CA1111863A - Fungicidal 1,2-dichlorocyanovinyl compounds - Google Patents

Abstract

Abstract of the Disclosure Novel biocidal compounds have the general structural formula

Description

111'1863 Detailed Description of the Invention This invention relates to novel biocidal 1,2-dichloro-cyanovinyl sulfides, sulfoxides and sulfones.

The novel compounds of this invention have the general structural formula Cl Cl R S()n C C C~N
wherein n is 0, 1, or 2 and R is selected from the group consisting of alkyl, alkylcarbalkoxy, cyclohexyl, halophenyl, benzyl, N,N-di-lower alkyl carbamoyl, hexamethyleneimino carbonyl, pyrimidyl, lower alkyl substituted pyrimidyl, benzimidazole, lower alkyl s~ stituted imidazole, benzothiazole and O,O-di-lower alkyl thio-phosphoryl; with the proviso that when n is 0, R is other than alkyl or cyclohexyl.

In the above description of the compounds of this inven-tion, where R is alkyl the term refers to straight and branched chsin alkyl rad~cals containing 1 to 12 carbon atoms. Illustra-tive examples include methyl, ethyl, propyl, butyl, sec-butyl, tert-butyl, pentyl, neopentyl, hexyl, heptyl, nonyl, decyl, dodecyl and the like and their position isomers. Particularly preferred are straight or branched chain alkyl radicals containing 3 to 9 carbon ato~s. Alkylcarbalkoxy refers to radicals of the formula ~1-~
o where Rl is a lower alkyl radical containing 1 to 4 carbon atoms and ~ is a divalent alkylene radical containing 1 to 4 carbon atoms. Illustrative examples include methylcarbethoxy, ethyl-carbomPthoxy, methylcarbopropoxy, propylcarbethoxy, and the like.

-2- ~

Where lower alkyl substituents are specified, the term includes straight and branched chain alkyl radicals containing l to 4 carbon atoms, i.e., methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl and tert-butyl.

The compounds are prepared by reacting trichloroacrylyl chloride with aqueous ammonia at a temperature of about -30C to about 100C, preferably about 0C to about 20C, to form tri-chloroacrylylamide. The trichloroacrylylamide is then dehydrated using a dehydrating agent such as, for example, phosphoryl chloride, phosphorus pentoxide, trifluoroacetic anhydride, pyridine or thionyl chloride. The resulting trichloroacrylo-nitrile is reacted with the appropriate mercaptan in the presence of an acid acceptor, such as, for example, triethylamine, potassium t-butoxide, sodium methoxide, or a ?hase transfer catalyst with sodium hydroxide, for example, benzyl triethyl-ammonium chloride and sodium hydroxide, to form the desired sulfide. The sulfoxide and sulfone derivatives are formed by reacting the sulfide with an oxidizing agent such as hydrogen peroxide or organic peracids, such as peracetic acid, performic acid, or m-chloroperoxybenzoic acid. The resulting product is a cis-trans-isomer m~xture of the 1,2-dichlorocyanovinyl compound.
Separation of the isomers can be effected by standard procedures, if desired, but is not necessary for utilization of these com-pounds as biocides.

This preparation can be illustrated by the following equations:
O
CC12-CClCCl + NH3 ~ CC12=CClCNH2 + HCl q POCl CC12=CClC ~ -dehydration ~ CC12~CClCN

CC12=CClCN + ~-SH ~~acceptor ~ R-S-CCl-CClCN
R-SCCl-CClCN oxidizin~ ~ R-S(O)n-CCl=CClCN
where n is 1 or 2.

The novel compounds of this invention are biocides in that they prevent, control or inhibit the growth of microorganisms selected from bacteria and fungi. Thus, another embodiment of this invention comprises a method of controlling microorganisms selected from bacteria and fungi by applying to the locus where such control is desired an effective amount of the novel compounds described above. Some of the compounds of this invention are particularly useful as soil fungicides, controlling the growth of fungi when incorporated into soil. The effective amount of the particular compound used will vary depending on the degree of control desired. Generally, about 0.5 to about 6 pounds per acre, preferably about 1 to about 4 pounds per acre, will be employed.
When used as a foliar fungicide to protect vegetation from fungus growth about 0.5 to about 6, preferably abou~ 1 to about4, pounds of compound dissolved or dispersed in 100 gallons of wa~er should be sprayed on the foliage to be protected. For other uses of the compounds of this invention to control microorganisms, one skilled in the art will be able, without undue experimentation, to determine the effective amount of the compound required to 2~ provide the desired degree of control.

Compounds of the above formula where n is O and R is alkyl or cyclohexyl exhibit little, if any, b~ocidal a~tivity when tested at the screening rates. See Table II below. These compounds, however, are novel and are useful in preparing biocidally active sulfoxides and sulf9nes. The compounds have the general structural formula~
R-S-~--C-C~N
wherein R is alkyl or cyclohexyl.

The following examples illustrate the preparation of typical compounds of this invention and demons~rate their utility as biocides.

EXAMPT F
This example illustrates the preparation of isopropyl 1,2-dichloro-2-cyanovinyl sulfide.

In a reaction vessel, 6.3 grams trichloroacrylylnitrile, ~.1 grams isopropyl mercaptan and 300 milligrams benzyl triethyl-L0 ammonium chloride were dissolved in 5 milliliters of benzene. To this was added 3.4 grams of 50~/O sodium hydroxide dissolved in 3 milliliters of water. The reaction mixture was stirred for four hours while main~aining the temperature at about 25~C. Then 100 milliliters water was added and the reaction mixture was extracted with methylene dichloride. The combined organic layers were dried over anhydrous magnesium sulfate and stripped of volatiles.
A yield of 8.0 grams of a light yellow oil having a refractive index - n30 s 1.5080 was obtained. The structure of the product was confirmed by IR and NMR.

This example illustrates the preparation of isopropyl 1,2-dichloro-2-cyanovinyl sulfoxide.

Four grams of isopropyl 1,2-dichloro-2-cyanovinyl sulfide, prepared in Example 1, was dissolved in 50 milliliters methylene dichloride and the solu~ion was cooled to 0C. Four grams of solid 85% m-chloroperbenæoic acid was added in portions over one half hour. The reaction mixture was stirred for two hours while the temperature was maintained at 0C. The reaction mixture was then filtered and washed with 5% potassium carbonate solution. The organic layer was dried over anhydrous magnesium sulfate and ~tripped of voLatiles. A yield of 3 grams of isopropyl 1,2-dichloro-2-cyanovinyl sulfoxide having a refractive index -`n30 _ 1.5112 was obtained. The structure of the product was confirmed by rR and NMR.

This example illustrates the preparation of isopropyl 1,2-dichloro-2-cyanovinyl sulfone.

Three grams of isopropyl 1,2-dichloro-2-cyanovinyl sul oxide, prepared in Example 2, was dissolved in 25 milliliters methylene dichloride and the resulting solution was cooled to 0C.
Then 3.3 grams of 85% m-chloroperbenzoic acid was added. The reaction mixt-~re was permit~ed to stir at 25C overnight. The reaction mixture was then filtered and washed with 5~ potassium carbonate solution. The organic layer was dried over anhydrous magnesium sulate and s~ripped of volatiles. A yield of 3 0 grams of a ~iquid product having a refractive index - n30 = 1.5020 was obtained~ The structure of the product was confirmed by IR and NMR.

This example illustxates the preparation of 1,2-dichloro-2-cyanovinyl-2',4',5'-trichlorophenyl sulfide.

In a reaction vesse~ 6.4 grams of 2,4,5-trichlorothio-phenol and 4.7 grams of trichloroacrylylnitrile were dissolved in 25 milliliters of methylene dichloride. Then 3.0 grams tri-ethylamine was added and the reaction mixture was permitted to stir overnight at room temperature. The reaction mixture was diluted with 100 milliliters of water and extracted with methylene dichloride. The combined organic layers were dried over anhydrous magnesium sulfate and stri~ped of volatiles. A yield of 8.6 grams of a yellow solid havlng a melt~ng point - m.p.-89-105C was obtained. The structure of the product was confirmed by NMR and This example illustrates the preparation of 1,2-dichloro-2-cyanovinyl-2-benz othiaz ole sulfide.

A solution of 3.3 grams 2-mercaptobenzoth~zole and

3.1 grams trichloroacrylylnitrile dissolved in 25 milliliters methylene chloride was prepared. While the reaction mixt~re was vigorously stlrred, 2.2 gr~ms triethylamine was added. The 20 react~on mixture was stirred overnight at 25C. The reac~ion mixture was diluted with 100 milliliters of water and extra~ted with methylene dichloride. The combine~ organic layers were dried over anhydrous magnesium sulfate and stripped of volatiles.

A yield of 4.8 grams of an orange solid having a melting point -m.p. ~ 80-86C was obtained. The structuxe of the product was confirmed by IR and NMR.

This example illustrates the preparation of O,O-diethyl-S-(1,2-dichloro-2-cyanovinyl) phosphorodithioate.

A solut~on of 4.4 grams of O,O-diethyl dithiophosphoric acid potassium salt and 3.1 grams of trichloroacrylylnitrile dissolved in 25 milliliters acetone was prepared. This reaction mixture was stirred overnight at 25C. Then 100 milliliters of e~her was added and the solu~ion was washed with water. The organic layer was dried over anhydrous magnesium sulfate and stripped of volatiles. A yieLd of 6.6 grams of an a~ber oil having a refractive index - n30 ~ 1.5079 was obtained. The structure of the prod~ct was confirmed by IR and NMR.

Other compounds illustrative of those em~odied in this invention have been prepared. These compounds, including those whose preparation is described in detail above, are listed in the following Table I. The compounds have been assigned numbers which are then used throughout the remainder of the specif~ation.

TABIE I
-Cl ICl R-S (O) n~C--C-C---N

Compound No n R
_ t) -C2H5 CH
3 ~~ 3 ~CH3

4 1 -CH~, `~C~13 ~CH3 21~CH3 - 6 0-n-C4H9 7 1n C4Hg 8 û-sec.-C4Hg 9 1-sec . -C4Hg lû 2-sec.-C4Hg ll O- ter t-C4H~

12 0CH2 CH2 IcH CH 3 _g_ ..

111~863 TAB13: I
continued Compound No. n R

14 2CH2 CH2 ~H C~3 , 8 17 16 1-n-C8H17 17 2-n-C8H17 18 0-n-CgHlg 19 1-n-CgHlg 2-n-CgHlg 21 -cH2-0-C-C2H5 o 2~ 1 -CH2~~¦~~C2H5 A

23 0 J~

24 1 {~3 2~ 2 {~3 ?fi3 TABLE
con tinued Compound No. n R

26 ~3Cl 27 0 ~Cl \=~Cl Cl 28 1 ~_Cl Cl 2~ 2 ~ Cl Cl 0 -CH2~

O ~CH2CH2CH3 31 0 -C-N\
5H2CH2C~I3 O ~:H2 - CH2 -C H2 \C H2 -CH2 -CH~

33 0 ~/
N~/
N ~ 3 1~11863 TABLE I
continued Compound No n R
, 1~ -CH

: ~S ~
38 1 -C~N~J

~ ~OC2H5 39 0 --~
~OC2H5 ~lllB6~

Ag stated above, the novel compounds of this invention are biocides. The compounds were tested for bactericidal Rnd fungicidal activity using the following test procedures.

IN VITRO BIOCIDE TESTS
In-Vitro Bactericide Bioassay Test chemicals are diluted in acetone to a concentration c of 2500 ppm. Test cultures are prepared by adding 0.1 milliliters of cultures of E, Coli, Staph. aureus, or Erwinia amylovora to 16 x 100 millimeter test tubes containing 5 mllliliters of sterile nutrient broth. One-tenth milliliter of the s~ock chemical solution is then added to each test tube for a finsl concentratlon of 50 ppm, and the tubes sre m2intalned at 27C for one week. Each tube i9 then examined for the presence sr absence of turbidity due to the growth of the bacterium, Chemicals which show control at 50 ppm are retested at progressively lower levels unt~ 1 the min~mum concentrat~on giving 75% or gre~ter control is determined. The re~ults sre shown in Table II.

In-Vitro Fun~ic~-de Bio~ssa~
Test chemicals are diluted in acetone to a concen~ration of 2500 ppm. Tes t cul~ures are prepared by adding 0.1 mllliliters of cultures of ei~her A~&~ ni~er or Penicillium i~:alicusn to 16 x 100 m~llimeter test tubes containing 5 millili~ers of s erile malt extract broth. One ~enth milliliter of the stock chemical so7 ution 1~ then added to each tes ~ tube for a final con-c~ntration of 50 ppm, and the tubes are mainta~ned at 27C for one week. Ea2h tube is ~hen examined for the prF~sence or absence of a mycelial ma~ Chemica~s which show control at 50 ppm are retested ` 13--~111863 at progressively lower levels until the minimum concentration giving 75% or greater control i9 determined. The results are shown in Table II.

FOLIAR PREVENTATIVE FUNGICIDE TESTS
1. Bean_Rust Test chemicals are dissolved in an appropriate solvent and then further diluted with a 50:50 acetone:w~ter solution.
Pinto bean plants (Phaseolus vul~aris), approximately 15 centi-meters tall, are inverted and dippet into the solutiun for 2-3 seconds. Test concentrations range fr~m 1000 ppm downward. After the leaves ha~e dried, they are inoculated with a water suspension of spores of the bean rust fungus (UromYce~ phaseoli) and the plant~ are placed ~n an environment of lOOZ humidity for 24 hours.
The plants are then removed from the humidity chamber and held until dlsease pustules appear on the leaves. Effectiveness is recordet as percent reduction in number of pustules a~ comp~red to untreated inoculated plants. The result~ are shown ~n Table II.

2. Bean Powdery Mildew Test chemicals are dissolved in an appropriate solvent and then further diluted with a 5~:50 acetone:water soluti~n.
Pinto bean plants (Phaseolus ~&~ ), approxim~tely 15 centi-meters tall, are inverted and dipped into the solution for 2-3 seconds. Te~t concentrations range from 1000 ppm downward. After the leave~ have drled, they are dus~ed with ~pore~ of the powdery mildew fungus (Erysiphe poly~oni) and the plants are re~ained in the greenhouse until the fungal growth appears in the leaf surface.
Effectiveness is recorded as percent of the leaf surface free of ~111863 .
fungal growth as compared to untreated inoculated plants. The results are shown in Table II.

SOIL FUNGICIDE TEST
Rhizoctonia 80 lani Rhizoctonia solani is cultured on Potato Dextrose Agar plates. After several weeks, sclerotia are fonmed. To prepare the inoculum~ portions of the plates with the heaviest sclerotial fonmulation are placed in a blender with about 60-75 milliliters of water. After a short blending period, a thick slurry of 8cleroti~ J mycelia, water and agar is fonmed.

Five milliliters of the above su~pension are added to 4 K8 of sterile 90il in ~ 5 gallon ~oil incorporator and thoroughly mixed into the soil. Four hundred grams of the inoculated soil is weighed into each one pint paper can (Fonda #106) and a small quantity of clean dry ~and i~ pLaced in a depression in the center of the 90il. One milliliter of solvent (Acetone/H20) contai~ing an appropriate amount of the test compound is then added to the sand in each pot and the chemicals are ~horoughly ~ncorporated into the soil. Final concentrations of the test chQm~caLs are 50, 25, 10, 5, 1 ppm. Finally, 5 pinto bean (Phaseolu~ sp.) seeds are planted in each pot.

The pots are maintained in a greenhou~e at 21G for 3 weeks. Efficacy of the test chemicals is determined by ~x2m~ning the stems of the plants for lesions. The results are shown in Table III.

~ill863 Fusar~um solani Fu~arium solani f. sp. phseoli is cultured via mass transfer on V-8 agar plates. The spores are washed off the plates with tap water. Spore concentration is checked with a hemocyto-meter and is adjusted to give a final concentration of mæcroconidia of 2 x 106 conidia/mill~liter.

Four Kg sterile soil is placed in a l9L (5 gallon) soil incorporator. Four milliliters of the conidial suspension is added to the soil which is mixed to give a final concentration of 2 x 103 conidia/gram soil. Four hundred grams of the inoculated ~oll is weighed into each one pint paper can (Fonda #106) and a small quantity of clean dry sand is placed in a depre~sion in the center of the soil. One milliliter of solvent (acetone/H20) con-taining an appropriate amount of the tes t compound is then added to the sand ~n each pot and the chemicals are thoroughly i~oorporated i~to the soil. Final concentrations of the test chemicals are 50, 25, 10, 5, 1 ppm~ Finally, 5 pinto beans (Phaseolus 8p. ) seeds are planted in each pot~

The pots are maintained in a greenhouce at 21C for three weeks. Efficacy of the test chemicals is determined by examining the stems of the plants for lesiuns. The results are shown in Ta~le III.

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~11'1863 TABLE III
SOIL FUNGICIDE
TEST
Rhizoc tonia Fusarium Compound No. solani~ ppm solaniL ppm 4* 1.4 .8 4 1.8 1.5 1.6 1.2 7 6 2.3 23 1.8 16 50 11 . 5 17 50 16 . 5 22 7 7.5 24 - 2.4 Compound No. 4 was run through the 30il fungicide evaluation twice, ~11 other compounds~were tested once.

-2û -The novel compounds of this invention are generally applied to the locus where control of bacteria or fungi is desired in the form of formulations containing an effective amount of the compound and an inert carrier. Such formulations generally take ~he form of dusts, wettable powders, solutions, emulsifiable concentrates or the like. Such formulations normally contain up to about 80% by weight of the active ingredient.

Dusts are free-flowing powder compositions containing the active compound impregnated on a particulate carrier. The particle size of the carrier is usually ln the range of from about 30 to 50 microns. Examples of suitable carriers are talc, bentonit~, diatomaceous earth, and pyrophyllite. Anticaking and antistatic agent~ can be added, if desired.

Wettable powders are finely divided compositions com-L5 prising a particulate carrier impregnated wîth the active compound and additionally containing one or m~re surface act~ve agents.
The sl~rface act~ve agent~ promote rapid dlsper~ion of the powder in aqueous medium to form stable, ~prayable suspensions. A w~de variety of surface ~ctive agents can be used, for example, long chain fatty alcohols and alkali metal salts of the sulfated fatty alcohols, salts of sulfonic acid, esters of long chain fatty acids and polyhydric alcohols and the l~ke. A list of surface active agents suitab~e for use in agriculeur formulations can be found in Pe~ei~ide ~onr~~ or~ by Wade Van Valkenburg, Marce1 Dekker, Inc., N Y., 1973 at pagPs 79-84.

-2~-~1863 Granules comprise the active compound impregnated on a particula~ inert carrier having a particle size of 1 to 2 milli-meters in diameter The granules can be made by spraying a solu~ion of the active ingredient in a voLatile solvent onto the granular carrier. Suitable carriers in preparation of granules include clay, vermiculite, sawdust, granular carbon, and the like.

The active compounds can also be applied in the form of a solutioa in a suitable solvent. Solvents frequently used in biocidal formulations include kerosene, fuel oil, xylene, petroleum fractions with boiling ranges above xylene, and aromatic petroleum fractions rich in methylated naphthalenes.

Emulsifiable concentrates consist of an oil solution of the active compound along with an emulsifying agent. Prior to u~e the concentrate is diluted with water to form a suspended emulsion of oil droplets. The emulsifier~ used are usually a mixture of anionic and nonionic surfactants. Other additive~
such as spread~ng agents and stickers can be included in the emulsifiable concentrate if de3ired.

Claims (10)

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

1. A compound having the general structural formula wherein R is alkyl or cyclohexyl.

2. The compound of Claim 1 wherein R is ethyl.

3. The compound of Claim 1 wherein R is isopropyl.

4. The compound of Claim 1 wherein R is n-butyl.

5. The compound of Claim 1 wherein R is sec-butyl.

6. The compound of Claim 1 wherein R is tert-butyl.

7. The compound of Claim 1 wherein R is 1-methylbutyl.

8. The compound of Claim 1 wherein R is n-octyl.

9. The compound of Claim 1 wherein R is n-nonyl.

10. The compound of Claim 1 wherein R is cyclohexyl.