# Patent

## Title
7.beta.-Acylamino-3-(alkanesulfonamidoalkyl substituted

## Abstract

This application is a continuation-in-part of application Ser. No. 555,884, filed on Mar. 6, 1975, now U.S. Pat. No. 3,989,824.

## Background
This invention relates to the control of insects. This invention further relates to compositions for controlling insects and acarids that can be applied directly to these organisms, their eggs or to substrates, particularly plants, that are infested with these organisms.

Numerous phosphorus compounds have been disclosed as being effective control agents for insects and acarids. For example, U.S. Pat. No. 2,754,242 teaches using alkyl bis(halophenyl)phosphinates to kill two-spotted spider mites. Many of these compounds are not practical for commercial use, since they must be present at relatively high concentration levels (500 parts per million or more) to be effective. The in-use cost of these prior art materials may therefore be so high as to exclude them for large-scale applications.

It has now been found that certain tertiary bis(halophenyl)phosphines, phosphine oxides and phosphine sulfides are remarkably effective insecticides and acaricides that can be employed at lower concentration levels than heretofore possible using many structurally related prior art materials, including those disclosed in the aforementioned U.S. Pat. No. 2,754,242.

This invention provides a method for killing insects and sterilizing eggs of insects and acarids by applying to said insects, said eggs or to substrates susceptible to infestation with said insects or acarids an insecticidally and ovicidally effective amount of a phosphorus compound exhibiting the formula: ##STR1## wherein R is selected from the group consisting of alkyl radicals containing between 1 and 12 carbon atoms, alkenyl and alkynyl radicals containing between 2 and 12 carbon atoms, cycloalkyl, aryl, alkaryl, aralkyl and haloalkyl radicals, X represents a halogen atom selected from the group consisting of fluorine, chlorine, bromine and iodine atoms and Z represents oxygen or sulfur.

The present insecticides and ovicides are tertiary bis(p-halophenyl)phosphines, phosphine oxides and phosphine sulfides. When R of the preceding formulae represents an alkyl radical, it may contain one or more halogen atoms as substituents. These compounds effectively control insects at considerably lower concentrations that can be achieved using structurally related compounds, such as the aforementioned bis(halophenyl)phosphinates that are disclosed in the chemical and patent literature. The comparative efficacy of the present compounds and the criticality of the substituents on both the phenyl radicals and the phosphorus atom are demonstrated in the accompanying examples. In addition to killing the nymph and adult stages of insects, the present compounds also inhibit development of the eggs of both insects and acarids. At lower concentrations the present compounds function as chemosterilants.

While many known insecticides and ovicides are effective when sprayed onto infested plant leaves, the present compounds are unique in that they can also be applied to the soil surrounding the roots of the plant and are transported by the plant to the leaves, where insects and eggs are killed.

Many of the present tertiary bis(halophenyl)phosphines are disclosed in the chemical literature. The phosphines are conveniently prepared by reacting the appropriate halophenyl magnesium halide and dichloroorganophosphine. The dichloroorganophosphines are either available from commercial suppliers or can be synthesized using known preparative methods, for example those disclosed in "Organophosphorus Compounds" by G. M. Kosolapoff, published by John Wiley and Sons, Inc. The resultant bis(halophenyl)organophosphine is readily converted to the corresponding phosphine oxide or phosphine sulfide by reacting the phosphine with hydrogen peroxide or elemental sulfur, respectively.

Alternatively, the phosphine oxides can be prepared directly from a halophenylmagnesium halide by reacting it with the appropriate organophosphonic dichloride, ##STR2##

The following examples provide specific methods for preparing and using representative compounds encompassed by the accompanying claims. All parts and percentages are by weight.

To 900 cc. of a solution containing 1.143 moles of p-chlorophenylmagnesium bromide dissolved in tetrahydrofuran was added 73 g. (0.55 mole) of methylphosphonic dichloride ##STR3## dissolved in 400 cc. of tetrahydrofuran. The addition required two hours, during which time the reaction mixture was stirred and the temperature maintained at between 30.degree. and 40.degree. C. Following completion of the addition the reaction mixture was heated to the boiling point for one hour, cooled and then extracted using 2 liters of chloroform. The chloroform layer was then dried using anhydrous magnesium sulfate and the solvent removed under reduced pressure. The solid residue was recrystallized once from benzene to yield 90 g. of a white solid that melted between 167.degree. and 169.degree. C. Analysis of the recrystallized product revealed a phosphorus content of 10.9% and a chlorine content of 22.3%. The calculated phosphorus and chlorine content of bis(p-chlorophenyl)methylphosphine oxide is 10.9 and 24.9%, respectively. The structure of the compound was confirmed by nuclear magnetic resonance.

To a solution containing 69 g. (0.39 mole) of chloromethylphosphonic dichloride and 400 cc. tetrahydrofuran was added 285 cc. of a tetrahydrofuran solution containing 0.789 mole of p-chlorophenylmagnesium bromide. The addition was dropwise and required two hours, during which time the temperature of the reaction mixture was maintained at 30.degree. C. Following completion of the addition the mixture was stirred for two hours while the temperature was maintained at 60.degree. C. After the mixture had cooled to ambient temperature 400 cc. of water were gradually added, followed by 1200 cc. of methylene chloride. The organic layer was then separated, dried using anhydrous magnesium sulfate and the methylene chloride removed under reduced pressure. The residue was passed through a column of neutral alumina using ethyl acetate as the eluent. The white solid obtained following removal of the eluent and one recrystallization of the residue from benzene weighed 90 g., melted between 114.degree. and 117.degree. C. and exhibited the following analysis: chlorine - 32.8%; phosphorus - 9.89%. The calculated values for bis(p-chlorophenyl)chloromethylphosphine oxide are 33.3 and 9.70%, respectively. The nuclear magnetic resonance spectrum was consistent with the desired structure.

To 12.6 g. of magnesium turnings was gradually added a solution containing 96 g. (0.50 mole) of p-chlorobromobenzene and 180 cc. tetrahydrofuran. The reaction mixture was stirred and maintained under a nitrogen atmosphere during the addition, following which the contents of the vessel were heated to reflux temperature for two hours. When the reaction mixture had cooled, a solution of methyldichlorophosphine (29.3 g., 0.25 mole) in 25 cc. tetrahydrofuran was gradually added. Following completion of this addition the reaction mixture was heated to reflux temperature for two hours. When the mixture had cooled it was slowly poured into 500 cc. of cold water and then acidified to a pH of 5 using aqueous hydrochloric acid. The resultant aqueous solution was extracted using chloroform. The organic layer was then dried over anhydrous magnesium sulfate and the chloroform removed under reduced pressure. The residue remaining following removal of the chloroform weighed 64 g. and was distilled, the fraction boiling at between 155 and 160 under a pressure of 0.5 mm. Hg being collected. This distillate converted to a white solid upon cooling. The solid material weighed 34 g. and exhibited the following analysis: Found     Calculated ______________________________________ Phosphorus    10.9%       11.5% Chlorine      25.9%       26.4% ______________________________________

Bis(p-chlorophenyl)propylphosphine was prepared by reacting 0.2 mole of propyldichlorophosphine with 0.4 mole of p-chlorophenylmagnesium bromide. The product was isolated by chloroform extraction and distillation as previously described. The portion boiling between 160.degree. and 165.degree. C. under a pressure of 2 mm. Hg was collected. The analysis corresponded to bis(p-chlorophenyl)propylphosphine.

An 18 g. (0.061 mole) portion of the phosphine was combined with 150 cc. benzene, followed by 2.1 g. (0.065 mole) of sulfur. The resultant mixture was stirred for one hour and the solvent removed under reduced pressure. Following one recrystallization from diethyl ether the solid product weighed 16 g. and melted between 102.degree. and 107.degree. C. This product was found to contain 9.21% phosphorus, 22.2% chlorine and 8.33% sulfur. The calculated values for bis(p-chlorophenyl) propylphosphine sulfide are 9.42, 21.6 and 9.73%, respectively.

When employed to control insects and acarids the present phosphines, phosphine oxides and phosphine sulfides can be applied directly onto the insects, eggs, infested plants or to plants and other substrates which are susceptible to infestation by insects and acarids. The long term residual activity and low phytotoxicity that characterize the present toxicants makes it possible to apply these compounds to plants several days, and in some instances weeks, prior to the time when the plant will be exposed to insects or acarids.

The present compounds are conventionally applied to plants as a liquid spray, solid dust or a wettable powder.

Compositions suitable for spraying are usually prepared by diluting liquid concentrates or wettable powders containing between 10 and 90% of the active toxicant. To avoid the expense of transporting formulations containing large amounts of inert diluents, the final dilution is usually performed at the location where the composition will be applied. The concentration of toxicant in a spray for large scale applications is between 10 and 1000 parts per million (ppm), preferably between 100 and 500 parts per million.

Solid dust compositions, which are generally applied over a relatively small area, contain between 1 and 50% by weight of active toxicant, preferably between 1 and 10%.

The concentration of toxicant required in a given formulation will be dependent upon a number of parameters including the method of application, i.e. whether at ground level or from aircraft, the activity of the particular toxicant against a given insect or acarid and weather conditions in the area being treated.

In the preparation of dust compositions or wettable powders, the present toxicants can be blended with many commonly employed finely divided solids, such as fuller's earth, attapulgite, bentonite, pyrophyllite, vermiculite, diatomaceous earth, talc, chalk, gypsum, wood flour, and the like. The finely divided carrier is ground or mixed with the toxicant or wetted with a dispersion of the toxicant in a volatile liquid. Depending upon the proportions of ingredients, these compositions can be employed as concentrates and subsequently diluted with additional solid carriers to obtain the desired amount of active toxicant. Also, such concentrate dust compositions can be incorporated in intimate admixture with surface active dispersing agents such as ionic or nonionic emulsifying or dispersing agents to form spray concentrates. Such concentrates are readily dispersible in liquid carriers to form spray compositions or liquid formulations containing the toxicants in any desired amount. The choice of surface active agent and amount employed are determined by the ability of the agent to facilitate the dispersing of the concentrate in the liquid carrier to produce the desired liquid composition. Suitable liquid carriers include water, methanol, ethanol, isopropanol, methyl ethyl ketone, acetone, methylene chloride, chlorobenzene, toluene, xylene, and petroleum distillates. Among the preferred petroleum distillates are those boiling almost entirely under 205.degree. C. at atmospheric pressure and having a flash point above about 30.degree. C.

Alternatively, the toxicant may be compounded with a suitable water-immiscible organic liquid and a surface active dispersing agent to produce emulsifiable concentrates which may be further diluted with water and oil to form spray mixtures in the form of oil-in-water emulsions. In such compositions, the carrier comprises an aqueous emulsion, i.e. a mixture of water-immiscible solvent, emulsifying agent and water. Preferred dispersing agents which may be employed in these compositions are oil soluble and include the condensation products of alkylene oxides with phenols and organic or inorganic acids, polyoxyethylene derivatives of sorbitan esters, alkylarylsulfonates, complex ether alcohols, mahogany soaps and the like. Suitable organic liquids to be employed in the compositions include petroleum distillates, hexanol, liquid halohydrocarbons and synthetic organic oils. The surface active dispersing agents are usually employed in the liquid dispersions and aqueous emulsions in the amount of from about 1 to about 20 percent by weight of the combined weight of the dispersing agent and the active toxicant.

The following examples demonstrate the efficacy of the present compounds as insecticides and ovicides. Formulations were prepared by dissolving the compound to be tested in a mixture of acetone and a liquid alkyl-aryl polyether alcohol type surfactant (Triton.RTM. X-155) and diluting the resultant composition to the desired concentration using a water-acetone mixture such that the final formulation contained 10% acetone and 10 parts per million (ppm) of the surfactant.

The activity of a given compound as a contact acaricide against the two-spotted spider mite (Tetranychus urticae) was determined by transferring adult and nymph mites to the leaves of Sieva lima bean plants. Twenty four hours following the transfer the leaves were either sprayed with or dipped into the aforementioned formulation containing 200 ppm of the compound to be tested. If the compound was to be evaluated as a systemic acaricide and ovicide 21 cc. of a formulation containing 520 ppm of the active compound was poured into the soil surrounding the infested plant.

Nine to twelve days following application of the formulation the leaves of all plants were examined using a microscope to determine the number of dead mites and eggs.

The following compounds were found to be effective contact type acaricides at a concentration of 200 ppm, in that they killed at least 70% of the adult mites, nymphs and/or eggs.

The following compounds, which are structurally related to the present acaricides, were ineffective in controlling spider mites or their eggs (less than 30% of mites or eggs killed) at a concentration of 200 ppm.

Two of the most effective acaricides, bis(p-chlorophenyl)methylphosphine oxide (A) and bis(p-chlorophenyl) chloromethylphosphine oxide (B) were evaluated further to ascertain the lowest concentration at which these compounds are effective. The data from this test are summarized in the following table, together with the results obtained using N'(4-chloro-o-tolyl)N,N-dimethylformamidine (Galecron.RTM.), a commercially accepted miticide and ovicide. All plant were rated twelve days after being sprayed with the test formulation. CONCENTRA-   % CONTROL   NO. OF COM-     TION         OF ADULT    DEAD POUND    (PPM)        MITES       EGGS ______________________________________ A        400          100         525 100          68          545 25          53          -- B        400          100         605 100          90          670 25          94          -- Galecron.sup..RTM. 400          65          135 (control) 100          0           -- 25          0           -- ______________________________________

A formulation containing 100 ppm of bis(p-chlorophenyl)chloromethylphosphine oxide was poured onto the soil surrounding the roots of a Sieva lima bean plant which was infested with spider mites and eggs. Six days later 97% of the adult mites and 90% of the eggs were dead on one leaf. Examination of a second leaf revealed that 100% of the eggs had been killed.

This example demonstrates the efficacy of bis(p-chlorophenyl)methylphosphine oxide as an insecticide and ovicide for the Mexican bean beetle.

Newly hatched Mexican bean beetles were confined in a cage for two days together with a number of untreated bean plants. On the third day the beetles were classified according to sex. Seven female and five male beetles were confined in a cage together with six bean plants which had been previously treated with an aqueous dispersion of the test compound. The dispersion was prepared by dissolving the required amount of compound in a small amount of acetone together with 1000 parts per million (ppm) of a nonionic surfactant, an alkyl aryl polyether alcohol available as Triton.RTM. X-155 from the Rohm and Haas Company. The amount of acetone employed was calculated such that the final dispersion obtained following addition of the required amount of water contained 100 ppm of the surfactant. The resultant dispersion containing a specified concentration of the test compound was sprayed onto the leaves of the bean plants just prior to introduction of the beetles. Two days following this introduction a mortality count was taken. On the following day any egg clusters present were collected and six untreated plants were placed in the cage together with the beetles. The egg clusters, together with the area of the leaf on which they resided, were removed and placed in a petri dish which remained for five days in an incubator maintained at a temperature of 78.degree. C. and a relative humidity of 90%. Egg clusters were also collected on the next two days from both the treated and untreated plants. Following removal from the incubator the egg clusters were placed in transparent containers together with untreated bean plant leaves. The percentage of eggs from each cluster which produced larvae was observed and recorded. Any larvae which emerged were transferred to untreated bean plants for observation.

The compounds tested were bis(p-chlorophenyl)methylphosphine oxide (A) and bis(p-chlorophenyl)chloromethylphosphine oxide (B). While neither compound killed adult Mexican bean beetles, both compounds are effective ovicides, as demonstrated by the data in the accompanying table. Only a small fraction of the eggs matured into larvae. The number of egg clusters deposited was significantly reduced relative to beetles which fed on only untreated leaves. The two compounds tested exercise control by significantly reducing the second generation population. Concentra-          No. of Egg % Egg Viability.sup.1 tion  No. of Live Clusters  Untreated Treated Compound (ppm) Adults  Evaluated Leaves   Leaves __________________________________________________________________________ A     260   12      6  (untreated) 0,0,0,0,10,10 6  (treated)       0,0,0,0,0,0 A     130   12      9  (untreated) 0,0,0,0,0,0,0, 3  (treated) 0,100    0,0,0 B     260   10      4  (untreated) 0,0,0,0 7  (treated)       0,0,0,0,0,75,50 B     130   12      3  (untreated) 0,0,50 5  (treated)       0,100,100,25,0 Control --    13      12        100      -- __________________________________________________________________________ .sup.1 Values given for each cluster evaluated.?

Four pair of adult Mexican bean beetles were allowed to feed on untreated bean plants for several days and then transferred to a cage containing bean plants which had previously been sprayed to run-off with an aqueous dispersion containing 260 ppm of either bis(p-chlorophenyl)isopropylphosphine oxide or bis(p-chorophenyl)t-butylphosphine oxide. All of the beetles were dead after feeding on the treated foliage. A control group of the same size which was feeding on untreated plants exhibited no adverse effects.

The dispersion employed to spray the bean plants was prepared as described in the preceding Example 6.

## Claims

1. A method for killing insects and sterilizing their eggs by applying to said insects, eggs or to substrates susceptible to infestation with said insects an insecticidally and ovicidally effective amount of a phosphorus compound exhibiting the formula: ##STR4## wherein R is selected from the group consisting of alkyl and haloalkyl radicals containing between 1 and 12 carbon atoms, X represents a halogen atom selected from the group consisting of fluorine, chlorine, bromine and iodine and Z represents oxygen or sulfur.

2. The method of claim 1 wherein the phosphorus compound is present in combination with an inert liquid or inert solid diluent at a concentration of between 1 and about 500 parts per million.

3. The method of claim 1 wherein X is chlorine.

4. The method of claim 1 wherein R is a methyl, chloromethyl, ethyl, isopropyl or t-butyl radical.

5. The method of claim 1 wherein the substrate is a plant.

6. The method of claim 5 wherein the phosphorus compound is applied to the leaves of said plant.

7. The method of claim 5 wherein the phosphorus compound is applied to the soil adjacent to the roots of said plant.