GB1586462A - Phenonyalkanoic acids and derivatives thereof useful as herbicides - Google Patents

Abstract

The compounds of the general formula I can be used as herbicides. They are prepared by reacting a compound of the formula II with a phenol of the formula III. The symbols used in the formulae are defined in Claim 1. <IMAGE>

Description

(54) IMPROVEMENTS IN AND RELATING TO PHENOXYALKANOIC ACIDS AND DERIVATIVES THEREOF USEFUL AS HERBICIDES (71) We, SHELL INTERNATIONALE RESEARCH MAATSCHAPPIJ B.V., a company organized under the laws of the Netherlands, of 30, Carel van Bylandtlaan, The Hague, the Netherlands, do hereby declare the invention for which we pray that a patent may be granted to us, and the method by which it is to be performed to be particularly described in and by the following statement:- 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 invention relates further to a method of eradicating or controlling weeds by 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 chloro-2-methylphenoxy)propionic acid and 2-(2,4-dichlorophenoxy)propionic acid and their alkali metal and dimethylamine salts can be used to combat broadleaved weeds. It is also known that one of the optical isomers of substituted phenoxy propionic acids has a greater herbicidal activity than the other isomer.

The more active isomer is normally obtained by applying optical resolution techniques to the racemate but these techniques are laborious and have also the drawback of producing the less active isomer which is of considerably less use and therefore may have 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 dextrarotatory 2-(2,4-dichlorophenoxy)propionic acid described in British Patent Specification No. 1,114,040.

Thus, the present invention provides a process for the preparation of an isomer of a phenoxy-alkanoic acid derivative having the following general formula and possessing the R or S configuration at the carbon atom marked *:

wherein the or each R independently represents an alkyl group of up to 4 carbon atoms; n is 0 or an integer up to 4; the or each Hal independently represents a halogen atom; m is 0 or an integer up to 5; Kl represents a hydrogen atom, one equivalent of a metal ion, an optionally alkyl and/or alkenyl 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 *:

with a phenol of formula III:

wherein the group X-O- is a group which will leave the molecule and be replaced by a deprotonated phenol of formula III, and Hal, R, m and n have the meanings given for the general formula I, in the presence of a base and under conditions of elevated temperature.

The process according to the present invention is particularly suitable for the preparation of isomers of phenoxy-propionic acid derivatives of the general formula I, i.e., compounds wherein R2 represents a methyl group. Preferably the process is carried out using an S isomer of formula II to produce an R isomer of formula I.

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.SO2.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 arylsulphonyl group, e.g. methane-sulphonyl or para-toluenesulphonyl.

Reaction between the lactic acid derivative II and the phenol III is most suitably carried out at temperatures between 50"C and 200"C, preferably between 130"C and 170"C.

As with all stereospecific processes the reaction conditions must be carefully selected and tested for each particular case to ensure that the optical purity of the required product is unaffected 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 Nethyl-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 a solvent for the reaction, but a different solvent such as tetrahydrofuran or a higher ether may be employed if desired.

The S or R isomer of the lactic acid derivative III used as starting material 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 or 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 *:

wherein X and R' 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, temperatures in the range -5"C to +800C are suitable, room temperature often being convenient. The acid halide or corresponding acid anhydride or halogenated aldehyde is suitably selected from one of the following: V.SO,.Q, V.CO.Q, O(CO.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.

An especially useful starting material which is cheap and readily available, is SH+)-lactic acid i.e. the S isomer of compound IV in which R' is a hydrogen atom.

Esters of this acid may conveniently 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 used as a starting material or converted into any desired lactic acid derivative IV by a transesterification procedure.

It will be appreciated that in the production of compounds of general formula I, wherein R' is other than hydrogen, it may according to the circumstances be convenient to introduce the R' substituent into the starting material IV or, alternatively, it may be desirable to start-with the free acid (R'=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 S4+)-lactic acid, or preferably with S-(-)-ethyl lactate and then to esterify or transesterify the R+)-phenoxy propionic acid or its ethyl ester obtained,.

Good yields may also be obtained starting from S-(-)-linevyl lactate 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 remove the ester grouping at an intermediate stage or during-the last stage in the process, and if desired to convert the acid obtained into the corresponding salt by reacting it with an appropriate base.

Preferably, in the general formula I any alkyl or alkenyl group contains up to 6 carbon atoms, and any aryl or aralkyl group has up to 10 carbon atoms. Unless otherwise specified, a halogen atom is preferably a chlorine or fluorine atom.

The single isomers of formula I wherein R, n, Hal, m and R2 are as defined hereinabove and R1 represents an optionally alkyl substituted ammonium ion, or an optionally substituted alkyl, cycloalkyl, alkenyl, aryl or aralkyl group are believed to be novel compounds, and the invention therefore provides these isomers per se.

Preferably a novel isomer is in the R configuration and preferably R represents a methyl group; n is 0 or 1; Hal represents a chlorine atom; m is 1, 2 or 3; R' represents an ammonium ion substituted by I or 2 alkyl groups of up to 20 carbon atoms, or an alkyl group of up to 12 carbon atoms; and R2 represents a methyl group.

The process according to the invention may be used to produce selective herbicides for cereal crops, which are active against broad-leaved weeds. The invention therefore further provides a herbicidal composition comprising a carrier and, as active ingredient, an isomer having been prepared by the process according to the invention, or a novel isomer according to the invention, and also provides a method of eradicating or controlling broad-leaved weeds at a locus, which comprises applying to the locus a herbicidally effective amount of an isomer or a composition according to the invention.

It may be advantageous to use as herbicides long-chain esters of phenoxy propionic acids since these compounds are oil-soluble which facilitates their handling, in that they can easily be mixed with commercial wild oat herbicides. In our co-pending application No. 32,087/76 (Serial No. 1,586,463) mixtures of R-(+)-phenoxy propionic acid derivatives with certain alanine derivatives have been described and claimed.

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 following examples illustrate the invention.

Example I.

Preparation of R-(+)-2-(4-chloro-2-methylphenoxy)-propionic acid potassium salt (a) S-(-)-ethyl lactate mesylate ([&alpha;]D25=-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 (6.0 mol.) was stirred with 6.0 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 dilute sulphuric acid. It was then washed with water until neutral. 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 [&alpha;]D25 of +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 resulting solid filtered, 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 filtered, washed and dried. The yield of R-(+)-2- (4-chloro-2-methylphenoxy)propionic acid was 83%, m.p. 83-850C and optical rotation [(X]D3= +14.620 (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 [a]024 of +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 were obtained using conventional 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 ([&alpha;]D25=-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 6 litres). The combined organic layers were concentrated and then washed with 2 x 1200 ml water, 2 x 1800 ml I 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 [a]025 of +29.5 (C3, ethanol).

(b) 5 moles of the ester prepared according to III(a) were treated with 5.25 moles of linevol in 1300 ml toluene in the presence of 0.15 mol. concentrated H2SO4. 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: [aS]DS= +19.1 (C3, ethanol).

TABLE I

c o 0 NC - C - route optical rotation Cl H' 3 0+ o I o x - NH2(CH3)2 acid 1(b) + anhydrous HN(CH3)2 23 - +6.90 (C2, ethanol) 0 x = NH3-C(CH3)2-CH2-C(CH3) acid + tertiary-octyl amine 0+ 25 x = NH1-C(CH3)2-(CH2)6-C(CH,)3 acid + amine [a]= +5.60 (C3, ethanol) X C7-C9alkyl acid + linevol a a125- + D - 17.60 (C4, ethanol) x = Nl13Cl12(CH2)7CH= CH(CH2)7'CH, acid + amine [a 2D5= + 340 (C3, ethanol) X = noctyl acid + l-octanol [a]2J'5 = +14.90 (C51 ethanol) a linevol is a mixture of primary C7-C9 alcohols.

Example IV.

According to the procedure described in Example l(b) R-(+)-2-(2,4- dichlorophenoxy)propionic acid was obtained by reacting R--(+)-2-(2,4- dichlorophenoxy)propionic acid ethyl ester with formic acid under reflux conditions in the presence of 2N NCl. The free acid was obtained in 95.5% yield. m.p. 121-122 C and had an [&alpha;]D25.5 of +28 (C1.4, ethanol).

The R-(+)-acid obtained was used to prepare some derivatives by conventional techniques such as the potassium salt, the dimethylammonium salt, the tert.-octylammonium salt as well as the salts obtained by reacting R-(+)-2- (2,4-dichlorophenoxy)propionic acid with NH2-C(CH3)2-(CH2)6-C(CH3)3 and NH2-CH2-(CH2)7-CH=CH-(CH2)7-CH2([&alpha;]D25.5=+3.74 , C3, ethanol).

Example V.

According to the method described in Example I(a) R-(+)-2-(2,4,5trichlorophenoxy)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 120 C. 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.

39-42 C and [&alpha;]D25.5 = + 51.3 (C3, ethanol).

Part of the compound obtained was used to prepare the corresponding 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 of solvent. The linevol ester was obtained as an oil in quantitative yield. [a]02L5 = +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 give S-(-)-linev'yl lactate in 76% yield ([&alpha;]D23=-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 ([&alpha;]D23=-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), 2N 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-2methylphenoxy)propionic acid linevol ester in 68% yield ([&alpha;]D25= +17.17 (C3, ethanol).

Claims (16)

1. WHAT WE CLAIM IS: 1. A process for the preparation of an isomer of a phenoxy-alkanoic acid derivative having the following general formula and possessing the R or S configuration at the carbon atom marked *:

   wherein the or each R independently represents an alkyl group of up to 4 carbon atoms; n isO or an integer up to 4; the or each Hal independently represents a halogen atom; m is 0 or an integer up to 5; R1 represents a hydrogen atom, one equivalent of a metal ion, an optionally alkyl and/or alkenyl 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 Ill possessing the S or R configuration at the carbon atom marked *:

   with a phenol of formula III:

   wherein the group X-O- is a group which will leave the molecule and be replaced by a deprotonated phenol of formula III, and Hal, R, m and n have the meanings given for the general formula I, in the presence of a base and under conditions of elevated temperature.
2. 2. A process as claimed in claim 1, wherein a compound of formula II is used wherein 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. 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. 4. A process as claimed in claim 3, wherein the leaving group X-O- is a methane sulphonyl or para-toluenesulphonyl group.
5. 5. A process as claimed in any one of claims I to 4, wherein R2 represents a methyl group.
6. 6. A process as claimed in any one of claims I to 5, wherein the reaction between 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.
7. 7. A process as claimed in any one of claims I to 6, wherein the base is an alkali metal carbonate or bicarbonate.
8. 8. A process as claimed in any one of claims I to 7, wherein an isomer of a compound according to formula I is prepared wherein any alkyl or alkenyl group contains up to 6 carbon atoms, any aryl or aralkyl group has up to 10 carbon atoms, and any halogen atom is fluorine or chlorine.
9. 9. A process as claimed in claim 1, carried out substantially as described in any one of the Examples herein.
10. 10. An R or S isomer of a compound of the formula I given in claim 1, whenever prepared by a process as claimed in any one of claims I to 9.
11. i I. An isomer of a compound of the general formula:

    possessing the R or S configuration at the carbon atom marked *, wherein the or each R independently represents an alkyl group of up to 4 carbon atoms; n is 0 or an integer up to 4; the or each Hal independently represents a halogen atom; m is0 or an integer up to 5; R' represents an optionally alkyl and/or alkenyl 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.
12. 12. An isomer as claimed in claim 11, having the R configuration.
13. 13. An isomer as claimed in claim 11 or claim 12, wherein R represents a methyl group; n is 0 or 1; Hal represents a chlorine atom; mis 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.
14. 14. An isomer as claimed in claim 11 and named in any one of the Examples herein.
15. 15. A herbicidal composition comprising a carrier and, as active ingredient, at least one isomer as claimed in any one of claims 10 to 14.
16. 16. A method of eradicating or controlling broad-leaved weeds at a locus which comprises applying to the locus a herbicidally active amount of an isomer as claimed in any one of claims 10 to 14 or a composition as claimed in claim 15.