~reospecific processes the reaction conditions must be carefully selected and tested for each particular case to ensure that the optical integrity of the required product is un-affected by these conditions. One such condition is the nature of the base present in the reaction between the lactic acid derivative II
and the phenol III; the base may be organic or inorganic and particular examples are N-ethyl-morpholine or an alkali metal carbonate or bi-carbonate. Especially good results have been obtained with anhydrous sodium carbonate.
The phenol III may be employed as the solvent for the reaction but an (additional) solvent such as tetrahydrofuran or a higher ether may be employed.
The lactic acid derivative II used as starting materi~l in the process for the preparation of R-(+)-phenoxy propionic acid derivatives according to the invention may be readily prepared by reaction of an acid halide of formula X-halide or the corresponding acid anhydride or halogenated aldehyde with a derivative of lactic acid of formula IV
possessing the S- or R-configuration at the carbon atom marked ~:
COOR
HO ~ H (IV) wherein X and R1 have the meanings hereinbefore specified. Preferably, the reaction is carried out in the presence of a base, for example an organic nitrogenous base, e.g. pyridine or a trialkylamine, such as triethylamine. Generally, reaction takes 94~8 place at room temperature but, if desired, cemperatures in the range -5 C to +80 C may be employed. The acid halide or corresponding acid anhydride or halogenated aldehyde may be selected from one of the following: V.S02.Q, V.CO.Q, (C.Q)2 and H.CO.CV3, wherein Q and V
have the meaning hereinbefore specified. Preferably an alkylsulphonyl or arylsulphonyl halide is employed, for example, methanesulphonyl chloride or para-toluenesulphonyl chloride.
Compound IV is a cheap readily available material where R
represents a hydrogen atom, i.e., it is S-(+)-lactic acid. The remsining compounds embraced by formula IV, the esters, may con-veniently be prepared from S-(+)-lactic acid by an esterification reaction with the appropriate alcohol. Alternatively, since S-(-)-ethyl lactate is also a readily available compound this can be converted into the desired lactic acid derivative IV by a trans-esterification procedure.
It will be appreciated that in the production of compounds ofgeneral formula I, wherein R is other than hydrogen, it may ac-cording to the circumstances be convenient to introduce the R
substituent into the starting material IV or, alternatively, it may be desirable to start wibh the acid (II; R1=H) and introduce the R substituent at a later stage or at the final stage in the process.
For instance, in the preparation of long-chain esters of the phenoxy-propionic acids, it is very convenient to start with S-(+)-lactic acid, or preferably with S-(-)-ethyl lactate (II; R=H
or ethyl) and then to transesterify the R-(+)-phenoxy propionic acid ethyl ester obtained under normal transesterification conditions.
~ 1 59~
It was foulld that good yields could also be obtained starting from S~ linevyl lac-tate by reacting that compound (which can be prepared from S-~)-lactic acid and linevol) with methane sulphonyl chloride followed by reaction of the product with 4-chloro-2-methyl phenol.
Equally it may be convenient in the production of compounds of formula I, wherein R is hydrogen, to start with an ester and re-move the ester grouping at an intermediate or during the last stage in the process and to convert the acid obtained into the corre-sponding salt by reacting it with an appropriate base.
Preferably, in the general formula I the alkyl, alkenyl and alkylene groups contain up to 6 carbon atoms, the aryl, aralkyl, and alkaryl groups up to 10 carbon atoms, the halogen atom unless other-wise specified is a chlorine or fluorine atom and the hetero atoms are oxygen and nitrogen.
The phenoxy propionic acid derivatives of formula I (in particular the R-(+)-isomers), wherein R, n, Hal, m and R are as defined hereinabove and R represents an optionPlly alkyl sub-stituted a~monium ion, or an optionally substituted alkyl, cyclo-alkyl, alkenyl, aryl or aralkyl group are believed to be novel compounds.
The process according to the invention produces selective herbicides for cereal crops, which are active against broad-leaved weeds. It is advantageous to use long-chain esters of phenoxy propionic acids since these compounds appear to be oil-soluble which facilitate their handling, in that they can easily be mixed with commercial wild oat herbicides.
In order to denote the absolute configuration of the products, starting materials and intermediates used in the process according to the invention and R- and S-notation has been employed as stated in Experientia, Volume 12, pages 81-94, 1956.
The process according to the invention will now be illustrated by the following Examples.
EXAMPLE I - Preparation of R-(+)-2-(4-chloro-2-methylphenoxy)-propionic acid potassium salt (a) S-(-)-ethyl lactate mesylate (C ~ ]D5= -64.89 ) was prepared in 79% yield from S-(-)-ethyl lactate, methanesulphonyl chloride and pyridine using a molar ratio of 1:1:1.05.
The mesylate (6.o mol.) was stirred with 6.o moles of 4-chloro-
2-methylphenol and anhydrous sodium carbonate (3.3 mol.) at 100-114 C
for 17 hours. The mixture was then cooled, filtered, and the filter cake washed several times with toluene, water, 2N NaOH and then with diluted sulphuric acid and neutral with water. The mixture was dried azeotropically and the toluene removed in vacuo to yield 866 g (59%) of R-(+)-2-(4-chloro-2-methylphenoxy)propionic acid ethyl ester, possessing an ra ]D5 f +22.9 (C3; methanol).
(b) A portion of the R-(+)-(4-chloro-2-methylphenoxy)propionic acid ethyl ester was hydrolysed by refluxing with formic acid and 2 molar HCl for 7 hours. The solution was then added to ice/water and the 3L~L594~8 resulting solid fi:ltered, washed with water, taken up in diethyl ether and extracted with sodium hydrogen carbonate in water. The aqueous solution was neutralized with concentrated hydrochloric acid to precipitate the acid which was filte:red, washed and dried.
The yield of R-(+)-2-(4-chloro-2-methylphenoxy)propionic acid was 83%, m.p. 83-85 C and optical rotation [ a ~D3= +14.62 (C2, ethanol).
(c) An aqueous solution of the potassium salt of R-(+)-2-(4-chloro-2-methylphenoxy)propionic acid was prepared by addition of 0.395 mol.
of the acid to a stirred solution of potassium hydroxide (0.395 mol.) in water ~30 ml), with ice-cooling. The resulting solution was diluted to 121 ml with water to make a 70% w/v acid equivalent solution.
The salt possessed an ~ ~D f +3.6 (C3, water).
EXAMPLE II
Using R-(+)-2-(4-chloro-2-methylphenoxy)propionic acid, prepared as described in Example I(b) a number of derivatives was obtained using conventionPl techniques. The compounds obtained as well as their optical rotation data are given in Table I.
EXAMPLE III - Preparation of R-(+)-2-(2,4-dichlorophenoxy)propionic acid linevol ester via S-(-)-ethyl lactate (a) S-(-)-ethyl lactate mesylate ( C ~ ~ 25= -65.14 ) was prepared in 81% yield from S-(-)-ethyl lactate, methane sulphonyl chloride and pyridine in a molar ratio of 1:1:1.05.
12 mol. of the mesylate obtained were stirred with 12 mol.
2,4-dichlorophenol at 90-122 C for 8 hours. Over the first 5 hours anhydrous sodium carbonate (6.6 moles) was added in 5 equal portions.
The mixture was filtered and washed with hot toluene (total volume ~L594~8 6 litres). The combined oreanic layers were concentrated and then washed with 2 x 1200 ml water, 2 x 1800 ml 1 M NaOH and then diluted sulphuric acid and water to neutrality (4 x 1200 ml). The solution was dried azeotropically and evaporated to yield 9.6 moles (80%) of R-(+)-2-(2,4-dichlorophenoxy)propionic acid ethyl ester, possessing an Ca ~ D5 f +29.5 (C3, ethanol).
(b) 5 moles of the ester prepared according to III(a) were treated with 5.25 moles of linevol 79, in 1300 ml toluene in the presence of 0.15 mol. concentrated H2S04. The mixture was refluxed with removal of the ethanol-toluene azeotrope, for 8 hours. The solution was cooled, washed with water (3 x 500 ml) and dried azeotropically and the solvent removed in vacuo. A quantitative yield of the linevol ester(s) of R-(+)-2-(2,4-dichlorophenoxy)propionic acid was obtained:
~ ~ 25= +19 1 (C3, ethanol)-~1594~8 . . . .
O O ~ O
,,+, ~U ~ ~ ~ C~
h o o_ ~ o, o ~1C~
~ ~D U~
.~ ~ + + + +
0~11 1111 11 ~1 ~ U~
C\.l Q c~l Q c~l Q C\l Q ~ Q
~I r~ ~, r~ ,~
.
_ ~rl ~0 h ~1 h + ~ a ~ ~ ~~
~ 1 C~
_ + + + + + ~1 rd td rl~1 rl rl c~ O
~ l ~1~
~ ~ .~
,_ ~ ~
r~ ~1 ~C ~ I O
_ ~ N IN ,~_~ ~N
r ~ ~ _ u~
$
O --c~ y 1~ o ~/ ~ ~ .
~ ll ll ll ll ll ll C) X ~ X X X ~C
~S~4~8 EXAMPLE IV
According to ~he procedure described in Example I(b) R-(+) 2-(2,4-dichlorophenoxy)propionic acid was obtained by re-acting R-(+)-2-(2,4-dichlorophenoxy)propionic acid ethyl ester with formic acid under reflux conditions in the presence of 2N
HCl. The free acid was obtained in 95.5% yield, m.p. 121-122C and had an ~ ] D5 5 f +28 (C1.4, ethanol).
The R-(+)-acid obtained was used to prepare some deriva-tives by conventional techniques such as the potassium salt, the dimethyl-ammonium salt, the tert.-octylammonium salt as well as the salts obtained by reacting R-(+)-2-(2,4-dichlorophenoxy)propionic acid 2 ( 3)2 (CH2)6-C(CH3)3 and NH2-cH2-(cH2)7-cH=cH-(cH2) -CH
( Ca ~25-5 = +3.74 , C3,ethanol).
EXAMPLE V
According to the method described in Example I(a) R-(+)-2-(2,4,5-trichlorophenoxy)propionic acid ethyl ester was prepared by stirring S-(-)-ethyl lactate mesylate with 2,4,5-trichlorophenol and sodium carbonate for 2.5 hours at 120C. After filtration, washing with water, NaOH and again water R-(+)-2-(2,4,5-trichlorophenoxy)propionic acid ethyl ester was obtained in 80~ yield, m.p. 39-42C and ¦ ~ ~D5-5 = +51-3 (C3, ethanol).
Part of the compound obtained was used to prepare the corre-sponding linevol ester by a transesterification process. After heating R-(+)-2-(2,4,5-trichlorophenoxy)propionic acid ethyl ester with linevol in the presence of concentrated sulphuric acid for 10 hours at reflux temperature (119 C), the solution was washed with water and stripped off solvent. The linevol ester was obtained as an oil in qUantitQtiVe yield. C ~ ]D5 5 =+40.2 (C3, ethanol).
EXAMPLE VI - Preparation of R-(+)-2-(4-chloro-2-methylphenoxy)propionic linevol ester via S-(-)-linevyl lactate (a) S-(+)-lactic acid (1.5 m), linevol 79 (1 m), benzene (250 ml) and concentrated sulphuric acid (0.05 m) were refluxed, removing water azeotropically for 2 hours. The benzene solution was then washed with water (3 x 500 ml) to neutrality and azeotropically dried and solvent was removed in vacuo to eive S-(-)-linevyl lactate in 76% yield ( r a ~ 23 = -12.62 ).
(b) S-(-)-linevyl lactate (0.5 m), triethylamine (0.54 m) and toluene (200 ml) were stirred together while methane sulphonyl chloride (0.54 m) was added, keeping the temperature in the range 20-30 C. The toluene solution was washed with water (3 x 250 ml), 2N HCl (100 ml) and with water to neutrality, then azeotropically dried and toluene removed in vacuo to yield S-(-)-linevyl lactate mesylate in 97% yield ( r a ~D3=
-40.34 (C2, ethanol).
(c) S-(-)-linevyl lactate mesylate (0~4 m), 4-chloro-2-methylphenol (0.4 m), anhydrous sodium carbonate (0.4 m) and toluene (40 ml) were stirred together at 130-135 C for 8 hours. The organic solution was then washed with water (2 x 300 ml), 2~ sodium hydroxide (2 x 100 ml) and with water to neutrality. The solution was dried azeotropically and evaporated in vacuo to give R-(+)-2-(4-chloro-2-methylphenoxy)propionic acid linevol ester in 68% yield ( r ~D5 = +17.17 (C3, ethanol)).
for 17 hours. The mixture was then cooled, filtered, and the filter cake washed several times with toluene, water, 2N NaOH and then with diluted sulphuric acid and neutral with water. The mixture was dried azeotropically and the toluene removed in vacuo to yield 866 g (59%) of R-(+)-2-(4-chloro-2-methylphenoxy)propionic acid ethyl ester, possessing an ra ]D5 f +22.9 (C3; methanol).
(b) A portion of the R-(+)-(4-chloro-2-methylphenoxy)propionic acid ethyl ester was hydrolysed by refluxing with formic acid and 2 molar HCl for 7 hours. The solution was then added to ice/water and the 3L~L594~8 resulting solid fi:ltered, washed with water, taken up in diethyl ether and extracted with sodium hydrogen carbonate in water. The aqueous solution was neutralized with concentrated hydrochloric acid to precipitate the acid which was filte:red, washed and dried.
The yield of R-(+)-2-(4-chloro-2-methylphenoxy)propionic acid was 83%, m.p. 83-85 C and optical rotation [ a ~D3= +14.62 (C2, ethanol).
(c) An aqueous solution of the potassium salt of R-(+)-2-(4-chloro-2-methylphenoxy)propionic acid was prepared by addition of 0.395 mol.
of the acid to a stirred solution of potassium hydroxide (0.395 mol.) in water ~30 ml), with ice-cooling. The resulting solution was diluted to 121 ml with water to make a 70% w/v acid equivalent solution.
The salt possessed an ~ ~D f +3.6 (C3, water).
EXAMPLE II
Using R-(+)-2-(4-chloro-2-methylphenoxy)propionic acid, prepared as described in Example I(b) a number of derivatives was obtained using conventionPl techniques. The compounds obtained as well as their optical rotation data are given in Table I.
EXAMPLE III - Preparation of R-(+)-2-(2,4-dichlorophenoxy)propionic acid linevol ester via S-(-)-ethyl lactate (a) S-(-)-ethyl lactate mesylate ( C ~ ~ 25= -65.14 ) was prepared in 81% yield from S-(-)-ethyl lactate, methane sulphonyl chloride and pyridine in a molar ratio of 1:1:1.05.
12 mol. of the mesylate obtained were stirred with 12 mol.
2,4-dichlorophenol at 90-122 C for 8 hours. Over the first 5 hours anhydrous sodium carbonate (6.6 moles) was added in 5 equal portions.
The mixture was filtered and washed with hot toluene (total volume ~L594~8 6 litres). The combined oreanic layers were concentrated and then washed with 2 x 1200 ml water, 2 x 1800 ml 1 M NaOH and then diluted sulphuric acid and water to neutrality (4 x 1200 ml). The solution was dried azeotropically and evaporated to yield 9.6 moles (80%) of R-(+)-2-(2,4-dichlorophenoxy)propionic acid ethyl ester, possessing an Ca ~ D5 f +29.5 (C3, ethanol).
(b) 5 moles of the ester prepared according to III(a) were treated with 5.25 moles of linevol 79, in 1300 ml toluene in the presence of 0.15 mol. concentrated H2S04. The mixture was refluxed with removal of the ethanol-toluene azeotrope, for 8 hours. The solution was cooled, washed with water (3 x 500 ml) and dried azeotropically and the solvent removed in vacuo. A quantitative yield of the linevol ester(s) of R-(+)-2-(2,4-dichlorophenoxy)propionic acid was obtained:
~ ~ 25= +19 1 (C3, ethanol)-~1594~8 . . . .
O O ~ O
,,+, ~U ~ ~ ~ C~
h o o_ ~ o, o ~1C~
~ ~D U~
.~ ~ + + + +
0~11 1111 11 ~1 ~ U~
C\.l Q c~l Q c~l Q C\l Q ~ Q
~I r~ ~, r~ ,~
.
_ ~rl ~0 h ~1 h + ~ a ~ ~ ~~
~ 1 C~
_ + + + + + ~1 rd td rl~1 rl rl c~ O
~ l ~1~
~ ~ .~
,_ ~ ~
r~ ~1 ~C ~ I O
_ ~ N IN ,~_~ ~N
r ~ ~ _ u~
$
O --c~ y 1~ o ~/ ~ ~ .
~ ll ll ll ll ll ll C) X ~ X X X ~C
~S~4~8 EXAMPLE IV
According to ~he procedure described in Example I(b) R-(+) 2-(2,4-dichlorophenoxy)propionic acid was obtained by re-acting R-(+)-2-(2,4-dichlorophenoxy)propionic acid ethyl ester with formic acid under reflux conditions in the presence of 2N
HCl. The free acid was obtained in 95.5% yield, m.p. 121-122C and had an ~ ] D5 5 f +28 (C1.4, ethanol).
The R-(+)-acid obtained was used to prepare some deriva-tives by conventional techniques such as the potassium salt, the dimethyl-ammonium salt, the tert.-octylammonium salt as well as the salts obtained by reacting R-(+)-2-(2,4-dichlorophenoxy)propionic acid 2 ( 3)2 (CH2)6-C(CH3)3 and NH2-cH2-(cH2)7-cH=cH-(cH2) -CH
( Ca ~25-5 = +3.74 , C3,ethanol).
EXAMPLE V
According to the method described in Example I(a) R-(+)-2-(2,4,5-trichlorophenoxy)propionic acid ethyl ester was prepared by stirring S-(-)-ethyl lactate mesylate with 2,4,5-trichlorophenol and sodium carbonate for 2.5 hours at 120C. After filtration, washing with water, NaOH and again water R-(+)-2-(2,4,5-trichlorophenoxy)propionic acid ethyl ester was obtained in 80~ yield, m.p. 39-42C and ¦ ~ ~D5-5 = +51-3 (C3, ethanol).
Part of the compound obtained was used to prepare the corre-sponding linevol ester by a transesterification process. After heating R-(+)-2-(2,4,5-trichlorophenoxy)propionic acid ethyl ester with linevol in the presence of concentrated sulphuric acid for 10 hours at reflux temperature (119 C), the solution was washed with water and stripped off solvent. The linevol ester was obtained as an oil in qUantitQtiVe yield. C ~ ]D5 5 =+40.2 (C3, ethanol).
EXAMPLE VI - Preparation of R-(+)-2-(4-chloro-2-methylphenoxy)propionic linevol ester via S-(-)-linevyl lactate (a) S-(+)-lactic acid (1.5 m), linevol 79 (1 m), benzene (250 ml) and concentrated sulphuric acid (0.05 m) were refluxed, removing water azeotropically for 2 hours. The benzene solution was then washed with water (3 x 500 ml) to neutrality and azeotropically dried and solvent was removed in vacuo to eive S-(-)-linevyl lactate in 76% yield ( r a ~ 23 = -12.62 ).
(b) S-(-)-linevyl lactate (0.5 m), triethylamine (0.54 m) and toluene (200 ml) were stirred together while methane sulphonyl chloride (0.54 m) was added, keeping the temperature in the range 20-30 C. The toluene solution was washed with water (3 x 250 ml), 2N HCl (100 ml) and with water to neutrality, then azeotropically dried and toluene removed in vacuo to yield S-(-)-linevyl lactate mesylate in 97% yield ( r a ~D3=
-40.34 (C2, ethanol).
(c) S-(-)-linevyl lactate mesylate (0~4 m), 4-chloro-2-methylphenol (0.4 m), anhydrous sodium carbonate (0.4 m) and toluene (40 ml) were stirred together at 130-135 C for 8 hours. The organic solution was then washed with water (2 x 300 ml), 2~ sodium hydroxide (2 x 100 ml) and with water to neutrality. The solution was dried azeotropically and evaporated in vacuo to give R-(+)-2-(4-chloro-2-methylphenoxy)propionic acid linevol ester in 68% yield ( r ~D5 = +17.17 (C3, ethanol)).
Claims (19)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A process for the preparation of phenoxy-alkanoic acid derivatives having the following general formula and possessing the R- or S- configuration at the carbon atom marked x:
(I) wherein R represents an alkyl group of up to 4 carbon atoms; n is 0 or an integer up to 4; Hal represents a halogen atom; m is 0 or an integer up to 5; the total of n and m is 0 or an integer up to 5, R1 represents a hydrogen atom, a metal-salt forming or an optionally alkyl substituted ammonium ion, or an optionally substituted alkyl, cycloalkyl, alkenyl, aryl or aralkyl group;
and R2 represents an alkyl group of up to 4 carbon atoms, which comprises reacting a derivative of lactic acid of formula II
possessing the S- or R- configuration at the carbon atom marked x:
(II) with a phenol of formula III:
(III) (wherein the group X-O- is a group which will leave the molecule and be re-placed by a deprotonated phenol of formula III, and Hal, R, m and n have the meanings hereinbefore specified) in the presence of a base and under condi-tions of elevated temperature to produce a compound of formula I with the required configuration.
(I) wherein R represents an alkyl group of up to 4 carbon atoms; n is 0 or an integer up to 4; Hal represents a halogen atom; m is 0 or an integer up to 5; the total of n and m is 0 or an integer up to 5, R1 represents a hydrogen atom, a metal-salt forming or an optionally alkyl substituted ammonium ion, or an optionally substituted alkyl, cycloalkyl, alkenyl, aryl or aralkyl group;
and R2 represents an alkyl group of up to 4 carbon atoms, which comprises reacting a derivative of lactic acid of formula II
possessing the S- or R- configuration at the carbon atom marked x:
(II) with a phenol of formula III:
(III) (wherein the group X-O- is a group which will leave the molecule and be re-placed by a deprotonated phenol of formula III, and Hal, R, m and n have the meanings hereinbefore specified) in the presence of a base and under condi-tions of elevated temperature to produce a compound of formula I with the required configuration.
2. A process as claimed in claim 1, wherein a compound of formula II is used, wherein R represents a methyl group and the leaving group X-O- is an -O.SO2.Q, -O.CO.Q or -O.CH(OH).CV3 group, wherein Q represents a hydrocarbyl group and V represents a halogen atom.
3. A process as claimed in claim 2, wherein the leaving group X-O- is an alkylsulphonyl or arylsulphonyl group containing up to 10 carbon atoms.
4. A process as claimed in claim 3, wherein the leaving group is a methano sulphonyl group or a para-toluene sulphonyl group.
5. A process as claimed in claim 1, 2 or 3, wherein the reaction be-tween the lactic acid derivative of formula II and the phenol of formula III
is carried out at a temperature between 50°C and 200°C.
is carried out at a temperature between 50°C and 200°C.
6. A process as claimed in claim 1, 2 or 3, wherein the reaction be-tween the lactic acid derivative of formula II and the phenol of formula III
is carried out at a temperature between 130°C and 170°C.
is carried out at a temperature between 130°C and 170°C.
7. A process as claimed in claim 1, wherein the reaction between the lactic acid derivative of formula II and the phenol of formula III is carried out in the presence of a base.
8. A process as claimed in claim 7, wherein the base applied is an alkali metal carbonate or bicarbonate.
9. A process as claimed in claim 7, wherein the base applied is anhy-drous sodium carbonate.
10. A process as claimed in claim 1, wherein a lactic acid derivative of formula II is used which has keen prepared by reacting an acid halide of for-mula X-halide or the corresponding acid anhydride or a halogenated aldehyde with a derivative of lactic acid of formula IV possessing the S- or R- con-figuration at the carbon atom marked x:
wherein X and R1 have the meanings hereinbefore specified.
wherein X and R1 have the meanings hereinbefore specified.
11. A process as claimed in claim 10, wherein the reaction is carried out at a temperature in the range -5°C to +80°C.
12. A process as claimed in claim 10 or 11, wherein the process is carr-ied out in the presence of an organic base.
13. A process as claimed in claim 10 or 11, wherein the lactic acid derivative of formula IV is reacted with a compound V.SO2.Q, V.CO.Q, O(CO.Q)2 or H.CO.CV3, wherein Q and V are as defined in claim 2.
14. A process as claimed in claim 10 or 11, wherein the lactic acid derivative of formula IV is reacted with an alkyl sulphonyl halide or with an arylsulphonyl halide.
15. A process as claimed in claim 10 or 11, wherein the lactic acid derivative of formula IV is reacted with methane sulphonyl chloride or para-toluene sulphonyl chloride.
16. A process as claimed in claim 1, 2 or 3, wherein a compound accord-ing to formula I is prepared, wherein the alkyl, alkenyl and alkylene groups contain up to 6 carbon atoms, the aryl, aralkyl and alkaryl groups up to 10 carbon atoms, the halogen atoms are fluorine or chlorine and the hetero atoms are oxygen or nitrogen.
17. Phenoxy-propionic acid derivatives of the general formula:
possessing the R- or S-configuration at the carbon atom marked x, wherein R
represents an alkyl group of up to 4 carbon atoms; n is 0 or an integer up to 4; Hal represents a halogen atom; m is 0 or an integer up to 5; the total of n and m is 0 or an integer up to 5 and R1 represents an optionally alkyl substi-tuted ammonium ion or an optionally substituted alkyl, cycloalkyl, alkenyl, aryl or aralkyl group; and R2 represents a methyl group.
possessing the R- or S-configuration at the carbon atom marked x, wherein R
represents an alkyl group of up to 4 carbon atoms; n is 0 or an integer up to 4; Hal represents a halogen atom; m is 0 or an integer up to 5; the total of n and m is 0 or an integer up to 5 and R1 represents an optionally alkyl substi-tuted ammonium ion or an optionally substituted alkyl, cycloalkyl, alkenyl, aryl or aralkyl group; and R2 represents a methyl group.
18. Phenoxy-propionic acid derivatives as claimed in claim 17, possessing the R-configuration at the carbon atom marked x in formula I wherein R repre-sents a methyl group; n is 0 or 1; Hal represents a chlorine atom; m is 1, 2 or 3; R1 represents an ammonium ion substituted by one or two alkyl groups of up to 20 carbon atoms or an alkyl group of up to 12 carbon atoms; and R2 represents a methyl group.
19. A method of eradicating or controlling broad-leaved weeds which com-prises applying to a locus a herbicidally active amount of a compound of for-mula I as claimed in claim 17 or 18.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB32086/76 | 1976-08-02 | ||
| GB3208676A GB1586462A (en) | 1976-08-02 | 1976-08-02 | Phenonyalkanoic acids and derivatives thereof useful as herbicides |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1159468A true CA1159468A (en) | 1983-12-27 |
Family
ID=10333007
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000282664A Expired CA1159468A (en) | 1976-08-02 | 1977-07-13 | Stereospecific isomers of phenoxyalkanoic acid derivatives |
Country Status (11)
| Country | Link |
|---|---|
| JP (1) | JPS5318526A (en) |
| BE (1) | BE857192A (en) |
| CA (1) | CA1159468A (en) |
| CH (1) | CH630883A5 (en) |
| DD (1) | DD132429A5 (en) |
| DE (1) | DE2734667A1 (en) |
| FR (1) | FR2371414A1 (en) |
| GB (1) | GB1586462A (en) |
| HU (1) | HU179789B (en) |
| NL (1) | NL7708416A (en) |
| SU (1) | SU824892A3 (en) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE878446A (en) * | 1978-08-28 | 1980-02-27 | Ppg Industries Inc | TRICHLORO-PHENOXY-ALKANOIC ACIDS FREE OF CHLORINATED DIBENZO-P-DIOXINS AND THEIR PREPARATION |
| CA1147348A (en) * | 1978-09-19 | 1983-05-31 | Willem Eveleens | Process for the preparation of optically active 2-phenoxy propionic acids and herbicidal preparations containing such acids |
| JPS579701A (en) * | 1980-06-20 | 1982-01-19 | Kumiai Chem Ind Co Ltd | Herbicide containing optically active (+)-2-pentenoic acid compound |
| US7129274B1 (en) | 1999-11-05 | 2006-10-31 | Emisphere Technologies Inc. | Phenoxy carboxylic acid compounds and compositions for delivering active agents |
| US7279597B1 (en) | 1999-11-05 | 2007-10-09 | Emisphere Technologies, Inc. | Phenyl amine carboxylic acid compounds and compositions for delivering active agents |
| DE102007056817A1 (en) * | 2007-11-23 | 2009-05-28 | Lanxess Deutschland Gmbh | n-alkyl ester of R - (+) - MCPP acid |
| CN106366020B (en) * | 2016-08-31 | 2018-12-11 | 京博农化科技股份有限公司 | A kind of method of synthesis of chiral fenoxanil |
| CN107473962B (en) * | 2017-08-09 | 2021-12-07 | 科顺防水科技股份有限公司 | Preparation method of (R) -2- (4-chloro-2-methylphenoxy) octyl propionate root-resisting agent |
| CN108752205B (en) * | 2018-06-28 | 2021-03-26 | 科顺防水科技股份有限公司 | Improved industrial production process of (R) -2- (4-chloro-2-methylphenoxy) octyl propionate root-resisting agent |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1065062B (en) * | 1975-08-08 | 1985-02-25 | Hoffmann La Roche | REPLACED BOSSILIC ALFA ARILOSSICAR ACID ESTERS |
-
1976
- 1976-08-02 GB GB3208676A patent/GB1586462A/en not_active Expired
-
1977
- 1977-07-13 CA CA000282664A patent/CA1159468A/en not_active Expired
- 1977-07-27 BE BE1008303A patent/BE857192A/en not_active IP Right Cessation
- 1977-07-29 NL NL7708416A patent/NL7708416A/en not_active Application Discontinuation
- 1977-07-29 CH CH944577A patent/CH630883A5/en not_active IP Right Cessation
- 1977-08-01 DD DD20037077A patent/DD132429A5/en unknown
- 1977-08-01 HU HUSE001866 patent/HU179789B/en unknown
- 1977-08-01 JP JP9149477A patent/JPS5318526A/en active Pending
- 1977-08-01 FR FR7723613A patent/FR2371414A1/en active Granted
- 1977-08-01 SU SU772505801A patent/SU824892A3/en active
- 1977-08-01 DE DE19772734667 patent/DE2734667A1/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| FR2371414A1 (en) | 1978-06-16 |
| JPS5318526A (en) | 1978-02-20 |
| NL7708416A (en) | 1978-02-06 |
| BE857192A (en) | 1978-01-27 |
| GB1586462A (en) | 1981-03-18 |
| CH630883A5 (en) | 1982-07-15 |
| DE2734667A1 (en) | 1978-02-09 |
| DD132429A5 (en) | 1978-09-27 |
| FR2371414B1 (en) | 1980-02-01 |
| HU179789B (en) | 1982-12-28 |
| SU824892A3 (en) | 1981-04-23 |
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