Pyridazinothionophosphoric (-phosphonic) acid esters
United States Patent Lorenz et al.  
 1 Apr. 15, 1975 1 PYRIDAZINOTHIONOPHOSPHORIC (-PHOSPHONIC) ACID ESTERS [75] Inventors: Walter Lorenz,  
 WuppertalCronenberg; Ingeborg Hammann, Cologne, both of Germany [73] Assignee: Bayer Aktiengesellschaft,  
 Leverkusen, Germany [22] Filed: Sept. 23, 1970 [211 App]. No.: 74,864  
 [30] Foreign Application Priority Data Oct. 7, 1969 Germany 1950491 [52] U.S. Cl 260/250 AP; 424/250 [51] Int. Cl C07d 51/04 [58] Field of Search 260/250 [56] References Cited UNITED STATES PATENTS 3,100,206 8/1963 Rigterink 260/250 A 3,544,572 12/1970 Fest .f. 260/250 A Primary Examiner- Nicholas S. Rizzo Attorney, Agent, or FirmBurgess, Dinklage &amp;  
 Sprung [57] ABSTRACT Pyridazinothionophosphoric (-phosphonic) acid esters which possess arthropodicidal, especially insecticidal or acaricidal, properties. The compounds have the structure l R O-P I in which R is a lower alkyl or phenyl radical, R is a branched or straight-chain lower alkyl radical, and R is a branched or straight-chain lower alkoxy or alkyl or phenyl radical.  
 11 Claims, No Drawings in which R&#39;is a lower alkyl or phenyl radical.  
 R, is a branched or straight-chain lower alkyl radical.  
 and  
 R is a branched or straight-chain lower alkoxy or alkyl or phenyl radical.  
  These compounds are distinguished by a strong insecticidal and acaricidal activity.  
  The&#39;invention also provides a process for the production of a pyridazinothionophosphoric (-phosphonic) acid ester of the formula (I) in which a thionophosphoric (-phosphonic) acid ester halide of the formula \ll Hal 11 2 is reacted with a o-hydroxypyridazino derivative of the formula R Won (1 11 in which R. R, and R have the meanings stated above. and  
  Hal stands for a halogen atom in the presence of an acid acceptor or in the form of an alkali metal. alkaline earth metal or ammonium salt.  
  Surprisingly, the pyridazinothionophosphoric (phosphonic) acid esters according to the invention show a considerably stronger insecticidal and acaricidal activity than the known hydroxypyridazino(thiono)- phosphoric acid esters of analogous constitution and the same direction of activity. The substances according to the invention therefore represent a genuine enrichment of the art.  
  lf 3-methyl-o-hydroxypyridazine and 0,0-diethylthionophosphoric acid ester chloride are used as starting materials, the reaction course can be represented by the following formula scheme:  
 IIIa 11a The starting materials to be used are unambiguously defined generally by the formulae (ll) and (Ill).  
  Advantageously. R is a branched or straight-chain alkyl radical with l to 4 carbon atoms. such as methyl. n-. iso-. sec.- or tert.-butyl and especially of 2 to 3 carbon atoms such as ethyl. nor iso-propyl; and R is such a radical or alkoxy of l to 4 carbon atoms or phenyl. preferably methyl, ethyl. ethoxy. nor iso-propoxy and. again. phenyl. Hal is preferably a chlorine atom. Preferably. R is a methyl or phenyl radical.  
  As examples of the thionophosphoric (-phosphonic) acid ester halides which can be used, there are mentioned in particular: 0,0-diethyl-, 0,0-diisopropyl-. 0.0-dibutyl-. 0,0-ditert.- butyl-, 0-ethyl-O-isopropyl-. 0-ethyl-0-propyl-, O-ethyl- 0-butyl-. O-isopropyl-O-butyl and O-propyl-O-butylthionophosphoric acid ester chloride or bromide. 0-ethyl-ethane-, 0-propyl-ethane-, ()-isopropyl-ethane-. O-ethyl-propane- 0-cthyI-isopropane-. 0ethyl-butane-. O-isopropyl-propane-. 0-ethyl-benzene-. O-isopropylbenzeneand O-butylbenzene-thionophosphonic acid ester chloride or bromide.  
  The acid halides and pyridazine derivatives to be used as starting materials are known and can be prepared according to known methods.  
  The reaction may be carried out in the presence of a solvent which term includes a mere diluent. All inert organic solvents are suitable. These include all aliphatic and aromatic (possibly chlorinated) hydrocarbons. such as benzene. toluene, xylene. benzine. methylene chloride. chloroform. carbon tetrachloride. chlorobenzene; ethers. such as diethyl ether. dibutyl ether. dioxane; ketones. such as acetone. methylethyl ketone. methylisopropyl ketone. methylisobutyl ketone; nitriles, in particular acetonitrile; and the like.  
  As acid acceptors, all customary acid-binding agents are suitable. Particularly suitable have proved to be alkali metal carbonates and alcoholates, such as sodium and potassium carbonate, methylate or ethylate; aliphatic. aromatic or heterocyclic amines. for example triethylamine, dimethylamine. dimethylaniline. dimethylbenzylamine, pyridine. and the like.  
  The reaction temperatures can be varied within a fairly wide range. In general, the reaction is carried out at about 10 to C. preferably at 40 to 50C.  
 The reaction is. in general, carried out at normal pressure.  
  When carrying out the process. the starting components may be reacted in equimolar proportion in a suitable solvent at the temperatures stated. optionally in the presence of an acid acceptor. After several hours stirring of the mixture at elevated temperature, the generally yellow mixture is poured into water. taken up with a hydrocarbon, preferably benzene. and worked up in known manner.  
  The substances according to the invention are obtained in most cases in the form of colorless to slightly yellow-colored, viscous, water-insoluble oils which cannot be distilled without decomposition but can. by so-called slight distillation&#34; (prolonged heating at moderately elevated temperatures under reduced pressure), be freed from the last volatile components and S I -Q 2 BE (I in this way be purified. For their characterization, the refractive index is particularly suitable.  
  Crystalline substances are characterized by their melting points.  
  The products according to the invention have, with only slight phytotoxicity, an outstanding insecticidal and acaricidal effectiveness. ln addition. some of them are distinguished by a rodenticidal side-effect.  
 The pesticidal effect sets in rapidly and is long lasting. By reason of these surprising, technologically valuable properties, the new substances can be used for the control of noxious sucking and biting insects, as well as mites, above all in crop protection.  
  To the sucking insects there belong, in the main, aphids (Aphidae) such as the green peach aphid (Myzus persicue), the bean aphid (Doralisfabue), the bird cherry aphid (RllUlJtllOSlp/lllfll pudi), the pea aphid (Macrorriplzum pisi) and the potato aphid (Macrosiplium solamfolii), the currant gall aphid (Cryptomyzus korschelti). the mealy apple aphid (Sappaplzis muli), the mealy plum aphid (Hyalopterus arundinis) and the cherry black-fly (Myzus cerasi); in addition, scales and mealybugs (Coccina), for example the oleander scale (Aspidiorus hea&#39;erae) and the soft scale (Leccmizmz liesperidum) as well as the grape mealybug (Psemloc&#39;occ&#39;us maririmus); thrips (Thysanoptera), such as Her-(ino- Ilirips femoralis. and bugs, for example the beet bug (Piesma quadruta), the cotton bug (D \&#39;.s&#39;dercus intermezlius). the bed bug (Cimex lectularius), the assassin bug (R/iodnius prolLrus) and Chagas bug (Triatoma infesiuns) and, further, cicadas, such as Euscelis bilobutus and Neplzotelrix bipunctutus; and the like.  
  ln the case of the biting insects, above all there should be mentioned butterfly caterpillars (Lepidoptera) such as the diamond-back moth (Plutella maculipennis&#39;), the gypsy moth (L \&#39;mantria dispar), the browntail moth (Euproctis clirysorrhoea) and tent caterpillar (Malacosomu neusrriu); further, the cabbage moth (Mamestra brassicae) and the cutworm (Agrotis .segetum). the large white butterfly (Pieris brassic&#39;ae), the small winter moth (C/zeimumbia brumatu), the green oak tortrix moth (Tortrix \iiltltllldl, the fall armyworm (Luphygma frugiperda) and cotton worm (Prodenia lirum), the ermine moth (Hyponomeuta padella), the Mediterranean flour moth (Epliesliu kuhniella) and greater wax moth (Galleria mellonella); and the like.  
  Also to be classed with the biting insects are beetles (Coleoptera), for example the granary weevil (Sitp/u&#39;lus granarius (alum/m granaria), the Colorado beetle (Leptinomrsu decemlineata), the dock beetle (Gasrrophysa viridula), the mustard beetle (Phaedon c0- cllleuriae), the blossom beetle (Meligerlies aeneus), the raspberry beetle (Bylurus romenrosus), the bean weevil (Bruc&#39;liidius Acantlzoscelizles obtains), the leather beetle (Dermesles frischi), the khapra beetle (Trogoderma grcmarium), the flour beetle (Tribolium castaneum), the northern corn billbug (Calandra or Silopln&#39;lus zeamais), the drugstore beetle (Stegobium paniceum the yellow mealworm (Ienebrio molllor) and the saw-toothed grain beetle (Oryzuep/zilus .s&#39;urinamensis), and also species living in the soil, for example wireworms (Agriotes spec.) and larvae of the cockchafer (Melolontlia nzelolontha); cockroaches, such as the German cockroach (bluttella germanica), American cockroach (Periplanetu americana), Madeira cockroach (Leucophaea or Rhyparobia madeirac), Oriental cockroach (Blarta orientalis), the giant cockroach (Blaberus fuscus) as well as Hensc/mutedeniu flexiriltu; further Orthoptera, for example the house cricket (Ac/rem domesticus); termites such as the eastern subterranean termite (Reticulitermesflavipes) and Hymenoptera such as ants, for example the garden ant (Lasius niger); and the like.  
  The Diptera comprise essentially the flies, such as the vinegar fly (Drosophila melanogaster), the Mediterranean fruit fly (Ceratitis capilata), the house fly (Musca domesticu), the little house fly (Fannia canicularis), the black blow fly (Phormiu aegina) and bluebottle fly (CaIlip/zora eryI/zrocep/zula) as well as the stable fly (Szomoxys calcitrans); further, gnats, for example mosquitoes such as the yellow fever mosquito (Aedes aeg vpti), the northern house mosquito (Culex pipiens) and the malaria mosquito (Anopheles slephensi); and the like.  
  With the mites (Acari) there are classed, in particular, the spider mites (Tetranychidae) such as the twospotted spider mite (Terranychus telarius Tetrunycus althaeae or Tetranychus urticae) and the European red mite (Paratetranyclzus pilosus Panonyc/zus ulmi blister mites, for example the currant blister mite (Eriop/iyes ribis) and tarsonemids, for example the broad mite (Hemirarsonemus lotus) and the Cyclamen mite (Tarsonemus pallidus); finally, ticks, such as the relapsing-fever tick (Ornit/wdorus moubata); and the like.  
  When applied against hygiene pests and pests of stored products, particularly flies and mosquitoes, the new compounds are also distinguished by an outstanding residual activity on wood and clay, as well as a good stability to alkali on limed substrates.  
  The active compounds according to the instant invention can be utilized, if desired, in the form of the usual formulations or compositions with conventional inert (i.e. plant compatible or herbicidally inert) pesticide diluents or extenders, i.e. diluents or extenders of the type usable in conventional pesticide formulations or compositions, e.g. conventional pesticide dispersible carrier vehicles such as solutions, emulsions, suspensions, emulsifiable concentrates, spray powders, pastes, soluble powders, dusting agents, granules, etc. These are prepared in known manner, for instance by extending the active compounds with conventional pesticide dispersible liquid diluent carriers and/or dispersible solid carriers optionally with the use of carrier vehicle assistants, e.g. conventional pesticide surface-active agents, including emulsifying agents and/or dispersing agents, whereby, for example, in the case where water is used as diluent, organic solvents may be added asauxiliary solvents. The following may be chiefly considered for use as conventional carrier vehicles for this purpose: inert dispersible liquid diluent carriers, including inert organic solvents, such as aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), halogenated, especially chlorinated, aromatic hydrocarbons (e.g. chlorobenzenes, etc.), paraffins (e.g. petroleum fractions), chlorinated aliphatic hydrocarbons (e.g. methylene chloride. etc. alcohols (e.g. methanol, ethanol, propanol, butanol, etc.), amines (e.g. ethanolamine, etc.), ethers, ether-alcohols, (e.g. glycol monomethyl ether, etc.), amides (e.g. dimethyl formamide, etc. sulfoxides (e.g. dimethyl sulfoxide, etc. ketones (e.g. acetone, etc.) and/or water; as well as inert dispersible finely divided solid carriers, such as ground natural minerals (e.g. kaolins, alumina, silica, chalk, i.e. calcium carbonate, talc, kieselguhr, etc.) and ground synthetic minerals (e.g, highly dispersed silicic acid, silicates, e.g. alkali silicates, etc); whereas the following may be chiefly considered for use as conventional carrier vehicle assistants, e. g. surface-active agents, for this purpose: emulsifying agents. such as non-ionic and/or anionic emulsifying agents (e.g. polyethylene oxide esters of fatty acids, polyethylene oxide ethers of fatty alcohols, alkyl sulfonates, aryl sulfonates, etc., and especially alkyl arylpolyglycol ethers, magnesium stearate, sodium oleate, etc.); and/or dispersing agents, such as lignin. sulfite waste liquors.  
 ,methyl cellulose, etc.  
  Such active compounds may be employed alone or in the form of mixtures with one another and/or with such solid and/or liquid dispersible carrier vehicles and/or with other known compatible active agents, especially plant protection agents, such as other acaricides and insecticides, or rodenticides, fungicides, herbicides, bactericides, etc., if desired, or in the form of particular dosage preparations for specific application made therefrom, such as solutions, emulsions, suspensions, powders, pastes, and granules which are thus ready for use.  
  As concerns commerically marketed preparations, these generally contemplate carrier composition mixtures in which the active compound is present in an amount substantially between about 01-95% by weight, and preferably 05-90% by weight, of the mix ture, whereas carrier composition mixtures suitable for direct application or field application generally contemplate those in which the active compound is present in an amount substantially between about 0.000540% preferably 0005-571, by weight of the mixture. Thus, the present invention contemplates over-all compositions which comprise mixtures of a conventional dispersible carrier vehicle such as (l) a dispersible inert finely divided carrier solid, and/or (2) a dispersible carrier liquid such as an inert organic solvent and/or water preferably including a surface-active effective amount ofa carrier vehicle assistant, e.g. a surface-active agent, such as an emulsifying agent and/or a dispersing agent. and an amount of the active compound which is effective for the purpose in question and which is generally between about (LOCOS-95%, and preferably 0005-9571, by weight of the mixture.  
  The active compounds can also be used in accordance with the well known ultra-low-volume process with good success, i.e. by applying such compound if normally a liquid, or by applying a liquid composition containing the same, via very effective atomizing equipment, in finely divided form, e.g. average particle diameter of from 50-100 microns, or even less, i.e. mist form, for example by airplane crop spraying techniques. Only up to at most about a few liters/hectare are needed, and often amounts only up to about 1 quart/acre, preferably 21 6 fluid ounces/acre, are sufficient. In this process it is possible to use highly concentrated liquid compositions with said liquid carrier vehicles containing from about to about 95% by weight of active compound or even the active substance alone, e.g. about 20-l007: by weight of the active compound.  
  Furthermore, the present invention contemplates methods of selectively killing, combating or controlling pests, e.g. arthropods, i.e. insects and acarids, and more particularly methods of combating at least one of insects and acarids which comprises applying to at least one of correspondingly (a) such insects, (b) such acarids. and (c) the corresponding habitat thereof. i.e. the locus to be protected, a correspondingly combative or toxic amount, i.e. an arthropodicidally, especially insecticidally or acaricidally, effective amount of the particular active compound of the invention alone or together with a carrier vehicle as noted above. The instant formulations or compositions are applied in the usual manner, for instance by spraying, atomizing, vaporizing. scattering, dusting, watering, squirting, sprinkling, pouring, fumigating, and the like.  
  It will be realized, of course, that the concentration of the particular active compound utilized in admixture with the carrier vehicle will depend upon the intended application. Therefore. in special cases it is possible to go above or below the aforementioned concentration ranges.  
  Surprisingly, the new compounds, compared with the active compounds of analogous constitution and the same direction of activity hitherto known from the literature, are distinguished by a substantially better effectiveness, with considerably lower toxicity to warmblooded animals. They therefore represent a genuine enrichment of the art. This unexpected superiority, as well as the outstanding activity of the compounds whichcan be prepared according to the process, is illustrated by the experimental results given in the following examples:  
 EXAMPLE 1 Plutella test Solvent: 3 parts by weight acetone Emulsifier: 1 part by weight alkylaryl polyglycol ether To produce a suitable preparation of active compound, 1 part by weight of the active compound is mixed with the stated amount of solvent containing the stated amount of emulsifier and the concentrate is diluted with water to the desired concentration.  
  Cabbage leaves (Brassica oleracea) are sprayed with the preparation of the active compound until dew moist and are then infested with caterpillars of the diamondback moth (Plutella maculipennis).  
  After the specified periods of time, the degree of destruction is determined as a percentage: 100% means that all the caterpillars-are killed whereas 0% means that none of the caterpillars are killed.  
  The active compounds, the concentrations of the active compounds, the evaluation times and the results can be seen from Table l.  
 Table l Plutel la Les t) Active compound Concentration of Degree of (constitution) active compound destruction in 7. in 7. after 3 days (A) 2 Z Q&#39; 0.1 100 0. 01 0 (known) ll O. l 100 2) (c H 0.01 100 0 001 100 C H S 2 \Il (3) W 0.1 100 ll C11 0. 1 100 (1) tc a o) 5 0.01 100 j q 0. 001 90 EXAMPLE 2 Cabbage leaves (Brassicu oleracea) are sprayed with the preparation of the active compound until dripping Phaedon larvae test wet and then infested with mustard beetle larvae (Phae- Solvent: 3 parts by weight acetone don z&#39;oc&#39;ltleariae). Emulsifier: 1 part by weight alkylaryl polyglycol After the specified periods of time, the degree of deether struction is determined as a percentage: 100% means To produce a suitable preparation of active comthat all the beetle larvae are killed.07r means that none pound, 1 part by weight of the active compound is of the beetle larvae are killed.  
 mixed with the stated amount of solvent containing the The active compounds, the concentration of the acstated amount of emulsifier, and the concentrate is ditive compounds, the times of evaluation and the results luted with water to the desired concentration. can be seen from Table 2.  
 Table 2 (Phaedon larvae tes t) Active compound Concentration of Degree of (constitution) active compound destruction in l. in 7. after 3 days fi 0.01 (B) (CH O) P-O OH 0.001 0 (known) If aw Continued (Phaedon larvae test) Active compound (constitution) active compound destruction in l. in I. after 3 days OH 0.01 100 (A) (C H O) Q 0.001  
 (known) ii 0.01 100 2 2 &#39;fl 0.001 100 z sj. 3) N 0.01 100 0 3 0 0.001 100 i1 U &#39;Q 0.01 100 0.001 100 EXAMPLE 3 Myzus test (contact action) Solvent: 3 parts by weight acetone Emulsifier: 1 part by weight alkylaryl polyglycol ether To produce a suitable preparation-of active compound. 1 part by weight of the active compound is mixed with the stated amount of solvent containing the stated amount of emulsifier and the concentratevis diluted with water to the desired concentration.  
 Table 3 A,  
  (Mxzus test) r g g I Active compound Concentration of Degree (constitution) &#39;active compound destruction in Z, in 2. after 24 hours 0.1 100 (A) (c H P-OQ- .01 98 2 2 0. 001 0.0001 0 (known) 1 0.1 100 3 W 0.01 99 C H 0 0.001 2 5 II 1 0.01 100 (C2H5O) 2P O CH3 0.001  
  CQHBJ 0.1 100 5 fi fi a 0.01 100 0 11 0 0.001 100 0.0001 70 EXAMPLE 4 Tetranychus test Solvent: 3 parts by weight acetone Emulsifier: 1 part by weight alkylaryl polyglycol 6 ether To produce a suitable preparation of active compound. l part by weight of the active compound is mixed with the stated amount of solvent containing the stated amount of emulsifier and the concentrate so ob- 65 tained is diluted with water to the desired concentration.  
 Bean plants (Plmseulusvulgaris). which have a height 55 of approximately 10-30 cm., are sprayed with the prep- Table 4 (Tetranxchus &#39;tcst) Active compound Concentration of Degree of (constitution) active compound destruction in Z, in Z, after 48 hours r. (B) (CI-1 0) fi 0. l 98 i 0,01 0  
 (known) (A) (c H o) OH 0.1 95  
 (known) a (2) (C H O) W 0.1 100 0.01 40 I 1) (c H o) P-ofic 0.1 100 2 5 2 3 0.01 40 (s) wficrn o 1 100 CQHBQ 0.01 90 EXAMPLE 5 48.5 g (0.48 mole) 3-methylpyridazone-(6) [prepared according to O. Poppenberg. Ber. Dtsch. Chem. Ges. 34 3264 (1901). (m.p. l43C)] are dissolved in 250ml acetonitrile. After addition of 66 g (0.48 mole) Formula once with a 2N solution of sodium hydroxide, then with water until there is a neutral reaction, and finally it is dried over sodium sulphate. After the solvent has been distilled off. there remain behind 81 g (77.2% of theory) of 0,0-diethyl- O-I 3-methylpyridazine-(6)-yl]- thionophosphoric acid ester in the form of a dark-red, undistillable oil with the refractive index n L5 139.  
  l\ P S Calc. for C ,H, -,N- O;.PS (molecular weight 262.3 )2 10.68%: 11.8171: l2.23/r; Found: 10.6471: l2.09/1; l2.33/1.  
 EXAMPLE 6 In a manner analogous to that of Example 5 the folowing compounds can be prepared:  
 Physical properties s ll 21 CH -QO-PWC- 2 n 1.4988  
  H fi 2 5 21 (5) e11 n 1.5250  
  0 21 CH n 1.5890  
 3 oc n D i. 2 W B 2 m.p. 1oec m.p. 95 97C m.p. 12o 122c It will be realized that all of the foregoing compounds contemplated by the present invention possess the de sired selective pesticidal. especially arthropodicidal. i.e. insecticidal or acaricidal. properties for combating insects and acarids. and that such compounds have a low phytotoxicity and a correspondingly low mammalian toxicity.  
  As may be used herein. the terms arthropod&#34;. arthropodicidal&#34; and arthropodicide contemplate specifically both insects and acarids. Thus. the insects and acarids may be considered herein collectively as arthropods to be combated in accordance with the invention. and accordingly the insecticidal and/or acaricidal activity may be termed arthropodicidal activity. and the concomitant combative or effective amount used will be an arthropodicidally effective amount which in effect means an insecticidally or acaricidally effective amount of the active compound for the desired purposes.  
  It will be appreciated that the instant specification and examplesare set forth by way of illustration and not limitation. and that various modifications and changes may be made without departing from the spirit and scope of the present invention.  
 What is claimed is:  
  1. Pyridazinothionophosphoric (-phosphonic) acid esters of the general formula in which R is a lower alkyl or phenyl radical,  
 R is a branched or straight-chain lower alkyl radical,  
 and  
 R is a branched or straight-chain lower alkoxy or alkyl or phenyl radical.  
  2. Compounds according to claim 1 in which R is a methyl or phenyl radical, R is an alkyl radical with l-4 carbon atoms. and R is an alkyl radical with 1-4 carbon atoms. or an alkoxy radical of l to 4 carbon atoms or a phenyl radical.  
  3. Compounds according to claim 2 in which R is an ethyl or propyl radical and R is a methyl, ethyl. ethoxy. propoxy or phenyl radical.  
  4. Compound according to claim 1 wherein such compound is 0.0-diethyl--l3-phenylpyridazine (6)- yll-thionophosphoric acid ester of the formula S ll  6. Compound according to claim 1, wherein such compound is 0.0-diethyl-O-[3-methylpyridazine-(6)- yll-thionophosphoric acid ester of the formula s ll (10 5 0) 2P-OQNH3 8. Compound according to claim I, wherein such compound is O-ethyl-0-[3-methylpyridazine-(6)-yl]- ethane-thionophosphonic acid ester of the formula CH S \ll P-O w 9. Compound according to claim 1, wherein such compound is ()-ethyl-0-[3-methylpyridazine-(6)-yl]- benzene-thionophosphonic acid ester of the formula CHBQO-EQ (6) 10. Compound according to claim 1, wherein such compound is ()-ethyl-O-[3-phenylpyridazine-(6)-yl]- methane-thionophosphonic acid ester of the formula S Hf S Eu.  
 11. A compound having the formula wherein R and R represent an alkyl group of l-4 car-