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Tiếng Việt
(en)Compounds of the formula ##STR1## wherein A is selected from the group consisting of hydrogen, alkyl, aryl, and heterocyclic;
Y and Z are independently selected from the group consisting of O, S, and N--R;
R is selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted phenyl, and substituted or unsubstituted heterocyclic; and
X is selected from the group consisting of I and Br.
are disclosed to useful as antimicrobials.
Y and Z are independently selected from the group consisting of O, S, and N--R;
R is selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted phenyl, and substituted or unsubstituted heterocyclic; and
X is selected from the group consisting of I and Br.
are disclosed to useful as antimicrobials.
1.ApplicationNumber: US-53077090-A
1.PublishNumber: US-5292762-A
2.Date Publish: 19940308
3.Inventor: HSU; ADAM C.
4.Inventor Harmonized: HSU ADAM C(US)
5.Country: US
6.Claims:
(en)Compounds of the formula ##STR1## wherein A is selected from the group consisting of hydrogen, alkyl, aryl, and heterocyclic;
Y and Z are independently selected from the group consisting of O, S, and N--R;
R is selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted phenyl, and substituted or unsubstituted heterocyclic; and
X is selected from the group consisting of I and Br.
are disclosed to useful as antimicrobials.
7.Description:
(en)This application is a continuation-in-part of Ser. No. 370,373 of Jun. 22, 1988.
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to control of microorganisms.
2. Description of the Prior Art
Certain classes of iodopropargyl compounds have been proposed as fungicides or microbicides but no compound within those classes has achieved commercial success.
U.S. Pat. No. 4,616,004 to Edwards discloses fungicidal activity for compounds of the formula ##STR2##
U.S. Pat. No. 4,639,460 to Rose shows compounds of the formula ##STR3## as fungicides.
U.S. Pat. No. 4,520,023 to Schmitt shows 3-(3-iodopropargyl)benzo-1,2,3-triazolin-4-ones and their use as microbicidal agents.
There was no suggestion in the prior art that compounds within the formula of the present invention would have utility in controlling microorganisms.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide new compounds for controlling microorganisms.
A further object is to provide methods of making such compounds, methods of using them, compositions comprising such compounds, and uses of such compositions.
These objects, and others which will become apparent from the following disclosure, are achieved by the present invention which comprises in one aspect compounds of the formula ##STR4## wherein A is selected from the group consisting of hydrogen, alkyl, aryl, and heterocyclic;
Y and Z are independently selected from the group consisting of O, S, and N--R,
R is selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted phenyl, and substituted or unsubstituted heterocyclic; and
X is selected from the group consisting of I and Br.
In another aspect the invention comprises a method of preparing such compound comprising reacting compound of the formula ##STR5## with an iodinating or brominating agent.
A further aspect comprises using a composition comprising the compounds, or the compound itself, to protect a material selected from the group consisting of wood, paint, adhesive, glue, paper, textile, leather, plastics, cardboard, lubricants, cosmetics, food, caulking, feed and industrial cooling water from microorganisms.
DETAILED DESCRIPTION OF THE INVENTION AND THE PREFERRED EMBODIMENT
The compounds of the invention are of formula I as set forth above. The more preferred embodiments are those wherein A is selected from the group consisting of hydrogen; (C 1 to C 18 ) straight or branched alkyl; (C 3 to C 8 ) cycloalkyl; (C 3 to C 6 ) alkenyl; (C 3 to C 5 ) alkynyl; (C 7 to C 12 ) aralkyl; (C 6 to C 12 ) aryl; (C 6 to C 12 ) aryl substituted with 1 to 3 substituents selected from the group consisting of halogen, (C 1 to C 4 ) alkyl, (C 1 to C 4 ) alkoxy, nitro, cyano, carboxyl (C 1 to C 4 ) alkoxycarbonyl, (C 1 to C 4 ) alkyl thio, -S(O)nR 2 where n is 1 or 2 and R 2 is (C 1 -C 4 ) alkyl; and a halo-substituted, nitro-substituted, or un-substituted moiety selected from the group consisting of 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyridyl, 3-pyridyl, and 4-pyridyl. A cannot be R 4 S- where R 4 is any moiety. Examples of heterocyclic R substituents are furyl, thienyl, pyridyl, and the like.
The iodopropargyl compounds, i.e., those wherein X is I, are preferred. The 5-one compounds, i.e., those wherein Y is O, are also preferred.
As stated above, compositions comprising a compound according to formula I and either an agronomically acceptable carrier, a cosmetic agent, a cutting oil, a soap or synthetic detergent, a stabilizer, a film forming material, or the like have a wide range of utility for protecting against or controlling microorganisms from a wide variety of classes including fungus, bacteria, algae, viruses and yeasts. The preferred utilities of the compositions are to protect wood, paint, adhesive, glue, paper, textile, leather, plastics, cardboard, lubricants, cosmetics, food, caulking, feed and industrial cooling water from microorganisms.
The following lists specific industries and applications of the compounds or compositions.
______________________________________Industry Application______________________________________Adhesives, Sealants Adhesives Caulks sealantsagriculture/food chain adjuvant preservation agricultural active ingredient agricultural chemical preservative agricultural formulations preservation animal feed preservation dairy chemicals fertilizer preservation food preservation food processing chemicals grain preservation post-harvest produce protection sugar processing tobaccoConstruction products asphalt/concrete cement modifiers construction products roof mastics synthetic stucco wall mastics joint cementCosmetics and toiletries Cosmetics raw materials for cosmetics, toiletries toiletriesDisinfectants, antiseptics antiseptic disinfectantEmulsions, dispersions aqueous dispersions dispersed pigments latex photographic emulsions pigment slurries polymer laticesformulated household fabric softenersproducts polishes waxes hand dish detergents raw materials liquid detergents hand soapsIndustrial processing, misc electrodeposition paint, baths, rinses. electrodeposition pre-treatment, post rinses Industrial fluids preservation pasteurization baths process aid preservationIndustrial water treatment air washers cooling towers cooling water water cooling preservation/treatment of wooden cooling tower slats and structural members can warmers brewery pasteurization closed loop water cooling systemsLaundry household laundry products laundered goods laundry wash water sanitizers-laundryLeather, Leather products leather and hide leather and hide productsLubricants, hydraulic aids automotive lubricants and fluids conveyor lubricants greases hydraulic fluids lubricantsMedical devices diagnostic enzymes diagnostic kits medical devicesmetalworking & related cutting fluidsapp's Metal cleaning metalworking fluidsOdor control (active air conditioningingredient) animal bedding cat litter chemical toilet prep'ns deodorizers humidifiers industrial deodorants sanitary formulations toilet bowlsPaints and coatings coating emulsions paintsPaper and wood pulp, absorbant materials of paper andtheir products wood pulp packaging materials of paper and wood pulp paper products paper treatment soap wrap wood pulp wood pulp productspaper mill paper mill slimicides pulp and paper slurriesPetroleum refining, fuels aviation fuels (jet fuel, aviation gas) crude oils burner, diesel and turbine fuel oils coal slurries diesel fuel additives diesel fuels fuels gasoline heating oils hydrocarbons Kerosene liquefied petroleum gas petrochemical feedstocks petroleum products, storage, transportation and production recycled petroleum products residual fuel oils turbine oilsPhotographic Chemicals Photographic processing - washand process water, rinses photoprocessing Photoplate processing chemicals (developers, stabilizers etc)Printing Fountain solutions (printing) Ink components (pigments, resins, solvents, etc) Inkssanitizers (active) sanitizers sanitizers-dairy sanitizers-dental sanitizers-fermentation sanitizers-food preparation sanitizers-food processing sanitizers-medical sanitizers-rendering sanitizers-veterinarySoaps, detergents, cleaners cleaners detergents household cleaners industrial cleaners liquid soaps oil and grease remover powdered soaps raw materials for cleaning products soaps surfactantsTextiles, textile products bonded fabrics burlap canvas canvas goods carpet backing carpets clothing coated fabrics curtains draperies engineering textiles fibers geotextiles goods made of textiles knitted fabrics nets nonwoven fabrics rope rugs textile accessories textile products textiles upholstery woven fabrics yarnTextile processing dye fixatives dyes fiber lubricants hand modifiers sizes Textile processing fluidsTherapeutic (active or animal health/veterinarypreservative) aquaculture dental human health pharmaceutical/therapeuticwater purification charcoal beds deionization resins filters membranes reverse osmosis membranes ultrafilters Water purification water purificiation pipes, tubingwood applications lazures (wood stains) wood wood productsMiscellaneous alcohols bedding incorporating water or gels ceramic contact lens cases-leaching electronic circuitry electronics chemicals enzymes-food production enzymes enzymes-industrial gel cushions marine antifoulants mildewcides wood plastics laundry mining natural rubber latex oil field injection waters including enhanced recover injection fluids, drilling, fracturing and completion fluids pipes plastics polymer systems polymers and resins (synthetic and natural) reagent preservation rubber rubber products skin remover solid protective/decorative films stains swimming pools waste treatment water beds______________________________________
The amounts of the compound to be used depend on the application. The useful amounts for a particular application are similar to amounts used for other microbiocide compounds.
The compound can be used in combination with other microbicides. The term "microbicide" is considered equivalent to "antimicrobial" as used herein.
Compounds of formula I can be prepared by a variety of methods. One suitable method comprises reacting a compound of the formula ##STR6## with an iodinating or brominating agent.
Suitable iodinating or brominating agents include, for example, iodine, bromine, an iodine-amino compound such as morpholineiodine complex, morpholine-bromine complex, N-bromosuccinimide ("NBS") and N-iodosuccinimide ("NIS"), the latter being the most preferred.
When an iodine, bromine, or iodo-amino compound is used, base should also be used, preferably sodium or potassium hydroxide, and solvent such as methanol, ethanol, and aqueous ethanol should also be used.
When NIS or NBS is used, a catalyst such as, for example, silver nitrate, or the like, should be used in presence of solvent such as acetone, methyl ethyl ketone, tetrahydrofuran, and the like.
Reaction times of about 20 minutes to about 24 hours have been utilized successfully with reaction temperatures of about 0° C. to about 25° C.
Suitable methods of application of compounds of formula I to control fungi, bacteria, algae, viruses, yeasts, and the like are in amounts and with carriers, etc., as well known in the art.
The following examples are presented to illustrate a few embodiments of the invention. All parts and percentages are by weight unless otherwise indicated.
EXAMPLES
Some representative compounds the invention are the following:
______________________________________Com-pound #______________________________________ 1. 2-(4-chlorophenyl)-4-(3-iodopropargyl)-1,3,4- oxadiazolin-5-one 2. 2-(2-methylphenyl)-4-(3-iodopropargyl)-1,3,4- oxadiazolin-5-one3. 2-(4-methylphenyl)-4-(3-iodopropargyl)-1,3,4- oxadiazolin-5-one4. 2-(3-methylphenyl)-4-(3-iodopropargyl)-1,3,4- oxadiazolin-5-one5. 2-(2-chlorophenyl)-4-(3-iodopropargyl)-1,3,4- oxadiazolin-5-one6. 2-(3-chlorophenyl)-4-(3-iodopropargyl)-1,3,4- oxadiazolin-5-one7. 2-(2-thienyl)-4-(3-iodopropargyl)-1,3,4-oxadiazolin-5-one8. 2-n-propyl-4-(3-iodopropargyl)-1,3,4-oxadiazolin-5-one9. 2-(4-nitrophenyl)-4-(3-iodopropargyl)-1,3,4-oxadiazolin- 5-one10. 2-(3-nitrophenyl)-4-(3-iodopropargyl)-1,3,4-oxadiazolin- 5-one11. 2-(2-nitrophenyl)-4-(3-iodopropargyl)-1,3,4-oxadiazolin- 5-one12. 2-(4-trifluoromethylphenyl)-4-(3-iodopropargyl)-1,3,4- oxadiazolin-5-one13. 2-(2-methoxyphenyl)-4-(3-iodopropargyl)-1,3,4- oxadiazolin-5-one14. 2-(4-methoxyphenyl)-4-(3-iodopropargyl)-1,3,4- oxadiazolin-5-one15. 2-(3-methoxyphenyl)-4-(3-iodopropargyl)-1,3,4- oxadiazolin-5-one16. 2-(4-bromophenyl)-4-(3-iodopropargyl)-1,3,4- oxadiazolin-5-one.17. 2-(2-fluorophenyl)-4-(3-iodopropargyl)-1,3,4- oxadiazolin-5-one18. 2-(2-furyl)-4-(3-iodopropargyl)-1,3,4-oxadiazolin-5-one19. 1-(3-iodopropargyl)-3-(4-methylphenyl)-4-ethyl-1,2,4- triazolin-5-one20. 1-(3-iodopropargyl)-3-(4-chlorophenyl)-4-ethyl-1,2,4- triazolin-5-one21. 1-(3-iodopropargyl)-3-phenyl-4-ethyl-1,2,4-triazolin-5- one22. 1-(3-iodopropargyl)-3-(4-nitrophenyl)-4-ethyl-1,2,4- triazolin-5-one23. 1-(3-iodopropargyl)-3-(4-methoxyphenyl)-4-ethyl-1,2,4- triazolin-5-one24. 1-(3-iodopropargyl)-3-(2-thienyl)-4-ethyl-1,2,4,-triazolin- 5-one25. 1-(3-iodopropargyl)-3-(3-methylphenyl)-4-ethyl-1,2,4- triazolin-5-one26. 1-(3-iodopropargyl)-3-(2-methylphenyl)-4-ethyl-1,2,4- triazolin-5-one27. 1-(3-iodopropargyl)-3-(3-fluorophenyl)-4-ethyl-1,2,4- triazolin-5-one28. 1-(3-iodopropargyl)-3-(1-naphthyl)-4-ethyl-1,2,4- triazolin-5-one29. 1-(3-iodopropargyl)-3-(2-naphthyl)-4-ethyl-1,2,4- triazolin-5-one30. 1-(3-iodopropargyl)-3-(4-bromophenyl)-4-ethyl-1,2,4- triazolin-5-one31. 1-(3-iodopropargyl)-3-(2-fluorophenyl)-4-ethyl-1,2,4- triazolin-5-one32. 1-(3-iodopropargyl)-3-(4-fluorophenyl)-4-ethyl-1,2,4- triazolin-5-one33. 1-(3-iodopropargyl)-3-(3-pyridyl)-4-ethyl-1,2,4- triazolin-5-one34. 1-(3-iodopropargyl)-3-(2-methoxyphenyl)-4-ethyl-1,2,4- triazolin-5-one35. 1-(3-iodopropargyl)-3-(3-nitrophenyl)-4-ethyl-1,2,4- triazolin-5-one36. 1-(3-iodopropargyl)-3-(3-chlorophenyl)-4-ethyl-1,2,4- triazolin-5-one37. 1-(3-iodopropargyl)-3-(3-bromophenyl)-4-ethyl-1,2,4- triazolin-5-one38. 1-(3-iodopropargyl)-3-(3-methoxyphenyl)-4-ethyl-1,2,4- triazolin-5-one39. 1-(3-iodopropargyl)-3-(3-ethoxyphenyl)-4-ethyl-1,2,4- triazolin-5-one40. 1-(3-iodopropargyl-3-(4-methylphenyl)-4 n-butyl-1,2,4- triazolin-5-one41. 1-(3-iodopropargyl)-3-(4-methylphenyl)-4-i-propyl-1,2,4- triazolin-5-one42. 1-(3-iodopropargyl)-3-n-propyl-4-ethyl-1,2,4-triazolin- 5-one43. 1-(3-iodopropargyl)-3-(4-chlorophenyl)-4-phenyl-1,2,4- triazolin-5-one44. 1-(3-iodopropargyl)-3-(2-chlorophenyl)-4-ethyl-1,2,4- triazolin-5-one45. 1-(3-iodopropargyl)-3-(4-chlorophenyl)-4-(4- chlorophenyl)-1,2,4-triazolin-5-one46. 1-(3-iodopropargyl)-3-(4-chlorophenyl)-4-(4- methylphenyl)-1,2,4-triazolin-5-one47. 1-(3-iodopropargyl)-3-methyl-4-phenyl-1,2,4-triazolin- 5-one48. 1-(3-iodopropargyl)-3-methyl-4-(4-chlorophenyl)-1,2,4- triazolin-5-one49. 1-(3-iodopropargyl)-4-(4-chlorophenyl)-1,2,4-triazoline- 5-one50. 1-(3-iodopropargyl)-4-phenyl-1,2,4-triazolin-5-one51. 1-(3-iodopropargyl)-3-(4-bromophenyl)-4-methyl-1,2,4- triazolin-5-one52. 1-(3-iodopropargyl)-3-(4-chlorophenyl)-4-methyl-1,2,4- triazolin-5-one53. 1-(3-iodopropargyl)-3-(4-fluorophenyl)-4-methyl-1,2,4- triazolin-5-one54. 1-(3-iodopropargyl)-3-(3-chlorophenyl)-4-methyl-1,2,4- triazolin-5-one55. 1-(3-iodopropargyl)-3-(3-bromophenyl)-4-methyl-1,2,4- triazolin-5-one56. 1-(3-iodopropargyl)-3-(3-fluorophenyl)-4-methyl-1,2,4- triazolin-5-one57. 1-(3-iodopropargyl)-3-(2-fluorophenyl)-4-methyl-1,2,4- triazolin-5-one58. 1-(3-iodopropargyl)-3-t-butyl-4-phenyl-1,2,4-triazolin- 5-one59. 2-phenyl-4-iodopropargyl-1,3,4-thiadiazolin-5-one______________________________________
Table (1) shows the structures and the physical data of these representative compounds.
TABLE 1__________________________________________________________________________Physical Data ##STR7## (II) ##STR8## (III) ##STR9## (IV) NMR Chemical ShiftsNO. Formula A R Melting Point (ppm)__________________________________________________________________________ 1. II 4-Cl-ph -- 151-152° C. 2. II 2-Me-ph -- 152-154° C. 3. II 4-Me-ph -- 174-175° C. 4. II 3-Me-ph -- 114-115° C. 5. II 2-Cl-ph -- 104-107° C. 6. II 3-Cl-ph -- 124-126° C. 7. II 2-thiophene -- 149-151° C. 8. II n-propyl -- 42-46° C. 4.60(2H, s, CH.sub.2), 2.55 (2H, t, CH.sub.2), 1.74(2H, m CH.sub.2), 1.02(3H, t, CH.sub.3) 9. II 4-NO.sub.2 -ph -- 176-178° C.10. II 3-NO.sub.2 -ph -- 99.5-102° C. II 2-NO.sub.2 -ph -- 116-120° C. II 4-CF.sub.3 -ph -- 144-147° C. II 2-MeO-ph -- 115-117° C. II 4-MeO-ph -- 171-173° C. II 3-MeO-ph -- 128-130° C. II 4-Br-ph -- 159-162° C. II 2-F-ph -- 139-142° C. II furyl-2 -- 140-142° C. III 4-Me-ph Et 141-145° C.20. III 4-Cl-ph Et 115-120° C. III ph Et 144-148° C. III 4-NO.sub. 2 -ph Et 184-187° C. III 4-OMe-ph Et oil 7.20(4H, aromatic H), 4.75(2H, s, CH.sub.2) 3.84 (3H, s, CH.sub.3), 3.75 (2H, q, CH.sub.2) 1.28 (3H, t, CH.sub.3) III 2-thiophene Et 134-136° C. III 3-Me-ph Et oil 7.34(4H, m, arom. H), 4.78(2H, s, CH.sub.2), 3.80 (2H, q, CH.sub.2), 2.40 (3H, s, CH.sub.3), 1.25 (3H, t, CH.sub.3) III 2-Me-ph Et oil 7.35(4H, m, arom. H), 4.80(2H, s, CH.sub.2), 3.56 (2H, q, CH.sub.2), 2.29 (3H, s, CH.sub.3) 1.12 (3H, t, CH.sub.3) III 2-F-ph Et 104-107° C. III 1-naphthyl Et 148-152° C. III 2-naphthyl Et 63-70° C.30. III 4-Br-ph Et 125-126° C. III 2-F-ph Et 121-124° C. III 4-F-ph Et 108-111° C. III 3-pyridyl Et 129-131° C. III 3-OMe-ph Et 127-130° C. III 3-NO.sub.2 -ph Et 153-158° C. III 3-Cl-ph Et -- 7.60(4H, m, arom. H), 4.81(2H, s, CH.sub.2), 3.85 (2H, q, CH.sub.2), 1.32 (3H, t, CH.sub.3) III 3-Br-ph Et -- 7.80 to 7.40 (4H, m, arom. H), 4.80 (2H, s, CH.sub.2), 3.84 (2H, q, CH.sub.2), 1.30(3H, t, (CH.sub.3) III 3-OMe-ph Et -- 7.50 to 7.00(4H, m, arom. H), 4.80 (2H, s, CH.sub.2), 3.85(4H, m, CH.sub.3 & CH.sub.2), 1.30 (3H, t, CH.sub.3) III 3-OEt-ph Et -- 7.50 to 7.00 (4H, m, arom. H), 4.80 (2H, s, CH.sub.2), 4.10 (2H, q, CH.sub.2), 3.84 (2H, q, CH.sub.2), 1.46 (3H, t, CH.sub.3), 1.26 (3H, t, CH.sub.3)40. III 4-Me-ph n-Bu -- 7.40(4H, q, arom. H), 4.78(2H, s, CH.sub.2), 3.80 (2H, t, CH.sub.2), 2.44 (3H, s, CH.sub.3), 1.62 (2H, m, CH.sub.2), 1.30 (2H, m, CH.sub.2), 0.85(3H, t, CH.sub.3) III 4-Me-ph i-pro -- 7.38(4h, q, arom. H), 4.75 (2H, s, CH.sub.2), 4.26 (1H, m, CH), 2.45 (3H, s, CH.sub.3), 1.55 (6H, d, 2-CH.sub.3) 1.55 (6H, d, 2-CH.sub.3) III n-prop Et 89-93° C. III 4-Cl-ph ph 193-195° C. III 2-Cl-ph Et 86-89° C. III 4-Cl-ph 4-Cl-ph 171-177° C. III 4-Cl-ph 4-Me-ph 179-183° C. III Me ph 179-182° C. III Me 4-Cl-ph 129-131° C. III H 4-Cl-ph 147-149° C.50. III H ph 192-193° C. III 4-Br-ph Me 145-150° C. III 4-Cl-ph Me 148-152° C. III 4-F-ph Me 122-125° C. III 3-Cl-ph Me 78-82° C. III 3-Br-ph Me 89-94° C. III 3-F-ph Ne 124-129° C. III 2-F-ph Me 121-126° C. III t-Butyl ph 170-174° C. IV ph -- 117-119° C.60 II 1-naphthyl -- 167-169° C.61 II Me -- 90-96° C.62 II n-C.sub.17 H.sub.35 -- 41-46° C.63 II n-C.sub.4 H.sub.9 -- oil 4.60(2H, s, CH.sub.2), 2.60 (2H, t, CH.sub.2), 1.70 (2H, m, CH.sub.2), 1.42 (2H, m, CH.sub.2), 0.95 (3H, t, CH.sub.3)64 II t-C.sub.4 H.sub.9 -- 90-93° C.65 II 3-Br-ph -- 127-129° C.66 II 4-F-ph -- 127-129° C.67 II 3-F-ph -- 127-129° C.68 II ph -- 137-139° C.69 II 2-EtO-ph -- 138-142° C.70 II 3-EtO-ph -- 129-132° C.71 II 2-Cl, 4-NO.sub.2 -ph -- 161-166° C.72 II 4-ph-ph -- 183-186° C. II 3,5-(OMe).sub.2 -ph -- 161-165° C. II 2,5-(OMe).sub.2 -ph -- 144-147° C. II 3,4,5-(OMe).sub.3 -ph -- 135-137° C. II 2,5-Cl.sub.2 -ph -- 121-123° C. II n-Heptyl -- Oil 4.62(2H, s, CH.sub.2), 2.58(2H, t, CH.sub.2), 1.70(2H, m, CH.sub.2). 1.32(12H,m 4CH.sub.2), 0.90(3H, t, CH.sub.3) III t-Bu 3-F-ph 151-160° C. III t-Bu Me Oil 4.72(2H, s, CH.sub.2), 3.42(3H, s, CH.sub.3), 1.40(9H, s, 3CH.sub.3)80. III t-Bu Et Oil 4.70(2H, s, CH.sub.2), 3.88(2H, q, CH.sub.2), 1.38(12H, m, 4CH.sub.3) III Me Et Oil 4.68(2H, s, CH.sub.2), 3.72(2H, q, CH.sub.2), 2.26(3H, s, CH.sub.3), 1.30(3H, t, CH.sub.3) III n-Bu Et Oil 4.82(2H, s, CH.sub.2), 3.70(2H, q, CH.sub.2), 2.40(2H, t, CH.sub.2), 1.66(2H, m, CH.sub.2), 1.38(5H, m), 0.98(3H, t, CH.sub.3) III t-Bu 3-MeO-ph 168-170° C. III n-Pr 4-Cl-ph 50-56° C. III n-Pr ph 106-112° C. III t-Bu 4-Cl-ph 168-171° C. III Me 4-Me-ph 166-170° C. III Me 4-MeO-ph 200-203° C. III n-Pr 4-MeO-ph Oil 7.22(4H, q, arom. H), 4.76(2H, s, CH.sub.2), 3.85(3H, s, CH.sub.3), 2.40(2H, t, CH.sub.2), 1.58(2H, m, CH.sub.2), 0.90(3H, t, CH.sub.3)90. III n-Pr 3-MeO-ph 109-112° C. III n-Pr 2-MeO-ph Oil 7.55-7.02(4H, m, arom. H), 4.78(2H, s, CH.sub.2), 3.86(3H, s, CH.sub.3), 2.32(2H, q, CH.sub.2), 1.60(2H, m, CH.sub.2), 0.90(3H, t, CH.sub.3) III Me n-Hexyl Oil 4.70(2H, s, CH.sub.2), 3.60(2H, t, CH.sub.2), 2.26(3H, s, CH.sub.3 ), 1.64(2H, m, CH.sub.2), 1.34(6H, m, 3CH.sub.2), 0.91(3H, t, CH.sub.3) III Me Benzyl 170-172° C. III Me Cyclohexyl 103-106° C. III H 3-Cl-ph 112-115° C. III H 3-Me-ph 153-156° C. III H 2-Me-ph 132-134° C. III H 2-Cl-ph 139-140° C. III H 4-Me-ph 165-170° C.100. III H n-Bu 66-70° C.101. III H Et Oil 7.42(1H, s) 4.64(2H, s, CH.sub.2), 3.70(2H, q, CH.sub.2), 1.34(3H, t, CH.sub.3)102. III H 4-F-ph 124-127° C.103. III H 4-MeO-ph 117-120° C.104. III H 4-NO.sub.2 -ph 165-166° C.105. III H 4-Br-ph 175-177° C.106. III H 2,4-Cl.sub.2 -ph 148-151° C.107. III H 3,4-Cl.sub.2 -ph 160-161° C.108. III H 3,5-Cl.sub.2 -ph 101-105° C.109. III H 3-F-ph 172-175° C.110. III H 3-Br-ph 105-110° C.111. III H 2-F-ph 115-120° C.112. III H Cyclohexyl 118-122° C.113. III H Benzyl 119-124° C.114. III H n-Hexyl Oil 7.45(1H, s, olefinic H), 4.74(2H, s, CH.sub.2), 3.64(2H, t, CH.sub.2), 1.72(2H, m, CH.sub.2), 1.35(6H, m, 3CH.sub.2). 0.90(3H, t, CH.sub.3)115. III H 2,6-Cl.sub.2 -ph 115-120° C.116. III H 3,5-Me.sub.2 -ph 80-85° C.117. III H 2,4-Me.sub.2 -ph 119-124° C.118. III H 4-Et-ph 129-132° C.119. III H 3-Et-ph 82-87° C.120. III H n-Octyl Oil 7.44(1H, s, olefinic H), 4.72(2H, s, CH.sub.2), 3.62(2H, t, CH.sub.2), 1.72(2H, m, CH.sub.2), 1.30(10H, m, 5CH.sub.2), 0.90(3H, t, CH.sub.3)121. III H n-Dodecyl 50-52° C.__________________________________________________________________________
EXAMPLE 1
Preparation of 2-(4-Chlorophenyl)-4-3-Iodopropargyl) -1,3,4-Oxadiazolin-5-one (Compound #1)
To the suspension of 4-chlorobenzhydrazide (8.53 g, 0.05 mole) in methylene chloride (100 ml), equipped with a magnetic stirring bar, a nitrogen inlet, a dropping funnel, and an outlet connected to diluted base solution for trapping the HCl gas, was dropwise added trichloromethyl chloroformate (5.94 g, 0.03 mole). After addition, the reaction mixture was heated to reflux for 2 hr. The reaction was cooled down to room temperature and poured into a mixture of water (500 ml) and hexane (200 ml) and stirred for 10 to 20 min. The resultant precipitate was collected by suction-filtration and was washed with hexane to give a solid product. The product was dried in air at room temperature overnight yielding 5.5 g (60% yield) of 2-(4-chlorophenyl)-1,3,4-oxadiazolin-5-one as a solid, m.p.=225°-227° C. NMR and IR spectra showed the desired structure. Without further purification, this product was subjected to the next step.
To the suspension of 2-(4-chlorophenyl)-1,3,4-oxadiazolin-5-one (2 g, 0.01 mole) in acetone (50 ml) was added potassium carbonate (2 g, 0.015 mole), followed by propargyl bromide (1.6 g of 80% in toluene, 0.0106 mole) with magnetic stirring under nitrogen for 3 hr. The reaction mixture was cooled down to room temperature. The suspension was filtered by suction-filtration and the solid was washed with acetone. The filtrate was concentrated to about 10 ml and was poured into water (200 ml). The resultant precipitate was collected by suction-filtration and washed with water and hexane affording 0.85 g (36% yield), after drying in air, of 2-(4-chlorophenyl)-4-propargyl-1,3,4-oxadiazolin-5-one as a solid. m.p.=125°-127° C. NMR and IR spectra showed the desired structure. Without further purification, this compound was subjected to the next step.
To the suspension of 2-(4-chlorophenyl)-4-propargyl-1,3,4-oxadiazolin-5-one (0.6 g, 0.00256 mole) in acetone (20 ml) with magnetic stirring at room temperature was added N-iodosuccinimide (0.6 g, 0.00266 mole), followed by silver nitrate (0.040 g, 0.00024 mole). The reaction mixture was stirred at room temperature for one hour. The suspension was filtered gravitationally and the solid was rinsed with acetone. The filtrate was poured into water (300 ml). The resultant precipitate was collected by suction-filtration and air-dried to give 0.8 g (92% yield), of 2-(4-chlorophenyl)-4-(3-iodopropargyl)-1,3,4-oxadiazolin-5-one as a solid. m.p.=151°-152° C. The proton NKM spectrum was consistent with the desired structure.
EXAMPLE 2
1-(3-Iodopropargyl)-3-(4-chlorophenyl)-4-ethyl-1,2,4-triazolin-5-one (Compound #20)
To a suspension of 4-chlorobenzhydrazide (98.5 g, 0.05 mole) in tetrahydrofuran (100 ml) at room temperature ethylisocyanate (4.2 g, 0.05 mole) was added slowly with magnetic stirring. The reaction was slightly exothermic and the reaction mixture turned to a thick paste. Stirring was continued an additional 30 min after which the solid was collected by suction-filtration and washed with a small amount of tetrahydrofuran and dried to provide 11.6 g (96.6% yield), of 1-(4chlorobenzoyl)-4-ethyl semicarbazide as a white solid., m.p.=242°-243° C. The above semicarbazide (10 g, 0.0414 mole) was dissolved in 1N sodium hydroxide solution (100 ml) and was refluxed with stirring for 16 hr. The solution was cooled down to about 10° C. by an ice bath and was neutralized by conc. hydrogen chloride until pH 2. The resultant white solid was collected by suction-filtration and washed with water to give 8.65 g (93.5% yield) of 3-(4-chlorophenyl)-4-ethyl-1,2,4-triazolin-5-one as a white solid. m.p.=190°-197° C. A proton NMR spectrum was consistent with the desired structure.
To the solution of 3-(4-chlorophenyl)-4-ethyl-1,2,4-triazolin-5-one (2.23 g, 0.01 mole) in dry acetone (40 ml) was added, at room temperature, potassium carbonate (1.67 g, 0.012 mole) followed by propargyl bromide (1.8 g of 80% in toluene, 0.012 mole). The reaction mixture was then refluxed with stirring for 6 hr. The mixture was cooled down to room temperature and solvent was evaporated to give a residue. The product was purified by crystallization from hexane/ether, affording 1.8 g (69.2% yield) of 1-propargyl-3-(4-chlorophenyl)-4-ethyl-1,2,4-triazolin-5-one as a white solid. m.p.=115°-119° C. A proton NMR spectrum was consistent with the desired structure.
To the solution of 1-propargyl-3-(4-chlorophenyl)-4-ethyl-1,2,4-triazolin-5-one (1.0 g , 3.82 mmole) in dry acetone (20 ml) was added N-iodosuccinimide (0.95 g, 4.2 mmole), followed by silver nitrate (50 mg, 0.29 mmole) with magnetic stirring at room temperature. The reaction mixture was stirred for 1 hr. The resultant suspension was filtered and the filtrate was poured into water (250 ml). A yellowish white solid slowly precipitated out and was collected by suction-filtration and washed with water to give 1.12 g (76% yield) of 1-(3-iodopropargyl)-3-(4-chloro-phenyl)-4-ethyl-1,2,4-triazolin-5-one as a light yellow solid. m.p.=115°-120° C. A proton NMR spectrum was consistent with the desired compound.
EXAMPLE 3
Preparation of 2-phenyl-4-iodopropargyl-1,3,4-thiadiazolin-5-one (Compound 59)
A. Preparation of Thiobenzhydrazide
A cold solution of S-(thiobenzoly)thioglycolic acid (12.25 g, 57.6 mmole) in 1N NAOH (60 ml, 60 mmole NAOH) was slowly added to a solution of hydrazine monohydrate (6 g, 123.8 mmole) in 5 ml of water at about 5° C. with magnetic stirring. After the addition, the resultant yellow suspension was stirred at room temperature for one hour. The mixture was cooled down to 5° C. and was acidified with conc. HCl until pH=6. The yellow solid was collected by suction-filtration and was washed with water to afford 3.70 g, after drying in air. m.p.=66°-68° C.
B. Preparation of 2-phenyl-1,3,4-thiadiazolin-5-one
To a solution of thiobenzhydrazide (3.7 g, 24.34 mmole) in methylene chloride (50 ml), equipped with magnetic stirrer, nitrogen inlet, and an outlet connected to a trap containing a diluted NAOH solution, was added trichloromethyl chloroformate (4 g, 20.2 mmole). The reaction mixture was stirred at room temperature for one hour. The mixture was diluted with methylene chloride (100 ml) and washed with water (3×50 ml) and brine. The organic layer was dried over MgSO 4 . After the drying agent was filtered off the filtrate was concentrated to a residue. The residue was triturated with hexane and the solid product was collected by suction-filtration to give 3.7 g as a powder. m.p.=140°-143° C.
C. Preparation of 2-phenyl-4-propargyl-1,3,4-thiadiazolin-5-one
To the solution of 2-phenyl-1,3,4-thiadiazolin-5-one (3 g, 16.85 mmole) in dry acetone (30 ml) under nitrogen with magnetic stirring was added potassium carbonate (3 g, 22 mmole), followed by propargyl bromide (3 g, 80% in toluene, 20 mmole) at room temperature. The mixture was refluxed for one hour. The reaction mixture was cooled down to room temperature and the solid was filtered off by suction-filtration. The filtrate was diluted with ether (200 ml) and washed with water (2×50 ml) and brine. The organic layer was dried over sodium sulfate. After the drying agent was filtered off the filtrate was concentrated to about 5 ml. Hexane was added to precipitate out the product. The product was collected by suction-filtration and washed with a little hexane to afford 2 g of 2-phenyl-4-propargyl-1,3,4-thiadiazolin-5-one as a powder. m.p.=73°-75° C.
D. Preparation of 2-phenyl4-iodopropargyl-1,3,4-thiadiazolin-5-one
To the solution of 2-phenyl-4-propargyl-1,3,4-thiadiazolin-5-one (1.6 g, 7.4 mmole) in dry acetone (25 ml) under nitrogen with magnetic stirring was added catalytic amount of silver nitrate 0.1 g, 0.58 mmole), followed by N-iodosuccinimide (1.85 g, 8.15 mmole). The reaction mixture was stirred at room temperature for 20 hours. The solid was filtered off by suction-filtration through a Celite filter. The filtrate was diluted with water (200 ml) and extracted with ethyl acetate (2×100 ml). The organic layer was washed with water (2×50 ml), brine, and dried over sodium sulfate. The drying agent was filtered off and the filtrate was concentrated to give a residue. The residue was triturated with hexane and the product was collected by suction-filtration to give 1.75 g as a semicrystalline compound. m.p.=117°-119° C. Proton NMR spectrum showed the desired compound.
EXAMPLE 4
Biocidal Evaluations of Compounds
A minimum inhibitory concentration (MIC) value is obtained using a broth, two-fold serial dilution test performed as follows: A stock solution or dispersion of the test compound, typically at a concentration of 1%, is made in a 5:3:2 solvent solution of acetone, methanol, and water. A volume of the stock solution is dispensed into culture media to give an initial starting test concentration of 500 PPM. 250 ppm, or 12 5 ppm compound.
When the test is ready to be done, each vessel in the dilution series, except the first vessel, contains an equal volume of compound free broth. The first vessel contains twice the volume of broth with the starting concentration of test compound. One half of the broth from the first vessel is transferred to the second vessel. After being mixed, one half the resulting volume is removed from the second vessel and transferred to the third vessel. The entire cycle is repeated sufficiently to give a series of concentrations amounting to 500, 250, 125, 63, 31, 16, 8, and 4 ppm or 250, 125, 63, 32, 16, 8, 4, 2, 1, 0.5, 0.25, and 0. 12 (or 100, 50, 25, 12.5, 6.2, 3.1, 1.6, and 0.8), respectively.
Each vessel is then inoculated with a cell suspension of the appropriate test organism. Bacteria are grown in broth and fungi on agar slants and algae is grown in cooling tower media for a time and at a temperature appropriate to the species being tested. At the end of the growth period, the broth is vortexed to disperse the cells. In the case of fungi, the spores are harvested by pipetting water onto the slant and dislodging the spores with a sterile loop. The cell/spore suspension is standardized by controlling incubation time, temperature, and the volume of the diluent. The suspension is then used to inoculate the vessels containing the broth compound. The vessels are then incubated at the appropriate temperature. After the incubation, the vessels are examined for growth/no growth. The minimum inhibitory concentration (NEC) is defined as the lowest concentration of compound that results in complete inhibition of growth of the test organism.
The organisms tested to demonstrate biocidal activity include:
BACTERIA:
Pseudomonas fluorescens (Ps.fl), gram negative
Pseudomonas aerugenosa (Ps.ae), gram negative
Escherichia coli (E.c), gram negative
Staphylococcus aureus (S.a), gram positive
FUNGI:
Aspergillus niger (A.n)
Aureobasidium pullulans (A.p)
ALGAE:
Chlorella pyroidenosa (see Table 5)
TABLE 2______________________________________Biocidal EvaluationThe Result of Minimum Inhibitory Concentration (MIC) Tests MIC (ppm)Compound # Psfl Psae Ecol Saur Anig Apul______________________________________ 1. >100 >100 >100 >100 <0.8 <0.8 2. >100 >100 >100 >100 <0.8 <0.8 3. 100 >100 >100 >100 >100 <0.8 4. 100 >100 >100 >100 2 <0.8 5. >100 >100 >100 50 <0.8 <0.8 6. >100 >100 >100 13 <0.8 <0.8 7. 50 50 25 13 <0.8 <0.8 8. 50 100 25 25 <0.8 <0.8 9. >100 >100 >100 >100 <0.8 <0.810. 13 13 13 6 <0.8 <0.811. 50 100 >100 50 <0.8 <0.812. >100 >100 >100 >100 <0.8 <0.813. >500 >500 >500 >500 250 814. >500 >500 >500 >500 500 3215. >500 125 >500 >500 63 <416. >500 125 125 >500 125 <417. >500 >500 >500 >500 8 <418. >500 >500 >500 >500 <4 <419. 100 25 50 25 <0.8 <0.820. 100 25 50 13 <0.8 <0.821. >100 100 50 25 <0.8 1.622. >100 >100 >100 50 6.3 323. >100 >100 >100 50 13 324. >100 >100 >100 100 6 325. >100 >100 50 25 <0.8 <0.826. >100 >100 50 1.6 <0.8 1.627. 50 100 >100 100 100 228. >100 >100 >100 50 25 <0.829. 100 >100 >100 25 6.3 <0.830. >100 >100 50 13 <0.8 <0.831. >100 50 50 25 1.6 <0.832. 100 50 50 25 <0.8 <0.833. >100 50 25 25 13 2534. >100 >100 >100 50 13 1335. >100 >100 >100 50 25 636. 100 >100 >100 >100 <0.8 337. 100 100 >100 100 <0.8 338. >100 100 >100 >100 2 6.339. >100 >100 >100 >100 2 6.340. >100 >100 >100 >100 50 2541. >100 >100 >100 >100 6.3 6.342. >100 >100 >100 50 13 643. 100 50 >100 >100 6 <0.844. >100 >100 >100 25 13 645. >100 >100 >100 >100 >100 >10046. >100 >100 >100 >100 >100 >10047. 63 63 63 125 16 848. 16 250 250 32 16 <449. 32 32 63 125 8 <450. >500 >500 >500 >500 63 <451. 63 250 63 63 32 <452. 63 250 32 125 32 <453. 16 63 32 32 <4 <454. 16 125 32 32 8 <455. 16 125 32 32 8 <456. 16 125 16 32 <4 <457. 32 125 32 63 8 <458. 16 125 63 125 32 1659 250 >250 >250 250 <4 461 250 125 32 32 <4 <462 250 250 250 250 <4 <463 250 250 250 500 <4 <464 250 250 250 500 <4 <465 250 250 250 500 <4 <466 8 63 32 250 <4 <467 8 32 16 <4 <4 <468 63 125 >500 125 <4 1669 >250 >250 >250 >250 4 >25070 63 63 >500 125 <4 --71 125 63 >500 250 8 --72 >500 >500 >500 >500 >500 >50073 >250 >250 >250 >250 >250 >25074 >250 >250 >250 >250 250 >25075 >250 >250 >250 >250 >250 876 >250 >250 >250 >250 2 877 -- 63 >250 8 <0.12 16787980 32 250 250 32 4 --81 32 250 250 63 16 --82 32 125 250 32 2 --83 125 250 >250 250 32 --84 63 250 250 63 16 885 125 >250 >250 63 16 886 >250 >250 >250 >250 32 3287 -- >250 >250 >250 8 --88 -- >250 >250 >250 63 --89 -- >250 >250 250 16 890 -- >250 >250 250 32 1691 -- >250 >250 >250 >250 >25092 -- 250 >250 125 4 493 -- 125 >250 63 8 894 -- >250 >250 250 16 895 32 250 >250 63 <0.12 --96 125 >250 >250 >250 <0.12 --97 63 >250 >250 125 4 498 63 >250 >250 125 4 499 >250 >250 >250 >250 8 4100 63 125 125 125 1 2101 63 250 >250 63 16 8102 63 >250 250 63 0.25 2103 125 >250 >250 63 1 4104 63 125 125 63 <0.12 <0.12105 125 250 >250 >250 <0.12 <0.12106 125 >250 >250 >250 >250 >250107 -- 125 >250 250 2 16108 250 >250 >250 250 2 4109 >250 >250 >250 >250 32 16110 -- >250 >250 125 2 1111 -- >250 >250 >250 2 1112 -- >250 >250 >250 2 2113 -- >250 >250 >250 0.25 0.25114 -- >250 >250 >250 -- --115 -- 250 >250 250 32 16116 -- >250 >250 250 16 8117 -- >250 >250 >250 32 8118 -- 63 250 250 16 8119 -- 125 >250 250 32 8120 -- 63 >250 4 <0.12 <0.12121 -- >250 >250 >250 >250 >250______________________________________
EXAMPLE 5
In-Vitro Plant Fungicide Tests of Compounds
The organisms employed in the test are:
PYU Pythium ultimum (Oomycete)
PHY Phytophthora capsici (Oomycete)
PIR Piricularia oryzae (Ascomycete)
FM Cochliobolus sativus (Ascomycete)
BOC Botrytis cinerea (Ascomycete)
FUS Fusarium roseum (Ascomycete)
SEP Septoria nodorum (Ascomycete)
RHI Rhizoctonia solani (Basidiomycete)
XAN Xanthomonas campestris (bacterium)
Methods
1. Culture maintenance: Transfers in steps 1 and 2 are done in a laminar flow hood. All 8 fungi and the bacterium used in this test are transferred and maintained on potato dextrose agar plates each week (2 plates/organism). Organisms are used when they are the following ages: a. 1 week old: PYU, PHY, RHI; b. 2 weeks old: XAN, PIR, BOC, HEL, FUS, SEP, COL, MON, CER, UST, ALT; c. 3 weeks old: PSH, VEN. Pythium ultimum and Phytophthora capsici are transferred to asparagine-sucrose broth shake cultures (ASB). Rhizoctonia solani, Fusarium roseum, and Zanthomonas campestris are mainted in yeast extract-dextrose broth (YDB) on a shaker. Culture flasks are inoculated with 6 mycelial plugs each (except for Pythium which is inoculated with only 3 plugs) taken from PDA plates. All liquid shaker cultures are used after 2 days growth.
2. Inoculum preparation. Conidia and mycelium from PIR, BOC, HEL, SEP, COL, MON, CER, PSH, UST and ALT are lightly scraped off into YDB so that mostly conidia are used as inoculum. The conidial suspension is strained through a double layer of cheesecloth to remove mycelial clumps. One plate produces enough conidia or mycelium to inoculate 100 n-d of YDB. XAN broth culture is poured (1 ml culture/100 ml broth) into YDB. PYU, PHY, RFU and FUS cultures are ground up (2-3 5 second bursts in a blender) and an but Pythium and Phytophthora are filtered through a double layer of sterile cheesecloth to remove large mycelial clumps. Ten ml of the culture solutions of R. solani and F. roseum are added to 90 ml of YSB and 10 ml of the P. capsici is added to 90 ml ASB. Two ml of the culture solution of P. ultimum is added to 98 ml of ASB. Care must be made not to overinoculate (e.g. solutions should appear fairly dear to the eye, yet when held up to light a faint cloudiness should be visible) or standards will not behave properly. The inoculum mixtures are placed in microtiter plates using a 12-tipped pipet. 175 μl (single dose) or 100 μl (dose-response test) of inoculum broth is placed in each well of the microtiter plates. The plates with inoculated media are placed in the refrigerator overnight. There are two replications per treatment.
3. Addition of compounds. This operation is carried out in a chemistry hood. Six microtiter plates have 245 microtiters of sterile water added to their wells ahead of time. 10 mg a.i. of the compounds are placed in 1 ml 1:1 acetone:methanol. 5 microliters of this solution is pipetted into the microtiter plates containing the sterile water according to the grid. There are 45 compounds and 3 scattered control treatments per plate. There are 2 replicates per treatment. 25 microtiters of solution is transferred to the inoculated plates with a 96 well replicator. The replicator is flame sterilized with alcohol, rinsed with sterile water, and blotted on sterile paper towells between each transfer.
TABLE 3__________________________________________________________________________The Results of In-Vitro Plant Fungicide TestsDose % ControlCompound (PPM) PYU XAN PIR PHY BOC HEL RHI FUS SEP__________________________________________________________________________ 1. 25 100 0 100 100 100 100 100 100 100 2. 25 95 0 75 95 0 75 100 100 95 3. 25 100 0 75 75 0 90 95 100 95 4. 25 100 0 95 95 0 100 90 100 100 5. 25 100 0 100 100 50 95 100 100 100 6. 25 100 0 100 100 100 100 100 100 100 7. 25 100 0 100 100 100 100 100 100 100 8. 25 100 0 100 100 100 100 100 100 100 9. 25 0 0 0 0 0 75 90 100 0 10. 25 50 0 0 100 0 90 0 100 100 11. 25 100 0 100 95 90 95 100 100 100 12. 25 95 0 95 90 50 100 90 100 100 13. 25 100 0 100 100 0 100 100 100 100 14. 25 100 0 100 100 0 100 100 100 100 15. 25 100 0 100 100 0 100 100 100 100 16. 25 100 0 100 100 0 100 100 100 100 17. 25 95 0 100 100 0 100 95 100 100 18. 25 -- 0 100 100 75 100 100 100 100 19. 25 100 0 100 100 0 95 100 100 100 20. 25 100 0 100 100 0 95 100 100 100 21. 25 100 0 100 100 0 100 100 100 100 22. 25 100 0 100 100 0 100 100 100 100 23. 25 100 0 100 100 0 100 100 100 100 24. 25 100 0 100 100 95 100 100 100 100 25. 25 100 0 100 100 0 100 75 100 100 26. 25 100 0 100 100 75 100 100 100 100 27. 25 100 0 95 100 0 75 95 90 50 28. 25 95 0 100 100 0 95 100 95 100 29. 25 100 0 100 100 0 100 100 95 75 30. 25 100 0 100 100 0 100 100 100 100 31. 25 100 0 100 100 0 100 100 100 100 32. 25 100 0 100 100 0 100 100 100 100 33. 25 100 0 100 100 0 100 100 100 100 34. 25 50 0 100 50 0 0 50 0 75 35. 25 0 0 0 0 0 0 0 0 0 36. 25 50 0 100 100 0 100 100 90 100 37. 25 -- -- -- -- -- -- -- -- -- 38. 25 90 0 100 95 0 100 100 100 --39 25 100 0 100 100 0 100 100 100 10040 25 50 0 100 50 0 0 0 50 7541 25 0 0 0 0 0 0 0 042 25 50 0 100 100 0 100 100 90 10043 25 90 0 100 95 0 100 100 100 --44 25 90 0 100 95 0 100 100 100 --45 25 0 0 90 0 0 0 0 50 046 25 0 0 100 0 0 50 50 100 047 25 100 0 100 100 100 100 100 100 10048 25 100 0 100 100 100 100 100 100 10049 25 100 0 100 100 100 100 100 100 10050 25 100 0 95 100 100 95 95 95 9551 25 100 0 100 100 100 100 100 100 10052 25 100 0 100 100 100 100 100 100 10053 25 100 0 100 100 100 100 100 100 10054 25 100 0 100 100 100 100 100 100 10055 25 100 0 100 100 100 100 100 100 10056 25 100 0 100 100 100 100 100 100 10057 25 100 0 100 100 100 100 100 100 10058 25 100 0 100 100 90 100 100 100 10059 25 100 0 100 100 100 100 100 100 10060 25 0 0 100 0 0 50 0 0 061 25 100 0 100 100 100 100 100 100 10062 25 0 0 0 0 0 0 0 0 063 25 100 0 100 100 100 100 100 100 10064 25 100 0 100 100 100 100 100 100 10065 25 100 0 100 100 100 100 100 100 10066 25 100 0 95 100 100 100 100 100 1067 25 100 0 100 100 100 100 100 100 10068 25 100 0 100 100 90 100 100 100 10069 25 100 0 100 95 50 95 50 0 9570 25 100 0 100 100 75 100 100 100 10071 25 100 0 100 100 90 100 100 100 10072 25 100 0 100 100 0 50 75 0 9573 25 0 0 0 50 0 50 0 0 074 25 100 0 100 100 0 75 100 0 075 25 90 0 75 90 0 0 100 0 076 12 0 0 100 100 0 0 50 0 5077 -- -- -- -- -- -- -- -- -- --78 25 100 0 100 100 0 75 100 100 10079 25 100 0 100 100 75 100 100 100 5080 25 100 0 100 100 50 100 100 100 5081 25 100 0 100 100 0 100 100 0 082 25 100 0 100 100 100 100 100 100 10083 25 100 0 100 100 0 75 100 100 5084 25 100 0 100 100 50 100 100 100 10085 25 100 0 100 100 50 100 100 100 10086 25 100 0 100 100 100 75 100 100 10087 -- -- -- -- -- -- -- -- -- --88 -- -- -- -- -- -- -- -- -- --95 25 100 0 100 100 100 100 100 100 10096 25 100 0 100 100 100 100 100 100 10097 -- -- -- -- -- -- -- -- -- --98 25 -- -- -- 100 -- -- 100 100 --99 25 -- -- -- 100 -- -- 100 100 --100 25 100 0 100 100 100 100 100 100 100101 25 100 0 100 100 90 100 100 100 100102 25 100 0 100 100 100 100 100 100 100103 25 100 0 100 100 100 100 100 100 100104 25 100 0 -- 100 95 0 90 90 100105 25 100 0 -- 100 100 75 100 100 100106 25 100 0 100 100 100 100 100 100 100107 25 100 0 100 100 100 100 100 100 100108 25 100 0 100 100 100 100 100 100 100109 25 100 0 100 100 100 100 100 100 100110 25 100 0 100 100 100 100 100 100 100111 25 100 50 100 100 100 100 100 100 100112 25 100 0 100 100 100 100 100 100 100113 25 100 0 100 100 100 100 100 100 100114 25 100 0 100 100 100 100 100 100 100__________________________________________________________________________
EXAMPLE 6
Agricultural Fungicide Evaluations of Compounds
The compounds of this invention were tested for fungicidal activity in vivo against cucumber downy mildew (CDM), rice blast (RB), rice sheath blight (RSB), tomato late blight (TLB), wheat powdery mildew (WPM), wheat stem rust (WSR) and wheat leaf rust (WLR) and the results are shown in Table 4. In tests on cereals (except for rice plants used for testing rice blast), the plants were trimmed about 24 hours prior to the application of the fungicide compound to provide a uniform plant height and to facilitate uniform application of the compound and inoculation with the fungus. The compounds were dissolved in a 2:1:1 mixture of water, acetone, and methanol, sprayed onto the plants, allowed to dry (four to six hours), and then the plants were inoculated with the fungus. Each test utilized control plants which were sprayed with the water, acetone, and methanol mixture and inoculated with the fungus. The remainder of the technique of each of the tests is given below and the results are reported as percent disease control (percentages of plants treated with the compounds of the present invention lacking disease signs or symptoms compared to the untreated control plants).
Cucumber Downy Mildew (CDM)
Pseudoperonospora cubensis was maintained on leaves of live Marketer cucumber plants in a constant temperature room at 65° F. to 75° F. in humid air with moderate light intensity for 7 to 8 days. A water suspension of the spores from infested leaves was obtained and the spore concentration was adjusted to about 100,000 per ml of water.
Marketer cucumber seedlings were inoculated by spraying the underside of the leaves with a DeVilbiss atomizer until small droplets were observed on the leaves. The inoculated plants were incubated in a mist chamber for 24 hours at about 70° F. and then subsequently incubated for 6 to 7 days in a controlled temperature room under mist at 65° F. to 75° F. Seven days after inoculation, the percent disease control was determined.
Rice Blast (RB)
Nato rice plants were inoculated with Piricularia oryzae (about 20,000 conidia per ml) by spraying the leaves and stems with an airbrush until a uniform film of inoculum was observed on the leaves. The inoculated plants were incubated in a humid environment (75° F. to 85° F.) for about 24 hours, then placed in a greenhouse environment (70° F. to 75° F.). Seven to eight days after inoculation, the percent disease control was determined.
Rice Sheath Blight (RSB)
Pellicularia filamentosa (f. sp. sasiki) was cultured on an autoclaved mixture of crushed rice seeds and potato dextrose broth (100 gms of rice seeds per 30 ml of potato dextrose broth) in a 500 ml Erlenmeyer flask. After 10 days, the culture was blended in a blender to produce a uniform inoculum. Approximately one teaspoon of inoculum was spread among Lebonnet rice seedlings on the soil surface of each pot (3 inch diameter). The inoculated seedlings were incubated for 5 days in a humidity cabinet (85° F. to 90° F.). Percent disease controls were determined immediately after removing the seedlings from the cabinet.
Tomato Late Blight (TLB)
Phytophthora infestans was cultured on four week old Pixie tomato plants in a controlled environment room (65° F. to 70° F. and 100% relative humidity). After storage, the spores were washed from the leaves with water and dispersed by DeVilbiss atomizer over three week old Pixie tomato plants which had been sprayed previously with experimental fungicides. The inoculated plants were placed in a humidity cabinet at 70° F. and constant mist for 24 hours for infection. The plants were then moved to the controlled environment room as above and scored after three more days incubation. Disease control levels were recorded as percent control four days after inoculation and five days after spraying the compounds.
Wheat Powdery Mildew (WPM)
Erysiphe graminis (f. sp. tritici) was cultured on Pennol wheat seedlings in a controlled temperature room at 65° F. to 75° F. Mildew spores were shaken from the culture plants onto Pennol wheat seedlings which had been sprayed previously with the fungicide compound. The inoculated seedlings were kept in a controlled temperature room at 65° F. to 75° F. and subirrigated. The percent disease control was rated 8 to 10 days after the inoculation.
Wheat Stem Rust (WSR)
Puccinis graminis (f. sp. Race 15B-2) was cultured on Wanzer wheat seedlings for a period of 14 days in a greenhouse. A water suspension of the spores from infested plants was obtained and the spore concentration was adjusted to about 200,000 spores per ml of deionized water. Wanzer wheat plants which had been previously treated with the fungicide compounds were inoculated by applying the stem rust spore suspension, until runoff, with a DeVilbiss atomizer at 5 lbs. per square inch air pressure. After inoculation, the plants were placed in a humid environment at approximately 75° F. where they were exposed to 12 hours of continuous darkness followed by a minimum of 3 to 4 hours of light having an intensity of about 500 footcandles. The temperature in the chamber did not exceed 85° F. At the end of the light period, the plants were placed in a greenhouse where they were permitted to grow for a period of two weeks at which time the percent disease control was determined.
Wheat Leaf Rust (WLR)
Puccinis recondita (f. sp. tritici Races PKB and PLD) was cultured on seven day old wheat (cultivar Fielder) over a 14 day period in the greenhouse. Spores were collected from the leaves with a cyclone vacuum or by settling on aluminum foil. The spores were cleaned by sieving through a 250 micron opening screen and stored or used fresh. Storage employed sealed bags in an Ultralow freezer. When stored, spores must be heat shocked for two minutes at 40° F. before use. A spore suspension is prepared from dry uredia by adding 20 mg (9.5 million) per ml of Soltrol oil. The suspension is dispensed into gelatin capsules (0.7 ml capacity) which attach to the oil atomizers. One capsule is used per flat of twenty of the two inch square pots of seven day old Fielder wheat. After waiting for at least 15 minutes for the oil to evaporate from the wheat leaves, the plants are placed in a dark mist chamber (18°-20° C. and 100% relative humidity) for 24 hours. The plants are then put in the greenhouse for the latent period and scored after 10 days for disease levels. Protective and curative tests were inoculated one day after and two days, respectively, before spraying the plants with the test chemicals.
TABLE 4______________________________________Green House Test Results of Plant diseases ControlCom- Rate % Controlpound (ppm) CDM RB SNW TLB WLR WPM______________________________________ 1. 200 90 0 80 0 50 0 2. 200 80 75 80 0 90 75 3. 200 70 0 80 0 50 85 4. 200 90 90 90 0 80 75 5. 200 0 75 50 90 80 75 6. 200 80 75 90 0 90 75 7. 200 50 90 80 50 0 0 8. 200 0 50 0 0 0 0 9. 200 0 0 0 0 50 0 10. 200 50 90 80 0 80 75 11. 200 50 0 80 0 50 50 12. 200 0 0 0 0 0 0 13. 200 0 0 0 0 0 0 14. -- -- -- -- -- -- -- 15. 200 0 0 0 0 50 0 16. 200 0 0 0 0 50 0 17. 200 0 50 0 0 80 0 18. 200 -- 75 50 0 80 0 19. 200 75 0 0 80 90 0 20. 200 90 75 50 70 80 75 21. 200 80 0 50 80 50 0 22. 200 50 50 50 0 50 0 23. 200 50 75 0 70 50 75 24. 200 70 0 50 95 80 85 25. 200 90 90 80 95 80 0 26. 200 0 0 0 95 0 50 27. 200 80 0 0 85 80 0 28. 200 70 75 0 80 80 0 29. 200 90 0 50 80 80 90 30. 200 95 0 0 80 80 75 31. 200 50 90 50 85 80 75 32. 200 0 0 50 90 80 0 33. 200 0 0 0 70 50 85 34. 200 90 99 80 80 80 85 35. 200 70 -- 0 0 50 0 36. 200 70 -- 50 85 95 0 37. 200 0 50 0 0 25 75 38. 200 70 0 0 0 0 039 200 0 0 50 90 80 040 200 50 0 0 80 50 9041 200 0 0 0 70 50 8542 200 0 -- 0 85 50 043 200 70 -- -- 0 50 044 200 70 -- 50 85 95 045 200 0 50 0 0 25 7546 200 70 0 0 0 0 047 200 0 -- 50 -- 80 048 200 50 -- 50 -- 50 9049 200 0 -- 80 85 50 050 200 0 -- 0 0 50 051 200 0 -- 0 90 50 052 200 0 -- 0 0 80 053 200 0 -- 0 0 80 054 200 0 -- 80 0 80 8555 200 70 -- 50 0 80 056 200 0 -- 50 0 80 5057 200 70 -- 80 85 80 10058 200 95 -- 0 70 90 9059 200 90 0 50 0 50 060 200 85 -- 0 0 0 061 200 0 -- -- 50 0 062 -- -- -- -- -- -- --63 200 90 -- -- 50 90 064 -- -- -- -- -- -- --65 200 90 -- -- 90 90 066 200 75 -- -- 0 99 067 200 85 -- -- 95 90 068 200 50 -- -- 50 99 069 -- -- -- -- -- -- --70 200 80 -- -- 0 0 071 -- -- -- -- -- -- --72 -- -- -- -- -- -- --73 200 90 -- -- 0 85 8574 200 0 -- -- 50 75 075 200 0 -- -- 0 95 076 200 90 -- -- 0 95 077 -- -- -- -- -- -- --78 -- -- -- -- -- -- --79 200 75 -- -- 75 85 080 200 50 -- -- 75 75 081 200 0 -- -- 0 75 082 200 50 -- -- 0 0 083 200 85 -- -- 75 95 084 -- -- -- -- -- -- --85 -- -- -- -- -- -- --86 200 75 -- -- 85 75 087 -- -- -- -- -- -- --88 200 90 -- -- 0 0 089 -- -- -- -- -- -- --90 -- -- -- -- -- -- --91 -- -- -- -- -- -- --92 200 70 -- -- -- 95 093 200 95 -- -- 0 75 094 200 100 -- -- 0 90 095 -- -- -- -- -- -- --96 200 90 -- -- 0 99 097 -- -- -- -- -- -- --98 200 90 -- -- 90 95 099 -- -- -- -- -- -- --100 -- -- -- -- -- -- --101 200 0 -- -- 0 0 0102 200 0 -- -- 0 75 0103 200 0 -- -- 0 50 0104 -- -- -- -- -- -- --105 -- -- -- -- -- -- --106 -- -- -- -- -- -- --107 -- -- -- -- -- -- --108 -- -- -- -- -- -- --109 -- -- -- -- -- -- --110 200 -- -- 50 75 80 0111 -- -- -- -- -- -- --112 -- -- -- -- -- -- --113 -- -- -- -- -- -- --114 200 -- -- 50 75 90 0115 -- -- -- -- -- -- --116 200 100 -- -- 75 90 0______________________________________
TABLE 5______________________________________Antialgal Test Results Against Green Alga MIC (ppm)Compound # Chlorella______________________________________ 85 0.25 87 4 88 <0.12 89 <0.12 90 <0.12107 <0.12108 8109 8110 4111 >250112 0.25113 8114 8120 125121 <0.12______________________________________
1.PublishNumber: US-5292762-A
2.Date Publish: 19940308
3.Inventor: HSU; ADAM C.
4.Inventor Harmonized: HSU ADAM C(US)
5.Country: US
6.Claims:
(en)Compounds of the formula ##STR1## wherein A is selected from the group consisting of hydrogen, alkyl, aryl, and heterocyclic;
Y and Z are independently selected from the group consisting of O, S, and N--R;
R is selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted phenyl, and substituted or unsubstituted heterocyclic; and
X is selected from the group consisting of I and Br.
are disclosed to useful as antimicrobials.
7.Description:
(en)This application is a continuation-in-part of Ser. No. 370,373 of Jun. 22, 1988.
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to control of microorganisms.
2. Description of the Prior Art
Certain classes of iodopropargyl compounds have been proposed as fungicides or microbicides but no compound within those classes has achieved commercial success.
U.S. Pat. No. 4,616,004 to Edwards discloses fungicidal activity for compounds of the formula ##STR2##
U.S. Pat. No. 4,639,460 to Rose shows compounds of the formula ##STR3## as fungicides.
U.S. Pat. No. 4,520,023 to Schmitt shows 3-(3-iodopropargyl)benzo-1,2,3-triazolin-4-ones and their use as microbicidal agents.
There was no suggestion in the prior art that compounds within the formula of the present invention would have utility in controlling microorganisms.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide new compounds for controlling microorganisms.
A further object is to provide methods of making such compounds, methods of using them, compositions comprising such compounds, and uses of such compositions.
These objects, and others which will become apparent from the following disclosure, are achieved by the present invention which comprises in one aspect compounds of the formula ##STR4## wherein A is selected from the group consisting of hydrogen, alkyl, aryl, and heterocyclic;
Y and Z are independently selected from the group consisting of O, S, and N--R,
R is selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted phenyl, and substituted or unsubstituted heterocyclic; and
X is selected from the group consisting of I and Br.
In another aspect the invention comprises a method of preparing such compound comprising reacting compound of the formula ##STR5## with an iodinating or brominating agent.
A further aspect comprises using a composition comprising the compounds, or the compound itself, to protect a material selected from the group consisting of wood, paint, adhesive, glue, paper, textile, leather, plastics, cardboard, lubricants, cosmetics, food, caulking, feed and industrial cooling water from microorganisms.
DETAILED DESCRIPTION OF THE INVENTION AND THE PREFERRED EMBODIMENT
The compounds of the invention are of formula I as set forth above. The more preferred embodiments are those wherein A is selected from the group consisting of hydrogen; (C 1 to C 18 ) straight or branched alkyl; (C 3 to C 8 ) cycloalkyl; (C 3 to C 6 ) alkenyl; (C 3 to C 5 ) alkynyl; (C 7 to C 12 ) aralkyl; (C 6 to C 12 ) aryl; (C 6 to C 12 ) aryl substituted with 1 to 3 substituents selected from the group consisting of halogen, (C 1 to C 4 ) alkyl, (C 1 to C 4 ) alkoxy, nitro, cyano, carboxyl (C 1 to C 4 ) alkoxycarbonyl, (C 1 to C 4 ) alkyl thio, -S(O)nR 2 where n is 1 or 2 and R 2 is (C 1 -C 4 ) alkyl; and a halo-substituted, nitro-substituted, or un-substituted moiety selected from the group consisting of 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyridyl, 3-pyridyl, and 4-pyridyl. A cannot be R 4 S- where R 4 is any moiety. Examples of heterocyclic R substituents are furyl, thienyl, pyridyl, and the like.
The iodopropargyl compounds, i.e., those wherein X is I, are preferred. The 5-one compounds, i.e., those wherein Y is O, are also preferred.
As stated above, compositions comprising a compound according to formula I and either an agronomically acceptable carrier, a cosmetic agent, a cutting oil, a soap or synthetic detergent, a stabilizer, a film forming material, or the like have a wide range of utility for protecting against or controlling microorganisms from a wide variety of classes including fungus, bacteria, algae, viruses and yeasts. The preferred utilities of the compositions are to protect wood, paint, adhesive, glue, paper, textile, leather, plastics, cardboard, lubricants, cosmetics, food, caulking, feed and industrial cooling water from microorganisms.
The following lists specific industries and applications of the compounds or compositions.
______________________________________Industry Application______________________________________Adhesives, Sealants Adhesives Caulks sealantsagriculture/food chain adjuvant preservation agricultural active ingredient agricultural chemical preservative agricultural formulations preservation animal feed preservation dairy chemicals fertilizer preservation food preservation food processing chemicals grain preservation post-harvest produce protection sugar processing tobaccoConstruction products asphalt/concrete cement modifiers construction products roof mastics synthetic stucco wall mastics joint cementCosmetics and toiletries Cosmetics raw materials for cosmetics, toiletries toiletriesDisinfectants, antiseptics antiseptic disinfectantEmulsions, dispersions aqueous dispersions dispersed pigments latex photographic emulsions pigment slurries polymer laticesformulated household fabric softenersproducts polishes waxes hand dish detergents raw materials liquid detergents hand soapsIndustrial processing, misc electrodeposition paint, baths, rinses. electrodeposition pre-treatment, post rinses Industrial fluids preservation pasteurization baths process aid preservationIndustrial water treatment air washers cooling towers cooling water water cooling preservation/treatment of wooden cooling tower slats and structural members can warmers brewery pasteurization closed loop water cooling systemsLaundry household laundry products laundered goods laundry wash water sanitizers-laundryLeather, Leather products leather and hide leather and hide productsLubricants, hydraulic aids automotive lubricants and fluids conveyor lubricants greases hydraulic fluids lubricantsMedical devices diagnostic enzymes diagnostic kits medical devicesmetalworking & related cutting fluidsapp's Metal cleaning metalworking fluidsOdor control (active air conditioningingredient) animal bedding cat litter chemical toilet prep'ns deodorizers humidifiers industrial deodorants sanitary formulations toilet bowlsPaints and coatings coating emulsions paintsPaper and wood pulp, absorbant materials of paper andtheir products wood pulp packaging materials of paper and wood pulp paper products paper treatment soap wrap wood pulp wood pulp productspaper mill paper mill slimicides pulp and paper slurriesPetroleum refining, fuels aviation fuels (jet fuel, aviation gas) crude oils burner, diesel and turbine fuel oils coal slurries diesel fuel additives diesel fuels fuels gasoline heating oils hydrocarbons Kerosene liquefied petroleum gas petrochemical feedstocks petroleum products, storage, transportation and production recycled petroleum products residual fuel oils turbine oilsPhotographic Chemicals Photographic processing - washand process water, rinses photoprocessing Photoplate processing chemicals (developers, stabilizers etc)Printing Fountain solutions (printing) Ink components (pigments, resins, solvents, etc) Inkssanitizers (active) sanitizers sanitizers-dairy sanitizers-dental sanitizers-fermentation sanitizers-food preparation sanitizers-food processing sanitizers-medical sanitizers-rendering sanitizers-veterinarySoaps, detergents, cleaners cleaners detergents household cleaners industrial cleaners liquid soaps oil and grease remover powdered soaps raw materials for cleaning products soaps surfactantsTextiles, textile products bonded fabrics burlap canvas canvas goods carpet backing carpets clothing coated fabrics curtains draperies engineering textiles fibers geotextiles goods made of textiles knitted fabrics nets nonwoven fabrics rope rugs textile accessories textile products textiles upholstery woven fabrics yarnTextile processing dye fixatives dyes fiber lubricants hand modifiers sizes Textile processing fluidsTherapeutic (active or animal health/veterinarypreservative) aquaculture dental human health pharmaceutical/therapeuticwater purification charcoal beds deionization resins filters membranes reverse osmosis membranes ultrafilters Water purification water purificiation pipes, tubingwood applications lazures (wood stains) wood wood productsMiscellaneous alcohols bedding incorporating water or gels ceramic contact lens cases-leaching electronic circuitry electronics chemicals enzymes-food production enzymes enzymes-industrial gel cushions marine antifoulants mildewcides wood plastics laundry mining natural rubber latex oil field injection waters including enhanced recover injection fluids, drilling, fracturing and completion fluids pipes plastics polymer systems polymers and resins (synthetic and natural) reagent preservation rubber rubber products skin remover solid protective/decorative films stains swimming pools waste treatment water beds______________________________________
The amounts of the compound to be used depend on the application. The useful amounts for a particular application are similar to amounts used for other microbiocide compounds.
The compound can be used in combination with other microbicides. The term "microbicide" is considered equivalent to "antimicrobial" as used herein.
Compounds of formula I can be prepared by a variety of methods. One suitable method comprises reacting a compound of the formula ##STR6## with an iodinating or brominating agent.
Suitable iodinating or brominating agents include, for example, iodine, bromine, an iodine-amino compound such as morpholineiodine complex, morpholine-bromine complex, N-bromosuccinimide ("NBS") and N-iodosuccinimide ("NIS"), the latter being the most preferred.
When an iodine, bromine, or iodo-amino compound is used, base should also be used, preferably sodium or potassium hydroxide, and solvent such as methanol, ethanol, and aqueous ethanol should also be used.
When NIS or NBS is used, a catalyst such as, for example, silver nitrate, or the like, should be used in presence of solvent such as acetone, methyl ethyl ketone, tetrahydrofuran, and the like.
Reaction times of about 20 minutes to about 24 hours have been utilized successfully with reaction temperatures of about 0° C. to about 25° C.
Suitable methods of application of compounds of formula I to control fungi, bacteria, algae, viruses, yeasts, and the like are in amounts and with carriers, etc., as well known in the art.
The following examples are presented to illustrate a few embodiments of the invention. All parts and percentages are by weight unless otherwise indicated.
EXAMPLES
Some representative compounds the invention are the following:
______________________________________Com-pound #______________________________________ 1. 2-(4-chlorophenyl)-4-(3-iodopropargyl)-1,3,4- oxadiazolin-5-one 2. 2-(2-methylphenyl)-4-(3-iodopropargyl)-1,3,4- oxadiazolin-5-one3. 2-(4-methylphenyl)-4-(3-iodopropargyl)-1,3,4- oxadiazolin-5-one4. 2-(3-methylphenyl)-4-(3-iodopropargyl)-1,3,4- oxadiazolin-5-one5. 2-(2-chlorophenyl)-4-(3-iodopropargyl)-1,3,4- oxadiazolin-5-one6. 2-(3-chlorophenyl)-4-(3-iodopropargyl)-1,3,4- oxadiazolin-5-one7. 2-(2-thienyl)-4-(3-iodopropargyl)-1,3,4-oxadiazolin-5-one8. 2-n-propyl-4-(3-iodopropargyl)-1,3,4-oxadiazolin-5-one9. 2-(4-nitrophenyl)-4-(3-iodopropargyl)-1,3,4-oxadiazolin- 5-one10. 2-(3-nitrophenyl)-4-(3-iodopropargyl)-1,3,4-oxadiazolin- 5-one11. 2-(2-nitrophenyl)-4-(3-iodopropargyl)-1,3,4-oxadiazolin- 5-one12. 2-(4-trifluoromethylphenyl)-4-(3-iodopropargyl)-1,3,4- oxadiazolin-5-one13. 2-(2-methoxyphenyl)-4-(3-iodopropargyl)-1,3,4- oxadiazolin-5-one14. 2-(4-methoxyphenyl)-4-(3-iodopropargyl)-1,3,4- oxadiazolin-5-one15. 2-(3-methoxyphenyl)-4-(3-iodopropargyl)-1,3,4- oxadiazolin-5-one16. 2-(4-bromophenyl)-4-(3-iodopropargyl)-1,3,4- oxadiazolin-5-one.17. 2-(2-fluorophenyl)-4-(3-iodopropargyl)-1,3,4- oxadiazolin-5-one18. 2-(2-furyl)-4-(3-iodopropargyl)-1,3,4-oxadiazolin-5-one19. 1-(3-iodopropargyl)-3-(4-methylphenyl)-4-ethyl-1,2,4- triazolin-5-one20. 1-(3-iodopropargyl)-3-(4-chlorophenyl)-4-ethyl-1,2,4- triazolin-5-one21. 1-(3-iodopropargyl)-3-phenyl-4-ethyl-1,2,4-triazolin-5- one22. 1-(3-iodopropargyl)-3-(4-nitrophenyl)-4-ethyl-1,2,4- triazolin-5-one23. 1-(3-iodopropargyl)-3-(4-methoxyphenyl)-4-ethyl-1,2,4- triazolin-5-one24. 1-(3-iodopropargyl)-3-(2-thienyl)-4-ethyl-1,2,4,-triazolin- 5-one25. 1-(3-iodopropargyl)-3-(3-methylphenyl)-4-ethyl-1,2,4- triazolin-5-one26. 1-(3-iodopropargyl)-3-(2-methylphenyl)-4-ethyl-1,2,4- triazolin-5-one27. 1-(3-iodopropargyl)-3-(3-fluorophenyl)-4-ethyl-1,2,4- triazolin-5-one28. 1-(3-iodopropargyl)-3-(1-naphthyl)-4-ethyl-1,2,4- triazolin-5-one29. 1-(3-iodopropargyl)-3-(2-naphthyl)-4-ethyl-1,2,4- triazolin-5-one30. 1-(3-iodopropargyl)-3-(4-bromophenyl)-4-ethyl-1,2,4- triazolin-5-one31. 1-(3-iodopropargyl)-3-(2-fluorophenyl)-4-ethyl-1,2,4- triazolin-5-one32. 1-(3-iodopropargyl)-3-(4-fluorophenyl)-4-ethyl-1,2,4- triazolin-5-one33. 1-(3-iodopropargyl)-3-(3-pyridyl)-4-ethyl-1,2,4- triazolin-5-one34. 1-(3-iodopropargyl)-3-(2-methoxyphenyl)-4-ethyl-1,2,4- triazolin-5-one35. 1-(3-iodopropargyl)-3-(3-nitrophenyl)-4-ethyl-1,2,4- triazolin-5-one36. 1-(3-iodopropargyl)-3-(3-chlorophenyl)-4-ethyl-1,2,4- triazolin-5-one37. 1-(3-iodopropargyl)-3-(3-bromophenyl)-4-ethyl-1,2,4- triazolin-5-one38. 1-(3-iodopropargyl)-3-(3-methoxyphenyl)-4-ethyl-1,2,4- triazolin-5-one39. 1-(3-iodopropargyl)-3-(3-ethoxyphenyl)-4-ethyl-1,2,4- triazolin-5-one40. 1-(3-iodopropargyl-3-(4-methylphenyl)-4 n-butyl-1,2,4- triazolin-5-one41. 1-(3-iodopropargyl)-3-(4-methylphenyl)-4-i-propyl-1,2,4- triazolin-5-one42. 1-(3-iodopropargyl)-3-n-propyl-4-ethyl-1,2,4-triazolin- 5-one43. 1-(3-iodopropargyl)-3-(4-chlorophenyl)-4-phenyl-1,2,4- triazolin-5-one44. 1-(3-iodopropargyl)-3-(2-chlorophenyl)-4-ethyl-1,2,4- triazolin-5-one45. 1-(3-iodopropargyl)-3-(4-chlorophenyl)-4-(4- chlorophenyl)-1,2,4-triazolin-5-one46. 1-(3-iodopropargyl)-3-(4-chlorophenyl)-4-(4- methylphenyl)-1,2,4-triazolin-5-one47. 1-(3-iodopropargyl)-3-methyl-4-phenyl-1,2,4-triazolin- 5-one48. 1-(3-iodopropargyl)-3-methyl-4-(4-chlorophenyl)-1,2,4- triazolin-5-one49. 1-(3-iodopropargyl)-4-(4-chlorophenyl)-1,2,4-triazoline- 5-one50. 1-(3-iodopropargyl)-4-phenyl-1,2,4-triazolin-5-one51. 1-(3-iodopropargyl)-3-(4-bromophenyl)-4-methyl-1,2,4- triazolin-5-one52. 1-(3-iodopropargyl)-3-(4-chlorophenyl)-4-methyl-1,2,4- triazolin-5-one53. 1-(3-iodopropargyl)-3-(4-fluorophenyl)-4-methyl-1,2,4- triazolin-5-one54. 1-(3-iodopropargyl)-3-(3-chlorophenyl)-4-methyl-1,2,4- triazolin-5-one55. 1-(3-iodopropargyl)-3-(3-bromophenyl)-4-methyl-1,2,4- triazolin-5-one56. 1-(3-iodopropargyl)-3-(3-fluorophenyl)-4-methyl-1,2,4- triazolin-5-one57. 1-(3-iodopropargyl)-3-(2-fluorophenyl)-4-methyl-1,2,4- triazolin-5-one58. 1-(3-iodopropargyl)-3-t-butyl-4-phenyl-1,2,4-triazolin- 5-one59. 2-phenyl-4-iodopropargyl-1,3,4-thiadiazolin-5-one______________________________________
Table (1) shows the structures and the physical data of these representative compounds.
TABLE 1__________________________________________________________________________Physical Data ##STR7## (II) ##STR8## (III) ##STR9## (IV) NMR Chemical ShiftsNO. Formula A R Melting Point (ppm)__________________________________________________________________________ 1. II 4-Cl-ph -- 151-152° C. 2. II 2-Me-ph -- 152-154° C. 3. II 4-Me-ph -- 174-175° C. 4. II 3-Me-ph -- 114-115° C. 5. II 2-Cl-ph -- 104-107° C. 6. II 3-Cl-ph -- 124-126° C. 7. II 2-thiophene -- 149-151° C. 8. II n-propyl -- 42-46° C. 4.60(2H, s, CH.sub.2), 2.55 (2H, t, CH.sub.2), 1.74(2H, m CH.sub.2), 1.02(3H, t, CH.sub.3) 9. II 4-NO.sub.2 -ph -- 176-178° C.10. II 3-NO.sub.2 -ph -- 99.5-102° C. II 2-NO.sub.2 -ph -- 116-120° C. II 4-CF.sub.3 -ph -- 144-147° C. II 2-MeO-ph -- 115-117° C. II 4-MeO-ph -- 171-173° C. II 3-MeO-ph -- 128-130° C. II 4-Br-ph -- 159-162° C. II 2-F-ph -- 139-142° C. II furyl-2 -- 140-142° C. III 4-Me-ph Et 141-145° C.20. III 4-Cl-ph Et 115-120° C. III ph Et 144-148° C. III 4-NO.sub. 2 -ph Et 184-187° C. III 4-OMe-ph Et oil 7.20(4H, aromatic H), 4.75(2H, s, CH.sub.2) 3.84 (3H, s, CH.sub.3), 3.75 (2H, q, CH.sub.2) 1.28 (3H, t, CH.sub.3) III 2-thiophene Et 134-136° C. III 3-Me-ph Et oil 7.34(4H, m, arom. H), 4.78(2H, s, CH.sub.2), 3.80 (2H, q, CH.sub.2), 2.40 (3H, s, CH.sub.3), 1.25 (3H, t, CH.sub.3) III 2-Me-ph Et oil 7.35(4H, m, arom. H), 4.80(2H, s, CH.sub.2), 3.56 (2H, q, CH.sub.2), 2.29 (3H, s, CH.sub.3) 1.12 (3H, t, CH.sub.3) III 2-F-ph Et 104-107° C. III 1-naphthyl Et 148-152° C. III 2-naphthyl Et 63-70° C.30. III 4-Br-ph Et 125-126° C. III 2-F-ph Et 121-124° C. III 4-F-ph Et 108-111° C. III 3-pyridyl Et 129-131° C. III 3-OMe-ph Et 127-130° C. III 3-NO.sub.2 -ph Et 153-158° C. III 3-Cl-ph Et -- 7.60(4H, m, arom. H), 4.81(2H, s, CH.sub.2), 3.85 (2H, q, CH.sub.2), 1.32 (3H, t, CH.sub.3) III 3-Br-ph Et -- 7.80 to 7.40 (4H, m, arom. H), 4.80 (2H, s, CH.sub.2), 3.84 (2H, q, CH.sub.2), 1.30(3H, t, (CH.sub.3) III 3-OMe-ph Et -- 7.50 to 7.00(4H, m, arom. H), 4.80 (2H, s, CH.sub.2), 3.85(4H, m, CH.sub.3 & CH.sub.2), 1.30 (3H, t, CH.sub.3) III 3-OEt-ph Et -- 7.50 to 7.00 (4H, m, arom. H), 4.80 (2H, s, CH.sub.2), 4.10 (2H, q, CH.sub.2), 3.84 (2H, q, CH.sub.2), 1.46 (3H, t, CH.sub.3), 1.26 (3H, t, CH.sub.3)40. III 4-Me-ph n-Bu -- 7.40(4H, q, arom. H), 4.78(2H, s, CH.sub.2), 3.80 (2H, t, CH.sub.2), 2.44 (3H, s, CH.sub.3), 1.62 (2H, m, CH.sub.2), 1.30 (2H, m, CH.sub.2), 0.85(3H, t, CH.sub.3) III 4-Me-ph i-pro -- 7.38(4h, q, arom. H), 4.75 (2H, s, CH.sub.2), 4.26 (1H, m, CH), 2.45 (3H, s, CH.sub.3), 1.55 (6H, d, 2-CH.sub.3) 1.55 (6H, d, 2-CH.sub.3) III n-prop Et 89-93° C. III 4-Cl-ph ph 193-195° C. III 2-Cl-ph Et 86-89° C. III 4-Cl-ph 4-Cl-ph 171-177° C. III 4-Cl-ph 4-Me-ph 179-183° C. III Me ph 179-182° C. III Me 4-Cl-ph 129-131° C. III H 4-Cl-ph 147-149° C.50. III H ph 192-193° C. III 4-Br-ph Me 145-150° C. III 4-Cl-ph Me 148-152° C. III 4-F-ph Me 122-125° C. III 3-Cl-ph Me 78-82° C. III 3-Br-ph Me 89-94° C. III 3-F-ph Ne 124-129° C. III 2-F-ph Me 121-126° C. III t-Butyl ph 170-174° C. IV ph -- 117-119° C.60 II 1-naphthyl -- 167-169° C.61 II Me -- 90-96° C.62 II n-C.sub.17 H.sub.35 -- 41-46° C.63 II n-C.sub.4 H.sub.9 -- oil 4.60(2H, s, CH.sub.2), 2.60 (2H, t, CH.sub.2), 1.70 (2H, m, CH.sub.2), 1.42 (2H, m, CH.sub.2), 0.95 (3H, t, CH.sub.3)64 II t-C.sub.4 H.sub.9 -- 90-93° C.65 II 3-Br-ph -- 127-129° C.66 II 4-F-ph -- 127-129° C.67 II 3-F-ph -- 127-129° C.68 II ph -- 137-139° C.69 II 2-EtO-ph -- 138-142° C.70 II 3-EtO-ph -- 129-132° C.71 II 2-Cl, 4-NO.sub.2 -ph -- 161-166° C.72 II 4-ph-ph -- 183-186° C. II 3,5-(OMe).sub.2 -ph -- 161-165° C. II 2,5-(OMe).sub.2 -ph -- 144-147° C. II 3,4,5-(OMe).sub.3 -ph -- 135-137° C. II 2,5-Cl.sub.2 -ph -- 121-123° C. II n-Heptyl -- Oil 4.62(2H, s, CH.sub.2), 2.58(2H, t, CH.sub.2), 1.70(2H, m, CH.sub.2). 1.32(12H,m 4CH.sub.2), 0.90(3H, t, CH.sub.3) III t-Bu 3-F-ph 151-160° C. III t-Bu Me Oil 4.72(2H, s, CH.sub.2), 3.42(3H, s, CH.sub.3), 1.40(9H, s, 3CH.sub.3)80. III t-Bu Et Oil 4.70(2H, s, CH.sub.2), 3.88(2H, q, CH.sub.2), 1.38(12H, m, 4CH.sub.3) III Me Et Oil 4.68(2H, s, CH.sub.2), 3.72(2H, q, CH.sub.2), 2.26(3H, s, CH.sub.3), 1.30(3H, t, CH.sub.3) III n-Bu Et Oil 4.82(2H, s, CH.sub.2), 3.70(2H, q, CH.sub.2), 2.40(2H, t, CH.sub.2), 1.66(2H, m, CH.sub.2), 1.38(5H, m), 0.98(3H, t, CH.sub.3) III t-Bu 3-MeO-ph 168-170° C. III n-Pr 4-Cl-ph 50-56° C. III n-Pr ph 106-112° C. III t-Bu 4-Cl-ph 168-171° C. III Me 4-Me-ph 166-170° C. III Me 4-MeO-ph 200-203° C. III n-Pr 4-MeO-ph Oil 7.22(4H, q, arom. H), 4.76(2H, s, CH.sub.2), 3.85(3H, s, CH.sub.3), 2.40(2H, t, CH.sub.2), 1.58(2H, m, CH.sub.2), 0.90(3H, t, CH.sub.3)90. III n-Pr 3-MeO-ph 109-112° C. III n-Pr 2-MeO-ph Oil 7.55-7.02(4H, m, arom. H), 4.78(2H, s, CH.sub.2), 3.86(3H, s, CH.sub.3), 2.32(2H, q, CH.sub.2), 1.60(2H, m, CH.sub.2), 0.90(3H, t, CH.sub.3) III Me n-Hexyl Oil 4.70(2H, s, CH.sub.2), 3.60(2H, t, CH.sub.2), 2.26(3H, s, CH.sub.3 ), 1.64(2H, m, CH.sub.2), 1.34(6H, m, 3CH.sub.2), 0.91(3H, t, CH.sub.3) III Me Benzyl 170-172° C. III Me Cyclohexyl 103-106° C. III H 3-Cl-ph 112-115° C. III H 3-Me-ph 153-156° C. III H 2-Me-ph 132-134° C. III H 2-Cl-ph 139-140° C. III H 4-Me-ph 165-170° C.100. III H n-Bu 66-70° C.101. III H Et Oil 7.42(1H, s) 4.64(2H, s, CH.sub.2), 3.70(2H, q, CH.sub.2), 1.34(3H, t, CH.sub.3)102. III H 4-F-ph 124-127° C.103. III H 4-MeO-ph 117-120° C.104. III H 4-NO.sub.2 -ph 165-166° C.105. III H 4-Br-ph 175-177° C.106. III H 2,4-Cl.sub.2 -ph 148-151° C.107. III H 3,4-Cl.sub.2 -ph 160-161° C.108. III H 3,5-Cl.sub.2 -ph 101-105° C.109. III H 3-F-ph 172-175° C.110. III H 3-Br-ph 105-110° C.111. III H 2-F-ph 115-120° C.112. III H Cyclohexyl 118-122° C.113. III H Benzyl 119-124° C.114. III H n-Hexyl Oil 7.45(1H, s, olefinic H), 4.74(2H, s, CH.sub.2), 3.64(2H, t, CH.sub.2), 1.72(2H, m, CH.sub.2), 1.35(6H, m, 3CH.sub.2). 0.90(3H, t, CH.sub.3)115. III H 2,6-Cl.sub.2 -ph 115-120° C.116. III H 3,5-Me.sub.2 -ph 80-85° C.117. III H 2,4-Me.sub.2 -ph 119-124° C.118. III H 4-Et-ph 129-132° C.119. III H 3-Et-ph 82-87° C.120. III H n-Octyl Oil 7.44(1H, s, olefinic H), 4.72(2H, s, CH.sub.2), 3.62(2H, t, CH.sub.2), 1.72(2H, m, CH.sub.2), 1.30(10H, m, 5CH.sub.2), 0.90(3H, t, CH.sub.3)121. III H n-Dodecyl 50-52° C.__________________________________________________________________________
EXAMPLE 1
Preparation of 2-(4-Chlorophenyl)-4-3-Iodopropargyl) -1,3,4-Oxadiazolin-5-one (Compound #1)
To the suspension of 4-chlorobenzhydrazide (8.53 g, 0.05 mole) in methylene chloride (100 ml), equipped with a magnetic stirring bar, a nitrogen inlet, a dropping funnel, and an outlet connected to diluted base solution for trapping the HCl gas, was dropwise added trichloromethyl chloroformate (5.94 g, 0.03 mole). After addition, the reaction mixture was heated to reflux for 2 hr. The reaction was cooled down to room temperature and poured into a mixture of water (500 ml) and hexane (200 ml) and stirred for 10 to 20 min. The resultant precipitate was collected by suction-filtration and was washed with hexane to give a solid product. The product was dried in air at room temperature overnight yielding 5.5 g (60% yield) of 2-(4-chlorophenyl)-1,3,4-oxadiazolin-5-one as a solid, m.p.=225°-227° C. NMR and IR spectra showed the desired structure. Without further purification, this product was subjected to the next step.
To the suspension of 2-(4-chlorophenyl)-1,3,4-oxadiazolin-5-one (2 g, 0.01 mole) in acetone (50 ml) was added potassium carbonate (2 g, 0.015 mole), followed by propargyl bromide (1.6 g of 80% in toluene, 0.0106 mole) with magnetic stirring under nitrogen for 3 hr. The reaction mixture was cooled down to room temperature. The suspension was filtered by suction-filtration and the solid was washed with acetone. The filtrate was concentrated to about 10 ml and was poured into water (200 ml). The resultant precipitate was collected by suction-filtration and washed with water and hexane affording 0.85 g (36% yield), after drying in air, of 2-(4-chlorophenyl)-4-propargyl-1,3,4-oxadiazolin-5-one as a solid. m.p.=125°-127° C. NMR and IR spectra showed the desired structure. Without further purification, this compound was subjected to the next step.
To the suspension of 2-(4-chlorophenyl)-4-propargyl-1,3,4-oxadiazolin-5-one (0.6 g, 0.00256 mole) in acetone (20 ml) with magnetic stirring at room temperature was added N-iodosuccinimide (0.6 g, 0.00266 mole), followed by silver nitrate (0.040 g, 0.00024 mole). The reaction mixture was stirred at room temperature for one hour. The suspension was filtered gravitationally and the solid was rinsed with acetone. The filtrate was poured into water (300 ml). The resultant precipitate was collected by suction-filtration and air-dried to give 0.8 g (92% yield), of 2-(4-chlorophenyl)-4-(3-iodopropargyl)-1,3,4-oxadiazolin-5-one as a solid. m.p.=151°-152° C. The proton NKM spectrum was consistent with the desired structure.
EXAMPLE 2
1-(3-Iodopropargyl)-3-(4-chlorophenyl)-4-ethyl-1,2,4-triazolin-5-one (Compound #20)
To a suspension of 4-chlorobenzhydrazide (98.5 g, 0.05 mole) in tetrahydrofuran (100 ml) at room temperature ethylisocyanate (4.2 g, 0.05 mole) was added slowly with magnetic stirring. The reaction was slightly exothermic and the reaction mixture turned to a thick paste. Stirring was continued an additional 30 min after which the solid was collected by suction-filtration and washed with a small amount of tetrahydrofuran and dried to provide 11.6 g (96.6% yield), of 1-(4chlorobenzoyl)-4-ethyl semicarbazide as a white solid., m.p.=242°-243° C. The above semicarbazide (10 g, 0.0414 mole) was dissolved in 1N sodium hydroxide solution (100 ml) and was refluxed with stirring for 16 hr. The solution was cooled down to about 10° C. by an ice bath and was neutralized by conc. hydrogen chloride until pH 2. The resultant white solid was collected by suction-filtration and washed with water to give 8.65 g (93.5% yield) of 3-(4-chlorophenyl)-4-ethyl-1,2,4-triazolin-5-one as a white solid. m.p.=190°-197° C. A proton NMR spectrum was consistent with the desired structure.
To the solution of 3-(4-chlorophenyl)-4-ethyl-1,2,4-triazolin-5-one (2.23 g, 0.01 mole) in dry acetone (40 ml) was added, at room temperature, potassium carbonate (1.67 g, 0.012 mole) followed by propargyl bromide (1.8 g of 80% in toluene, 0.012 mole). The reaction mixture was then refluxed with stirring for 6 hr. The mixture was cooled down to room temperature and solvent was evaporated to give a residue. The product was purified by crystallization from hexane/ether, affording 1.8 g (69.2% yield) of 1-propargyl-3-(4-chlorophenyl)-4-ethyl-1,2,4-triazolin-5-one as a white solid. m.p.=115°-119° C. A proton NMR spectrum was consistent with the desired structure.
To the solution of 1-propargyl-3-(4-chlorophenyl)-4-ethyl-1,2,4-triazolin-5-one (1.0 g , 3.82 mmole) in dry acetone (20 ml) was added N-iodosuccinimide (0.95 g, 4.2 mmole), followed by silver nitrate (50 mg, 0.29 mmole) with magnetic stirring at room temperature. The reaction mixture was stirred for 1 hr. The resultant suspension was filtered and the filtrate was poured into water (250 ml). A yellowish white solid slowly precipitated out and was collected by suction-filtration and washed with water to give 1.12 g (76% yield) of 1-(3-iodopropargyl)-3-(4-chloro-phenyl)-4-ethyl-1,2,4-triazolin-5-one as a light yellow solid. m.p.=115°-120° C. A proton NMR spectrum was consistent with the desired compound.
EXAMPLE 3
Preparation of 2-phenyl-4-iodopropargyl-1,3,4-thiadiazolin-5-one (Compound 59)
A. Preparation of Thiobenzhydrazide
A cold solution of S-(thiobenzoly)thioglycolic acid (12.25 g, 57.6 mmole) in 1N NAOH (60 ml, 60 mmole NAOH) was slowly added to a solution of hydrazine monohydrate (6 g, 123.8 mmole) in 5 ml of water at about 5° C. with magnetic stirring. After the addition, the resultant yellow suspension was stirred at room temperature for one hour. The mixture was cooled down to 5° C. and was acidified with conc. HCl until pH=6. The yellow solid was collected by suction-filtration and was washed with water to afford 3.70 g, after drying in air. m.p.=66°-68° C.
B. Preparation of 2-phenyl-1,3,4-thiadiazolin-5-one
To a solution of thiobenzhydrazide (3.7 g, 24.34 mmole) in methylene chloride (50 ml), equipped with magnetic stirrer, nitrogen inlet, and an outlet connected to a trap containing a diluted NAOH solution, was added trichloromethyl chloroformate (4 g, 20.2 mmole). The reaction mixture was stirred at room temperature for one hour. The mixture was diluted with methylene chloride (100 ml) and washed with water (3×50 ml) and brine. The organic layer was dried over MgSO 4 . After the drying agent was filtered off the filtrate was concentrated to a residue. The residue was triturated with hexane and the solid product was collected by suction-filtration to give 3.7 g as a powder. m.p.=140°-143° C.
C. Preparation of 2-phenyl-4-propargyl-1,3,4-thiadiazolin-5-one
To the solution of 2-phenyl-1,3,4-thiadiazolin-5-one (3 g, 16.85 mmole) in dry acetone (30 ml) under nitrogen with magnetic stirring was added potassium carbonate (3 g, 22 mmole), followed by propargyl bromide (3 g, 80% in toluene, 20 mmole) at room temperature. The mixture was refluxed for one hour. The reaction mixture was cooled down to room temperature and the solid was filtered off by suction-filtration. The filtrate was diluted with ether (200 ml) and washed with water (2×50 ml) and brine. The organic layer was dried over sodium sulfate. After the drying agent was filtered off the filtrate was concentrated to about 5 ml. Hexane was added to precipitate out the product. The product was collected by suction-filtration and washed with a little hexane to afford 2 g of 2-phenyl-4-propargyl-1,3,4-thiadiazolin-5-one as a powder. m.p.=73°-75° C.
D. Preparation of 2-phenyl4-iodopropargyl-1,3,4-thiadiazolin-5-one
To the solution of 2-phenyl-4-propargyl-1,3,4-thiadiazolin-5-one (1.6 g, 7.4 mmole) in dry acetone (25 ml) under nitrogen with magnetic stirring was added catalytic amount of silver nitrate 0.1 g, 0.58 mmole), followed by N-iodosuccinimide (1.85 g, 8.15 mmole). The reaction mixture was stirred at room temperature for 20 hours. The solid was filtered off by suction-filtration through a Celite filter. The filtrate was diluted with water (200 ml) and extracted with ethyl acetate (2×100 ml). The organic layer was washed with water (2×50 ml), brine, and dried over sodium sulfate. The drying agent was filtered off and the filtrate was concentrated to give a residue. The residue was triturated with hexane and the product was collected by suction-filtration to give 1.75 g as a semicrystalline compound. m.p.=117°-119° C. Proton NMR spectrum showed the desired compound.
EXAMPLE 4
Biocidal Evaluations of Compounds
A minimum inhibitory concentration (MIC) value is obtained using a broth, two-fold serial dilution test performed as follows: A stock solution or dispersion of the test compound, typically at a concentration of 1%, is made in a 5:3:2 solvent solution of acetone, methanol, and water. A volume of the stock solution is dispensed into culture media to give an initial starting test concentration of 500 PPM. 250 ppm, or 12 5 ppm compound.
When the test is ready to be done, each vessel in the dilution series, except the first vessel, contains an equal volume of compound free broth. The first vessel contains twice the volume of broth with the starting concentration of test compound. One half of the broth from the first vessel is transferred to the second vessel. After being mixed, one half the resulting volume is removed from the second vessel and transferred to the third vessel. The entire cycle is repeated sufficiently to give a series of concentrations amounting to 500, 250, 125, 63, 31, 16, 8, and 4 ppm or 250, 125, 63, 32, 16, 8, 4, 2, 1, 0.5, 0.25, and 0. 12 (or 100, 50, 25, 12.5, 6.2, 3.1, 1.6, and 0.8), respectively.
Each vessel is then inoculated with a cell suspension of the appropriate test organism. Bacteria are grown in broth and fungi on agar slants and algae is grown in cooling tower media for a time and at a temperature appropriate to the species being tested. At the end of the growth period, the broth is vortexed to disperse the cells. In the case of fungi, the spores are harvested by pipetting water onto the slant and dislodging the spores with a sterile loop. The cell/spore suspension is standardized by controlling incubation time, temperature, and the volume of the diluent. The suspension is then used to inoculate the vessels containing the broth compound. The vessels are then incubated at the appropriate temperature. After the incubation, the vessels are examined for growth/no growth. The minimum inhibitory concentration (NEC) is defined as the lowest concentration of compound that results in complete inhibition of growth of the test organism.
The organisms tested to demonstrate biocidal activity include:
BACTERIA:
Pseudomonas fluorescens (Ps.fl), gram negative
Pseudomonas aerugenosa (Ps.ae), gram negative
Escherichia coli (E.c), gram negative
Staphylococcus aureus (S.a), gram positive
FUNGI:
Aspergillus niger (A.n)
Aureobasidium pullulans (A.p)
ALGAE:
Chlorella pyroidenosa (see Table 5)
TABLE 2______________________________________Biocidal EvaluationThe Result of Minimum Inhibitory Concentration (MIC) Tests MIC (ppm)Compound # Psfl Psae Ecol Saur Anig Apul______________________________________ 1. >100 >100 >100 >100 <0.8 <0.8 2. >100 >100 >100 >100 <0.8 <0.8 3. 100 >100 >100 >100 >100 <0.8 4. 100 >100 >100 >100 2 <0.8 5. >100 >100 >100 50 <0.8 <0.8 6. >100 >100 >100 13 <0.8 <0.8 7. 50 50 25 13 <0.8 <0.8 8. 50 100 25 25 <0.8 <0.8 9. >100 >100 >100 >100 <0.8 <0.810. 13 13 13 6 <0.8 <0.811. 50 100 >100 50 <0.8 <0.812. >100 >100 >100 >100 <0.8 <0.813. >500 >500 >500 >500 250 814. >500 >500 >500 >500 500 3215. >500 125 >500 >500 63 <416. >500 125 125 >500 125 <417. >500 >500 >500 >500 8 <418. >500 >500 >500 >500 <4 <419. 100 25 50 25 <0.8 <0.820. 100 25 50 13 <0.8 <0.821. >100 100 50 25 <0.8 1.622. >100 >100 >100 50 6.3 323. >100 >100 >100 50 13 324. >100 >100 >100 100 6 325. >100 >100 50 25 <0.8 <0.826. >100 >100 50 1.6 <0.8 1.627. 50 100 >100 100 100 228. >100 >100 >100 50 25 <0.829. 100 >100 >100 25 6.3 <0.830. >100 >100 50 13 <0.8 <0.831. >100 50 50 25 1.6 <0.832. 100 50 50 25 <0.8 <0.833. >100 50 25 25 13 2534. >100 >100 >100 50 13 1335. >100 >100 >100 50 25 636. 100 >100 >100 >100 <0.8 337. 100 100 >100 100 <0.8 338. >100 100 >100 >100 2 6.339. >100 >100 >100 >100 2 6.340. >100 >100 >100 >100 50 2541. >100 >100 >100 >100 6.3 6.342. >100 >100 >100 50 13 643. 100 50 >100 >100 6 <0.844. >100 >100 >100 25 13 645. >100 >100 >100 >100 >100 >10046. >100 >100 >100 >100 >100 >10047. 63 63 63 125 16 848. 16 250 250 32 16 <449. 32 32 63 125 8 <450. >500 >500 >500 >500 63 <451. 63 250 63 63 32 <452. 63 250 32 125 32 <453. 16 63 32 32 <4 <454. 16 125 32 32 8 <455. 16 125 32 32 8 <456. 16 125 16 32 <4 <457. 32 125 32 63 8 <458. 16 125 63 125 32 1659 250 >250 >250 250 <4 461 250 125 32 32 <4 <462 250 250 250 250 <4 <463 250 250 250 500 <4 <464 250 250 250 500 <4 <465 250 250 250 500 <4 <466 8 63 32 250 <4 <467 8 32 16 <4 <4 <468 63 125 >500 125 <4 1669 >250 >250 >250 >250 4 >25070 63 63 >500 125 <4 --71 125 63 >500 250 8 --72 >500 >500 >500 >500 >500 >50073 >250 >250 >250 >250 >250 >25074 >250 >250 >250 >250 250 >25075 >250 >250 >250 >250 >250 876 >250 >250 >250 >250 2 877 -- 63 >250 8 <0.12 16787980 32 250 250 32 4 --81 32 250 250 63 16 --82 32 125 250 32 2 --83 125 250 >250 250 32 --84 63 250 250 63 16 885 125 >250 >250 63 16 886 >250 >250 >250 >250 32 3287 -- >250 >250 >250 8 --88 -- >250 >250 >250 63 --89 -- >250 >250 250 16 890 -- >250 >250 250 32 1691 -- >250 >250 >250 >250 >25092 -- 250 >250 125 4 493 -- 125 >250 63 8 894 -- >250 >250 250 16 895 32 250 >250 63 <0.12 --96 125 >250 >250 >250 <0.12 --97 63 >250 >250 125 4 498 63 >250 >250 125 4 499 >250 >250 >250 >250 8 4100 63 125 125 125 1 2101 63 250 >250 63 16 8102 63 >250 250 63 0.25 2103 125 >250 >250 63 1 4104 63 125 125 63 <0.12 <0.12105 125 250 >250 >250 <0.12 <0.12106 125 >250 >250 >250 >250 >250107 -- 125 >250 250 2 16108 250 >250 >250 250 2 4109 >250 >250 >250 >250 32 16110 -- >250 >250 125 2 1111 -- >250 >250 >250 2 1112 -- >250 >250 >250 2 2113 -- >250 >250 >250 0.25 0.25114 -- >250 >250 >250 -- --115 -- 250 >250 250 32 16116 -- >250 >250 250 16 8117 -- >250 >250 >250 32 8118 -- 63 250 250 16 8119 -- 125 >250 250 32 8120 -- 63 >250 4 <0.12 <0.12121 -- >250 >250 >250 >250 >250______________________________________
EXAMPLE 5
In-Vitro Plant Fungicide Tests of Compounds
The organisms employed in the test are:
PYU Pythium ultimum (Oomycete)
PHY Phytophthora capsici (Oomycete)
PIR Piricularia oryzae (Ascomycete)
FM Cochliobolus sativus (Ascomycete)
BOC Botrytis cinerea (Ascomycete)
FUS Fusarium roseum (Ascomycete)
SEP Septoria nodorum (Ascomycete)
RHI Rhizoctonia solani (Basidiomycete)
XAN Xanthomonas campestris (bacterium)
Methods
1. Culture maintenance: Transfers in steps 1 and 2 are done in a laminar flow hood. All 8 fungi and the bacterium used in this test are transferred and maintained on potato dextrose agar plates each week (2 plates/organism). Organisms are used when they are the following ages: a. 1 week old: PYU, PHY, RHI; b. 2 weeks old: XAN, PIR, BOC, HEL, FUS, SEP, COL, MON, CER, UST, ALT; c. 3 weeks old: PSH, VEN. Pythium ultimum and Phytophthora capsici are transferred to asparagine-sucrose broth shake cultures (ASB). Rhizoctonia solani, Fusarium roseum, and Zanthomonas campestris are mainted in yeast extract-dextrose broth (YDB) on a shaker. Culture flasks are inoculated with 6 mycelial plugs each (except for Pythium which is inoculated with only 3 plugs) taken from PDA plates. All liquid shaker cultures are used after 2 days growth.
2. Inoculum preparation. Conidia and mycelium from PIR, BOC, HEL, SEP, COL, MON, CER, PSH, UST and ALT are lightly scraped off into YDB so that mostly conidia are used as inoculum. The conidial suspension is strained through a double layer of cheesecloth to remove mycelial clumps. One plate produces enough conidia or mycelium to inoculate 100 n-d of YDB. XAN broth culture is poured (1 ml culture/100 ml broth) into YDB. PYU, PHY, RFU and FUS cultures are ground up (2-3 5 second bursts in a blender) and an but Pythium and Phytophthora are filtered through a double layer of sterile cheesecloth to remove large mycelial clumps. Ten ml of the culture solutions of R. solani and F. roseum are added to 90 ml of YSB and 10 ml of the P. capsici is added to 90 ml ASB. Two ml of the culture solution of P. ultimum is added to 98 ml of ASB. Care must be made not to overinoculate (e.g. solutions should appear fairly dear to the eye, yet when held up to light a faint cloudiness should be visible) or standards will not behave properly. The inoculum mixtures are placed in microtiter plates using a 12-tipped pipet. 175 μl (single dose) or 100 μl (dose-response test) of inoculum broth is placed in each well of the microtiter plates. The plates with inoculated media are placed in the refrigerator overnight. There are two replications per treatment.
3. Addition of compounds. This operation is carried out in a chemistry hood. Six microtiter plates have 245 microtiters of sterile water added to their wells ahead of time. 10 mg a.i. of the compounds are placed in 1 ml 1:1 acetone:methanol. 5 microliters of this solution is pipetted into the microtiter plates containing the sterile water according to the grid. There are 45 compounds and 3 scattered control treatments per plate. There are 2 replicates per treatment. 25 microtiters of solution is transferred to the inoculated plates with a 96 well replicator. The replicator is flame sterilized with alcohol, rinsed with sterile water, and blotted on sterile paper towells between each transfer.
TABLE 3__________________________________________________________________________The Results of In-Vitro Plant Fungicide TestsDose % ControlCompound (PPM) PYU XAN PIR PHY BOC HEL RHI FUS SEP__________________________________________________________________________ 1. 25 100 0 100 100 100 100 100 100 100 2. 25 95 0 75 95 0 75 100 100 95 3. 25 100 0 75 75 0 90 95 100 95 4. 25 100 0 95 95 0 100 90 100 100 5. 25 100 0 100 100 50 95 100 100 100 6. 25 100 0 100 100 100 100 100 100 100 7. 25 100 0 100 100 100 100 100 100 100 8. 25 100 0 100 100 100 100 100 100 100 9. 25 0 0 0 0 0 75 90 100 0 10. 25 50 0 0 100 0 90 0 100 100 11. 25 100 0 100 95 90 95 100 100 100 12. 25 95 0 95 90 50 100 90 100 100 13. 25 100 0 100 100 0 100 100 100 100 14. 25 100 0 100 100 0 100 100 100 100 15. 25 100 0 100 100 0 100 100 100 100 16. 25 100 0 100 100 0 100 100 100 100 17. 25 95 0 100 100 0 100 95 100 100 18. 25 -- 0 100 100 75 100 100 100 100 19. 25 100 0 100 100 0 95 100 100 100 20. 25 100 0 100 100 0 95 100 100 100 21. 25 100 0 100 100 0 100 100 100 100 22. 25 100 0 100 100 0 100 100 100 100 23. 25 100 0 100 100 0 100 100 100 100 24. 25 100 0 100 100 95 100 100 100 100 25. 25 100 0 100 100 0 100 75 100 100 26. 25 100 0 100 100 75 100 100 100 100 27. 25 100 0 95 100 0 75 95 90 50 28. 25 95 0 100 100 0 95 100 95 100 29. 25 100 0 100 100 0 100 100 95 75 30. 25 100 0 100 100 0 100 100 100 100 31. 25 100 0 100 100 0 100 100 100 100 32. 25 100 0 100 100 0 100 100 100 100 33. 25 100 0 100 100 0 100 100 100 100 34. 25 50 0 100 50 0 0 50 0 75 35. 25 0 0 0 0 0 0 0 0 0 36. 25 50 0 100 100 0 100 100 90 100 37. 25 -- -- -- -- -- -- -- -- -- 38. 25 90 0 100 95 0 100 100 100 --39 25 100 0 100 100 0 100 100 100 10040 25 50 0 100 50 0 0 0 50 7541 25 0 0 0 0 0 0 0 042 25 50 0 100 100 0 100 100 90 10043 25 90 0 100 95 0 100 100 100 --44 25 90 0 100 95 0 100 100 100 --45 25 0 0 90 0 0 0 0 50 046 25 0 0 100 0 0 50 50 100 047 25 100 0 100 100 100 100 100 100 10048 25 100 0 100 100 100 100 100 100 10049 25 100 0 100 100 100 100 100 100 10050 25 100 0 95 100 100 95 95 95 9551 25 100 0 100 100 100 100 100 100 10052 25 100 0 100 100 100 100 100 100 10053 25 100 0 100 100 100 100 100 100 10054 25 100 0 100 100 100 100 100 100 10055 25 100 0 100 100 100 100 100 100 10056 25 100 0 100 100 100 100 100 100 10057 25 100 0 100 100 100 100 100 100 10058 25 100 0 100 100 90 100 100 100 10059 25 100 0 100 100 100 100 100 100 10060 25 0 0 100 0 0 50 0 0 061 25 100 0 100 100 100 100 100 100 10062 25 0 0 0 0 0 0 0 0 063 25 100 0 100 100 100 100 100 100 10064 25 100 0 100 100 100 100 100 100 10065 25 100 0 100 100 100 100 100 100 10066 25 100 0 95 100 100 100 100 100 1067 25 100 0 100 100 100 100 100 100 10068 25 100 0 100 100 90 100 100 100 10069 25 100 0 100 95 50 95 50 0 9570 25 100 0 100 100 75 100 100 100 10071 25 100 0 100 100 90 100 100 100 10072 25 100 0 100 100 0 50 75 0 9573 25 0 0 0 50 0 50 0 0 074 25 100 0 100 100 0 75 100 0 075 25 90 0 75 90 0 0 100 0 076 12 0 0 100 100 0 0 50 0 5077 -- -- -- -- -- -- -- -- -- --78 25 100 0 100 100 0 75 100 100 10079 25 100 0 100 100 75 100 100 100 5080 25 100 0 100 100 50 100 100 100 5081 25 100 0 100 100 0 100 100 0 082 25 100 0 100 100 100 100 100 100 10083 25 100 0 100 100 0 75 100 100 5084 25 100 0 100 100 50 100 100 100 10085 25 100 0 100 100 50 100 100 100 10086 25 100 0 100 100 100 75 100 100 10087 -- -- -- -- -- -- -- -- -- --88 -- -- -- -- -- -- -- -- -- --95 25 100 0 100 100 100 100 100 100 10096 25 100 0 100 100 100 100 100 100 10097 -- -- -- -- -- -- -- -- -- --98 25 -- -- -- 100 -- -- 100 100 --99 25 -- -- -- 100 -- -- 100 100 --100 25 100 0 100 100 100 100 100 100 100101 25 100 0 100 100 90 100 100 100 100102 25 100 0 100 100 100 100 100 100 100103 25 100 0 100 100 100 100 100 100 100104 25 100 0 -- 100 95 0 90 90 100105 25 100 0 -- 100 100 75 100 100 100106 25 100 0 100 100 100 100 100 100 100107 25 100 0 100 100 100 100 100 100 100108 25 100 0 100 100 100 100 100 100 100109 25 100 0 100 100 100 100 100 100 100110 25 100 0 100 100 100 100 100 100 100111 25 100 50 100 100 100 100 100 100 100112 25 100 0 100 100 100 100 100 100 100113 25 100 0 100 100 100 100 100 100 100114 25 100 0 100 100 100 100 100 100 100__________________________________________________________________________
EXAMPLE 6
Agricultural Fungicide Evaluations of Compounds
The compounds of this invention were tested for fungicidal activity in vivo against cucumber downy mildew (CDM), rice blast (RB), rice sheath blight (RSB), tomato late blight (TLB), wheat powdery mildew (WPM), wheat stem rust (WSR) and wheat leaf rust (WLR) and the results are shown in Table 4. In tests on cereals (except for rice plants used for testing rice blast), the plants were trimmed about 24 hours prior to the application of the fungicide compound to provide a uniform plant height and to facilitate uniform application of the compound and inoculation with the fungus. The compounds were dissolved in a 2:1:1 mixture of water, acetone, and methanol, sprayed onto the plants, allowed to dry (four to six hours), and then the plants were inoculated with the fungus. Each test utilized control plants which were sprayed with the water, acetone, and methanol mixture and inoculated with the fungus. The remainder of the technique of each of the tests is given below and the results are reported as percent disease control (percentages of plants treated with the compounds of the present invention lacking disease signs or symptoms compared to the untreated control plants).
Cucumber Downy Mildew (CDM)
Pseudoperonospora cubensis was maintained on leaves of live Marketer cucumber plants in a constant temperature room at 65° F. to 75° F. in humid air with moderate light intensity for 7 to 8 days. A water suspension of the spores from infested leaves was obtained and the spore concentration was adjusted to about 100,000 per ml of water.
Marketer cucumber seedlings were inoculated by spraying the underside of the leaves with a DeVilbiss atomizer until small droplets were observed on the leaves. The inoculated plants were incubated in a mist chamber for 24 hours at about 70° F. and then subsequently incubated for 6 to 7 days in a controlled temperature room under mist at 65° F. to 75° F. Seven days after inoculation, the percent disease control was determined.
Rice Blast (RB)
Nato rice plants were inoculated with Piricularia oryzae (about 20,000 conidia per ml) by spraying the leaves and stems with an airbrush until a uniform film of inoculum was observed on the leaves. The inoculated plants were incubated in a humid environment (75° F. to 85° F.) for about 24 hours, then placed in a greenhouse environment (70° F. to 75° F.). Seven to eight days after inoculation, the percent disease control was determined.
Rice Sheath Blight (RSB)
Pellicularia filamentosa (f. sp. sasiki) was cultured on an autoclaved mixture of crushed rice seeds and potato dextrose broth (100 gms of rice seeds per 30 ml of potato dextrose broth) in a 500 ml Erlenmeyer flask. After 10 days, the culture was blended in a blender to produce a uniform inoculum. Approximately one teaspoon of inoculum was spread among Lebonnet rice seedlings on the soil surface of each pot (3 inch diameter). The inoculated seedlings were incubated for 5 days in a humidity cabinet (85° F. to 90° F.). Percent disease controls were determined immediately after removing the seedlings from the cabinet.
Tomato Late Blight (TLB)
Phytophthora infestans was cultured on four week old Pixie tomato plants in a controlled environment room (65° F. to 70° F. and 100% relative humidity). After storage, the spores were washed from the leaves with water and dispersed by DeVilbiss atomizer over three week old Pixie tomato plants which had been sprayed previously with experimental fungicides. The inoculated plants were placed in a humidity cabinet at 70° F. and constant mist for 24 hours for infection. The plants were then moved to the controlled environment room as above and scored after three more days incubation. Disease control levels were recorded as percent control four days after inoculation and five days after spraying the compounds.
Wheat Powdery Mildew (WPM)
Erysiphe graminis (f. sp. tritici) was cultured on Pennol wheat seedlings in a controlled temperature room at 65° F. to 75° F. Mildew spores were shaken from the culture plants onto Pennol wheat seedlings which had been sprayed previously with the fungicide compound. The inoculated seedlings were kept in a controlled temperature room at 65° F. to 75° F. and subirrigated. The percent disease control was rated 8 to 10 days after the inoculation.
Wheat Stem Rust (WSR)
Puccinis graminis (f. sp. Race 15B-2) was cultured on Wanzer wheat seedlings for a period of 14 days in a greenhouse. A water suspension of the spores from infested plants was obtained and the spore concentration was adjusted to about 200,000 spores per ml of deionized water. Wanzer wheat plants which had been previously treated with the fungicide compounds were inoculated by applying the stem rust spore suspension, until runoff, with a DeVilbiss atomizer at 5 lbs. per square inch air pressure. After inoculation, the plants were placed in a humid environment at approximately 75° F. where they were exposed to 12 hours of continuous darkness followed by a minimum of 3 to 4 hours of light having an intensity of about 500 footcandles. The temperature in the chamber did not exceed 85° F. At the end of the light period, the plants were placed in a greenhouse where they were permitted to grow for a period of two weeks at which time the percent disease control was determined.
Wheat Leaf Rust (WLR)
Puccinis recondita (f. sp. tritici Races PKB and PLD) was cultured on seven day old wheat (cultivar Fielder) over a 14 day period in the greenhouse. Spores were collected from the leaves with a cyclone vacuum or by settling on aluminum foil. The spores were cleaned by sieving through a 250 micron opening screen and stored or used fresh. Storage employed sealed bags in an Ultralow freezer. When stored, spores must be heat shocked for two minutes at 40° F. before use. A spore suspension is prepared from dry uredia by adding 20 mg (9.5 million) per ml of Soltrol oil. The suspension is dispensed into gelatin capsules (0.7 ml capacity) which attach to the oil atomizers. One capsule is used per flat of twenty of the two inch square pots of seven day old Fielder wheat. After waiting for at least 15 minutes for the oil to evaporate from the wheat leaves, the plants are placed in a dark mist chamber (18°-20° C. and 100% relative humidity) for 24 hours. The plants are then put in the greenhouse for the latent period and scored after 10 days for disease levels. Protective and curative tests were inoculated one day after and two days, respectively, before spraying the plants with the test chemicals.
TABLE 4______________________________________Green House Test Results of Plant diseases ControlCom- Rate % Controlpound (ppm) CDM RB SNW TLB WLR WPM______________________________________ 1. 200 90 0 80 0 50 0 2. 200 80 75 80 0 90 75 3. 200 70 0 80 0 50 85 4. 200 90 90 90 0 80 75 5. 200 0 75 50 90 80 75 6. 200 80 75 90 0 90 75 7. 200 50 90 80 50 0 0 8. 200 0 50 0 0 0 0 9. 200 0 0 0 0 50 0 10. 200 50 90 80 0 80 75 11. 200 50 0 80 0 50 50 12. 200 0 0 0 0 0 0 13. 200 0 0 0 0 0 0 14. -- -- -- -- -- -- -- 15. 200 0 0 0 0 50 0 16. 200 0 0 0 0 50 0 17. 200 0 50 0 0 80 0 18. 200 -- 75 50 0 80 0 19. 200 75 0 0 80 90 0 20. 200 90 75 50 70 80 75 21. 200 80 0 50 80 50 0 22. 200 50 50 50 0 50 0 23. 200 50 75 0 70 50 75 24. 200 70 0 50 95 80 85 25. 200 90 90 80 95 80 0 26. 200 0 0 0 95 0 50 27. 200 80 0 0 85 80 0 28. 200 70 75 0 80 80 0 29. 200 90 0 50 80 80 90 30. 200 95 0 0 80 80 75 31. 200 50 90 50 85 80 75 32. 200 0 0 50 90 80 0 33. 200 0 0 0 70 50 85 34. 200 90 99 80 80 80 85 35. 200 70 -- 0 0 50 0 36. 200 70 -- 50 85 95 0 37. 200 0 50 0 0 25 75 38. 200 70 0 0 0 0 039 200 0 0 50 90 80 040 200 50 0 0 80 50 9041 200 0 0 0 70 50 8542 200 0 -- 0 85 50 043 200 70 -- -- 0 50 044 200 70 -- 50 85 95 045 200 0 50 0 0 25 7546 200 70 0 0 0 0 047 200 0 -- 50 -- 80 048 200 50 -- 50 -- 50 9049 200 0 -- 80 85 50 050 200 0 -- 0 0 50 051 200 0 -- 0 90 50 052 200 0 -- 0 0 80 053 200 0 -- 0 0 80 054 200 0 -- 80 0 80 8555 200 70 -- 50 0 80 056 200 0 -- 50 0 80 5057 200 70 -- 80 85 80 10058 200 95 -- 0 70 90 9059 200 90 0 50 0 50 060 200 85 -- 0 0 0 061 200 0 -- -- 50 0 062 -- -- -- -- -- -- --63 200 90 -- -- 50 90 064 -- -- -- -- -- -- --65 200 90 -- -- 90 90 066 200 75 -- -- 0 99 067 200 85 -- -- 95 90 068 200 50 -- -- 50 99 069 -- -- -- -- -- -- --70 200 80 -- -- 0 0 071 -- -- -- -- -- -- --72 -- -- -- -- -- -- --73 200 90 -- -- 0 85 8574 200 0 -- -- 50 75 075 200 0 -- -- 0 95 076 200 90 -- -- 0 95 077 -- -- -- -- -- -- --78 -- -- -- -- -- -- --79 200 75 -- -- 75 85 080 200 50 -- -- 75 75 081 200 0 -- -- 0 75 082 200 50 -- -- 0 0 083 200 85 -- -- 75 95 084 -- -- -- -- -- -- --85 -- -- -- -- -- -- --86 200 75 -- -- 85 75 087 -- -- -- -- -- -- --88 200 90 -- -- 0 0 089 -- -- -- -- -- -- --90 -- -- -- -- -- -- --91 -- -- -- -- -- -- --92 200 70 -- -- -- 95 093 200 95 -- -- 0 75 094 200 100 -- -- 0 90 095 -- -- -- -- -- -- --96 200 90 -- -- 0 99 097 -- -- -- -- -- -- --98 200 90 -- -- 90 95 099 -- -- -- -- -- -- --100 -- -- -- -- -- -- --101 200 0 -- -- 0 0 0102 200 0 -- -- 0 75 0103 200 0 -- -- 0 50 0104 -- -- -- -- -- -- --105 -- -- -- -- -- -- --106 -- -- -- -- -- -- --107 -- -- -- -- -- -- --108 -- -- -- -- -- -- --109 -- -- -- -- -- -- --110 200 -- -- 50 75 80 0111 -- -- -- -- -- -- --112 -- -- -- -- -- -- --113 -- -- -- -- -- -- --114 200 -- -- 50 75 90 0115 -- -- -- -- -- -- --116 200 100 -- -- 75 90 0______________________________________
TABLE 5______________________________________Antialgal Test Results Against Green Alga MIC (ppm)Compound # Chlorella______________________________________ 85 0.25 87 4 88 <0.12 89 <0.12 90 <0.12107 <0.12108 8109 8110 4111 >250112 0.25113 8114 8120 125121 <0.12______________________________________
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