Photoactive bithienyl pesticides

This invention is in the field of bioaffecting heterocyclic organic chemical compounds which contain a bithienyl nucleus. More particularly, the invention includes certain bithienyl compounds per se, agricultural compositions containing the novel compounds, and the method of using a broad class of bithienyl compounds to control insects and acarids.
U.S. Pat. No. 3,050,442 discloses certain .alpha.-polythienyl compounds, including 5-phenyl-2,2'-bithienyl, and the utility of such compounds as nematicides. The phytotoxicity of the polythienyls is also disclosed and exemplified. The possible effect of light on the biological activity of the compounds is not mentioned.
The activity of certain polythienyl compounds, including 5-phenyl-2,2'-bithienyl, against a specific nematode injurious to pine is disclosed in Japanese Kokai No. 50-37256.
5-Phenyl-2,2'-bithienyl is reported to be phototoxic to Candida utilis, a fungus; see Experimentia, 37, 80 (1981). It was recently reported on the basis of non-foliar tests that 5-phenyl-2,2'-bithienyl is a photodynamic nematicide; see Photochem. Photobiol., 35, 615 (1982).
The phytotoxicity attributed to 5-phenyl-2,2'-bithienyl by earlier workers discourages testing this compound as a foliar insecticide or acaricide on plant crops. Notwithstanding this, according to the present invention, 5-phenyl-2,2'-bithienyl is effective against foliage-feeding insects and acarids, especially under irradiation with near ultraviolet light, plentifully available in sunlight. Furthermore, certain derivatives of 5-phenyl-2,2'-bithienyl are more effective as photoactive foliar insecticides and acaricides than the unsubstituted parent compound. Taking advantage of the activity levels attained in sunlight, the bithienyl compounds can be applied to the foliage at such low rates that phytotoxicity is not a problem.
The photoactive bithienyl compounds of this invention are represented by the following structural formula: ##STR2## wherein R.sub.1 is selected from hydrogen, halogen, alkyl, haloalkyl, alkoxy, and haloalkoxy; R.sub.2 is selected from hydrogen and halogen; R.sub.3 is selected from hydrogen, alkyl, phenyl, and thienyl; and R.sub.4 is selected from hydrogen, halogen, alkyl, and haloalkyl.
The terms "halo" and "halogen" when employed herein mean fluorine, chlorine or bromine. The terms "alkyl" and "alkoxy" imply a straight or branched hydrocarbon chain, preferably containing 1-6, especially 1-4, carbon atoms; "halo" coupled with either term means one or more hydrogen atoms has been replaced by halogen.
Among the bithienyl compounds encompassed by the aforesaid structural formula, those wherein at least one of R.sub.1, R.sub.2, R.sub.3, and R.sub.4 is other than hydrogen or alkyl are new compounds. The most active compounds are those wherein R.sub.1 is a 4-substituent, especially halogen or haloalkyl, e.g., trifluoromethyl; R.sub.2 and R.sub.3 are hydrogen; and R.sub.4 is hydrogen, halogen, or alkyl. In general, the greatest activity is displayed by those isomers having a 5-phenyl-2,2'-bithienyl nucleus.
The compounds are especially effective against insect species of the order Coleoptera, such as Colorado potato beetle (Leptinotarsa decemlineata), as well as other foliage-feeding insect and acarid species, as described in more detail below. The compounds are also effectively employed against mosquito larvae (Aedes aegypti). Although the activity of the bithienyl compounds of this invention is dramatically affected by near ultraviolet light (320-400 nm), they are also active in the dark, e.g., against southern corn rootworm (Diabrotica undecimpunctata howardi) and the root-knot nematode (Meloidogyne incognita) when incorporated into the soil.
The bithienyl compounds of this invention are prepared by methods known in the art. For example, they are prepared according to procedures described by Wynberg and Metselaar, Syn. Comm., 14, 1 (1984). The procedure will be clarified by reference to the following specific example.

EXAMPLE 3
5'-Methyl-5-phenyl[2,2'-bithienyl]
Under a nitrogen atmosphere, a stirred solution of 10.0 grams (0.071 mole) of 2-acetyl-5-methylthiophene, 7.0 grams (0.086 mole) of dimethylamine hydrochloride, 2.5 grams of paraformaldehyde and 0.4 ml of concentrated hydrochloric acid in 10 ml of ethanol was heated under reflux for 16 hours. The reaction mixture was concentrated under reduced pressure to a residual solid. The solid was recrystallized from methanol-diethyl ether to give 10.9 grams of 3-dimethylamino-1-(5-methyl-2-thienyl)propan-1-one hydrochloride; m.p. 145.degree.-147.degree. C.
To a stirred suspension of 1.2 grams (0.025 mole) of sodium cyanide in 70 ml of dimethylformamide was added dropwise a solution of 5.2 grams (10 moles) of freshly distilled benzaldehyde in 40 ml of dimethylformamide. The complete addition required 20 minutes. The reaction mixture was stirred for one hour. Separately, while the mixture stirred, 10.0 grams (0.043 mole) of 3-dimethylamino-1-(5-methyl-2-thienyl)propan-1-one hydrochloride was made alkaline in water with ammonium hydroxide, extracted with ethyl acetate, dried with sodium sulfate, filtered and concentrated. The so-prepared free Mannich base was dissolved in 40 ml of dimethylformamide and added dropwise to the benzaldehyde/sodium cyanide reaction mixture. The complete addition required one hour. The reaction mixture was stirred for an additional 16 hours, then concentrated under reduced pressure to a residual solid. The solid was taken up in water and extracted with three 100 ml portions of chloroform. The combined extracts were washed with water and dried with sodium sulfate. The organic layer was concentrated under reduced pressure to a solid residue. The solid was recrystallized from ethanol-water to give 8.3 grams of 1-phenyl-4(5-methyl-2-thienyl)-1,4-butanedione; m.p. 122.5.degree. C.
Under a nitrogen atmosphere a stirred solution of 3.0 grams (0.012 mole) of 1-phenyl-4-(5-methyl-2-thienyl)-1,4-butanedione and 3.0 grams (0.008 mole) of Lawesson's reagent in 100 ml of toluene was heated under reflux for one hour. The reaction mixture was concentrated under reduced pressure to a residue. The residue was subjected to column chromatography on silica gel using 15% methylene chloride-hexane as eluent. The appropriate fractions were combined and concentrated under reduced pressure to give 2.7 grams of 5'-methyl-5-phenyl[2,2'-bithienyl]; m.p. 102.degree. C.
The nmr spectrum was consistent with the proposed structure.
Analysis:
Calc'd for C.sub.15 H.sub.12 S.sub.2 : C 70.30; H 4.70; Found: C 70.28; H 4.98.
The following additional bithienyl compounds are prepared by similar techniques:
______________________________________Ex. Name m.p. (.degree.C.)______________________________________ 1 5-phenyl[2,2'-bithienyl] 119.5-121.5 2 4'-methyl-5-phenyl- 69-71 [2,2'-bithienyl] 4 5-(4-chlorophenyl)- 165-167 [2,2'-bithienyl] 5 5-chloro-5'-(4-chloro- 145-147 phenyl)[2,2'-bithienyl] 6 3'-methyl-5-(4-chloro- 79-81 phenyl)[2,2'-bithienyl] 7 5'-methyl-5-(4-chloro- 170-172 phenyl)[2,2'-bithienyl] 8 5-(4-chlorophenyl)- liquid 2,2',3,2"-terthienyl 9 5-(4-fluorophenyl)- 141-142 [2,2'-bithienyl]10 5'-chloro-5-(4-fluoro- 125-127 phenyl)[2,2'-bithienyl]11 5'-methyl-5-(4-fluoro- 142-144 phenyl)[2,2'-bithienyl]12 5-(4-methylphenyl)- 129.5-131 [2,2'-bithienyl]13 5-(4-trifluoromethyl- 174-176 phenyl)[2,2'-bithienyl]14 5-(4-methoxyphenyl)- 158-160 [2,2'-bithienyl]21 5-phenyl[2,3'-bithienyl] 155-15722 5-(4-trifluoromethylphenyl)- 174-176 [2,3'-bithienyl]23 4-phenyl[3,2'-bithienyl] liquid25 5-(4-chlorophenyl)-2- 120-121 phenyl[3,2'-bithienyl]28 5'-methyl-5-(4-methyl- 100-101 phenyl)[2,2'-bithienyl]29 5'-chloro-5-phenyl- 138-140 [2,2'-bithienyl]30 5'-bromo-5-phenyl- 128-130 [2,2'-bithienyl]31 5'-methyl-5-(4-methoxy- 160-162 phenyl)[2,2'-bithienyl]32 5'-ethyl-5-phenyl- 79-81 [2,2'-bithienyl]33 5-(3,4-difluorophenyl)- 140-142 [2,2'-bithienyl]34 5'-methyl-5-(3,4-dichloro- 126-128 phenyl)[2,2'-bithienyl]35 5'-methyl-5-(4-tri- 194-196 fluoromethylphenyl)- [2,2'-bithienyl]36 3-phenyl-5-(4-chloro- 74-77 phenyl)[2,2'-bithienyl]37 5'-methyl-5-(4-bromo- 177-179 phenyl)[2,2'-bithienyl]38 5'-methyl-4-phenyl- 98-101 5-(4-chlorophenyl)- [2,2'-bithienyl]39 4,5'-dimethyl- 5-(4-chlorophenyl)- [2,2'-bithienyl]40 5'-methyl-3-(1-methyl- ethyl)-5-(4-chlorophenyl)- [2,2'-bithienyl]41 5'-chloromethyl-5- (4-chlorophenyl)- [2,2'-bithienyl]42 5'-trifluoromethyl- 5-(4-chlorophenyl)- [2,2'-bithienyl]43 3,5'-dimethyl-5-(4- chlorophenyl)- [2,2'-bithienyl]44 5'-methyl-5- [4-(1,1,2,2-tetra- fluoroethoxy)phenyl]- [2,2'-bithienyl]______________________________________
In the normal use of the insecticidal and acaricidal bithienyl compounds of the present invention, the bithienyl compounds usually will not be employed free from admixture or dilution, but ordinarily will be used in a suitable formulated composition compatible with the method of application and comprising an insecticidally or acaricidally effective amount of bithienyl compound. The bithienyl compounds of this invention, like most pesticidal agents, may be blended with the agriculturally acceptable surface-active agents and carriers normally employed for facilitating the dispersion of active ingredients, recognizing the accepted fact that the formulation and mode of application of an insecticide may affect the activity of the material. The present bithienyl compounds may be applied, for example, as sprays, dusts, or granules to the area where pest control is desired, the type of application varying of course with the pest and the environment. Thus, the bithienyl compounds of this invention may be formulated as granules of large particles size, as powdery dusts, as wettable powders, as emulsifiable concentrates, as solutions, and the like.
Granules may comprise porous or nonporous particles, such as attapulgite clay or sand, for example, which serve as carriers for the bithienyl compounds. The granule particles are relatively large, a diameter of about 400-2500 microns typically. The particles are either impregnated with the bithienyl compound from solution or coated with the bithienyl compound, adhesive sometimes being employed. Granules generally contain 0.05-10%, preferably 0.5-5%, active ingredient as the insecticidally effective amount.
Dusts are admixtues of the bithienyl compounds with finely divided solids such as talc, attapulgite clay, kieselguhr, pyrophyllite, chalk, diatomaceous earths, calcium phosphates, calcium and magnesium carbonates, sulfur, flours, and other organic and inorganic solids which act as carriers for the insecticide or acaricide. These finely divided solids have an average particle size of less than about 50 microns. A typical dust formulation useful for controlling insects contains 1 part of bithienyl compound, such as 4'-methyl-5-phenyl[2,2'-bithienyl], and 99 parts of talc.
The bithienyl compounds of the present invention may be made into liquid concentrates by dissolution or emulsification in suitable liquids and into solid concentrates by admixture with talc, clays, and other known solid carriers used in the pesticide art. The concentrates are compositions containing, as an insecticidally effective amount, about 5-50% bithienyl compound and 95-50% inert material, which includes surface-active dispersing, emulsifying, and wetting agents, but even higher concentrations of active ingredient may be employed experimentally. The concentrates are diluted with water or other liquids for practical application as sprays, or with additional solid carrier for use as dusts.
A typical 50% wettable powder formulation would consist of 50.0% (wt/wt) of 5'-methyl-5-(4-chlorophenyl)[2,2'-bithienyl], 22.0% attapulgite diluent, 22.0% kaolin diluent, and 6.0% sodium salts of sulfonated Kraft lignin emulsifier.
Typical carriers for solid concentrates (also called wettable powders) include fuller's earth, clays, silicas, and other highly absorbent, readily wetted inorganic diluents. A solid concentrate formulation useful for controlling insects or acarids contains 1.5 parts each of sodium lignosulfonate and sodium laurylsulfate as wetting agents, 25 parts of 5'-methyl-5-phenyl[2,2'-bithienyl], and 72 parts of attapulgite clay.
Manufacturing concentrates are useful for shipping low melting products of this invention. Such concentrates are prepared by melting the low melting solid products together with one percent or more of a solvent to produce a concentrate which does not solidify on cooling to the freezing point of the pure product or below.
Useful liquid concentrates include the emulsifiable concentrates, which are homogeneous liquid or paste compositions readily dispersed in water or other liquid carriers. They may consist entirely of the bithienyl compound with a liquid or solid emulsifying agent, or they may also contain a liquid carrier such as xylene, heavy aromatic naphthas, isophorone and other relatively nonvolatile organic solvents. For application, these concentrates are dispersed in water or other liquid carriers and normally applied as sprays to areas to be treated.
A typical 50 gram per liter emulsifiable concentrate formulation would consist of 5.90% (wt/wt) of 5'-methyl-5-phenyl[2,2'-bithienyl]; as emulsifiers: 1.80% of a blend of the calcium salt of dodecylbenzene sulfonate and a nonionic 6-molar ethylene oxide condensation product of nonylphenol, 2.70% of a blend of the calcium salt of dodecylbenzene sulfonate and a nonionic 30-molar ethylene oxide condensation product of nonylphenol, 1.50% of a nonionic paste of polyalkylene glycol ether; and 88.10% refined xylene solvent.
Typical surface-active wetting, dispersing, and emulsifying agents used in pesticidal formulations include, for example, the alkyl and alkylaryl sulfonates and sulfates and their sodium salts; alkylamide sulfonates, including fatty methyl taurides; alkylaryl polyether alcohols, sulfated higher alcohols, polyvinyl alcohols; polyethylene oxides; sulfonated animal and vegetable oils; sulfonated petroleum oils; fatty acid esters of polyhydric alcohols and the ethylene oxide addition products of such esters; and the addition products of long-chain mercaptans and ethylene oxide. Many other types of useful surface-active agents are available in commerce. The surface-active agent, when used, normally comprises about 1-15% by weight of the insecticidal or acaricidal composition.
Other useful formulations include simple solutions of the active ingredient in a solvent in which it is completely soluble at the desired concentration, such as acetone or other organic solvents.
An insecticidally or acaricidally effective amount of bithienyl compound in an insecticidal or acaricidal composition diluted for application is normally in the range of about 0.001% to about 8% by weight. Many variations of spraying and dusting compositions known in the art may be used by substituting the bithienyl compounds of this invention into compositions known or apparent in the art.
The insecticidal or acaricidal compositions of this invention may be formulated with other active ingredients, including other insecticides, nematicides, acaricides, fungicides, plant growth regulators, fertilizers, etc. In using the compositions to control insects or acarids, it is only necessary that an insecticidally or acaricidally effective amount of bithienyl compound be applied to the locus where control is desired. Such locus may, e.g., be the insects themselves, plants upon which the insects feed, or the insect habitat. When the locus is soil, e.g., soil in which agricultural crops are or will be planted, the active compound may be applied to and optionally incorporated into the soil. For most applications, an insecticidally or acaricidally effective amount will be about 50 to 750 g per hectare, preferably 150 g to 500 g per hectare.
The insecticidal and acaricidal activity of the bithienyl compounds whose preparation is described above was evaluated as follows:
The bithienyl compounds were tested for insecticidal and acaricidal activity under near ultraviolet light (wavelength 320-400 nanometers) at an intensity of 1600-2400 microwatts/cm.sup.2 using test procedures adapted to the various organisms in the test. Regardless of the organism, foliage of whole plants or foliage removed from whole plants was sprayed to runoff with a 10% acetone-0.25% octylphenoxypolyethoxyethanol-water solution containing up to 200 ppm of the test compound.
Leaves infested with adult twospotted spider mites (Tetranychus urticae) were removed from culture plants and cut into segments containing 50-75 female mites. Each segment was placed on the upper leaf surface of a whole pinto bean (Phaseolus vulgaris) plant. After the mites had migrated to the under surfaces of the leaves, the leaf segments used to infest were removed and each plant sprayed with test chemical as described above. After the plants had dried, the entire plant and pot were placed in metal trays in a hood. A supply of water in the tray kept the plants turgid. Tests were conducted against both susceptible and phosphate resistant strains.
In tests utilizing pea aphid (Acyrtosiphon pisum), whole fava bean (Vicia faba) plants were sprayed with test chemical and allowed to dry as described above. Individual test plants in their pots were placed in 48 ounce containers. Ten adult pea aphids, selected for uniformity of size and vigor were counted into each container. Each container was covered with a glass petri dish and placed on a rack where they were held as described above.
In tests utilizing the Mexican bean beetle (Epilachna varivestis) or the southern armyworm (Spodoptera eridania), the pinto bean test plants were sprayed with test chemical and allowed to dry as previously described. Each test plant was cut off at the soil line and the stem was pushed through a small diameter hole punched in the bottom of an eight ounce waxed container. Ten first instar Mexican bean beetle or southern armyworm larvae were counted into each container. Each container was covered with a glass petri dish and, with the plant stem protruding from the bottom, placed on a holding rack which allowed the stem to remain in water throughout the exposure period.
The test results were collected and recorded at the end of a 48 hour exposure period. These data appear in Table 1.
TABLE 1______________________________________Foliar Test ResultsApplicationRate Insect Species (% Kill)Cpd. (ppm) TSM-S.sup.a TSM-R.sup.b SAW MBB PA______________________________________ 1 100 100 86 0 95 45 2 100 100 0 80 5 20 100 3 200 0 85 32 100 5 98 4 100 100 100 0 55 0 5 20 100 6 200 80 80 5 50 100 7 200 20 128 12 100 100 75 0 20 97 8 20 100 9 200 0 10 50 100 .sup. 100.sup.c 7010 50 10011 100 10012 50 10013 100 100 5 95 0 20 10014 100 10021 200 100 0 4 2822 100 10023 100 4225 20 10028 50 10029 50 10030 50 10031 50 10032 50 10033 50 10034 50 100______________________________________ .sup.a susceptible .sup.b resistant .sup.c 72 hr. exposure

Photoactive bithienyl pesticides

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Photochem. Photobiol., 35, 615 (1982), Gommers, et al.
Synthetic Communications, 14, 1 (1984), Wynberg, et al.