CA1169866A - Process for the manufacture of heterocyclically substituted 4-oxyphenoxy-alkanecarboxylic acid derivatives - Google Patents
Process for the manufacture of heterocyclically substituted 4-oxyphenoxy-alkanecarboxylic acid derivativesInfo
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- CA1169866A CA1169866A CA000383101A CA383101A CA1169866A CA 1169866 A CA1169866 A CA 1169866A CA 000383101 A CA000383101 A CA 000383101A CA 383101 A CA383101 A CA 383101A CA 1169866 A CA1169866 A CA 1169866A
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- halogen
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- alkoxy
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- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE
The preparation of herbicidal compounds of the formula (I) wherein R includes halogen, CF3 and NO2, A includes oxygen and sulfur, R1 is H
or alkyl and Z is a variety of groups including the carboxyl group and its functional derivatives, by reacting compounds of formulae II
(II) and III
The preparation of herbicidal compounds of the formula (I) wherein R includes halogen, CF3 and NO2, A includes oxygen and sulfur, R1 is H
or alkyl and Z is a variety of groups including the carboxyl group and its functional derivatives, by reacting compounds of formulae II
(II) and III
Description
Subject of the present invention is a process for the manufacture of
2-~4'-(benzoxazolyl-2'1-oxy, -kenzothiazolyl-2"-oxy and -kenzimidazolyl-2"-oxy)--phenoxy]-alkanecarboxylic acid derivatives of the formula I
(R) ~ /C-O- ~ O C-Z (I) in which R is halogen, CF3, N02, CN; aIkyl, alkoxy or alkylthio each having from 1 to 4 carbon atoms;
A is O, S, NH or N-(Cl-C4)-alkyl;
~ is H or (Cl-C4)-alkyl, Z is a group of the formLlae " R ~ ~ p ., -C-O-R -C-S-R -C-W / 4 , -C-N-N\ 7 , C-NR , CN, -CH2OH, -CH2-O-C-Rg~
2 C N ~ or -CH2-0-S02-R
m is an integer of from 0 to 2 R2 is H, (Cl-C12)-aIkyl optionally substituted with 1 to 6 halogen atoms, prefer-ably F, Cl, Br, and/or OH, (Cl-C6)-aIkoxy, (Cl-C4)-aIkylthio, (Cl-C6)-aIkoxy--(C2-C6)-alkoxy, halo-(Cl-C2)-alkoxy, methoxyethoxyethoxy, (C1-C4)-aIkylamino, di-(Cl-C4)-alkylamino, phenyl, oxiranyl and/or phenoxy, the latter one optionally mono- or disubstituted with halogen or (Cl~C4)-alkyl; (C5-&)-cycloaIkyl option-ally substituted with halogen or methyl; tC3-C6)-alkenyl, halo-(C3-&)-a~enyl or (C5-C6)-cycloalkenyl; (C3-C4)-aIkinyl optio~ally mono- or disubstituted with (Cl-C6)-alkyl, phenyl, halogen or (Cl-C2)alkoxy; phenyl optionally mono- to tri-substituted with (Cl-C4)-alkyl or -aIkoxy, halogen, N02 or CF3; furfuryl, tetra-hyd-ofurfuryl, a cation equivalent or an organic or inorganic base, or radicals of the formulae
(R) ~ /C-O- ~ O C-Z (I) in which R is halogen, CF3, N02, CN; aIkyl, alkoxy or alkylthio each having from 1 to 4 carbon atoms;
A is O, S, NH or N-(Cl-C4)-alkyl;
~ is H or (Cl-C4)-alkyl, Z is a group of the formLlae " R ~ ~ p ., -C-O-R -C-S-R -C-W / 4 , -C-N-N\ 7 , C-NR , CN, -CH2OH, -CH2-O-C-Rg~
2 C N ~ or -CH2-0-S02-R
m is an integer of from 0 to 2 R2 is H, (Cl-C12)-aIkyl optionally substituted with 1 to 6 halogen atoms, prefer-ably F, Cl, Br, and/or OH, (Cl-C6)-aIkoxy, (Cl-C4)-aIkylthio, (Cl-C6)-aIkoxy--(C2-C6)-alkoxy, halo-(Cl-C2)-alkoxy, methoxyethoxyethoxy, (C1-C4)-aIkylamino, di-(Cl-C4)-alkylamino, phenyl, oxiranyl and/or phenoxy, the latter one optionally mono- or disubstituted with halogen or (Cl~C4)-alkyl; (C5-&)-cycloaIkyl option-ally substituted with halogen or methyl; tC3-C6)-alkenyl, halo-(C3-&)-a~enyl or (C5-C6)-cycloalkenyl; (C3-C4)-aIkinyl optio~ally mono- or disubstituted with (Cl-C6)-alkyl, phenyl, halogen or (Cl-C2)alkoxy; phenyl optionally mono- to tri-substituted with (Cl-C4)-alkyl or -aIkoxy, halogen, N02 or CF3; furfuryl, tetra-hyd-ofurfuryl, a cation equivalent or an organic or inorganic base, or radicals of the formulae
3~
_ 3 _ ~IO~ 80/F 161 ,1 ,1 (C1-C~-alkyl -CH-COOH, -cI~-coo(C1-C4)alkyl or N=
~H or (c1-c4)-a R3 is (C1~C6)-alkyl, phenyl-(C1-c2)-alkyl~ the phenyl 5 radical optionally mono- or disubstituted with ~C1-C4)-alkyl and/or halogen; (C3-C6)-alkenyl or phenyl optionally mono- or disubstituted wi.th ~C1-C4)-al.kyl and/or halogen;
R4 and R5, being identical or different, each are H, (C1-C6)-alkyl, hydroxy-~C1-C6)-alkyl, (C5-C6)-cycloal]cyl 10 or phenyl optionally mono- to trisubstituted with (C1-C4)-alkyl or ~alkoxy, halogen or CE'3; with the proviso that R4 and R5 together are not phenyl; or togethe.r form a methylene chain havi.ng 2, 4 or 5 members, where one CH2 group can be substituted by O, NH or N(CE~3);
15 R6 is H or CH3;
R7 is H, CH3 ~ ~2 5 8 i~ El, CH3, C2H5 or phenyl;
Rg is (C1-C6)-alkyl optionally mono- to trisubsti.tutecl w.ith halogen, cyclopropyl, (C3-C6)-alkenyl, phenyl, (C1-C4)-20 alkylphenyl or -alkoxyphenyl, halophenyl, trifluoromethyl-phenyl or nitrophenyl; and R10 is (C1--C~)-alkyl or phenyl optionally mono-- or di-substituted with halogen, CF3, NO2 or (C1-C~)-alkyl.; whi.ch comprises reacting phenols of the formula II
R
HO ~ ~O-CH-Z ~II) 30 with compounds of the formula III
(R)m ~ ~ ( )n 11 (III) in which l fj~3~
n is 1 or 2, and Rll is an aliphaticl cycloaliphatic, araliphatic or aromatic group, in the presence of an acid binding agent.
The compo~mds of the formula I are known for example from German Offenlegungsschriften Nos. 2,640,730; 2,914,300 and 3,018,003. They are distinguished by an excellent herbicidal effect especially against weed grasses.It is known that the compounds of the formula I can be prepared for example by reaction of corresponding phenols of the formula II with 2-halobenz-oxazoles, 2-halobenzothiazoles and 2-halobenzimidazoles of the formula IV
(R) ~ \ ~ Hal (IV) (Hal = Cl or ~r). However, this reaction has the disadvantage of requiri.ng relatively long reaction times ~except if oxazole is used as reactant). For exaTnple, in the reaction of 2-(4'-hydroxyphenoxy)-propionic acid ethyl ester with 2-chlorobenzothiazole and potassium carbonate as base additive in acetonitrile, an 88.5 % yield of Z-[4'-(benzothiazol-2"-yl-oxy)-phenoxy]-propionic acid ethyl ester is obtained after refluxing for 30 hours. Because of these relatively drastic reaction conditions, paTtial saponification of the ester group Z in the phenol compound II and the final products I occurs with formation of the corresponding carboxylic acids. Under the above reaction conditions, irreversible alterations of the substituent Z of the other compoundsof the formulae I and II cannot be excluded, either.
In principle, all compounds of the formula I can be prepared according to the process of the invention. Preferably, the process is used for the manufacture of compounds of the formula I where R is F, Cl, Br, CF3 or N02 in 6-position,
_ 3 _ ~IO~ 80/F 161 ,1 ,1 (C1-C~-alkyl -CH-COOH, -cI~-coo(C1-C4)alkyl or N=
~H or (c1-c4)-a R3 is (C1~C6)-alkyl, phenyl-(C1-c2)-alkyl~ the phenyl 5 radical optionally mono- or disubstituted with ~C1-C4)-alkyl and/or halogen; (C3-C6)-alkenyl or phenyl optionally mono- or disubstituted wi.th ~C1-C4)-al.kyl and/or halogen;
R4 and R5, being identical or different, each are H, (C1-C6)-alkyl, hydroxy-~C1-C6)-alkyl, (C5-C6)-cycloal]cyl 10 or phenyl optionally mono- to trisubstituted with (C1-C4)-alkyl or ~alkoxy, halogen or CE'3; with the proviso that R4 and R5 together are not phenyl; or togethe.r form a methylene chain havi.ng 2, 4 or 5 members, where one CH2 group can be substituted by O, NH or N(CE~3);
15 R6 is H or CH3;
R7 is H, CH3 ~ ~2 5 8 i~ El, CH3, C2H5 or phenyl;
Rg is (C1-C6)-alkyl optionally mono- to trisubsti.tutecl w.ith halogen, cyclopropyl, (C3-C6)-alkenyl, phenyl, (C1-C4)-20 alkylphenyl or -alkoxyphenyl, halophenyl, trifluoromethyl-phenyl or nitrophenyl; and R10 is (C1--C~)-alkyl or phenyl optionally mono-- or di-substituted with halogen, CF3, NO2 or (C1-C~)-alkyl.; whi.ch comprises reacting phenols of the formula II
R
HO ~ ~O-CH-Z ~II) 30 with compounds of the formula III
(R)m ~ ~ ( )n 11 (III) in which l fj~3~
n is 1 or 2, and Rll is an aliphaticl cycloaliphatic, araliphatic or aromatic group, in the presence of an acid binding agent.
The compo~mds of the formula I are known for example from German Offenlegungsschriften Nos. 2,640,730; 2,914,300 and 3,018,003. They are distinguished by an excellent herbicidal effect especially against weed grasses.It is known that the compounds of the formula I can be prepared for example by reaction of corresponding phenols of the formula II with 2-halobenz-oxazoles, 2-halobenzothiazoles and 2-halobenzimidazoles of the formula IV
(R) ~ \ ~ Hal (IV) (Hal = Cl or ~r). However, this reaction has the disadvantage of requiri.ng relatively long reaction times ~except if oxazole is used as reactant). For exaTnple, in the reaction of 2-(4'-hydroxyphenoxy)-propionic acid ethyl ester with 2-chlorobenzothiazole and potassium carbonate as base additive in acetonitrile, an 88.5 % yield of Z-[4'-(benzothiazol-2"-yl-oxy)-phenoxy]-propionic acid ethyl ester is obtained after refluxing for 30 hours. Because of these relatively drastic reaction conditions, paTtial saponification of the ester group Z in the phenol compound II and the final products I occurs with formation of the corresponding carboxylic acids. Under the above reaction conditions, irreversible alterations of the substituent Z of the other compoundsof the formulae I and II cannot be excluded, either.
In principle, all compounds of the formula I can be prepared according to the process of the invention. Preferably, the process is used for the manufacture of compounds of the formula I where R is F, Cl, Br, CF3 or N02 in 6-position,
-4-;9f3~
5 - HOE 80/F 161 m is 0 or 1, R1 is methyl and Z is -COOR2.
When using optically active 2-(4'-hydroxyphenoxy)-; 5 alkanecarboxylic acid esters of the formula II as starting substances, optically active ~inal products as descrihed for example in German OffenleguncJsschrift No. 2,758,002 are obtained.
Irhe phenols of the ~ormula IX are known from the 10 literature (for example J. Org~ Chem. 39, 214 (1974)) orcan be prepared in ar1alogy to known processes. The compounds of the formula III can be manufactured according to known processes, for example from the corresponding 2~
mercartobenzoxazoles or 2-mercaptohenzothiazoles by alkyla-15 tiOI1 and su~se~uent oxidation with potassium permanganate,hydrogen pero~ide or organic peracids (see J. Chem. Soc.
1949, 3311; Eur. 3. Med. Chem. 1378, 171; J. Heterocycl.
Chem. 13, 491 (1976); Chem Pharm. Bull. 17, 1958 (1969)).
Because of the importance of the compounds I as plant 20 protecting agents, an improved manufacturing process was in great demand. The process of the invention avoids the disadvantages described above; after a relatively short reaction time it supp]:ies the compounds of the formula I
with high yields and in good purity, without adversely 25 affecting the functional groups present in the radical Z.
This was surprising and not to he expected from the state o~ the art. Although the reaction of 2-alkylsulfonylbenzo-thiazole derivatives with aliphatic alcohols, primary or secondary amines or CH-acidic compounds is known (see J.
30 Chem. Soc. 1~49, 3311; J. Heterocycl. Chem. 13, 491 (1976);
Eur. J. Med. Chem. 1978, 171), corresponding reactions with phenols so ar have not been described.
In principle~the radical R11 may be any aliphatic, cycloaliphatic, araliphatic or aromatic radical; advantageous-35 ly, however, startin~ substances are used in which Rl1 islow molecular weigl1t alkyl, alkenYl, alkoxyalk~yl or carb-- `
G'&~
alkoxyalkyl, or phenyl or benzyl, because such compounds are easy and cheap to obtain. Examples are: 2-methylsulfonyl-benzothiazole or -benzoxazole, 2-ethylsulfonyl-benzothiazole or -benzoxazole, 6-chloro-2-methylsulfonylbenzo-thiazole or -benzoxazole, 6-bromo-2-methylsulfonyl-benzothiazole, 6-chloro-2-methylsulfinyl-benzothiazole, ethyl(benzothiazol-2-y])-sulfonyl acetate, methyl~6-chlorobenzothiazol-2-yl)-sulfonyl acetate or 6-chloro-2-phenylsulfonyl-benzothiazole or -benzoxazole.
In the reaction of the invention, the nucleofuge -S(O)n-Rll group is replaced by the deprotonated phenol component. By contrast, when 6-chloro-2-methylsulfonylbenzothiazole is reacted with a phenol of the formula II with addition of potassium carbonate, potassium methylsulfinate is obtained in nearly quantitative yield, in addition to the intended compound I and potassium bicarbonate. The molar ratio of the reactants II and III is not critical and may be varied within wide limits. Since, however, separation of unreacted starting material requires additional operations, equimolar amounts or an excess of up to 10 % of compound II at most are preferabl~ used.
The process of the invention may be carried out in the presence or absence of solvents, preferably however in the presence of a solvent inert under the reaction conditions. Preferably polar aprotic solvents are used, for example acid amides such as dimethyl formamide, dimethyl acetam:ide or N-methylpyrrolidone, furthermore dimethyl sulfoxide, nitriles such as acetonitrile or propionitrile, ketones such as acetone, methylethylketone or methyliso-butylketone, ethers such as tetrahydrofuran or dioxan, or aromatic or aliphatic hydrocarbons such as chlorobenzene or cyclohexane.
Suitable acid binding agents are the usual organic bases, for example tertiary amines such as triethylamine, and especially inorganic bases such as alkali metal carbonates 31f~3 (Na2C03, K2C03). Ihey are used in at least equimolar amounts (relative to II), or in an exoe ss of frcm 5 to 20 ~.
rme prooe ss is advantageously carried out as follows: The compound of the formula II is heated with the basic compound in a solvent first to reaction temperature, thus forming at least in part the salt of the compound II. Subse-quently the heterocyclic compound of the formula III, optionally dissolved in the same solvent, is added, and the batch is stirred at elevated temperature until the reaction is complete. The reactants may also be introduced into the reactor in another order.
m e reaction temperature may be varied within a wide range of fram 20 to 160C. Preferably it is between 40 and 85C, optionally at the boiling point of the solvent used. me reaction time depends on the tem~erature, the solvent used and the ratio of II to III; it is reduced with rising temperature and in-creasing excess of II. me reaction is generally complete after 20 minutes to 8 hours. It is advantageous although not necessary to carry it out u~der a protec-tive gas; nitrogen being preferred as inert gas.
After completion of the reaction the salt formed is separated by filtra-tion and the solvent is distilled off. If necessary, excess II is removed by basic extraction.
2Q me compounds of the formula I obtained may be further purified by dis-tillation or chromatography; hcwever, because of the high purity degree of the products, this operation generally can be omitted.
The follcwing examples illustrate the invention.
EXAMPIES OF PREPAR~TION
Example 1 2-[4'-(6"-chlorokenzothiazol-2"-yl-oxy)-pheno~y]-propionic acid ethyl_ester 21 g (0.1 mol) of 2-(4'-hydroxyphenoxy)-propionic acid ethyl ester were ~ ~ `
~ 3~ ~ ~
refluxed for 1 1/2 hours with 16.6 g (0.12 mol) of potassium carbonate in 150 cc of aoe tonitrile. 24.75 g (0.1 mol) of 6-chloro-2-methylsulfonyl-benzothiazole dissolved in 100 cc of aoe tonitrile were added, and the batch was refluxed for a further 5 hours. The hot solution was filtered off frcm the salt portion and the solvent was distilled off. me remaining residue was dissolved in 200 cc of toluene, the solution was washed se~eral times with dilute NaHQ03 solu-tion, and dried over Na2SO4. After having distilled off the toluene, 37 g (98 ~ of theory) of 2-[4'-(6"-chlorobenzothiazol-2"-yl-oxy)-phenoxy]-propionic acid ethyl ester, m.p. 54 & were obtained.
Cl S~ ~ O-CH-COOC2H5 me salt residue (weight after drying: 21.85 g) was extracted several times with hot ethanol. After evaporation of the extracts, 11.3 g (97 % of th.) of potas-sium methylsulfinate were obtained.
In analogous manner, there were obta med:
Exam~
32.2 y (94 % of th.) of 2-[4'-(benzothiazol-2"-yl-oxy)-phenoxy~-pro-pionic acid ethyl ester having a boiling point of 201-204C/0.13 mbar ~ ~ O ~ ~O-CH-COOC2H5 after a reaction time of 6 hours with the use of 31 g (Ool mol) of 2-phen~l~
sulfonyl-benzothiazole.
Exa~lple 3 30.5 g (84 % of th.) of 2-[4'-(6"-chlorobenzothiazol-2"-yl-oxy)--p~enoxy]-propionic acid methyl ester having a boiling point of 226-228C/0.13 mbar 3~6~
Cl \\r 0 ~ H3 after a reaction time of 6 hours with the use of 19.6 g tO.l mol) of 2-(4'-hydroxyphenoxy)-propionic acid methyl ester and 23.2 g (0.1 mol) of 6-chloro-2-methylsulfinylbenzothiazole.
Exam~le 4 ,.
31.8 g (88.6 % of th.) of 2-[4'-(6'-chlorobenzoxazol-2"-yl-oxy)-phenoxy]-propionic acid ethyl ester having a boiling point of 81 - 82C
C~ >-- ~ O-CHCOOC2H5 after a reaction time of 30 minutes with the use of 23.2 g (0.1 mol) of
When using optically active 2-(4'-hydroxyphenoxy)-; 5 alkanecarboxylic acid esters of the formula II as starting substances, optically active ~inal products as descrihed for example in German OffenleguncJsschrift No. 2,758,002 are obtained.
Irhe phenols of the ~ormula IX are known from the 10 literature (for example J. Org~ Chem. 39, 214 (1974)) orcan be prepared in ar1alogy to known processes. The compounds of the formula III can be manufactured according to known processes, for example from the corresponding 2~
mercartobenzoxazoles or 2-mercaptohenzothiazoles by alkyla-15 tiOI1 and su~se~uent oxidation with potassium permanganate,hydrogen pero~ide or organic peracids (see J. Chem. Soc.
1949, 3311; Eur. 3. Med. Chem. 1378, 171; J. Heterocycl.
Chem. 13, 491 (1976); Chem Pharm. Bull. 17, 1958 (1969)).
Because of the importance of the compounds I as plant 20 protecting agents, an improved manufacturing process was in great demand. The process of the invention avoids the disadvantages described above; after a relatively short reaction time it supp]:ies the compounds of the formula I
with high yields and in good purity, without adversely 25 affecting the functional groups present in the radical Z.
This was surprising and not to he expected from the state o~ the art. Although the reaction of 2-alkylsulfonylbenzo-thiazole derivatives with aliphatic alcohols, primary or secondary amines or CH-acidic compounds is known (see J.
30 Chem. Soc. 1~49, 3311; J. Heterocycl. Chem. 13, 491 (1976);
Eur. J. Med. Chem. 1978, 171), corresponding reactions with phenols so ar have not been described.
In principle~the radical R11 may be any aliphatic, cycloaliphatic, araliphatic or aromatic radical; advantageous-35 ly, however, startin~ substances are used in which Rl1 islow molecular weigl1t alkyl, alkenYl, alkoxyalk~yl or carb-- `
G'&~
alkoxyalkyl, or phenyl or benzyl, because such compounds are easy and cheap to obtain. Examples are: 2-methylsulfonyl-benzothiazole or -benzoxazole, 2-ethylsulfonyl-benzothiazole or -benzoxazole, 6-chloro-2-methylsulfonylbenzo-thiazole or -benzoxazole, 6-bromo-2-methylsulfonyl-benzothiazole, 6-chloro-2-methylsulfinyl-benzothiazole, ethyl(benzothiazol-2-y])-sulfonyl acetate, methyl~6-chlorobenzothiazol-2-yl)-sulfonyl acetate or 6-chloro-2-phenylsulfonyl-benzothiazole or -benzoxazole.
In the reaction of the invention, the nucleofuge -S(O)n-Rll group is replaced by the deprotonated phenol component. By contrast, when 6-chloro-2-methylsulfonylbenzothiazole is reacted with a phenol of the formula II with addition of potassium carbonate, potassium methylsulfinate is obtained in nearly quantitative yield, in addition to the intended compound I and potassium bicarbonate. The molar ratio of the reactants II and III is not critical and may be varied within wide limits. Since, however, separation of unreacted starting material requires additional operations, equimolar amounts or an excess of up to 10 % of compound II at most are preferabl~ used.
The process of the invention may be carried out in the presence or absence of solvents, preferably however in the presence of a solvent inert under the reaction conditions. Preferably polar aprotic solvents are used, for example acid amides such as dimethyl formamide, dimethyl acetam:ide or N-methylpyrrolidone, furthermore dimethyl sulfoxide, nitriles such as acetonitrile or propionitrile, ketones such as acetone, methylethylketone or methyliso-butylketone, ethers such as tetrahydrofuran or dioxan, or aromatic or aliphatic hydrocarbons such as chlorobenzene or cyclohexane.
Suitable acid binding agents are the usual organic bases, for example tertiary amines such as triethylamine, and especially inorganic bases such as alkali metal carbonates 31f~3 (Na2C03, K2C03). Ihey are used in at least equimolar amounts (relative to II), or in an exoe ss of frcm 5 to 20 ~.
rme prooe ss is advantageously carried out as follows: The compound of the formula II is heated with the basic compound in a solvent first to reaction temperature, thus forming at least in part the salt of the compound II. Subse-quently the heterocyclic compound of the formula III, optionally dissolved in the same solvent, is added, and the batch is stirred at elevated temperature until the reaction is complete. The reactants may also be introduced into the reactor in another order.
m e reaction temperature may be varied within a wide range of fram 20 to 160C. Preferably it is between 40 and 85C, optionally at the boiling point of the solvent used. me reaction time depends on the tem~erature, the solvent used and the ratio of II to III; it is reduced with rising temperature and in-creasing excess of II. me reaction is generally complete after 20 minutes to 8 hours. It is advantageous although not necessary to carry it out u~der a protec-tive gas; nitrogen being preferred as inert gas.
After completion of the reaction the salt formed is separated by filtra-tion and the solvent is distilled off. If necessary, excess II is removed by basic extraction.
2Q me compounds of the formula I obtained may be further purified by dis-tillation or chromatography; hcwever, because of the high purity degree of the products, this operation generally can be omitted.
The follcwing examples illustrate the invention.
EXAMPIES OF PREPAR~TION
Example 1 2-[4'-(6"-chlorokenzothiazol-2"-yl-oxy)-pheno~y]-propionic acid ethyl_ester 21 g (0.1 mol) of 2-(4'-hydroxyphenoxy)-propionic acid ethyl ester were ~ ~ `
~ 3~ ~ ~
refluxed for 1 1/2 hours with 16.6 g (0.12 mol) of potassium carbonate in 150 cc of aoe tonitrile. 24.75 g (0.1 mol) of 6-chloro-2-methylsulfonyl-benzothiazole dissolved in 100 cc of aoe tonitrile were added, and the batch was refluxed for a further 5 hours. The hot solution was filtered off frcm the salt portion and the solvent was distilled off. me remaining residue was dissolved in 200 cc of toluene, the solution was washed se~eral times with dilute NaHQ03 solu-tion, and dried over Na2SO4. After having distilled off the toluene, 37 g (98 ~ of theory) of 2-[4'-(6"-chlorobenzothiazol-2"-yl-oxy)-phenoxy]-propionic acid ethyl ester, m.p. 54 & were obtained.
Cl S~ ~ O-CH-COOC2H5 me salt residue (weight after drying: 21.85 g) was extracted several times with hot ethanol. After evaporation of the extracts, 11.3 g (97 % of th.) of potas-sium methylsulfinate were obtained.
In analogous manner, there were obta med:
Exam~
32.2 y (94 % of th.) of 2-[4'-(benzothiazol-2"-yl-oxy)-phenoxy~-pro-pionic acid ethyl ester having a boiling point of 201-204C/0.13 mbar ~ ~ O ~ ~O-CH-COOC2H5 after a reaction time of 6 hours with the use of 31 g (Ool mol) of 2-phen~l~
sulfonyl-benzothiazole.
Exa~lple 3 30.5 g (84 % of th.) of 2-[4'-(6"-chlorobenzothiazol-2"-yl-oxy)--p~enoxy]-propionic acid methyl ester having a boiling point of 226-228C/0.13 mbar 3~6~
Cl \\r 0 ~ H3 after a reaction time of 6 hours with the use of 19.6 g tO.l mol) of 2-(4'-hydroxyphenoxy)-propionic acid methyl ester and 23.2 g (0.1 mol) of 6-chloro-2-methylsulfinylbenzothiazole.
Exam~le 4 ,.
31.8 g (88.6 % of th.) of 2-[4'-(6'-chlorobenzoxazol-2"-yl-oxy)-phenoxy]-propionic acid ethyl ester having a boiling point of 81 - 82C
C~ >-- ~ O-CHCOOC2H5 after a reaction time of 30 minutes with the use of 23.2 g (0.1 mol) of
6-chloro-2-methylsulfonyl-benzoxazole.
Example 5 36.5 g (94 ~ of th.) of D-(*~-2-~4-(6-chlorobenzothiazol-2-yl-oxy)-phenoxy]--propionic acid ethyl ester having a melting point of 53C and [o~]20 of 30.2 (c = lm, chloroform) Cl ~ ~ O-CU-COOC2~15 after a reaction time of 6 hours with the use of 21 g (0.1 mol) of D-(*)-2-(4'-hydroxyphenoxy)-propionicacid ethyl ester and 26~2 g (0.1 mol) of 6-chloro-- 2-ethylsulfonylbenzothiazole.
, ;'-" ' ' :
Example 5 36.5 g (94 ~ of th.) of D-(*~-2-~4-(6-chlorobenzothiazol-2-yl-oxy)-phenoxy]--propionic acid ethyl ester having a melting point of 53C and [o~]20 of 30.2 (c = lm, chloroform) Cl ~ ~ O-CU-COOC2~15 after a reaction time of 6 hours with the use of 21 g (0.1 mol) of D-(*)-2-(4'-hydroxyphenoxy)-propionicacid ethyl ester and 26~2 g (0.1 mol) of 6-chloro-- 2-ethylsulfonylbenzothiazole.
, ;'-" ' ' :
Claims (7)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A process for the manufacture of 2-(4'-(benzoxazolyl-2"-oxy, -benzothiazolyl-2"-oxy and -benzimidazolyl-2"-oxy)-phenoxy]-alkanecarboxylic acid derivatives of the formula I
(I) in which R is halogen, CF3, NO2, CN; alkyl, alkoxy or alkylthio each having from 1 to 4 carbon atoms;
A is O, S, NH or N-(C1-C4)-alkyl;
R1 is H or (C1-C4)-alkyl, Z is a group of the formula , , , , , CN, -CH2OH, , , or -CH2-O-SO2-R10;
m is an integer of from 0 to 2 R2 is H, (C1-C12)-alkyl optionally substituted with 1 to 6 halogen atoms, and/or OH, (C1-C6)-alkoxy, (C1-C4)-alkylthio, (C1-C6)-alkoxy-(C2-C6)-alkoxy, halo-(C1-C2)-alkoxy, methoxyethoxyethoxy, (C1-C4)-alkylamino, di-(C1-C4)-alkylamino, phenyl, oxiranyl and/or phenoxy, the latter one optionally mono- or disubstituted with halogen or (C1-C4)-alkyl; (C5-C6)-cycloalkyl optionally substituted with halogen or methyl; (C3-C6)-alkenyl, halo-(C3-C6)-alkenyl or (C5-C6)-cycloalkenyl;
(C3-C4)-alkinyl optionally mono- or disubstituted with (C1-C6)-alkyl, phenyl, halogen or (C1-C2)-alkoxy; phenyl optionally mono- to tri-substituted with (C1-C4)-alkyl or -alkoxy, halogen, NO2 or CF3; furfuryl, tetrahydrofurfuryl, a cation equivalent of an organic or inorganic base, or radicals of the formulae , or N = R3 is (C1-C6)-alkyl, phenyl-(C1-C2)-alkyl, the phenyl radical optionally mono- or disubstituted with (C1-C4)-alkyl and/or halogen; (C3-C6)-alkenyl or phenyl optionally mono- or disubstituted with (C1-C4)-alkyl and/or halogen;
R4 and R5, being identical or different, each are H, (C1-C6)-alkyl, hydroxy--(C1-C6)-alkyl, (C5-C6)-cycloalkyl or phenyl optionally mono- to trisubstituted with (C1-C4)-alkyl or -alkoxy, halogen or CF3;
with the proviso that R4 and R5 together are not phenyl; or together form a methylene chain having 2, 4 or 5 members, where one CH2 group can be substituted by O, NH or N(CH3);
R6 is H or CH3;
R7 is H, CH3 or C2H5;
R8 is H, CH3, C2H5 or phenyl;
R9 is (C1-6)-alkyl optionally mono- to trisubstituted with halogen, cyclopropyl, (C3-6)-alkenyl, phenyl, (C1-C4)-alkylphenyl or -alkoxyphenyl, halophenyl, tri-fluoromethylphenyl or nitrophenyl; and R10 is (C1-C4)-alkyl or phenyl optionally mono- or disubstituted with halogen, CF3, NO2 or (C1-C4)-alkyl; which comprises reacting phenols of the formula II
(II) with compounds of the formula III
(III) in which n is 1 or 2, and R11 is an aliphatic, cycloaliphatic, araliphatic or aromatic group, in the presence of an acid binding agent.
(I) in which R is halogen, CF3, NO2, CN; alkyl, alkoxy or alkylthio each having from 1 to 4 carbon atoms;
A is O, S, NH or N-(C1-C4)-alkyl;
R1 is H or (C1-C4)-alkyl, Z is a group of the formula , , , , , CN, -CH2OH, , , or -CH2-O-SO2-R10;
m is an integer of from 0 to 2 R2 is H, (C1-C12)-alkyl optionally substituted with 1 to 6 halogen atoms, and/or OH, (C1-C6)-alkoxy, (C1-C4)-alkylthio, (C1-C6)-alkoxy-(C2-C6)-alkoxy, halo-(C1-C2)-alkoxy, methoxyethoxyethoxy, (C1-C4)-alkylamino, di-(C1-C4)-alkylamino, phenyl, oxiranyl and/or phenoxy, the latter one optionally mono- or disubstituted with halogen or (C1-C4)-alkyl; (C5-C6)-cycloalkyl optionally substituted with halogen or methyl; (C3-C6)-alkenyl, halo-(C3-C6)-alkenyl or (C5-C6)-cycloalkenyl;
(C3-C4)-alkinyl optionally mono- or disubstituted with (C1-C6)-alkyl, phenyl, halogen or (C1-C2)-alkoxy; phenyl optionally mono- to tri-substituted with (C1-C4)-alkyl or -alkoxy, halogen, NO2 or CF3; furfuryl, tetrahydrofurfuryl, a cation equivalent of an organic or inorganic base, or radicals of the formulae , or N = R3 is (C1-C6)-alkyl, phenyl-(C1-C2)-alkyl, the phenyl radical optionally mono- or disubstituted with (C1-C4)-alkyl and/or halogen; (C3-C6)-alkenyl or phenyl optionally mono- or disubstituted with (C1-C4)-alkyl and/or halogen;
R4 and R5, being identical or different, each are H, (C1-C6)-alkyl, hydroxy--(C1-C6)-alkyl, (C5-C6)-cycloalkyl or phenyl optionally mono- to trisubstituted with (C1-C4)-alkyl or -alkoxy, halogen or CF3;
with the proviso that R4 and R5 together are not phenyl; or together form a methylene chain having 2, 4 or 5 members, where one CH2 group can be substituted by O, NH or N(CH3);
R6 is H or CH3;
R7 is H, CH3 or C2H5;
R8 is H, CH3, C2H5 or phenyl;
R9 is (C1-6)-alkyl optionally mono- to trisubstituted with halogen, cyclopropyl, (C3-6)-alkenyl, phenyl, (C1-C4)-alkylphenyl or -alkoxyphenyl, halophenyl, tri-fluoromethylphenyl or nitrophenyl; and R10 is (C1-C4)-alkyl or phenyl optionally mono- or disubstituted with halogen, CF3, NO2 or (C1-C4)-alkyl; which comprises reacting phenols of the formula II
(II) with compounds of the formula III
(III) in which n is 1 or 2, and R11 is an aliphatic, cycloaliphatic, araliphatic or aromatic group, in the presence of an acid binding agent.
2. A process as claimed in claim 1 wherein Z is a group of the formula -COOR2 wherein R2 is (C1-C12)-alkyl optionally substituted with 1 to 6 halogen atoms selected from fluorine, chlorine and bromine, or with hydroxyl.
3. A process as claimed in claim 1 or 2 wherein R is F, Cl, Br, CF3 or NO2 in the 6-position, m is 0 or 1, R1 is methyl, and Z is -COOR2.
4. A process as claimed in claim 1 wherein A is O or S, R is F, Cl, Br, CF3 or NO2 in the 6-position, m is 0 or 1, R1 is methyl, and Z is -COOR2 wherein R2 is lower alkyl.
5. A process as claimed in claim 1 wherein A is S, R is 6-Cl, m is 1, R1 is methyl, and Z is -COOC2H5.
6. A process as claimed in claim 1 wherein A is 0, R is 6-Cl, m is 1, R1 is methyl, and Z is -COOC2H5.
7. A process as claimed in claim 5 wherein the compound of formula (II) employed is D-(+)-2-(4'-hydroxyphenoxy)-propionic acid ethyl ester, whereby D-(+)-2-[4-(6-chlorobenzothiazol-2-yloxy)-phenoxy]-propionic acid ethyl ester is obtained.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000383101A CA1169866A (en) | 1981-08-03 | 1981-08-03 | Process for the manufacture of heterocyclically substituted 4-oxyphenoxy-alkanecarboxylic acid derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000383101A CA1169866A (en) | 1981-08-03 | 1981-08-03 | Process for the manufacture of heterocyclically substituted 4-oxyphenoxy-alkanecarboxylic acid derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1169866A true CA1169866A (en) | 1984-06-26 |
Family
ID=4120598
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000383101A Expired CA1169866A (en) | 1981-08-03 | 1981-08-03 | Process for the manufacture of heterocyclically substituted 4-oxyphenoxy-alkanecarboxylic acid derivatives |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA1169866A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5442074A (en) * | 1992-09-16 | 1995-08-15 | Bayer Aktiengesellschaft | Herbicidal fluorobenzothiazolyloxyacetamides |
-
1981
- 1981-08-03 CA CA000383101A patent/CA1169866A/en not_active Expired
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5442074A (en) * | 1992-09-16 | 1995-08-15 | Bayer Aktiengesellschaft | Herbicidal fluorobenzothiazolyloxyacetamides |
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