Patent Publication Number: US-4544651-A

Title: S-2-(Carboalkoxyvinyl) trithiophosphonate insecticides

Description:
This invention relates to a series of trithiophosphonate insecticides having the formula ##STR2## in which R 1  is methyl or ethyl; R 2  is a straight or branched chain alkyl group having from 3 to 5 carbon atoms; R 3  is hydrogen, methyl or carbomethoxy; and R 4  is an alkyl group having from 1 to 4 carbon atoms, together with insecticidal compositions containing such compounds, and methods for their use in controlling insects. 
     Preferably, R 2  is a branched alkyl group, most preferably a branched butyl group such as tertiary butyl or secondary butyl. 
     The term &#34;insects&#34; as used herein refers to the broad and commonly understood usage rather than to those creatures which in the strict biological sense are classified as insects, and includes, in addition to those belonging to the class Insecta, some classes of acarids such as spiders, mites, ticks, and the like, particularly mites. 
     As will be seen from the data which follows, the compounds of this invention demonstrate activity in controlling various types of insects, and particularly mites and Diabrotica. 
     The compounds of the present invention may be prepared in general by a two-step process represented by the following reactions: ##STR3## 
     In the first step the appropriate alkyl thionophosphine sulfide is reacted with two equivalents of a desired mercaptan in the presence of a base to produce a trithioic acid salt. In the second step, the trithioic acid salt is reacted with the appropriate alkynyl ester. 
     The starting alkyl thionophosphine sulfide for Reaction 1 may be obtained by the procedure described in P. E. Newallis, et al., Journal of Organic Chemistry, 1962, Vol. 27, p. 3829. 
     The first step (Reaction 1) is advantageously carried out at a temperature of from about -40° C. to about 150° C., preferably from about 0° C. to about 70° C., in an organic solvent in the presence of a base, particularly a tertiary amine. Suitable solvents include aromatic hydrocarbons such as benzene or toluene, ethers such as diethyl ether or tetrahydrofuran, and ketones such as acetone. Suitable tertiary amines include triethylamine, dimethylaniline, diethylaniline, and pyridine. Inorganic bases such as sodium hydroxide could be used in this step, but are less desirable as the resulting salts are less soluble in the solvents utilized. As the reaction is exothermic, the base is preferably added dropwise when operating on the laboratory scale. The product may be recovered by evaporating or distilling off the solvent. 
     The second step (Reaction 2) is conducted in an organic solvent such as that utilized in the first reaction, at a temperature of from about 20° C. to about 130° C., preferably from about 20° C. to 70° C. The product may be removed by evaporating or distilling off the solvent, and purification by either chromatography or distillation. 
    
    
     The following represent examples of the preparation of compounds of this invention. 
     EXAMPLE 1 
     Preparation of S-t-Butyl S-(2-Carboethoxy-1-vinyl)Ethylphosphonotrithioate (Compound 1 herein) 
     (a) To a slurry of 25.0 grams (g) (0.101 mole) of ethylthionophosphine sulfide in 140 milliliters (ml) of tetrahydrofuran, maintained under nitrogen and at room temperature, was added 23.9 ml (19.09 g, 0.212 mole) of 2-methyl-2-propanethiol. To the resultant solution was added 29.6 ml (21.5 g, 0.212 mole) of triethylamine dropwise and the reaction mixture was refluxed for 4 hours. After cooling, the mixture was evaporated to give 50.3 g of a viscous oil, the triethylamine salt of S-t-butyl ethylphosphonotrithioic acid. 
     (b) To a solution of 3.5 g (0.011 mole) of the triethylamine salt [obtained in step (a)] in 15 ml of tetrahydrofuran, maintained under nitrogen and at room temperature, was added dropwise a solution of 1.1 ml (1.08 g, 0.011 mole) of ethyl propiolate in 10 ml of tetrahydrofuran. The mixture was stirred at room temperature overnight. After addition of 10 ml of water, the mixture was extracted three times with 10 ml portions of ether. The ethereal layers were combined and washed with 20 ml of water and 20 ml of saturated sodium chloride, and dried with magnesium sulfate. Evaporation afforded a clear, orange oil which was further purified by a preparative, centrifugally-accelerated, thin-layer (4 mm, silica gel) chromatograph (with 95:5 hexane-acetone as eluent) to afford 1.24 g (36% of theoretical yield) of the title compound, a clear oil. The structure was confirmed by nuclear magnetic resonance, infrared, and mass spectroscopy. 
     EXAMPLE 2 
     Preparation of S-sec-Butyl S-(2-Carboethoxy-1-vinyl)Methylphosphonotrithioate (Compound  8 herein) 
     Following the procedure as shown in Example 1, step (b), 3.0 g (0.01 mole) of the triethylamine salt of S-sec-butyl methylphosphonotrithioic acid [prepared from methylthionophosphine sulfide, 1-methyl-1-propanethiol, and triethylamine by the procedure shown in Example 1, step (a)] and 2.9 ml (2.81 g, 0.30 mole) of ethyl propiolate afforded 1.30 g (44% of theoretical yield) of the purified title compound. The structure was confirmed by spectroscopic analysis as above. 
     EXAMPLE 3 
     Preparation of S-t-Butyl S-(2-Carbomethoxy-1-methyl-1-vinyl)Ethylphosphonotrithioate (Compound 7 herein) 
     To a solution of 3.55 g (0.0106 mole) of the triethylamine salt of S-t-butyl ethylphosphonotrithioate [prepared by the procedure of Example 1, part (a)] in 15 ml of tetrahydrofuran, maintained under nitrogen and at room temperature, was added dropwise a solution of 1.09 g (0.0111 mole) methyl 2-butynoate in 10 ml of tetrahydrofuran. The mixture was refluxed for 22 hours. On work-up [as in Example 1, step (b)] 0.33 g (10% of theoretical yield) of the purified title compound, an oil, was obtained. The structure was confirmed by nuclear magnetic resonance, infrared, and mass spectroscopy. 
     The following Table I depicts representative compounds of this invention, which may be prepared by the process previously described. Structures of these compounds were confirmed by analysis as above. 
     
                       TABLE I                                                     
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 ##STR4##                                                                 
Compound                               m.p., °C. or                
Number  R.sub.1 R.sub.2  R.sub.3 R.sub.4                                  
                                       n.sub.D.sup.30                     
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1       C.sub.2 H.sub.5                                                   
                t-C.sub.4 H.sub.9                                         
                         H       C.sub.2 H.sub.5                          
                                       1.5820                             
2       C.sub.2 H.sub.5                                                   
                sec-C.sub.4 H.sub.9                                       
                         H       C.sub.2 H.sub.5                          
                                       1.5738                             
3       C.sub.2 H.sub.5                                                   
                t-C.sub.4 H.sub.9                                         
                         H       CH.sub.3                                 
                                       1.5892                             
4       C.sub.2 H.sub.5                                                   
                n-C.sub.3 H.sub.7                                         
                         H       C.sub.2 H.sub.5                          
                                       1.5811                             
5       CH.sub.3                                                          
                t-C.sub.4 H.sub.9                                         
                         H       C.sub.2 H.sub.5                          
                                       1.5857                             
6       CH.sub.3                                                          
                t-C.sub.4 H.sub.9                                         
                         H       CH.sub.3                                 
                                       55-58                              
7       C.sub.2 H.sub.5                                                   
                t-C.sub.4 H.sub.9                                         
                         CH.sub.3                                         
                                 CH.sub.3                                 
                                       1.5830                             
8       CH.sub.3                                                          
                sec-C.sub.4 H.sub.9                                       
                         H       C.sub.2 H.sub.5                          
                                       1.5818                             
9       C.sub.2 H.sub.5                                                   
                sec-C.sub.4 H.sub.9                                       
                         COOCH.sub.3                                      
                                 CH.sub.3                                 
                                       thick oil                          
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     INSECTICIDAL EVALUATION TESTS 
     The compounds in Table I above were tested for insecticidal activity using the following testing procedures. LD-50 values, based on the results of these tests, and calculated according to dosage-mortality curves, are expressed in Table II. 
     Housefly [Musca domestica] 
     Test compounds were diluted in acetone and aliquots pipetted onto the bottom of aluminum dishes. To insure even spreading of the chemical on the bottom of the dishes, 1 ml of acetone containing 0.01% peanut oil was also added to each dish. After all solvents had evaporated, the dishes were placed in circular cardboard cages containing 25 female houseflies, 1-2 days old. The cages were covered on the bottom with cellophane and on the top with tulle netting, and each contained a sugar-water saturated cotton plug for maintenance of the flies. Mortality was recorded after 48 hours. Test levels ranged from 100 ug/25 female houseflies downward. The LD-50 values are expressed below in Table II under the heading &#34;HF-C&#34;, in terms of ug of the test compound per 25 female flies. 
     Black Bean Aphid [Aphis fabae (Scop.)] 
     Nasturtium plants (Tropaeolum sp.) approximately 5 cm tall, were transplanted into sandy loam soil in 3-inch clay pots and infested with 25-50 black bean aphids of mixed ages. Twenty-four hours later they were sprayed to the point of runoff with 50-50 acetone-water solutions of the test compounds. Treated plants were held in the greenhouse and mortality was recorded after 48 hours. Test concentrations ranged from 0.05% downward. The LD-50 values are expressed below in Table II under the heading &#34;BA-C&#34; in terms of percent of the test compound in the sprayed solution. 
     Tobacco Budworm [Heliothis virescens (Fabricius)] 
     (a) Contact: Test compounds were diluted in a 50--50 acetone-water solution. Cotton (Gossypium sp.) cotyledons were immersed in the test solutions for 2-3 seconds and placed on a wire screen to dry. The dried leaves were placed in petri dishes containing a moistened piece of filter paper and infested with 5 second-instar tobacco budworm larvae. The dishes were placed in a high humidity chamber for 5 days, and percent mortality of the larvae recorded. Test concentrations ranged from 0.1% downward. The LD-50 values are expressed below in Table II under the heading &#34;TBW-C&#34; in terms of percent of the test compound in the solution. 
     (b) Eggs: Paper towel patches of 2-day old eggs of the tobacco budworm were dipped in acetone solutions of the test compounds and placed in petri dishes containing a portion of larval rearing medium. Treated eggs were maintained at 78° F. and mortality was recorded after all control eggs had hatched and the young larvae were feeding on the media. Test concentrations ranged from 0.1% downward. The LD-50 values are expressed below in Table II under heading &#34;TBW-E&#34; in terms of percent of the test compound in the solution. 
     Western Spotted Cucumber Beetle Larvae [Diabrotica undecimpunctata undecimpunctata (Mannherheim)] 
     Ten grams of moist potting soil was placed in a plastic cup. Test compounds were dissolved in acetone or another appropriate solvent. A 0.05 ml aliquot of the test sample, diluted to the desired concentration, was added to the soil. The cup was capped and the soil was mixed on a vortex mixer for aproximately 15 seconds. An indentation was made on the surface of the soil and approximately 50 Diabrotica eggs were added. The eggs were covered with soil and maintained at room temperature (approximately 70° F. or 21° C.). Four days later a section of Romaine lettuce (Latuca sativa) leaf was placed in the treated cups. One week later the cups were examined for live larvae. Test concentrations ranged from 25 ppm downward. The LD-50 values are expressed below in Table II under the heading &#34;Diabrotica&#34; in terms of ppm of the test compound in the soil. 
     Acaricidal Evaluation Test 
     The two-spotted mite (2SM) [Tetranychus urticae (Koch)] was employed in tests for miticides. The test procedure was as follows: 
     Pinto bean plants (Phaseolus sp.) approximately 10 cm tall, were transplanted into sandy loam soil in 3-inch clay pots and thoroughly infested with two-spotted mites of mixed ages and sexes. Twenty-four hours later the infested plants were inverted and dipped for 2-3 seconds in 50--50 acetone-water solutions of the test compounds. Treated plants were held in the greenhouse, and 7 days later mortality was determined for both adult mites and the nymphs hatching from eggs which were on the plants at the time of treatment. Test concentrations ranged from 0.05% downward. The LD-50 values are expressed below in Table II under the headings &#34;2SM-A&#34; (i.e., adults) and &#34;2SM-E&#34; (i.e., eggs) in terms of percent concentration of the test compound in the solution. 
     
                       TABLE II                                                    
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(LD.sub.50)                                                               
                                          Dia-                            
                                          bro-                            
                                          tica,                           
Cmpd. HF-C,   BA-     2-SM      TBW       ppm                             
No.   μg   C, %    A, %  E, %  C, %  E, %  (soil)                      
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1     3       0.03    0.002 0.03  &gt;0.1  0.03  1                           
2     3       0.01    0.002 0.03  0.05  0.02  0.75                        
3     2       0.01    0.006 0.05  0.08  0.01  2                           
4     100     &gt;0.05   0.006 0.03  &gt;0.1  0.1   2                           
5     100     0.05    0.006 0.05  &gt;0.1  0.02  0.75                        
6     3       0.03    0.006 &gt;0.05 &gt;0.1  0.02  0.4                         
7     &lt;100    0.003   0.003 0.03  &lt;0.1  &lt;0.1  7.5                         
8     100     0.003   0.001 0.03  0.08  0.03  0.75                        
9     &gt;100    0.05    &gt;0.05 0.006 &gt;0.1  &gt;0.1  7.5                         
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 Key:                                                                     
 C = Contact Test                                                         
  E = Test on eggs                                                        
 A = Test on adults                                                       
 
    
     In practice, a pure compound can be used as an insecticide. However, in general, the compounds are first formulated with one or more inert (i.e. non-chemically reactive, plant compatible or herbicidally inert) carriers or diluents suitable for insecticidal use, before being applied. 
     The compositions or formulations, including a compound as described herein, may take any one of a number of solid or liquid forms. Examples of solid forms are dusts, granules, tablets, powders and the like. Examples of liquid forms are emulsions, solutions, suspensions, flowables, emulsifiable concentrates and pastes. Such compositions may contain, in addition to the active compound or compounds, various carriers or diluents; surface-active agents (wetting agents, dispersing agents and/or emulsifying agents); solvents (water, or organic solvents such as aromatic solvents or chlorinated aliphatic solvents); adhesives; thickeners; binders, anti-foaming agents; and other substances as mentioned herein. Solid carriers or diluents included in such compositions or formulations may include, for example, ground natural minerals such as kaolins, alumina, calcium carbonate, silica, kieselguhr, clays, etc.; ground synthetic minerals such as various silicates and aluminosilicates and ground vegetable products such as bark, cornmeal, sawdust, cellulose powder and the like. 
     To manufacture solid compositions, the active substances are mixed with solid carriers or diluents such as those mentioned above and the mixture is ground to the appropriate size. Granules can be manufactured by dissolving an active compound in an organic solvent and applying the mixture, for example, by atomization, onto an absorptive granulated inert material, such as silica. Adhesives may be utilized to assist in the incorporation of the compound onto the solid particles. 
     Wettable powders and pastes are obtained by mixing and grinding an active compound with one or more dispersing agents and/or solid carriers or diluents. Also included may be wetting agents and/or dispersing agents, for example, lignins, methyl cellulose, naphthalenesulfonic acid derivatives, fatty alcohol sulfates and various types of akali and alkaline earth metal salts of fatty acids. 
     Emulsifiable concentrates are generally obtained by dissolving the active compound in an organic solvent, for example, butanol, cyclohexanone, xylenes, or higher boiling aromatic hydrocarbons. To obtain suspensions or emulsions in water, wetting agents may also be added. 
     Flowables are prepared by mixing an active compound with one or more dispersing agents and/or solid additives, and a liquid (which may be water or an organic solvent) in which the active compound is relatively insoluble, and grinding the mixture. 
     Both liquid and solid compositions may be in microcapsule or encapsulated form, to permit release of the enclosed active compound at a controlled rate over a period of time. Liquid compositions of this type contain encapsulated droplets of approximately 1-50 microns in diameter, including the active compound and optionally a solvent. The encapsulating material is an inert porous membrane of a polymeric material. 
     Solid encapsulated compositions generally take the form of granules, in which the liquid containing the active component is trapped in the pores of the granular support by a porous polymeric membrane through which the active ingredient may migrate at a controlled rate, or which membrane breaks down at a controlled rate to permit escape of the active ingredient. 
     Typical encapsulating materials include natural and synthetic rubbers, cellulosic materials, styrene-butadiene copolymers, polyacrylonitriles, polyacrylates, polyamides, polyisocyanates, polyurethanes, mixed copolymers of the foregoing and starch xanthates. 
     It is possible to use highly concentrated liquid compositions containing up to about 95% by weight of the active compound, or even the 100% active compound alone, when applying the compound in the form of a finely divided liquid by use of various atomizing equipment, for example by airplane spraying techniques. For other purposes, however, the various types of compositions which can be utilized for these compounds will contain varying amounts of the compound according to the type of composition and the intended use. 
     In general, insecticidal compositions may contain from 5 to 95% of the active compound, more preferably from 10 to 85%. Some typical compositions will contain an active compound as follows: wettable powders: 25 to 80% active compound; oil suspensions, emulsions, solutions, flowables, and emulsifiable concentrates: 5 to 85% active compound; aqueous suspensions: 20 to 50% active compound; dusts and powders: 5 to 20% active compound; granules and pellets: 5 to 20% active compound. 
     In addition to the active compound and the various agents utilized in preparing compositions and formulations mentioned, such compositions may also contain one or more other active compounds of the type mentioned herein as well as other active pesticidal agents, such as herbicides, fungicides, insecticides, acaricides, nematocides, bactericides, and plant growth regulators. Such compounds may also contain soil disinfectants or fumigants and may further contain fertilizers, thus making it possible to provide a multi-purpose compositions containing one or more of the active compounds described herein as well as, optionally, other pesticides and also fertilizers, all intended and formulated for use at the same locus. 
     Control of insect pests is accomplished by applying a composition containing an insecticidally effective amount of an active compound as described herein to the insect, to a locus at which insecticidal control is desired, or to food sources (including seeds) on which the insects feed. For use in the last mentioned manner it is preferable to utilize a compound which is not volatile. Thus, control may be achieved by direct application of the active compounds to the insects and indirectly by application of the compounds to a locus to be protected (such as crop lands, grass ranges and forests), to a source of food for insects or to other insect habitats (for example, breeding or swarming areas). The rates of application of the active compound, and the concentration applied, will vary according to whether the compound or composition is being directly applied to the insect or indirectly, to a locus, food or habitat. In the latter case the rate of the application, depending on the nature of the insect or insects to be controlled, and the plant environment, will generally vary from about 0.01 to about 100 pounds per acre (about 0.012 to about 112 kg/ha). 
     It should be noted that the active compound need not be insecticidally active per se to effect insect control. The purposes of this invention are fully served if such compounds are rendered active by external influences, such as light or heat, or by some physiological action which occurs when the compound is ingested into the body of the insect. 
     Compositions containing one or more of the active compounds described, in an insecticidally effective amount, may be applied to the plant, locus or insect habitat in any conventional manner. 
     When used in connection with crop or other plant protection, application may be made in a preventive (i.e. before infestation) or eradicative manner (i.e., after infestation). Thus, powders and various liquid compositions containing the active compound can be applied by the use of power dusters, boom and hand sprayers and spray dusters, or applied from airplanes as dusts or sprays. When applied in the latter method they may be effective in very low dosages. 
     Compositions including active compounds may also be applied by addition to irrigation waters supplied to the field to be treated. This method of application permits penetration of the compounds into the soil as the water is absorbed therein. 
     Compositions including active compounds may additionally be used to protect plant seeds from being attacked by soil-borne insect pests after planting and during germination, by applying the composition to the seeds as a seed dressing. This is performed generally by mixing the seeds with an active composition in either liquid or solid form (preferably liquid) in a suitable mixing apparatus. Liquid compositions for this purpose may contain an adhesive or sticking agent, such as methyl cellulose, ethyl cellulose, etc., to assist the composition in adhering to the seed. If a solid composition is utilized for this purpose, an adhesive agent may be sprayed on the seeds during or after mixing. 
     For use as a soil insecticide, the active compound, or compositions containing it, may be mixed with the soil in any conventional manner, before, during or after planting of the plant seeds. Liquid compositions may be applied by spraying onto the surface or by incorporation in irrigation or sprayed water. Solid or liquid compositions containing an active compound may be incorporated into the soil prior to or during planting by discing, plowing or other mixing operations, in order to locate the active ingredient below the surface of the soil so as to be most effective in controlling undesirable larvae. 
     Some examples of compositions containing the active compounds of this invention are: 
     
         ______________________________________                                    
Component               Weight %                                          
______________________________________                                    
Composition A: Granular Solid                                             
Compound 1              10                                                
attapulgite clay granules                                                 
                        90                                                
Total                    100%                                             
Composition B: Wettable Powder                                            
Compound 2              80                                                
wetting agent (sodium dialkyl-                                            
                         1                                                
naphthalene sulfonate)                                                    
dispersing agent (sodium                                                  
                         4                                                
lignosulfonate)                                                           
diluent (aluminum magnesium                                               
                        15                                                
silicate)                                                                 
Total                    100%                                             
Composition C: Dilute Solution                                            
Compound 3               5                                                
solvent (xylene)        95                                                
Total                    100%                                             
Composition D: Emulsifiable Concentrate                                   
Compound 4              50                                                
Emulsifier (blend of metal                                                
                        10                                                
sulfonates and polyoxy-                                                   
ethylene ethers)                                                          
solvent (xylene)        40                                                
Total                    100%                                             
Composition E: Concentrated Solution                                      
Compound 5              90                                                
solvent (xylene)        10                                                
Total                    100%                                             
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