GB2188931A - Halogenated heterocyclic ether herbicides - Google Patents

Description

GB 2 188 931 A 1

SPECIFICATION

Halogenated heterocyclic ether herbicides The present invention relates to new halogenated heterocyclic ethers, to their preparation, to their use as 5 herbicides and plant growth regulators, and to formulated compositions containing them.

The present invention provides novel compounds of the formula 1 W-O-CH,-R 10 wherein R is 3-halo-2-thieny], 5-halo-3,4-dihydro-2H-pyran-6-yi, 2-halo-l -cyclopenten-l-yi, or 2-halo-l cyclohexen-l -yi in which halo is chloro or fluoro, and R' is the residue of a non-aromatic oxygen heterocyclic alcohol (R'OH), R' containing up to 16 carbon atoms, and including a monocyclic, bridged-cyclic or spirocyclic ring-system of 5 to 11 carbon atoms, one or more of which is an oxygen atom and the remainder of which are carbon atoms. The compounds are useful as herbicides for controlling (combatting) undesirable or unwanted 15 plants.

The non-aromatic oxygen heterocyclic group, W, represents the residue from known non-aromatic oxygen heterocyclic alcohols. For example, R' is a group selected from a) 20 0 1 25 r X Y 30 whereinWisa methyl orethy[group; Xisasinglebond or-CH(CH3)2-,Yisa single bond or-CH27-withthe proviso that both X and Y are not a single bond; and Z is H, or an optionally substituted alkyl group containing 1 to 4 carbon atoms; 35 b) R 4 R 5 R 3 R 6 2 R 7 40 R 2' CH 18 0 R 45 wherein each R 2 individually represents a hydrogen atom, a halogen atom, an optionally substituted alkyl, cycloalkyl or aryl group, each containing up to 6 (chain/ring) carbon atoms or two R 2 together represent an alkylene moiety of up to 6 carbon atoms, R3, R 4, R5 and R' each individually represents a hydrogen atom, a halogen atom having an atomic number of from 9 to 35, inclusive, an optionally substituted alky], alkoxy, alkylthio or aryl group of up to 6 carbon atoms or one of R 3 and R 4 and one of R' and R' together represent a 50 carbon-carbon bond or an epoxide moiety; R' and R 8 each represents a hydrogen atom or an optionally substituted alkyl group of up to 6 carbon atoms; or c) 4 5 55 R 3- R 6 Z 1 -CH R 7 d 60 Y \ X CH 2 2 GB 2 188 931 A 2 wherein R 3, R 4, R5, R' and R 7 each individually is a hydrogen atom or an alkyl group containing from 1 to 4 carbon atoms, W' is an oxygen atom or -CH27; X' is an oxygen atom or-CH2-; Y1 is a carbon-carbon bond, or an oxygen atom, -CH-2, _C2H47-, or-CHR9- in which R' is alkoxymethyl group containing from 1 to 4 carbon atoms in the alkoxy portion thereof; Z1 is a carbon-carbon bond, an oxygen atom, -CH2-, or-C2H4-; with the proviso that no two adjacent of W, X', Y1 and Z1 are simultaneously either oxygen atoms or-C2H47- and the 5 sum of the ring atoms in W, W, Y1 and Z1 is an integer of from 3 to 5.

Optional substituents in formulae 1, (a), (b) and (c) include 1 or more atoms of chlorine, fluorine and bromine.

Examples of compounds within the scope of the invention include 2-((3fluoro-2-thienyi)methoxy)-1,4- diethyi-7-oxabicyclo[2.2.1 1heptane, 2-((5-chloro-3,4dihydro-2H-pyran-6- yi)-methoxymethyi)-2- 10 ethyl oxaspi ro [4.51deca n e, 2-((2-fluoro-l-cyclohexen-lyi)methoxymethyi)-2-ethyitetrahydrofuran, 2-Q2fiuoro-l-cyciopenten-lyi)methoxymethyi)-2,5-dimethyitetrahydrofuran, and 2-((5-fluoro-3, 4dihydro-2Hpyran-6-yi)-methoxy)-1-methy]-4-isopropenyi-7-oxab icyclo[2.2. 1]-heptane.

The compounds of formula 1 may exhibit geometrical and optical isomerism and can be prepared in geometrical andlor opticaily-active forms, and as racemates. The various individual optically and geometrical 15 combinations of the materials of the invention usually have some different herbicidal properties. The present invention contemplates all the herbicidally active forms resulting from synthesis and deliberately formed mixtures.

The preferred non-aromatic oxygen-heterocyles providing the group R' include those of formula (a) in which (1) X is a single bond, Y is -CHT--, W is methyl and Z is a hydrogen atom or a 1-methylethyl group orW 20 and Z each is an ethyl or methyl group or (2) X is -C(CH3)7-, Y is -CHz-, and Z is a hydrogen atom. Preferably X is a single bond, Y is -CH2-, W is a methyl group and Z is a 1-methylethyl group or W and Z each is an ethyl or methyl group; those of formula (b) is which each R 2 independently is a hydrogen atom ora methyl group orthe two R % taken togetherform a pentamethylene group, R 3, R', R', R'and R' are hydrogen atoms and R 7 is a hydrogen 25 atom, a methyl or ethyl group; preferably each R 2 is a methyl group and R7 is a methyl or, especially, an ethyl group; and those of formula (c) in which W' is an oxygen atom or-CH2-, X' is an oxygen atom or-CH2-, Y1 is an oxygen atom, -CH27,-C2H47- or-CHR'- in which R' is methoxymethy], Z1 is an oxygen atom or-CH2-, and the sum of the ring atoms in W, W, Y1 and Z1 is an integer of from 3 to 5; preferably, (1) W' and Z1 are each -CHz- 30 and one of X' and Y1 is -CH2- and the other is an oxygen atom or (2) W' is -CHZ-, and X' and Z1 each is an oxygen atom and Y1 is -CH47-.

R is preferably a 3-chloro-2-thienyl or 3-fluoro-2-thienyl group.

A further aspect of the invention resides in the preparation of the compounds of formula 1, wherein the compounds of formula 1 of the invention are prepared by treating the appropriately substituted non-aromatic 35 oxygen-heterocyclic alcohol (RlOH) with a compound XCH211 in which R has the meaning in formula 1 and X is a leaving atom or group, for example a halogen atom, such as bromine, chlorine or iodine, or a sulphonate group, for example a mesyloxy, tosyloxy group or the like, preferably in the presence of a strong base and an inert diluent. The strong base is suitably an alkali metal hydride, hydroxide or carbonate, including, for example, sodium hydride, sodium hydroxide, potassium carbonate and the like. Inert diluents are suitably 40 organic solvents, such as ethers, aromatic hydrocarbons and the like, including, for example, diethyl ether, dimethylformamide, tetrahydrofuran, dimethyl sulfoxide, toluene, methylene chloride and the like. The reaction is usually carried out under normal pressures and ambient temperatures. Suitable temperatures for the reaction are from about 00 to about 120'C., preferably from about 200C to about 1000C. The product ethers are recovered and isolated by conventional techniques. In some cases, the ethers may be formed prior to 45 formation of the oxabicycloalkane system.

The reactants XCH2R are conventional kinds of etherification materials generally known in the art and are readily prepared by conventional methods known for preparing halides and sulfonates of alcohols.

For example, 1-(bromomethyi)-2-chlorocyclohexene is prepared by treating the corresponding alcohol with PBr3 in benzene. The alcohol is readily prepared by treating cyclohexanone with P0C13 in dimethylformamide 50 (M Ziegenbein and W. Lang, Chern. Ber, 93 page 2743 (1960) to give the corresponding aldehyde which is treated with Red-AI (sodium bis(2-methoxyethoxy)-aluminum hydride) in toluene to give the desired alcohol.

In a similar manner a 2-(chloromethyl)-3-halothiophene is prepared by treating a 3-halothiophene with formaldehyde and I-ICI. The 3-bromothiophene is obtained by bromination of thiophene followed by treatment with zinc dust; treating the resulting product with cuprous chloride in dimethylformamide gives the 55 corresponding chloro compound. The (5-h a 1 o-3,4-dihyd ro-2H-pyra n-6- VI) methyl ha lides are prepared from 5-halo-3,4-dihydro-2H-pyran-6-yi)methanols.

The oxabicycloalkanol reactants for preparing compounds wherein R' is a group of formula (a) are obtained generally by one or more of the following routes: directly by (a) epoxidation-cyclization of unsaturated cyclic alcohols with or without isolation of epoxy alcohol intermediates; and indirectly by (b) Dieis-Alder reactions 60 of furans with dienophiles or (c) Birch reduction.

Detailed routes are described below for the different ring systems.

In (a), the epoxidation-cyclization of unsaturated cyclic alcohols involves treatment in an inert solvent with an oxidizing agent followed by an acid. The alcohols are either (i) cycloal-3-en-l -ols, or (ii) cycloalk-3-ene-l - methanols. The cycloalk-3-en-l-ols are prepared from 1-oxaspiro(2.5)oct-5- enes by hydrogenolysis; from 65 3 GB 2 188 931 A 3 cycloalk-3-en-l -ones bytreatmentwith a Grignard reagent; by dealkylating or hydrolyzing, respectively, Diels-Aider adducts of vinyl ethers or esters prepared from dienes, such as isoprene, and vinyl ether or ester dienophiles in which the alpha-position of the vinyl group is substituted by alkyl, C02138, or CON(R%. The cycloalk-3-ene-1-methanols are (1) alpha-terpineol; (2) Diels-Alder adducts of allylic alcohols; or (3) products obtained from Diels-Alder adducts of alpha-beta unsaturated carbonyl compounds, such as acrylates, 5 crotonates, acrolein or alkyl vinyl ketones, by partial reduction or treatment with a Grignard reagent; or (4) from 1 -oxaspiro-(2.5)oct-5-enes by rearrangement and partial reduction of the resulting carbonyl compounds; from cycloalk-3-en-l -ones by partial reduction.

In (b), the Diels-Aldertype adducts of furan with dienophiles may require vigorous reaction conditions, including high pressure and low temperature, for example, as described in Dauben, W.G. et al., J. Amer. 10 Chem. Soc., 102, page 6894 (1980). When the dienophile is nitroethylene, the resulting product is partially hydrogenated, converted to the ketone, and reduced to the corresponding alcohol, e.g. by treatment with a hydride or metal. When this alcohol has the endo form, it can be epimerized with base or aluminum isopropoxide in the presence of a ketone to the corresponding exo alcohol.

Endo- and exo-oxabicycloalkanol intermediates can be separated by conventional methods, such as 15 crystallization, chromatography and the like, and the geometric forms can be resolved by classical resolution methods to give a substantially pure single, optical ly-active isomer.

Non-limiting illustrations of the preparation of representative Compounds ofthe Invention follow.

In one embodiment, R10 is derived from an alcohol having the formula 1 20 CH 3 0 OH 25 30 wherein Z has the above meaning. Compound 1 can be prepared from (1) cyclohex-3-en-l-ols by epoxydation cyclization, or (2) Diels-Aider adducts offurans, such as 2,5- dimethyifuran, with dienophiles, such as nitroethylene, as described below. 35 The epoxidation of cyclohex-3-en-l -ols into the corresponding epoxy- alcohol is effected by action of an oxidizing agent, particularly a peroxide, such as m-chloroperbenzoic acid, peracetic acid, tert-butyl hydropero xide (TBHP) or equivalent peroxide reagents. The oxidation to cis- alcohols with TBHP is conducted in the presence of an appropriate transition metal catalyst, e.g. vanadium. Preferably, the complex is an organic complex, for example, with beta-diketones, o-hydroxybenzaldehydes or ohydroxybenzophenones and 40 particularly with acetylacetone; for example, vanadium (]V) bis(2,4- pentanedionate) oxide is preferred. The reaction is suitably conducted in the presence of an inert solvent such as chlorinated hydrocarbons contain from 1 to 4 carbon atoms or a benzene ring, for example, carbon tetrachloride, chloroform, dichloromethane, chlorobenzene and 1,2- or 1,3-dichlorobenzene and the like. Ethers are generally those containing from 4 to 6 carbon atoms, for example, diethyl ether, methyl tert-butyl ether and diisoproply ether. Tetrahydrofuran and 45 dioxane are also useful. Suitable alkanes contain from 5 to 10 carbon atoms, for example, n-pentane, n-hexane, n-heptane, n-octane, n-nonane, n-decane and their isomers. Petroleum fractions rich in alkanes are also suitable. Petroleum ether is also suitable. Cyclohexane and methylcyclohexane are examples of useful cycloalkane solvents containing from 6 to 8 carbon atoms. Suitable aromatic hydrocarbon solvents contain from 6 to 10 carbon atoms, for example, benzene, toluene, o-, m- and p- xylene, the trimethylbenzenes, and the 50 like. The reaction is conducted at temperatures conveniently in the range of from about - 1 OOC to about 500C or slightly above. Generally, the temperature is from about -50C to about 40'C, preferably from about 10'C to about 300C. The molar ration of reactants can vary. Generally, a molar ratio ofcyclohex-3-en-l-ol to oxidizing agent is from about 0.8 to about 1. The reaction is usually conducted by forming a mixture of the alcohol and oxidizing agent, preferably while agitating the reaction mixture, e.g. by stirring, and maintaining the desired 55 reaction temperature. The resulting cis-epoxy-alcohol may be purified or converted without isolation into the 2-exo-hydroxy-7-oxabicyclo- [2.2.1 1heptane by cyclization as described below.

The cyclization (ring closure) step surprisingly gave a high yield of product having the exo-hydroxy configuration in the resulting 7-oxabicyclo[2.2.1 lheptan-2-ol. Many acids will catalyze this reaction, but a relatively strong acid such as sulfuric or p-toluenesulfonic acid is suitable. Preferably, the acid is methanesul- 60 fonic acid or an aryisuifonic acid, such as p-toluenesulfonic, benzenesulfonic acids, or the like. Ofthese, p-toluenesulfonic acid is preferred. The reaction is suitably conducted by adding the acid to the epoxy-alcohol contained in an inert solvent of the type previously described for use in the preparation of the epoxy-alcohol.

The reaction is conducted at a temperature conveniently in the range offrom about O'C to about 50'C or slightly above. Generally, the temperature is from about 5'C to about 40'C, preferably from about 110'C to 65 4 GB 2 188 931 A 4 about WC. The molar ratio of reactants can vary. Generally, the molar ratio of acid to epoxy-alcohol is from about 0.01 to about 0.10, and preferably from about 0.02 to about 0.04.

Thus, a 1,4-disubstituted-3-cyclohexen-1 -ol is converted mainly to 2-exohydroxy-1,4-disubstituted-7- oxabicyclo[2.2.1 1-heptane by treating it with an oxidizing agent, such as tert-butyl hydroperoxide, or m-chloroperhenzoic acid, and then a strong acid, such as ptoluenesulfonic acid. Especially useful for 5 obtaining a 2-exo-hydroxy-1,4-disubstituted-7-oxabicyclo-[2.2.1 1heptane is treatment of the corresponding 3-cyclohexen-l-ol with tert-butyl hydroperoxide and vanadium (R) bis(2,4- pentanedionate) oxide as catalyst in methylene chloride followed by treatment of the intermediate epoxide, preferably in situ, with a sulfonic acid, particularly p-toluenesulfonic acid. Also, acid present during the epoxidation step produces the desired product. 10 The epoxidation-cyclization is disclosed and claimed in U.S.patent 4,487, 945.

In situations where the endo form is desired, it can be obtained by oxidation of the 2-exo-hydroxy compound to the corresponding ketone followed by reduction of the ketone with sodium borohydride.

The 3-cyclohexen-1 -ols useful for the preparation of Compound 1 can also be synthesized as described below or obtained from natural souces (which offer the advantage of optically-active materials). 15 (a) where Z is 1-methylethyl, the starting compound is terpinen-4-ol, which occurs naturally. Terpinen-4-ol is converted to 2-exo-hyd roxy-1 -methyl -4-(1 -m ethyl-ethyi)-7-oxa bicycl o [2.2.11 hepta n e bytreatment with an oxidizing agent, for example, a peroxide such as m-chloroperbenzoic acid, peracetic acid or tert-butyl hydroperoxide, in an inert solvent in the presence of a strong acid. The spatial configuration of the terpinen-4-ol used is retained in the reaction product. Thus, ( ), (-) or (+) 2-exo-hydroxy-1-methyi-4-(1- 20 methylethyi)-7-oxabicyclo[2.2.1 1heptane can be obtained. 2-endo-Hydroxy- 1-methyi-4-(1 -methylethyi)-7 oxabicyclo[2.2.1 1heptane is known from Garside et aL, J. Chem. Soc., page 716-721 (1969).2-exo- and endo-Hydroxy-1-methyi-4-(1-methylethyi)-7-oxabicyclo[2.2.1]heptanes are converted to the ethers of the invention as described above. Although terpinen-4-ol occurs in nature in optically active and racemic forms, it can also be prepared by epoxidation of terpinolene, e.g. with peracetic acid in methylene chloride, followed by 25 reduction of the epoxide, e.g. with sodium diethylaluminum hydride in tetra hyd rofu ran.

(b) Preparation of 3-cyclohexen-l-ols can be effected from p-substituted phenols in which the substituent group corresponds to methyl in the formula 1 of the invention by procedures of the literature forthe Birch-type reduction of derivatives of benzene, many of which are detailed in Rodd's Chemistry of Carbon Compounds, Second Edition, VoL It, Part B, pages 1-4 (1968). In an example, paracresol is first methylated to protect the 30 hydroxy group yielding the corresponding p-methylanisole. This pmethylanisole is treated with a reducing agent such as lithium-ammonia or sodium ammonia and the resulting product is hydrolyzed to yield the corresponding 4-methyi-3-cyclohexen-1 -one. Treatment of this ketone with an appropriate organometallic (Grignard) reagent, ZMgBr or ZLI in which Z corresponds to that in the formula 1 of the invention and is aikyi, e.g. at 20-60'C in the presence of anhydrous ethers, yields the desired 1, 4-disubstituted-3-cyciohexen-1 -ol 35 intermediate. The 4-methyl-3-cyclohexen-1 -one can also be reduced, e.g. by hydrides, to the corresponding 3-cyclohexen-l-ol unsubstituted in position-4.

The 2-hydroxy-7-oxabicyclo[2.2.1 1heptanes useful as precursors of compounds of the invention can also be prepared from Diels-Alder adducts of suitably-substituted furans, as dienes, and dienophiles. For example, 2,5-dimehyifuran adds readily to nitroethylene to give 1,4-dimethyi-2nitrobicyclo-[2.2.1 lhept-5-ene. Similar 40 adducts can be prepared from 2,5-dialkylfurans and dienophiles such as acrolein and acrylate esters.

R R NO 2 NO 2 45 NO j 2 R R + CH H _\ /,,/ 11 2 0. 2 0 CH 2 50 R R In another embodiment of the invention, R10 isderivedfrom an alcohol having the formula 11 55 GB 2 188 931 A 5 CH 3 0 OH 5 10 wherein Z has the above meanings. Compounds 11 (2-oxabicyclo[2.2.11- heptan-6-ols) can be prepared from (1) terpenes, such as alpha-terpineol, or (2) Diels-Alder adducts of suitably substituted butadienes and dienophiles containing an oxygen function, as illustrated below. For example, (1) the compound is obtained 15 from naturally occurring terpenes. Most elementarily, alpha-pinene is treated with aqueous acid to form alpha-terpineol, itself a naturally occurring material. Alpha-Terpineol, either in racemic form or completely or partially optically active form, is oxidized, for example, with a peroxide such as hydrogen peroxide or m-chloroperbenzoic acid in a suitable solvent like methylene chloride, to yield a major amount of 1,3,3 trimethyi-2-oxabicyclo[2.2.2]octan-6-exo-oI (hydroxy group antito oxygencontaining bridge). Oxidation of 20 this alcohol, e.g. with N-bromoacetamide in aqueous acetone at 5'C, gives 1,3,3-trimethyi-2 oxabicyclo[2.2.2.[octan-6-one. Subsequent reduction of this ketone, for example with sodium borohydride in tert-butanol, yields a mixture of alcohols predominant in the endo isomer (hydroxy group syn to oxygen containing bridge). Conversion to the ether of formula 1 of the Invention follows the earlier described procedures with retention of configuration. 25 (2) Diels-Alder adducts are formedfrom suitably, readily available dienophiles including an acrylate ester, acrolein, methacrolein, methyl vinyl ketone, ally] alcohol, a crotonate ester and the like. The diene component is isoprene, 2,3-di methyl butad ien e and the like. For example, the Diels-Aider adducts lla are prepared by treating the portion of the compound of formula Ha above the dotted line 30 CH 35 CO 2 CH 3 with a dienophile (methyl acrylate) corresponding to the portion of the comound of formula lla below the 40 dotted line. Many such reactions are detailed in Rod's Chemistry of Carbon Compounds, Second Edition, Vol 11, Part B, pages 5-6 (1968). Treatment of Ha with the appropriate Grignard reagent (e.g. methyl magnesium bromide, ethyl magnesium bromide or the like) gives an alpha,alpha,4- trimethyi-(or triethyi)-cyciohex-3-ene 1-methanol of formula lib below.

45 CH 3 50 OH CH 3 55 CH 3 Alchol lib is oxidized, for example, with a peroxide, such as hydrogen peroxide or m-chloroperbenzoic acid, in a suitable solvent, such as methylene chloride, preferably in the presence of a strong acid, to yield a major amount of 1,3,3-trimethyi-2-oxabicyclo-[2.2.2]octan-6-exo-ol. This exo form can be converted, if desired, into 60 an endo-rich or substantially pure endo form. First, oxidation to the corresponding ketone, 1,3,3-trimethy]-2 oxabicyclo[2.2.2.1-octan-6-one, is effected with a suitable oxidizing agent. For example, the exo form is combined with oxalyl chloride and dimethyl suffoxide in methylene chloride followed by addition of triethylamine. Then, the resulting ketone is converted into the endoalcohol by reduction. For example, the ketone in a mixture of dimethoxyethane and tert-butanol is treated with sodium borohydride. Classical 65 6 GB 2 188 931 A 6 resolution can be applied to the 1,3,3-trialkyi-2-oxabicyclo[2.2.2]octan- 6-ols to give substantially pure individual optical forms. The 1,3,3-trialkyi-2-oxabicyclo[2.2.2]octan-6ols are converted into the desired ethers of the Invention, with retention of configuration. This reaction is carried out, preferably in the presence of a base, such as sodium hydride, and, if desired, an inert solvent, such as N,N-dimethylacetamide, N,N dimethylformamide, benzene, toluene or the like. The compounds of the invention can be recovered and 5 purified by conventional techniques.

In another embodiment of the invention, R10 is derived from an alcohol having the formula Ill CH 3 10 0 OH CH 3 3 ' 15 Ill can be prepared by condensation of 1,4-dibromo-2-methyl-2-butene with an alkyl acetoacetate, in the 20 presence of base, followed by thermolysis of the 2-isopropenyM acetylcyclopropanecarboxylate intermedi ate to a 1-acetyi-3-methyi-3-cyclopentenecarboxylate, which is hydrolyzed and decarboxylated to the corresponding ketone. Treatment of the ketone with two equivalents of Grignard reagent, methyl magnesium bromide, yields the corresponding alcohol derivative. This alcohol is epoxidized and cyclized to 1,3,3 trimethyl-2-oxabicyclo[2.2.1 1-heptan-exo-6-ol (111). This exo-alcohol can be oxidized to the corresponding 25 ketone followed by reduction to a corresponding endo-2-oxabicyclo[2.2. llheptan-6-ol as described for the compounds of formula 11 above. An example of one alternative method is the condensation of a 1,4-dibromo 2-methy]-2-butene with a malonic acid dialkyl ester, again using base, followed by thermolysis. The resulting cyclopentene derivative is treated with, e.g., sodium chloride in dimethyl sulfoxide to eliminate one of the ester functional groups. Treatment of the resulting mono ester with the Grignard reagent, methyl magnesium 30 bromide, yields the alcohol derivative described in the first methodology. See, also, Spurlocket al., Chemical Abstracts, 76:153024e (1972) for preparation of a 2-oxabicyclo[2. 2.1]heptan-6-ol.

Illustrative Embodiments The invention is illustrated by the following embodiments which describe the preparation of typical species 35 of the invention. The embodiments are presented for the purpose of illustration only and should not be regarded as limiting the invention in any way. The identity of the products, including intermediates, was confirmed by elemental, infrared and nuclear magnetic resonance (NIVIR) and mass spectral analyses as necessary.

40 Embodiment I( )-2-exo-Hydroxy-1-methyl-4-(1-methylethyi)-7-oxabicyclo[2. 2.11heptane To a solution of 22.3g of 85% m-chloroperbenzoic acid in 150 mi of methylene chloride was added over40 minutes a solution of 15.49 of ( )-terpinen-4-ol in 30 mi methylene chloride at a temperature of about O'C. The reaction mixture was stirred for 20 hours at room temperature, then cooled to 5'C. A solid was filtered and rinsed with cold methylene chloride. The combined filtrates were washed successively with one-eight 45

Claims (1)

1. saturated potassium carbonate, saturated sodium sulfite, and then water,

   dried and Claisen distilled to yield

   8.9 of product, b.p. 109-113'C at 8 mm Hq (1060 Pa). Recrystallization of the solidified distillate from pentane gave 5.5 g of the desired product, m.p. 42-58'C.

   Embodiment2- ( )-2-exo-Hydroxy-1-methy]-4-(1 -methyl ethyl)-7-oxa bicycl o [2.2.1 1heptane 50 To a solution of 30.8 g of W-terpinen-4-ol and 0.8 g of vanadium ([V) bis(2,4-pentanedionate) oxide in 300 m[ of methylene chloride was added 22.0 g of 90% tert-butyl hydroperoxide. The resulting reaction, initially mildly exothermic, was held at reflux for 2 hours, to obtain the epoxide, then 0.8 g of p-toluenesulfonic acid in m] of glyme was added. The resulting reaction mixture was refluxed for 1. 5 hours, and cooled, and 0.8 9 of anhydrous sodium acetate wa's added with stirring. After filtration, the filtrate was concentrated and Claisen 55 distilled to give 28.4 g of the desired product, b.p. 80-95oC (2 mm Hg; 270 Pa).

   Embodiment3- W-2-exo(2-Ch loro-1 -cylcohexen-1 -yi) methoxy-1 -methyl -4(1 -methyl ethyl)-7 oxabicyclo[2.2.11-heptane A suspension of 0.6 9 of sodium hydride from hexane-washed 50% oil- dispersion in 20 nal of anhydrous 60 dimethylformamide under N2 was stirred at ambient temperature while adding 1.6 g of the alcohol of Embodiment 2. The mixture was heated gradually to about 800C, stirred until hydrogen evolution had ceased (1.5 hours), cooled to ambient temperature, and treated dropwise with 2.0 g of 1 -(bromomethyl)-2 chlorocyclohexene with stirring for 2 days. Excess sodium hydride was decomposed by addition of 15 mi of water. The mixture was then diluted with ether, washed with water several times to remove dimethylforma- 65 7 GB 2 188 931 A 7 mide, shaken with brine, dried over Na2S04 and stripped of solventto yield 3.2 of dark brown oil. This crude product was chromatographed on a silica gel flash column (CH2C121Et20, by volume 9515 to yield 0.95 g of the desired ether as a yellowish oil.

   Embodiment 4 - ( )-2-exo-2-Chlorocyclopenten-1 -yImethoxy-1 -methyl-4-(1 methylethyl)-7-oxabicyclo[2.2.1 1- 5 heptane Following procedures similar to those described in Embodiment 3 above, the desired product was prepared by treating the alcohol of Embodiment2with 1-(bromomethyi)-2chlorocyclopenteneto yield the desired ether as a yellow liquid.

   10 Embodiments 5-8 Following procedures similar to those described in Embodiment 3 above, the desired product was prepared by treating the alcohols, R' OH, of Embodiments 5-8 with the desired halide, HalCH2R, to yield the ethers set out below:

   15 R101-1+HalCH2R->R1OCH2R Embodiment R'OH R WOCHR 5 2-ethyi-2-(hydroxy2-chlorocyclo- lightamber 20 methyi)1-oxaspiro- hexenyl syrup [4.51decane 6 2-ethy]-2-(hydroxy- 2-chlorocyclo- light amber methyl)- 1 -oxaspi ropentenyl oil 25 [4.51decane 7 2-ethyi-2-(hydroxy- 2-chiorocyclolightamber methyl)-1,7-dioxasp- hexenyl syrup iro[4.51decane 30 8 2-ethyi-2-(hydroxy- 2-chlorocyclo- lightamber methyl)-1,7-dioxasppentenyl syrup iro[4.51decane 35 Embodiment9- W-2-exo-(3-Ch 1 o ro-2-th ienyi) m ethoxy-1 -methyl-4-(1 - methyl ethy)-7 oxabicyclo[2.2.1 Iheptane To a stirred suspension of 1.2 equivalents of sodium hydride (from hexanewashed 50% oil-dispersion) in dry dimethylformamide under nitrogen was added 1 equivalent of the alcohol of Embodiment 2. The mixture was gradually heated to about 70-80'C. When hydrogen no longer evolved after about 1 hour at elevated 40 temperature, the mixture was cooled in an ice bath to 5-1 O'C for the dropwise addition of 1 equivalent of 2-(bromomethyi)-3-chlorothiophene. Stirring was continued at room temperature. The reaction mixture was recovered as described in Embodiment 3 above, and the desired product was purified by flash chromatogra phy on silica gel to give the desired ether as an amber oil.

   45 Embodiment 10- ( )-2-exo-(3-Chloro-2-thienyi)methoxy-1,4-diethyi-7oxabicyclo[2.2.1]heptane A 100 m] round bottom, 3-neck reaction flask equipped with a stirrer, an internal thermometer, a reflux condenser and a dropping funnel was charged with 0.96 g of 50% sodium hydride in mineral oil followed by mi of dimethyl sulfoxide. The mixture was stirred while 3.4 9 of 2-exo- hydroxy-1,4-diethyl-7- oxabicyclo[2.2.1 Iheptane was added dropwise and stirring was continued with heating to 80'C for 1 hour. The 50 resulting dark mixture was stirred at room temperature while 3.3 g of 2- (1-chloromethyi)-3-chlorothiophene was added dropwise accompanied by an exotherm to 450C. The stirred reaction mixture was heated to 800C for 1 hour, poured over ice water, acidified (HCI) and extracted thrice with methylene chloride. The combined extracts were washed twice with water, dried (M9S04), filtered, concentrated, and flash column chromatog raphed using silica gel and methylene chloride eluent to give two separate 1.0 9 amounts of the desired 55 product as a dark syrup.

   Embodiment 11 - (3-Ch 1 o ro-2-th ienyi) methyl ether of 2-ethyi-2(hydroxymethyi)-1,7-dioxaspiro[4.5]decane Following procedures similar to those described in Embodiment 9 above, the desired product was prepared by treating 2-ethyi-2-(hydroxymethyi)-1,7-dioxaspiro[4.5]decane with 2-(1bromomethyl)-3-chlorothiophene 60 to obtain the ether as an amber syrup.

   Embodiment 12- 3-Chloro-2-thienyimethyl ether of 2-ethyi-2(hydroxymethyi)-1-oxaspiro[4.5]decane Following procedures similar to those described in Embodiment 9 above, the desired product was prepared by treating 2-ethy]-2-(hydroxymethyi)-1-oxaspiro[4.5]decane with 2-(1bromomethyi)-3-chlorothiophene to 65 8 GB 2 188 931 A 8 obtain the ether as a light amber oil.

   For application, a compound of Formula 1 ordinarily is applied most effectively by formulating it with a suitable inert carrier or surface-active agent, or both. The invention, therefore, also includes compositions suitable for combatting unwanted plants, such compositions comprising an inert carrier or surface-active agent, or both, and as active ingredient at least one compound of Formula 1; and the preparation of such 5 compositions. Some of the compounds of Formula 1 are useful as selective herbicides, e.g. in soybeans, cotton, sugar beets and the like.

   The term "carrier- as used herein means an inert solid or liquid material, which may be inorganic or organic and of synthetic or natural origin, with which the active compound is mixed orformulated to facilitate its application to the plant, seed, soil or other object to be treated, or its storage, transport andlor handling. Any 10 of the materials customarily employed in formulating pesticides, herbicides, or fungicides - i.e. horticulturally acceptable carriers - are suitable.

   Suitable solid carriers are natural and synthetic clays and silicates, for example, natural silicas such as diatomaceous earths; magnesium silicates, for example, talcs; magnesium aluminum silicates, for example, attapulgites and vermiculites; aluminum silicates, for example, kaolinites, montmorillonites and micas; 15 calcium carbonate; calcium sulfate; synthetic hydrated silican oxides and synthetic calcium or aluminum silicates; elements such as, for example, carbon and sulfur; natural and synthetic resins such as, for example, coumarone resins, polyvinyl chloride and styrene polymers and copolymers; bitumen; waxes such as, for example, beeswax, paraffin wax, and chlorinated mineral waxes; solid fertilizers, for example, superphos phates; and ground, natural ly-occu rring, fibrous materials, such as ground corncobs. 20 Examples of suitable liquid carriers are water, alcohols such as isopropyl alcohol and glycols; ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone and cyclohexanone; ethers such as cellosolves; aromatic hydrocarbons such as benzene, toluene and xylene; petroleum fractions such as kerosene, light mineral oils; chlorinated hydrocarbons such as carbon tetrachloride, perch] o roethylene and trichlor omethane. Also suitable are liquefied, normally vaporous and gaseous compounds. Mixtures of different 25 liquids are often suitable.

   The surface-active agent may be an emulsifying agent or a dispersing agent or a wetting agent/ it may be nonionic or ionic. Any of the surface-active agents usually applied in formulating herbicides or insecticides may be used. Examples of suitable surface-active agents are the sodium and calcium salts of polyacrylic acids and lignin sulfonic acids; the condensation products of fatty acids or aliphatic amines or amides containing at 30 least 12 carbon atoms in the molecule with ethylene oxide andlor propylene oxide; fatty acid esters of glycerol, sorbitan, sucrose or pentaerythritol; condensates of these with ethylene oxide andlor propylene oxide; condensation products of fatty alcohols or alkyl phenols, for example, p-octylphenol or p-octylcresol, with ethylene oxide andlor propylene oxide; sulfates or sulfonates of these condensation products, alkali or alkaline earth metal salts, preferably sodium salts, of sulfuric or sulfonic acid esters containing at least 10 35 carbon atoms in the molecule, for example, sodium lauryl sulfate, sodium secondary alkyl sulfates, sodium salts of the sulfonated castor oil, and sodium alkylaryl sulfonates such as sodium dodecylbenzene sulfonate; and polymers of ethylene oxide and copolymers of ethylene oxide and propylene oxides.

   The compositions of the invention may be prepared as wettable powders, dusts, granules, solutions, emulsifiable concentrates, emulsions suspension concentrates and aerosols. Wettable powders are usually 40 compound to contain 25 to 75% by weight of active compound and usually contain, in addition to the solid carrier, 3-10% by weight of a dispersing agent, 2-15% of a surface-active agent and, where necessary, 0-10% by weight of stabilizer(s) andlor other additives such as penetrants or stickers. Dusts are usually formulated as a dust concentrate having a similar composition to that of a wettable powder but without a dispersant or surface-active agent, and are diluted in the field with further solid carrier to give a composition usually 45 containig 0-5-10% by weight of the active compound. Granules are usually prepared to have a size between and 100 BS mesh (1.676-0.152 mm), and may be manufactured by agglomeration or impregnation techniques. Generally, granules will contain 0.5-25% by weight of the active compound, 0-1 % by weight of additives such as stabilizers, slow release modifiers and binding agents. Emulsifiable concentrates usually contain, in addition to the solvent and, when necessary, cosolvent, 10- 50% weight per volume of the active 50 compound, 2-20% weight per volume emulsifiers and 0-20% weight per volume of appropriate additives such as stabilizers, penetrants and corrosion inhibitors. Suspension concentrates are compounded so as to obtain a stable, non-sedimenting, flowable product and usually contain 10-75% weight of the active compound, 05-5% weight of dispersing agents, 1-5% of surface-active agent, 0.1-10% weight of suspending agents, such as defoamers, corrosion inhibitors, stabilizers, penetrants and stickers, and as carrier, water or an 55 organic liquid in which the active compound is substantially insoluble; certain organic solids or inorganic salts may be dissolved in the carrierto assist in preventing sedimentation or as antifreeze agents for water.

   Of particular interest in current practice are water-dispersible granular formulations. These are in the form of dry, hard granules that are essentially dust-free, and are resistant to attrition on handling, thus minimizing the formation of dust. On contact with water, the granules readily disintegrate to form stable suspensions of 60 the particles of active material. Such formulations contain 90% or (up to 95%) more by weight of finely divided active material, 3-7% by weight of a blent of surfactants, which act as wetting, dispersing, suspending and binding agents, and may contain up to 3% by weight of a finely divided carrier, which acts as a resuspending agent.

   Aqueous dispersions and emulsions, for example, compositions obtained by diluting a wettable powder or 65 9 GB 2 188 931 A 9 a concentrate according to the invention with water, also lie within the scope of the present invention. The said emulsions may be of the water-in-oil or of the oil-in-water type, and may have thick, mayonnaise-like consistency.

   It is evident from the foregoing that this invention contemplates compositions containing as little as about 0.5% by weight to as much as about 95% by weight of a compound of Formula 1 as the active ingredient. 5 The compositions of the invention may also contain other ingredients, for example, other compounds possessing pesticidal, especially insecticidal, acaricidal, herbicidal or fungicidal properties, as are appropriate to the intended purpose.

   The invention also resides in the protection of a locus or area from undesirable plants, by applying a compound of Formula 1, ordinarily in a composition of one of the aforementioned types, to soil in which the 10 seeds of the unwanted plants are present, or to the foliage of the unwanted plants. The active compound, of course, is applied in an amount sufficient to exert the desired action.

   The amount of the compound of the invention to be used in combatting undesired plants will naturally depend on the condition of the plants, the degree of activity desired, the formulation used, the mode of application, the climate, the season of the year, and other variables. Recommendations as to precise amounts 15 are, therefore, not possible. In general, however, application to the locus to be protected of from 0.1 to 10.0 kg per hectare of the compound of Formula 1 will be satisfactory.

   Examples of activity with respect to plants In the following examples, the species of plants that were tested were: 20 Barnyardgrass (watergrass Echinochloa crus-gall! La rg e cra bg rass - Digitaria sanguinalis Downy brome - Bromus tectorum Yellow foxtail - Setaria lutescens Redroot pigweed - Amaranthus retrotlexus 25 Sicklepod - Cassia obtusifolia Velvetleaf -Abutilon theophrasti Garden cress - Lepidium sativum Johnson grass Sorghum halepense Morningglory - lpomoea sp. 30 Testprocedures The preemergence (soil) herbicidal activity of compounds of Formula 1 was evaluated by planting seeds of barnyardgrass, garden cress, downy brome, velvetleaf, yellow foxtail, and sicklepod or morninggiory in test tubes, nominally measuring 25X200 millimeters, filled about three- quarters full of untreated soil, in each case 35 covered on top with about 2.5 cubic centimeters of soil treated with a certain amount of test compound. The treated soil applied to the tubes containing the barnyardgrass and cress seeds contained one milligram of the test compound per tube, and contained 0.1 milligram of the test compound per each tube containing the seeds of the other plants. The dosages were approximately 20 and 2.0 pounds of test compound per acre, respectively (that is, approximately 22 and 2.2 kg per hectare respectively). The seeds were planted on top of 40 the treated soil and covered with about 1.5 cubic centimeters of untreated soil. The planted soil was held under controlled conditions of temperature, moisture, and light for 9 to 10 days. The amounts of germination and growth in each tube were evaluated on a 0 to 9 scale, the numeric ratings having the following meanings:

   Rating Meaning 45 9 No living tissue 8 Plant severely damaged, and expected to die 7 Plant badly damaged, but expected to live 6 Moderate damage, but complete recovery expected 5 Intermediate damage (probably unacceptable for crop plants) 50 3-4 Observable damage 1-2 Plant slightly affected, possibly by the chemical, possibly due to biological variablilty 0 No visible effect The postemergence (foliar) herbicidal activity of compounds of Formula 1 was evaluated by spraying 55 1 0-day-old large crabgrass plants, 13-day-old pigweed plants, 6-day-old johnsongrass plants, 9-day-velvetleaf plants, 9-day-old yellow foxtail plants and either 9-day-old sicklepod plants or 5-day-old morningglory plants to runoff with a liquid formulation of the test compound. The crabgrass and pigweed plants were sprayed with 2.4 millimeters of a 0.25% solution (aboutten pounds of the test compound per acre, that is, about 11 kg/ha), and other plants were sprayed with 2.4 milliliters of a 0.025% solution (about one pound of the test compound 60 per acre, that is, about 1.1 kg/ha). The sprayed plants were held under controlled conditions of temperature, moisture and light for 7 to 8 days, when the effect of the test compound was evaluated visually, the results being rated on the 0 to 9 scale described above.

   Results of the preemergence and postemergence herbicidal activity tests are set forth in Table 1.

   W W N C) c) IM 00 00 (D TABLE 1 Herbicidal activity Preemergence Postemergence Barnyard- Garden Downy Velvet- Yellow Sickle- Crab- PigJohnson- Velvet Yellow Sickle Compound grass Cress Brome leaf Foxtail pod grass weed grass leaf Foxtail pod 12 9 4 6 0 7 0 7 6 2 4 4 2 11 9 6 6 4 5 4 7 4 3 5 5 2 9 9 6 9 4 9 0 9 5 5 4 7 2 9 7 9 5 8 0 7 3 7 6 7 2 3 9 7 9 5 8 2 5 3 0 0 0 0 4 9 7 9 3 8 2 4 9 0 3 0 0 6 0 5 0 5 0 5 6 3 4 2 3 6 9 5 9 0 6 0 4 4 2 2 2 2 7 9 7 9 0 5 0 6 5 2 4 2 2 8 9 4 7 5 8 0 4 2 0 4 5 2 W 11 GB 2 188 931 A 11 Selectivity test procedures The preemergence activity of the compounds of Embodiments 9 and 10 was further determined with respect to certain common species of weeds, by spraying a formulation of the test compound on soil in small pots in which seeds of the plants had been sown. The postemergence herbicidal activity of compounds of Embodiments 9 and 10 was evaluated with respect to the weeds, by spraying a formulation of the test 5 compound on the foliage of the young growing plants. In each series of tests, the plants were grown in pots placed in narrow trays and sprayed with the formulation. The results of the tests at 1.0 and 0.25% 1b/acre, that is, about 1.1 and 0,28 kg/ha, were evaluated on the basis of the 0-9 scale described with respect to the earlier tests. The results of the tests showed observable damage by both materials against grass weeds such as Barnyard Grass, Downy Brome, Johnson-grass, Wild Oats, and Yellow Foxtaii in pre-emergence tests. The 10 material of Embodiment 10 also showed observable damage to broadleaf weeds, such as Morning Glory, Mustard, Pigweed, Sicklepod, and Velvetleaf in pre-emergence tests. The compounds of Embodiment 9 and also showed post-emergence activity against one or more of the above grass and broadleaf weeds.

   CLAIMS 15 1. A compound of the formula 1 R'-O-CH2-R 20 wherein Ris3-halo-2-thienyi,5-halo-3,4-dihydro-2H-pyran-6-yi,2-halocyclo1-penten-l-y ior2-halo-l- cyclohexen-l-yl in which halo is chloro orfluoro and R' is the residue of a non-aromatic oxygen-heterocyclic alcohol (RlOH), R' containing up to 16 carbon atoms, and including a monocyclic, bridged-cyclic or spirocyclic ring-system of 5 to 11 ring atoms, one or more of which is an oxygen atom and the remainder of which are carbon atoms. 25 2. A compound according to claim 1 wherein R' is a group selected from a) W 30 0 1 X yl7 35 z wherein W is a methyl or ethyl group; Xis a single bond or-CH(C143)2, Y is a single bond or-CH2- with the 40 proviso that both X and Y are not a single bond; Z is H, or an optionally substituted alkyl group containing 1 to 4 atoms; b) 4 5 45 R 1-1 R R 3 R 6 R 2 R 7 2 50 R CH 18 0 R wherein each R 2 individually represents a hydrogen atom, a halogen atom, an optionally substituted alkyl, cycloalkyl or aryl group, each containing up to 6 carbon atoms or two R 2 together represent an alkylene of up 55 to 6 carbon atoms, R 3, R 4, R 5 and R' each individually represents a hydrogen atom, a halogen atom having an atomic number of from 9 to 35, inclusive, an optionally substituted alkyl, alkoxy, alkylthio or aryl group each containing up to 6 carbon atoms or one of R' and R' and one of R' and R'together represent a carbon-carbon bond or an epoxide moiety; R 7 and R' each represents a hydrogen atom or an optionally substituted alkyl group containing up to 6 carbon atoms; 60 12 GB 2 188 931 A 12 or c) R 4 5 R 3 R 6 Z CH 2 R Y X CH 2 10 wherein R 3, R 4, R5, R'and R 7 each individually is a hydrogen atom or an alkyl group containing from 1 to 4 carbon atoms, W' is an oxygen atom or-CH2-; X' is an oxygen atom or-CH2-; Y1 is a carbon-carbon bond, or an oxygen atom, -CHz-, -C2H47-, CHR9- in which R9 is an alkoxymethyl group containing from 1 to 4 carbon 15 atoms in the alkoxy portion thereof; Z1 is a carbon-carbon bond, an oxygen atom, -CH27, or-C2H47; with the proviso that no two adjacent of W, X', Y1 and Z1 are simultaneously either oxygen atoms or-C2H4- and the sum of the ring atoms in W, X' and Z1 is an integer of from 3 to 5.

   3. A compound according to claim 2 wherein R' is a group of formula (a) in which(l) Xis a single bond, Y is -CH2--,W is methyl and Z is a hydrogen atom ora 1-methylethyl group orW and Z each is an ethyl group (2) X 20 is -C(CH3),-, Y is -CHz-, and Z is a hydrogen atom; formula (b) is which each R 2 independently is a hydrogen atom or a methyl group or the two R's taken togetherform a pentamethylene group, R 3, R 4, R 5, R6 and R' are hydrogen atoms and R 7 is a hydrogen atom, a methyl or ethyl group; or formula (c) in which W' is an oxygen atom or -CH2-, X' is an oxygen atom or -CH2-, Y1 is an oxygen atom 25 or-CHz, C2H47- or CHR9 in which R9 is methoxymethy], Z1 is an oxygen atom or-CH2-, and the sum of the ring atoms in W, W, Y1 and Z1 is an integer of from 3 to 5.

   4. A compound according to claim 3 wherein R' is a group of formula (a) wherein Xis a single bond; W is methyl and Z is ll-methylethyl orW and Z each is ethyl; formula (b) wherein each R 2 is a methyl group or taken together form a pentamethylene group; or 30 formula (c) wherein (1) W' and Z' are each -CH2, X' and Z1 each is an oxygen atom and Y1 is -C2H47-.

   5. A compound according to claim 4 wherein R' is a group of formula (a) wherein Xis a single bond and W and Z is 1 -methylethyl.

   6. A compound accorqing to claim 4, wherein R' is a group of formula (a) wherein Xis a single bond and W and X each is ethyl 35 7. A compound according to claim 4 wherein R' is a group of formula (b) wherein the R 2S taken together from a pentamethylene group and R 7 is an ethyl group.

   8. A compound according to claim 4 wherein R' is a group of formula (c) wherein W, Y1 and Z1 are -CHZ and X' is oxygen atom.

   9. A compound according to any preceding claim, wherein R is 3chlorothien-2-yi. 40 10. A process for the preparation of a compound of formula 1, as claimed in any of claims 1 to 9, wherein a compound of the formula R'-OH is reacted with a compound of the formula X- CH2R where R and R' are as defined in any preceding claim and X represents a leaving moiety.

   11. A compound of the general formula], whenever prepared by a process according to claim 10.

   12. A herbicidal composition comprising as active ingredient a herbicidally effective amount of a 45 compound according to any of claims 1 to 9, or 11, and at least one inert carrier andlor surface-active ingredient.

   13. A method of controlling undesirable plant growth at locus which comprises applying to the locus a herbicidally effective amount of a compound according to any of claims 1 to 9, or 11.

   14. Use of a compound of theformula],as claimed in any of claims 1 to 9, or 1 1,to combat undesired plant 50 growth.

   15. A compound of the general formula], or a process for the preparation of such a compound, substantially as hereinbefore described, with reference to the Examples.

   Printed for Her Majesty's Stationery Office by Croydon Printing Company (UK) Ltd, 8187, D8991685.

   Published by The Patent Office, 25 Southampton Buildings, London WC2A lAY, from which copies may be obtained.