IL29202A - Plant fungicidal compositions containing alpha,alpha-dialkyl-3-pyridine methanol - Google Patents

Description

PLANT FUNGICIDAL COMPOSITION S CONTAINING , o< -DIALKYL-3- PYRIDINE METHANOL ¾"aan D'no.ja riTToa mVaij? nunsn This invention concerns new fungicidal compounds and compositions useful for controlling fungi which attack food crops and ornamental plants, and the preparation and use of such compounds and compositions.

Both food crops and ornamental plants are subject to attack by many kinds of fungi, with serious damage thereby resulting. Great effort has been expended to find methods of combatting such fungi.

U.S. 2, 727, 895 discloses that substituted benzyl -pyridines and piperldines possess anticonvulsant, antibacterial, and antifungal activity. The compounds of the U.S. patent include, inter alia, as intermediates, α-phenyl -a-lower-alkyl-3-pyridyl methanes and methanols. It has now been found, however, that these compounds have relative minimal antifungal activity.

U.S. 3 , 153,0 6 discloses dialkyl-piperidyl methanols having antifungal and antibacterial activity. The piperldyl compounds are prepared from the related dialkyl-pyridyl-methanes. The piperidyl compounds, however, also show minl-mal plant antifungal activity.

It is the object of this invention to provide compounds and compositions and methods of using them, which have an entirely different order of magnitude of antifungal activity and are more effective in controlling certain fungi affecting food crops and ornamental plants, than the compounds previously employed.

More particularly, this Invention provides as new fungicides a, -dialkyl -substituted 3-pyridinemethanols OH wherein R and R are the same or different, and are C3"cl6 alkyl or c3"c8 cycloalkyl; and nonphytotoxic acid addition salts thereof. c3"cl6 means saturated aliphatic hydrocarbon radicals, both straight -chain and branched-chain, having from three to sixteen carbon atoms in the chain, and can be illustratively n-propyl, isopropyl, n-butyl, sec . -butyl, isobutyl, n-amyl, sec . -amyl, tert .amyl, n-hexyl, sec . -hexyl, tert . -hexyl, n-heptyl, isoheptyl, sec . -heptyl, n-octyl, isooctyl, sec . -octyl, n-nonyl, sec.-nonyl, isononyl, n-dexyl, sec . -decyl, isodecyl, n-dodecyl, sec . -dodecyl, hendecyl, tridecyl, tetradecyl, penta-decyl, hexadecyl, and the like.

C^-Cg Cycloalkyl means saturated monocylcic aliphatic hydrocarbon radicals having three to eight carbons in the ring and can be illustratively cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl.

Suitable salts of the bases represented by the above formula can be prepared employing for example the following acids: hydrochloric, hydrobromic, sulfuric, phosphoric, nitric, oxalic, methanesulfonic, p_-toluenesulfonic, maleic, and the like. It will be understood by those skilled in the art that suitable salts include those which are not substantially more phytotoxic than the free bases from which they are derived.

Compounds within the scope of the above generic formula, include, but are not limited to, the following: α,α-Bis (isopentyl) -3-pyridinemethanol hydrochloride -n-Amyl -a-n-hexyl -3 -pyridinemethanol ,α-Bis (n-undecyl) -3-pyridinemethanol a -n-Hexyl - -n-heptyl -3-pyridinemethanol - - - - chloride a-Isopentyl - -lsohexyl -3 -pyrldlnemethanol hydrobro-mlde α,α-Bis (n-hexyl) -3-pyrldlnemethanol hydrochloride ¾-n-Undecyl - -n-nonyl -3-pyrldlnemethanol sulfate α,α-Bis (isopentyl) -3-pyridinemethanol hydrobromlde -n-Dodecyl -a-n-octyl -3-pyrldlnemethanol phosphate α,α-Bis (n-hexyl) -3-pyrldlnemethanol sulfate α,α-Bis (n-undecyl) -3-pyrldlnemethanol phosphate α,α-Bis (sec . -nonyl) -3-pyrldinemethanol oxalate α,α-Bis (n-dodecyl) -3 -pyrldlnemethanol hydrochloride α,α-Bls (hendecyl) -3-pyrldlnemethanol hydrochloride α,a-Bis (n-octyl) -3-pyridlnemethanol hydrobromlde, and the like.

The fungicidal compounds of this invention can be synthesized by a preparative method taught by Wibaut et al., Rec. Tray. Chim., 77, 1057 (1958) . According to the Wibaut et al. method, 3-pyridyllithium prepared by the reaction of butyliithium with a 3-halopyridine in ether is allowed to react in a nitrogen atmosphere with a suitable dlalkyl ketone in ether solution at a temperature of about -50° to -60° C. to yield a,a-dialkyl -substituted 3-pyrldlnemethanol . The procedure can be suitably illustrated by the following description of the preparation of a, -bis (isopentyl) -3-pyrldlnemeth-anol .

To 200 ml. of anhydrous ethyl ether contained in a 1-liter, 3-neck, round-bottom flask equipped with a mechanical stirrer and cooled in an acetone-dry ice bath were added 5^· 6· (0.13 mole) of 15 percent solution of n-butyllithium in hexane, Nitrogen gas was continuously introduced into the reaction flask to prevent air oxidation of the n-butylllthium. When the temperature of the solution had fallen to -70°C., a solution of 16 g. (0.1 mole) of 3-bromopyridlne in 100 ml. of anhydrous ethyl ether was added dropwise while maintaining the reaction mixture temperature below -50°C. The reaction was allowed to proceed for about 5 minutes at -60°C. to assure complete conversion of the 3-bromopyridine to 3-pyrldyllithium. A solution of 17 g. (O.l mole) of diisopentyl ketone in 100 ml. of anhydrous ethyl ether was added dropwise while maintaining the reaction mixture temperature at -500 to -60°C. during the addition. The reaction product mixture was stirred for two hours at -60°C. and then allowed to warm to room temperature overnight .

The excess butyllithium was decomposed by the addition of 100 ml. of cold water to the reaction product mixture. The organic layer was separated and dried over anhydrous sodium sulfate overnight. The dry ether solution was filtered off, concentrated in vacuo, and distilled to yield a,a-bis(lso-pentyl) -3-pyridinemethanol as an oil having a boiling point of 13 °C. at 0.1 mm. The product was identified by infrared and n.m.r. spectra and by elemental analysis.

The nonphytotoxic acid addition salts are readily prepared by methods well known to the art. The free base is dissolved in ether, the solution cooled and saturated with, for example, anhydrous hydrogen chloride gas. The hydrochloric acid addition salt of the substituted 3-pyridinemethanol which precipitates is filtered off and purified by recrystallization.

In accordance with the present invention, the fungi-ci dally active compounds are applied to the infected or susceptible plant surfaces, suitably in a composition containing such a compound as the active ingredient. A convenient and dispersion or emulsion of the active ingredient.

The compositions of the present Invention desirably contain in addition to the substituted pyridinemethanol antifungal one or more of a plurality of additaments including water, polyhydroxy compounds, petroleum distillates, and other dispersion media, surface-active dispersing agents, emulsifiers, and finely divided inert solids. The concentration of the substituted pyridine antifungal in these compositions may vary depending on whether the composition is intended for direct ap-plication as a dust to plants or is Intended as an emulsiflable concentrate or a wettable powder designed to be subsequently diluted with additional inert carrier such as water to produce the ultimate treating composition.

The compounds and compositions of the present inven-tion are applied to plants in effective amounts, varying somewhat with the severity of the fungus infection and with other factors such as the environment in which treatment is conducted. In general, it will be found that an aqueous spray containing from about l6 to about 400 parts per million (ppm) of active material is satisfactory when treatment is to be carried out. in the greenhouse.

As is well understood in the art, a somewhat higher concentration of the fungicide is desirable when treatment is to be carried out in the field. In that case, the preferred range is from about 80 to about 600 ppm. of active ingredient.

Treating compositions are most conveniently formulated by preparing liquid or solid concentrates, which are subsequently diluted to the desired level for use. Emulsiflable liquid concentrates can be prepared by incorporating from about 1 to about 10 percent of the active ingredient and liquid. Such concentrates may be further diluted with water to form spray mixtures in the form of oil-in-water emulsions.

Such spray compositions then comprise active toxicant water-immiscible solvent, emulsifying agent, and water. Suitable emulsifying agents can be of the nonionic or ionic types or blends thereof, and include condensation products of alkylene oxides with phenols and organic acids, polyoxyethylene derivatives or sorbitan esters, complex ether-alcohols, ionics of the aralkyl sulfonate type, and the like. Suitable organic liquids to be employed include aromatic hydrocarbons, aliphatic hydrocarbons, cycloallphatlc hydrocarbons, and mixtures thereof such as petroleum distillates.

Solid concentrate mixtures can be prepared by incorporating from about 10 to about 50 percent of the substituted pyridinemethanol compound in a finely divided solid carrier such as bentonite, fuller's earth, diatomaceous earth, hydrat-ed silica, diatomaceous silica, expanded mica, talc, chalk, and the like. Such concentrates can be formulated, if desired, for direct use as dusting compositions, or can be diluted, if desired, with additional inert solid carriers to produce dusting powders containing around 0.05 to 1 percent by weight of the substituted pyridinemethanol. Alternatively, dispersing and/or wetting agents can be incorporated along with the substituted pyridinemethanol in the solid carrier to form wettable powder concentrates ranging from 10 to 25 percent concentration which subsequently can be dispersed in water or other aqueous carrier to form spray compositions. Suitable wetting and emulsifying agents include sodium lignosulfate, sulfonate-oxide condensate blends, sulfonated nonionic blends, anionic wetting agents, and the like.

Further the substituted pyridine toxicant can be incorporated in solutions, simple dispersions, aerosol formulations, and other media adaptable to be employed for treating vegetation.

In accordance with the present invention, the antl-fungal composition is applied to infected or susceptible plant surfaces in any convenient fashion such as spraying, dusting, dipping, or drenching. Spraying is preferable, especially when large numbers of plants are Involved, because of the rapidity and uniformity of treatment possible. In spraying, it is usually sufficient for the infected or susceptible surfaces to be thoroughly wet with the liquid dispersion employed. Good results have been obtained by employing spray compositions whether they be emulsions or aqueous dispersions of solid concentrates .

Example 1 The evaluation of the effectiveness of the fungicidal compounds of this invention against Erysiphe polygon!, the causative organism of bean powdery mildew, was accomplished in the greenhouse in the following manner.

Fungicidal compositions were prepared by dissolving 40 mgc of the compound to be tested in 1 ml . of a solution of cyclohexanone containing 55 rog« of sulfonate nonionic blend and diluting to a volume of 100 ml. with water. This composition then contained 400 ppm. of fungicide. To prepare a com-position containing 1000 ppm., 100 mg. of the compound to be tested was dissolved in 1 ml. of the cyclohexanone-sulfonate nonionic blend solution and then diluted to a volume of 100 ml. with water.

Three bean seeds (Kentucky Wonder variety) were planted in 4-inch clay pots and allowed to germinate. The plants were thinned to two plants per pot. Ten days after the day of planting the seeds, the test chemicals, compounded as described above, were sprayed on all leaf surfaces of the bean plants and allowed to dry. The plants were then placed in the greenhouse and Kentucky Wonder beans heavily infested with powdery mildew were placed above them for about five days, after which they were removed. At the end of five additional days (twenty days after planting) the plants were observed for development of the disease. The appearance of the treated plants was compared with that of untreated plants and ratings of the control of the fungus were recorded. The control rating scale used was as follows: 1 -- no control 2 — slight control 3 -- moderate control — good control -- complete control, no fungus Chart 1, which follows, sets forth the results of the testing of several substituted pyrldlnemethanols against Erysiphe polygon!. In the chart, Column 1 gives the name of the compound; Column 2, the rate in terms of ppm. at which the compound was applied to the test plants; and Column 3, the protection rating of the compound.

Chart 1 Application Protection Compound Rate Rating α,α-Bis (n-buty/l) -3 -pyridine - 400 ppm. 3 .5 methanol hydrochloride 80 2 16 3 α,α-Bis (isopentyl) -3 - 400 4 - pyridinemethanol 80 2.5 hydrochloride 16 2 3.2 3 α,α-Bis (n-undecyl) -3- 400 4.5 pyridinemethanol 80 3 16 2 α ,a -Bis (n-hexy 1 ) -3 - 400 5 pyridinemethanol 80 4+ hydrochloride 16 2.5 3.2 2 α,α-Bis (cyclohexylmethyl) -3 - 4oo 4.5 p idinemethanol 80 4 hydrochloride 16 1 .5 α,a-Bis (n-pentyl) -3-pyridine- 4 methanol a-(n-Hexyl) -a-isobutyl 400 3 - 3 -pyridinemethanol α,α-Bis (isobutyl) -3-pyridine- 400 3 methanol Example 2 The following experimental procedure was used to demonstrate the efficacy of certain compositions of this invention to inhibit the growth of Uromyces phaseoli var. typica, the causative organism of bean rust.

Bean plants were grown from seeds planned in sand contained in 4-inch plasti pots, three bean seeds of the Pinto variety being planted in each pot.

On the tenth day after planting the seeds, the bean plants were infected by spraying the foliage with a spore suspension of Uromyces phaseoli var. typica.

The compound to be tegted was weighed out and dis- solved in a mixture of aqueous 1 percent cyclohexanone as a solvent and aqueous 0.1 percent Tween 20 (a sulfonate-nonionic blend) as a surfactant to give a concentration of test compound of 400 ppm. A 5-ml. portion of this solution was placed in a test tube and diluted to a volume of 50 ml. with aqueous 0.085 percent sodium chloride solution to give a concentration of test compound of 40 ppm. The sodium chloride solution was used to provide an isotonic medium for the plants.. A bean plant was removed from the sand in a pot, the roots washed with water and the plant placed in a test tube containing a solution of the compound being tested. The plants in the test tubes were placed in the greenhouse for a period of 10 days. During this time, the roots of each plant were aerated for about 10 to 15 minutes four times daily, air being introduced into the bottom of the test tube via a capillary tube. At the end of 10 days, the plants were examined for evidence of the development of bean rust and compared with two plants which had been Inoculated with Uromyces phaseoli var. typica and placed in test tubes containing all ingredients except the test chemicals. The disease rating scale used was as follows: 1 — severe 2 — moderate severe 3 — moderate 4 — slight no disease Chart 2 Application Protection Compound Rate α,α-Bis (isopentyl) -3- 400 ppm. pyridlnemethanol hydrochloride α, -Bis (n-butyl) -3- 400 3.6 pyridlnemethanol 80 1.5 hydrochlorl de a- (n-Hepty1 ) -a- 400 isobutyl-3- pyrldinemethanol - (n-Hexyl ) - - 400 3- isobutyl-3- pyridlnemethanol α, -Bis (isobutyl) -3- 400 pyridlnemethanol

Claims (12)

29202/ 2

1. A plant fungicidal composition containing active ingredients and suitable plant fungicidal carriers wherein the active ingredient is selected from compounds having the following formula and acid addition salt thereof: - wherein R and R are the same or different, and are C -C alkyl or C -C- cycloalkyl. 3 lb 3 o J.

2. A plant fungicidal composition wherein the active ingredient is °(, o -bis(isopentyl)-3 -pyridine -methanol hydrochloride.

3. A plant fungicidal composition wherein the active ingredient is -bis(cyclohexylmethyl)-3-pyridinemethanol hydrochloride.

4. A plant fungicidal composition wherein the active ingredient is °(-bis(n-hexyl)-3-pyridinemethanol hydrochloride.

5. A plant fungicidal composition wherein the active ingredient is * ^ -bix(n-pentyl)-3-pyridine ethanol

6. A fungicidal composition for controlling fungi which attacks plants conprising an inert solid diluent, a wetting agent and a fungicidal proportion of a compound as defined in any of claims 1 to 5.

7. A concentrate for controlling fungi which attacks plants, suitable for dilution with water to yield a fungicidal spray, said concentrate comprising an inert solid diluent and a wetting agent in admixture with an amount within the range from about 10 to about 50 percent by weight of a compound as defined in any of claims 1 to 5.

8. A method for selectively controlling fungi which attack plants which comprises contacting a fungus-susceptible plant with aiungicidal amount of a compound or composition as defined in any of claims 1 to 7. 29202/2

9. The method of claim 8f wherein said compound is applied in a composition containing within the range of about 16 to about 400/ppm.-of an e^, ¾>< -dialkyl-substituted 3-pyridine ethanol.

10. The method of claim 8, wherein said compound is applied in a composition containing within the range of about 80 to about 600 ppm. of an V , ■> -dialkyl-substituted 3-pyridinemethanol.

11. The plant fungicidal compositions as in any of clairas 1 to 7 substantially as herein described with particular reference to any one of the specific examples.

12. The method for selectively controlling fungi which attack plants as in any of claims 8 to 10, substantially as herein described with particular reference to any one of the specific examples. S. HOROWITZ & CO; AGENTS FOR APPLICANTS