NO140979B - PYRAZOLE DERIVATIVES WITH HERBICID ACTIVITY - Google Patents

Description

The present invention relates to herbicide-active pyrazolium compounds with the following formula I:

where

R3 means C3-C7-cycloalkyl, phenyl or C^-C^-alkyl, R4 means C3-C7-cycloalkyl, C^-C^-alkyl or benzyl X means an anion with a charge of from 1 to 3, and m is an integer from 1 to 3.

The diketone precursors used in the preparation of the pyrazolium salts of formula I with the structure:

where , , m and X are as described above, is prepared by reacting a methyl ketone (II) with an alkylcarboxylic acid ester (III),

preferably the methyl or ethyl ester, in the presence of an alkali metal hydride, preferably sodium hydride, and an aprotic organic solvent, such as e.g. dimethylsulfoxide (DMSO), dimethylformamide (DMF), xylene, toluene, benzene or the like. The reaction is preferably carried out at a temperature between 0 and 40°C, and most preferably between 0 and 25°C. The reaction gives the (3-diketone which corresponds to the reactants used. The methyl ketone and the carboxylic acid ester react in equimolar amounts. However, it is usually desirable to use a small excess, i.e. up to approx. 10% excess, of the carboxylic acid ester in the reaction mixture. The reaction can be illustrated as follows:

where R^ and R^ are as defined above.

The process according to the invention for the preparation of the compounds of formula I comprises first, condensation of the diketone of formula IV with either hydrazine or a methyl-hydrazine to give the corresponding 3,5-disubstituted pyrazole which is methylated to give the desired pyrazolium salt of formula I. These reactions are listed below.

where R^/ R^f m and X are as defined above. The symbol' , / denotes alternative attachment points for the methyl substituent. Examples of anions which are suitable for use in the present invention are halides, such as e.g. chloride, bromide and iodide, sulfate, hydrogen sulfate, methyl sulfate, benzene sulfonate, perchlorate, C 2 -C 3 -alkylbenzene sulfonate, preferably p-toluenesulfonate, phosphate, C 3 -C 4 -alkanesulfonate,

where R,- is halogen, methyl, halomethyl or dihalomethyl 1,

Rg and R^ are halogen, Rg is hydrogen or methyl and Rg is chlorine

or methyl.

The diketone and hydrazine react in equimolar amounts.

A small surplus of up to approx. However, 10% of one of the reactants can be used with advantage. This reaction is usually carried out in the presence of a solvent, either protic or aprotic, at a temperature between 70 and 150°C and preferably between 80 and 120°C. Preferred solvents for these reactions are protic solvents, such as e.g. lower alkanols including methanol, ethanol, n-propanol, isopropanol, n-butanol and isobutanol. Aprotic solvents suitable for use in these reactions include xylene, toluene, benzene, dimethylsulfoxide, dimethylformamide and pyridine. The introduction of an acidic catalyst, such as p-toluenesulfonic acid, increases the speed of the condensation-cyclization reaction and can be used with advantage if the reaction is slow.

When hydrazine is used in initial condensation

of the diketone, the methylation of the resulting pyrazole is advantageously carried out by means of a known methylating agent, preferably in the presence of an acid acceptor, such as e.g. an alkali metal hydroxide,

an alkali metal alkoxide or a tertiary organic amine. Preferred acid acceptors include sodium or potassium hydroxide, sodium or potassium methoxide, -ethoxide, -propoxide or -t-butoxide, trimethylamine, triethylamine and pyridine.

The methylation of the pyrazole is preferably carried out in the presence of

of a solvent at a temperature between 50 and 200°C, preferably between 90 and -120°C. Preferred solvents include aromatic hydrocarbons such as toluene, xylene and chlorobenzene, ketones with 4 to 7 carbon atoms such as methyl isobutyl ketone (MIBK) and methyl butyl ketone (MBK), C2-C5 alcohols, dipolar aprotic solvents such as e.g. dimethyl sulfoxide (DMSO),

dimethylformamide (DMF), acetonitrile, nitrobenzene and N,N-dimethylacetamide and cyclic ethers such as e.g. dioxane and tetrahydrofuran.

Examples of methylating agents are: methyl halides, dimethyl sulphate, methyl phosphate, methyl hydrogen sulphate and methyl toluene sulphonate.

While the 3,5-disubstituted pyrazoles are combined with equimolar amounts of methylating agent, it is common practice to use an excess of methylating agent. Molar ratio between methylating agent and pyrazole in the range from 1:1 to 1.5:1

is preferred. Of course, double the amount of methylating agent is required when hydrazine is used.

In these methylation reactions it is often found that

upon cooling the reaction mixture, the solid or oily pyrazolium salt is separated, which is purified by separation from the organic layer. In some cases, especially when and R^ are very lipophilic (e.g. 3,5-dicyclohexyl-, 3-cyclohexyl-5-phenyl-

and 3-dodecyl-5-phenyl compounds), however, the separation of the pyrazolium salt from the organic phase cannot be carried out easily. In such cases, the product can be obtained by evaporating the solvent and dissolving the residue in chloroform, water

washing the chloroform layer and evaporating the chloroform to obtain the pyrazolium salt as a residue.

When methyltoluenesulfonate or methylsulfate are used as methylating agents, impure or hygroscopic materials are often obtained due to anionic impurities (such as HSO^ or SO^_). In such cases, the mixed anion is purified by passing an aqueous solution of this mixture through an anion exchange column. Alternatively, the aqueous solution of mixed anions can be converted to an iodide by using aqueous saturated potassium iodide or sodium iodide solution. The latter treatment yields the relatively water-insoluble iodide. Perchlorates are prepared by adding dilute aqueous perchloric acid to an aqueous pyrazolium salt solution to give the water-insoluble perchlorate. Further pure pyrazolium salts, e.g. CH^SC^ , HSO^ , SO^- or Cl can be converted by the above-mentioned method with anion-exchange chromatography into new pyrazolium salts, and into iodides and perchlorates as defined above. Pyrazolium halides are prepared as described above, except that the reaction is carried out in a sealed vessel or glass-lined bomb maintained at a temperature of approx. 100°C.

Another aspect of the present invention is to use a herbicidally effective amount of the compound of formula I as active substance in a herbicidal preparation for treating the leaves of unwanted plants. The active compound is used in an amount of between 0.028 and 1.12 g/m 2 and preferably in amounts between 0.056 and 0.56 g/m 2 . Surprisingly, these compounds can also be used as mildew control agents when applied to the leaves of plants in amounts between 0.02 8 and 1.12 kg/m<2>.

Pyrazolium salts of formula I where is phenyl,

R 1 is C 1 -C 4 -alkyl (preferably C 5 -C 4 ) and m and X are as

defined above, exhibits excellent selective control of broad-leaved plants after germination in the presence of small cereal plants, such as e.g. barley, wheat and rice. This is particularly surprising since the lower homologues, i.e. where R 1 is methyl, are ineffective as herbicides in all dosages tested. These compounds also exhibit surprising herbicidal activity before germination.

As will be observed later, the pyrazolium salts of formula I which are most unusual in their herbicidal effectiveness are those where R 1 is a C 1 -C 4 alkyl group and R 1 , m and X are as defined above. Preferred compounds are those where R 1 is C 1 -C 3 -cycloalkyl or phenyl, R 3 is C 3 -C 4 -cycloalkyl

and X and m are defined as above. These compounds are very effective as herbicides. They are particularly effective when applied to the leaves of unwanted plants and are effective against both broadleaf weeds and unwanted grasses. Furthermore, they can be used for the selective control of field oats, broad-leaved weeds and unwanted grass plants, especially finger millet, in the presence of small cereal plants such as e.g. barley, wheat and rice. Even more surprising is that said compounds also exhibit activity before germination.

It is an advantage that many of the pyrazolium salts of formula I exhibit a high degree of water solubility and thereby make it possible to prepare water concentrates from them. Among the preferred salts are the methyl sulfates, hydrogen sulfates, sulfates, chlorides and bromides. In practice, the aqueous concentrates can be applied di-

directly as a liquid spray on the leaves of unwanted broadleaf weeds and unwanted grasses. Alternatively, they can be further diluted with water and applied as a diluted aqueous spray to these unwanted plants.

Water-miscible concentrates are prepared by dissolving

from 15 to 95% of the compound in 85 to 50% of a water-miscible solvent such as water or another polar water-miscible solvent such as 2-methoxyethanol, methanol, propylene glycol, diethylene glycol, diethylene glycol monoethyl ether, forma-

mid and dimethylformamide. The application is carried out by adding a predetermined amount of the water-miscible concentrate to a spray tank and applying the mixture as such or in combination with a suitable diluent, such as an additional amount of water or one of the other solvents.

The performance of the product in all the above-mentioned compositions used in the form of liquid spray is unexpectedly improved by adding a surfactant or a mixture of such agents. Conventional anionic, cationic and anionic-nonionic surfactants can be used.

Examples of non-ionic surfactants

are: alkyl polyoxyethylene ethers, polyoxyethylene (20) sorbitan monolaurate, polyoxyethylene (20) sorbitan monooleate, alkyl aryl polyglycol ethers, alkyl phenol ethoxylates, trimethylnonyl polyethylene glycol ethers, alkyl phenol ethylene oxide condensates, octylphenoxy polyethoxyethanols, nonylphenyl polyethylene glycol ethers, condensates of polyoxyethylenes, polyoxypropylenes, aliphatic polyethers, aliphatic polyesters, alkylarylpolyoxyethylene glycols and the like.

Examples of anionic surfactants are: sodium dodecylbenzenesulphonate and the dioctyl ester of sodium sulphoraic acid.

Suitable cationic surfactants include dicocosdimethylammonium chloride, stearamidopropyldimethyl-betahydroxy-ethylammonium nitrate and the like.

These surfactants are preferably added to the spray tank in an amount of 0.1 to 5 volumes! to obtain one

good wetting of the spray solution on the leaves of the plants.

Herbicide concentrates containing surfactants are preferably made as aqueous spray solutions containing approx. 30 weight! of the appropriate pyrazolium salt, from 25 to 50 wt! water and the rest of the mixture (25 - 45 weight!) of a selected surfactant. Surfactants which are particularly useful in preparing suitable concentrates with such agents include the octyl phenol ethylene oxide condensate, an ethanolic solution of an alkylphenol ethoxylate, a polyglycol ether condensate prepared from ethylene oxide and an alkyl aryl polyglycol ether.

Other mixtures which can be advantageously used with the compound produced according to the invention include dust, dust concentrates and wettable powders.

Dust is usually produced by grinding together approx.

1 to 25 weight! of the active agent with from 99 to 25 weight! of a solid diluent such as kaolin, attapulgite, talc, pumice stone, diatomaceous earth, fuller's earth, wood flour or the like.

Dust concentrates are prepared in a similar manner except that 25 to 95 wt! of the active substance is ground with 75 to 5 weight! of the diluent.

Wettable powders are prepared in the same manner as solid concentrates except that 1 to 5 wt! of a dispersing agent such as the calcium salt of a polymerized alkylaryl sulfonic acid, sodium lignosulfonate or the sodium salt of concentrated naphthalene sulfonic acid is mixed with the mixture and 1 to 5 wt. of a surface-active agent such as, for example, polyoxyethylated vegetable oil, alkylphenoxypolyoxyethylene ethanol, or sodium alkyl naphthalene sulfonate is also mixed in.

In practice, the wettable powder is dispersed in water and applied as a liquid spray to the leaves of the unwanted plants. The amount of application must be sufficient to obtain 0.028 to

1.12 g/m 2 of the pyrazolium salt and, although 0.056 to 0.56 g/m 2 of said salt is usually sufficient for control of unwanted broadleaf weeds and grasses, it should be understood that amounts exceeding Ijl2 g/m 2 and as large as 2.24 g/m 2 can be used. These large quantities will naturally be used in areas such as roadsides, under power lines and along hedgerows on the border of property lines and fields.

In order to make the understanding of the invention easier, the following examples are given, mainly to illustrate certain more special details of it and also to illustrate the production of the starting materials which are applicable for this. If nothing else is stated, all parts and percentages are stated as parts and percentages by weight.

Example A

Preparation of 1,3-dicyclohexyl-1,3-propanedione.

Sodium hydride (39.5 g of 54 µg, 0.889 mol) is cooled with an ice bath to 18°C in a suitable flask equipped with a stirrer, condenser, drying tube, dropping funnel and thermometer. Dimethyl sulfoxide (700 ml), dried over 4A molecular sieve, is added slowly. After the addition has ended, the reaction mixture is stirred for 0.5 hour at room temperature. The ice bath is changed and a mixture of cyclohexane-carboxylic acid ethyl ester (138.8 g, 0.889 mol) and cyclohexylmethyl ketone (101.9 g, 0.80 mol) is added dropwise. No exotherm was observed. The reaction mixture becomes lighter in color and some bubbles are observed. After the addition is finished, the ice bath is removed and the reaction mixture is stirred overnight at room temperature. The thick, dark colored reaction mixture is poured over ice

(8 liters) containing phosphoric acid (50 ml) and extracted with ether. The ether is washed with water, dried and evaporated in vacuo to give a golden yellow oil (204 g) which smells strongly of the ester. The product can be purified by reaction with copper complexes according to conventional methods if desired. When it is pure, it occurs in the form of white crystals with a melting point of 50-52°C.

Anal. Calculated for C15H24O2: C, 76.22, H, 10.24

Found: C, 76.20, H, 10.03

Other g-diketones can be prepared from esters and ketones containing R, and R^ as previously defined. Thus, 1-cyclopropyl-3-phenyl-1,3-propanedione has been reported to be produced in solid form with m.p. 36-37°C from ethyl benzoate and cyclopropyl methyl ketone in the presence of sodium amide. Alternatively, it has been found that the same compound with m.p. 3'8-40°C can be prepared from ethyl cyclopropane carboxylate, acetone phenone and sodium hydride. Furthermore, a series of 1-alkyl-3-phenyl-1,3-propanediones has been prepared from carboxylic acid ethyl esters and acetonephenone in the presence of sodium amide. Illustrative examples are given in the table prepared according to the reaction: where R 1 and R 4 are given in Table I below.

Example B

Preparation of 3-cyclopropyl-1-methyl-5-phenylpyrazole and 5-cyclopropyl-1-methyl-3-phenylpyrazole.

1-Cyclopropyl-3-phenyl-1,3-propanedione (37.6 g, 0.2 mol) and 2-propanol (250 ml) are heated to reflux. Methylhydrazine (10.2 g, 0.22 mol) is then added dropwise and the solution is allowed to stand

under reflux until the reaction is complete (2.5 hours). The solution is then filtered and evaporated in vacuo to give a yellow oil (39.2 g, 99%). Examination of the product on a thin layer chromatography plate of silica gel developed with chloroform and iodine showed that a contaminant was present. The product is chromatographed on silica gel with chloroform and gives a white, cloudy oil. The isomers can be used as a mixture or isolated by conventional chemical separation techniques such as fractional crystallization.

Anal. Calculated for <C>13<H>14<N>2<:> C, 77.68, H, 7.26, N, 13.52

Found: C, 77.92, H, 7.33, N, 13.56.

The following pyrazoles with the structure:

is prepared by the method according to this example by using the appropriate 1,3-propanedione as a substitute for 1-cyclopropyl-3-phenyl-1,3-propanedione. The results of the procedure are set out in Table II below. The symbol indicates alternative positions for attachment of the methyl substituent.

Example i

Preparation of 3-cyclohexyl-1,2-dimethyl-5£enylpyrazolium methyl sulfate.

In a suitable reaction vessel, 1-methyl-3(5)-cyclohexyl-5(3)-phenylpyrazole (8.0 g, 0.033 mol) is dissolved in dry toluene and heated to approx. 65°C. Dimethyl sulfate (4.5 g, 0.035 mol) is then added and the mixture is heated to reflux. Tic (benzene) after 1\

hours shows a small residue of pyrazole. After 2 hours, the reaction mixture begins to darken and heating is discontinued. By off-

cooling, a white solid is formed which is filtered off and washed with dry toluene. This sticky white solid is vacuum dried at room temperature to a brittle solid. Hexane is then added

and the solid is broken up and collected by filtration. The solid (6.3 g, 50% yield) has a melting point of 48-51°C. By

exposed to air it becomes sticky (hygroscopic). When analyzing, the following is noted: Analysis. Calculated for C18H26<N>2SO4-H2O: C, 56.24, H, 7.34, N, 7.29

Found: C, 56.91, H, 7.33, N, 7.12

Example 2

Preparation of 5-cyclopropyl-1,2-dimethyl-3-phenylpyrazolium methyl sulfate.

A mixture of 3-cyclopropyl-1-methyl-5-phenylpyrazole and 5-cyclopropyl-1-methyl-3-phenylpyrazole (33.1 g, 0.167 mol) and dry toluene (250 ml) is heated to reflux and approx. 25 ml of solvent is removed with a Dean Stark trap. The solution is then cooled and dimethyl sulfate (18 mL/0.193 mol) is added. The reaction mixture is kept at 100°C for 2.5 hours. A yellow-brown oil is formed which solidifies on cooling. The solid is removed by filtration and dried under vacuum to give a cream-colored solid (49.5 g, 91.5!)

with a melting point of 163-170°C, whose analysis is as follows:

Calculated for C15H2()<N>2S04: C, 55 , 54 , H, 6.22, N, 8.64 S, 9.89

Found : C, 55.27, H, 6.23, N, 9.48, S, 9.99.

Following the procedure in the above example, the compounds in Table III below are prepared by replacing 3-cyclopropyl-1-methyl-5-phenylpyrazole with an appropriate 1-methylpyrazole of the general formula VII:

The following pyrazoles, when reacted with dimethyl sulfate according to the above method, give products which are a mixture of methyl sulfate and hydrogen sulfate salts. In such cases, the products are completely converted to iodides and/or perchlorate salts by dissolution in water and treatment with saturated potassium (or sodium) iodide or dilute perchloric acid, respectively. For example, by applying either:

where R4 is n~ cnii23' ^H3)3C~> cycloheptyl-, or

the methyl sulfate/hydrogen sulfate salts are not separated when the undecyl and cycloheptyl groups are used, upon cooling the reaction mixture.

In these cases, the reaction mixture, the residue, is evaporated in vacuo

is dissolved in water and used for the preparation of the iodide and/or perchlorate without any solvent extraction.

Example 3

Preparation of 5-cyclopropyl-1,2-dimethyl-3-phenylpyrazolium-

perchlorate.

An aqueous solution (500 ml) containing 10 g of 5-cyclopropyl-1,2-dimethyl-3-phenylpyrazolium methyl sulfate is extracted with ether. The aqueous layer is separated and treated with dilute perchloric acid (10 ml) to give a solid. After stirring for one hour, the solid is removed by filtration and dried to give a cream colored solid (6.1 g, 60!) mp 160-161°C.

By analysis, the following is achieved:

Calculated for C14H17C1N2O4: C, 53.75, H, 5.48, N, 8.96, Cl, 11.34

Found: C, 54.0, H, 5.40, N, 8.90, Cl, 11.48.

As indicated in Table IV below, many examples of perchlorates are prepared according to the method of Example 3 above by using the appropriate pure, technical or crude 1,2-dimethyl-3,5-substituted pyrazolium methyl sulfate salt as starting material with the structure:

Example 4

Preparation of 5-cyclopropyl-1,2-dimethyl-3-phenylpyrazolium iodide.

A solution of 5-cyclopropyl-1,2-dimethyl-3-phenylpyrazolium methyl sulfate (12.3 g) dissolved in water (100 ml) is extracted with ether. The aqueous layer is separated and treated with a saturated aqueous solution of potassium iodide. After stirring for 0.5 hour, the solid is separated by filtration and dried to give a straw-colored solid (4.7 g, 36!) with a melting point of 150-152°C. During analysis, the following is noted:

Calculated for C14H17N2I: C, 49.42, H, 5.04, N, 8.24

Found: C, 49.07, H, 5.06, N, 8.16.

Illustrative iodides in Table V below are prepared by the method described above in Example 4 by replacing 5-cyclopropyl-1,2-dimethyl-3-phenyl-pyrazolium methyl sulfate with an appropriate pyrazolium methyl sulfate salt with the structures:

The selective post-emergence herbicidal activity of the compounds according to the invention is demonstrated with the following tests where different monocotyledonous and dicotyledonous plants are treated with the test compounds dispersed in aqueous acetone mixtures. In the tests, the seedlings are grown in jiffy plates for approx. two weeks. The test compounds are dispersed in 50/50 acetone/water mixtures containing 0.51 of a polyoxyethylene sorbitan monolaurate surfactant sufficient to give approx. 0.056 to 0.45 g/m of active compound when applied to the plants through a spray nozzle operating at 2.8 kg/cm pressure for a predetermined time. After spraying, the plants are placed on greenhouse benches and treated in the usual way. Five weeks after the treatment, the seedlings are examined and graded according to the grading system listed below. The data obtained are reproduced in Tables VI and VII below, where it can be seen that the compounds are very effective in controlling many broadleaf weeds and unwanted grass plants.

Plant name abbreviation:

MU - Mustard (Brassica kaber)

PI - Sweet millet ( Amaranthus retroflexus) BA - Chickpea millet ( Echinochloa crusgalli) CR - Finger millet ( Digitaria sanguinalis) WO - Oats (Avena fatua)

WH - Wheat ( Tritisum aestivum)

MG - Wormwort (Ipomoea purpurea)

Barley" (Hordeum vulgare)

VL - "Velvetleaf" ( Abutilon theophrasti) FO - Green bush millet ( Setaria viridis) RI - Rice ( Oryza sativa)

The pre-germination activity of the compounds according to the invention is demonstrated by the following tests where a 50/50 acetone/water mixture containing 0.5 volume! of a surface-active agent consisting of polyoxyethylene sorbitan monolaurate and sufficient test compound to give 1.12 g/m 2 of said compound when the mixture is applied to pots in which seeds of the test plant species have been sown.

The pots are prepared on the same day they are treated with herbicide

to pour 100 ml of soil into each plastic pot as a base, then place seeds

of wormwood, tomato, field oats and nutsedge on this basis and they are covered with 50 ml of soil (1.0 to 1.3 cm). Seeds of each of the other 8 plant species listed below are mixed separately with soil and 50 ml of the soil-seed mixture is added to the pot. The pots are then tamped to level the soil and the soil is pre-moistened with water before the herbicide application. This pre-moistening ensures that the herbicide treatment solution is spread evenly over the surface of the pot and protects the weed seeds from being damaged by acetone. Each of the 12 weed species is contained in a separate pot. The pots are then placed on 25.4x30.5cm plates before chemical treatment.

The sown pots are treated with 5 ml of the test solution and then placed on benches in the greenhouse. The pots are watered after treatment and kept in the greenhouse for three weeks. The results of the treatment are then recorded and the values are given in Table VIII.

Plant species used to determine the effect of the herbicide before germination.

The grading system used in these tests is the same as described in example 7 above.

Claims (2)

1. Pyrazole derivatives with herbicidal activity, characterized in that they have the formula: where R 3 means C 3 -C 7 cycloalkyl, phenyl or C 1 -C 4 -alkyl, R4 means C3~C7-cycloalkyl, C1-C3-alkyl or benzyl, X means an anion with a charge of from 1 to 3, m is an integer from 1 to 3. 2. Compound according to claim 1, characterized in that R3 and R3 are both cyclohexyl.