Патент USA US3090731код для вставки
Unite 3,92,?21 ttes Patented May 21, 1963 1 2 approximately 100 nematodes were introduced embryo tray of 4 by 4 cm. having a cavity of Subsequently, the tray was closed by means of a ground glass guard in such manner as to admit into an 3.5 ccs. roughly a quan tity of oxygen su?icient to prevent immobilisation of the nematodes by lack of oxygen. By means of a binocular the vitality of the nematodes was determined after 4, 24, 48 and 140 hours respectively. 3,99%,721 TIEADEAZGLE Jan Hendrik Uhienbroek and Johan Dirk Biiloo, ‘Van Houtenlaan, Wcesp, Netherlands, assignors to North American Philips Qompany, Inc, New York, N.Y., a corporation of Delaware No Drawing. Filed Feb. 13, 1959, Ser. No. 792,953 Claims priority, application Netherlands Feb. 13, 1958 29 Claims. (Cl. 167—-33) In this manner the lowestconcentration of active com 10 pound in the suspension used was determined, which It is known that 1.2.4-thiadiazoles, in which both car bon atoms of the ring carry monovalent organic radicals resulted in 100% kill of the test specimen after 140 hours linked through sulphur, might be used for combating exposure. The tests were carried out on larvae of Heterodera noxious insects and larvae of them. These organic radi rostochiensis lured for two days from their cysts, Dity cals may be alkyl-, cycloalkyl-, aralkyl-, alkoxyalkyl-, 15 lenchus dipsaci and larvae of Anguina tritici (both speci aryloxyalkyl-, carbethoxyalkyl- or hydroxyalkyl groups. mens soaked for 17 hours from 'dry condition). The results of these tests are listed in Table I, which states the minimum lethal dosage of the investigated com It has now been found that 1.2.4-thiadiazoles, in which a. halogen atom is linked to one of the carbon atoms of the ring are active against noxious organisms and in par ticular have a nematocide effect. pound, killing all the test specimens within 140 hours’ 20 exposure. The present invention relates to a method of produc ing a means for combating noxious organisms and in par ticular nematodes, characterized in that a compound of The minimum lethal dosage stated is the con centration of the active compound of the suspension used, expressed in parts by weight of active compound per million parts by weight of diluent (water). the general formula: TABLE I Compound Mimi‘ N O—-Ol in which Hlg represents a halogen atom and R1 represents 30' alkyl-, cycloalkyl-, aryl- or aralkyl group, the aliphatic Heterodera Ditylenchus Ang'uz'na S a phenyl group or a group R2.S—-, in which R2 represents a whether or not substituted, saturated or unsaturated, chain whether or not being interrupted by oxygen or sul phur, is mixed with inert, solid or ?uid carriers, if de 35 sired with the addition of surface-active materials and/ or Nematodes rostochiensis CH3.OH2.CH(CH3).S. I1.C5H11.S ____________ _. represents a chlorine atom and R2 represents an alkyl 40 group with 1 to 12 carbon atoms such as methyl-, ethyl-, propyl-, isopropyl-, butyl-, isobutyl-, isoamyl-, hexyl- or 12 6 6 6 50 6 12 25 100 50 50 500 25 100 50 25 12 25 100 12 50 50 1,000 100 ___ 6 50 6 CH3.CH(CH:).CH2.CH2.S____ 6 100 12 n. O 61113.8 ____________________ __ 6 25 50 250 6 50 100 1,000 1, 000 4 3 12 50 100 500 15 25 25 12 12 12 1,000 1, 000 50 25 12 12 6 1, 000 6 1, 000 1, 000 50 . octyl group or an oxygen interrupted alkyl group such as an ethoxyethyl group or an unsaturated group, for example an allyl group and further compounds, in which 45 R2 represents a phenyl-, 4-chlorophenyl-, 4-methylphenyl . group or a benzyl- or 4-chlorobenzyl group or a phe tritici R1: dispersion agents. A satisfactory nematocide effect have, in particular, the compounds according .to the invention, in which I-Ilg dipsaci . . 4-—N 0 1. 06115. CH2.S _________ __ noxyethyl group. Excellent nematocides are compounds according to the Table II states the results of a series of tests with 3 invention in which Hlg is a chlorine atom and R1 repre 50 n.butylmercapto-S-chloro-l.2.4-thiadiazole in vitro, car sents a phenyl group, as well as those in which R2 repre ried out as before. The table states the percentage of sents an unbranched alkyl. group ‘comprising 51 to 6 car nematodes killed within 140 hours’ exposition under the bon atoms, an allyl group, an ethoxyethyl group or a in?uence of the thiadiazole referred to. phenyl-, 4-chlorophenyl or 4-methylphenyl group or a TABLE II 55 benzyl- or 4-chlorobenzyl group. Particularly those nematodes are attacked by com Concentration of active substance pounds according to the invention which cause eel worm diseases in plants, for example Heterodera species, for example larvae of Heterodera rostochz'ensis (potato cys ticolous eel worm), Meloidogyne species (root knob eel 60 worms) Ditylenchus species (stem eel worms), Praty lenchus species, Hoplolaimus species and larvae of An guina triiicz‘ (wheat gall eel worms). in parts per million Nematode 500 100 50 25 12 100 Heterodera rostuchiensz's (larvae)___ 100 100 100 100 Ditylenchus dipsaci ..... -_ 100 100 100 30 100 100 100 100 Anguinctritici (larvae)___ _ 6 3 100 90 -.-__ ___ 60 ___ Tests showing the nematocide etfect of compounds ac cording to the invention were carried out as follows. 65 The e?ect of three compounds on nematodes in the soil was investigated. The soil used was sandy, by its nature strongly infected with Pratylenchus pratensis. of polyethylenemonolaurate and subsequently suspended In separate tests, samples of 250 gms. of the soil were in 30 ccs. of water. By ‘diluting this suspension with mixed with suspensions of 50, 25 and 10 mgms. respec water suspensions of different concentrations were ob 70 tively of the substance to be tested in 12 ccs. of water tained which were used for carrying out the tests. and subsequently stored for 24 days in cups at approxi 1.5 ccs. of the suspension to be tested and subsequently mately 15° C. In order to prevent drying out of the 30 mgs. of the compound to be tested were ?nely ground with the addition of 5 drops of a solution of 5% 3,090,721 Goerdeler et al., Chem. Berichte 90, 182 et seq. and 892 et seq. (1957).) An amidin salt of isothiouroni-um salt soil the cups were covered‘ with a polythene foil. The nematodes were subsequentl-ywashed out of the soil in the manner referred to by 'I. W. Seinhorst and the sur in water in reacted with an equivalent quantity of per- ‘ chloromethylmercaptan with the addition of soda lye. Several of the compounds according to the invention, in which R1 represents the group R28 have, however, not yet been mentioned in the literature. These compounds vivors were counted (see Nematologica, vol. 1, pages 249 to 267 (1956)). The same was done with blank-tests without adding active substance to the soil. The tests were carried out ?ve times. Table III states the average result of these tests for each of the following compounds: UE 9:3-phenyl-5-chloro-1.2.4-thiadiazole, 10 compounds are inter alia those in which in the aforesaid I formula R2 represents one of the following groups: iso UE 18=B-methylmercapto-S-chloro-1.2.4-thiadiazole, UE 19':3-n.butylmercapto~5-chloro-1.2.4-thiadiazole, UE 32:3-n.propylrnercapto-5~chloro-1.2.4-thiadiazole. TABLE n1 Compound can be produced by the aforesaid method from iso~ thiouronium salts and perchloromethylmercaptan. Novel propyl, l-methylpropyl, 3-methylpropyl, namyl, n.hexyl, noctyl, n.dodecyl, allyl, ethoxyethyl, phenyl, '4-chl0ro phenyl, 4-methylphenyl and phenoxyethyl. 15 Mg. active Surviving Kill substance per hematodes percentage 250 g. of soil UE 9.-.; ..................... _. UE 1s; ....................... -. UE 19 ........................ -_ 50 52 87 25 10 72 75 83 82 0 420 __________ -_ so 24 96 25 55 90 10 40 0 534 50 30 25 UE 32 ________________________ __ 93 33 0 534 NE I 25 lul __________ _ 94 . 94 .......... .. 25 32 96 10 5 52 50 93 93 0 758 .......... __ O-Cl S 94 32 10 20 The production of a number of these novel compounds will be described in Examples I to V. Example I vI‘I-PHENYLMERCAPTQ-5(THLORO-l.‘2AJFHIADIAZOLE In a 3 litre ?ask, 188.5 gms. (1.0 mole) of phenyl isothiouroniumchloride were mixed with 186 gms. (1.0 30 mole) of perchloromethylmercaptan, 180 ccs. of water and 300 ccs. of methylenechloride, while cooling the ?ask with ice-water. Subsequently, a solution of 160Jgms. (4.0 mole) of sodium-hydroxide in 500 ccs. of water was Principally known methods maybe used for producing 35 slowly added to the mixture, while'stirring vigorously. The rate of adding the soda lye Was such that the tem the pesticidal preparations. Thus, ‘for example, the ac perature did not exceed 5° C. and the mixture did not tive compounds according to the invention may be mixed produce an alkaline reaction. After adding the whole with a pulverulent inert carrier, for'exa-mple chalk, dolo quantity, stirring was continued for half an hour. Sub mite, attapulgite, kaolin or pipe clay, or dissolved or dis persed in an inert solvent such‘ as toluene, xylene, aliphatic 40 sequently 25 ccs. of ammonia (25% by weight) were added and further stirred for 15 minutes, followed by neu ‘or aromatic ketones, ‘for example acetone, methyl-ethyl tralisation with hydrochloric acid. a ketone'or cyclohexanone, or mixtures of them with said The layer of methylene chloride, in which the reac hydrocarbons, if desired with the addition of surface-ac tion product is ‘dissolved, was separated, washed with tive materials and/or dispersion agentsj As an alterna 0.5 l. of water and dried on anhydrous sodium sulphate. tive, these preparations may be mixed with synthetic ter 45 After distilling off the methylene chloride the residue, tilisers. that is the crude reaction product, was crystallised from For example, a dust is prepared by grinding approxi petroleum ether (boiling range 40° C. to 60° C.). Yield mately 5 parts by weight of an active compound accord 148 gms. of 3-phenylmercapto-5-chloro~1.2.4-thiadiazole ing to the invention together with approximately 95 parts (yield 65%). Melting point 58° C. by weight of kieselguhr to an average particle size of ap 50 The compounds used in the Examples II to V'were pro proximately 10;r. . duced quite similarly. For example a wettable powder is produced by mixing ‘approximately 50 parts by weight of an active compound Example II according to the invention with approximately 5 parts by 3-n.OCTYLMERCAPT’O-?-CHLORO-l.2A-THIADLAZOLE' weight of oleylamido-methyltaurate, approximately 10 parts by weight of calciumligninsulfonate and approxi 55 22.4 gms. (yield 68%) of 3-n.octyl-mercapto-S-chloro 1.2.4-thiadiazole were obtained from 33.6 gms. (0.125 mately 35 parts by weight of dolomite (calcium-mag mole) of n.-octylisothiouronium bromide and 23.3 ‘gms. nesium carbonate), this mixture being ground to an aver (0.125 mole) of perchloromethylmercaptan. Boiling age particle size ‘of approximately 10;!“ point: 145° to 146° C. at 8 mms. mercury pressure. Miscible oils may, for example, be produced by dis solving approximately 25 parts by weight of an active 60 Example III compound according to the invention in a mixture of approximately 10 parts by weight of an active compound according to the invention in a mixture of approximately 10 parts by weight of polyoxyethylenesorbitan fatty acid ester, approximately 10 parts by weight of methylethyl ketone and approximately 55 parts by weight of xylene. The compounds according to the invention permit in general,.miscible oils of :high concentration to be pro duced. Thus, for example, 3-n.butylmercapto-S-chloro 70 1.2.4-thiadiazole with xylene can be worked up to a 3-ALLYLMERCAPTO-5-CHLORO-1.ZA-THIADIAZOLE 22.2 gms. (yield 46%) of 3-allylmercapto-5-chloro 1.2.4-thiadiazole were produced from 49.3 gms. (0.25 mole) of allylisothiouronium bromide and 46.5 gms. (0.25 mole) of perchloromethylmercaptan. Boiling point 115 117° C. at 15 mms. mercury pressure, Example IV v 3~(4=’-CHLOROBENZYL)MERCAPTO»5-CHLORO-1.2.4 THIADIAZOLE miscible roil containing 80 percent by weight of active 17 gms. (yield 46%) of 3-(4’-chlorobenzyl)mercapto material. This may be of importance in practice. 5-chloro-1.2.4-thiadiazole were produced ‘from 32 gms. The production of a number of the compounds accord (0.13 mole) of 4-chlorobenzylisothiouronium chloride ing the invention has already been described. (See I. 75 and 25' gms. (0.13 mole) of perchloromethylmercaptan. 3,090,721 6 5 After crystallisation from .ligroin the melting point was out in a solution of 12 gms. (0.120 mole) of cuprous chloride in 120 ccs. of concentrated hydrochloric acid. The 3-phenyl-5—chloro-1.2.4-thiadiazole was extracted with petroleum ether (‘boiling range 40° C. to 60° C.) from the reaction mixture. Yield 6.85 gms. (58%). Melting point 42° C. to 50° C. What is claimed is: 1. A composition for the control of nematode compris 52° C. Example V 3- (4'-NITROBENZYL) MERCAPTO-5-CHLORO-1 2.4 THIADIAZOLE 14.5 gms. (yield 59%) of 3-(4'-nitrobenzyl)mercapto 5-chloro-1.2.4-thiadiazole were obtained from 25 gms. (0.086 mole) of 4-nitrobenzylisothiouronium bromide and 16 gms. (0.086 mole) of perchloromethylmercap tan. ing as an active ingredient a thiadiazole compound cor After crystallization from a mixture of benzene 10 responding to the general formula: and ligroin '(l : l) the belting point was 97° C. In Table IV are listed the yields obtained by the .pro duction method described in the aforesaid examples and physical constants of several novel 5-chloro-1.2.4-thia 15 wherein Hal represents a halogen atom and R1 represents diazoles according to the invention. a radical selected from the group consisting of phenyl TABLE IV and the radical R28 wherein R2 represents a radical se 'lected from the group consisting of alkyl, alkoxy- alkyl, R2-—S——C—~—N II II N C——Cl allyl, phenyl, methylphenyl, chlorophenyl, benzyl, chlo Melting Boiling point ° 0. at mm. Yield, point, percent 20 mercury pressure robenzyl and phenoxyethyl in a nematocidal effective amount, a surface active material and a nematocide ad juvant as a carrier therefor. ° 0. 2. The composition of claim 1 wherein Hal represents a chlorine atom. 110° to 112° at 14 mm ____ __ 126° to 128° at 14 mm___ 122° to 124° at 14 mm... 102° 110° 145° 180° to to to to 25 _ 46 _ en 3. The composition of claim 1 wherein R2 represents an alkyl radical containing 1 to 12 carbon atoms. 104° at 0.7 mm._._. 112° at 0.02 mru____ 146° at 0.8 mm_____ 183° at 0.05 mm____ 12 65 échlorophenyl ______ __ 25 4-methylphenyl Phenoxyethyi 51 40 4-chlor0benzyl ______ -_ a-uitroheuzyl _______ -_ 46 59 It was moreover found that the compounds according to the invention can be produced from the correspond ing 5-amino-l.2.4-thiadiazoles according to the reaction of Sandmeyer, in which the amino compounds are con 4. The composition of claim 1 wherein R2 represents the ethoxyethyl radical. 5. The composition of claim 1 wherein R2 represents 30 an nnbranched alkyl radical containing from 1 to 6 car bon atoms. 6. A dust for combating nematodes comprising an in timate mixture of about 5 parts by weight of the active compound of claim 1 and about 95 parts by weight of 35 kieselguhr, said dust having an average particle size of approximately 10;!“ 7. A wettable powder for combating nematodes com prising an intimate mixture of about 50 parts by weight of the active compound of claim 1, about 5 parts by verted into diazonium compounds by means of nitrite, for 40 weight of oleylamidomethyllaurate, about 10 parts by example sodium nitrite, which diazoniurn compounds are Weight of calcium ligninsulfonate and about 35 parts by converted into S-chloro-1.2.4-thiadiazoles in the presence weight of dolomite, said powder having an average parti of copper powder and a chloride, or in the presence of, cle size of about 10a. for example, cuprous chloride. 8. A miscible oil for combating nematodes compris This method will be set out in the following examples. 45 ing a solution of about 25 parts by weight of the active compound of claim 1 in a mixture of about 55 parts by Example VI ‘3-BENZYLMERCAPTO-5—CHLORO-1.2.4-THIADIAZOLE 9.5 gms. (0.043 mole) of 3-benzyhnercapto-5-amino 1.2.4-thiadiazole were dissolved in 100 ccs. of acetic acid. Whilst cooling with ice a solution of 4.9 gms. (0.07 mole) of sodium nitrite in 50 ccs. of concentrated hydrochloric acid was added dropwise such that the temperature of the mixture did not exceed 20° C. After standing 15 min weight of xylene, of about 10 parts by weight of methyl ethyl-ketone and of about 10 parts by weight of polyoxy ethylene-sorbitan fatty acid ester. 9. A composition for the control of nematodes com prising as an active ingredient 3-phenyl-5-chloro-l,2,4 thiadiazole in a nematocidal effective amount, a surface active material and a nematocide adjuvant therefor. 10. A composition for the control of nematodes com prising as an active ingredient 3-alkylmercapto-5-chloro poured out while stirring, in a solution of 6 gms. of 55 1,2,4-thiadiazole in a nematocidal effective amount, a cuprous chloride in 100 ccs. of concentrated hydrochloric surface active material and a nematocide adjuvant there acid. After standing overnight, the mixture obtained for. was shaken with benzene at room temperature. After 11. A composition for the control of nematodes com concentration by evaporation, the benzenic solution prising as an active ingredient 3-ethoxyethylrnercapto-5 yielded 5.9 gms. (60%) of crude 3-benzylrnercapto-5 60 chloro-l,2,4-thiadiazole in a nematocidal effective amount, chloro-1.2.4-thiadiazole from which the pure compound a surface active material and a nematocide adjuvant was obtained by crystallization from methanol. Melt therefor. ing point 49° C. 12. A composition for the control of nematodes com EXAMPLE VII 65 prising as an active ingredient 3-phenylmercapto-5-chloro 3-PHENYL—5—CHLORO-1.2.4—THIADIAZOLE 1,2,4-thiadiazole in a nematocidal effective amount, a surface active material and a nematocide adjuvant there This compound was produced in a manner similar to for. that used in Example V1. 13. A composition for the control of nematodes com 10.6 gms. (0.06 mole) of 3-phenyl-5-amino-1.2.4-thia diazole were dissolved in 130 ccs. of acetic acid, followed 70 prising as an active ingredient 3~n-butylmercapto-5-chlo by adding, while stirring, a solution of 4.56 grns. (0.066 ro-l,2,4-thiadiazole in a nematocidal effective amount, a surface active material and a nematocide adjuvant there mole) of sodium nitrite in 45 ccs. of concentrated sul for. phuric acid. The temperature was kept between 5° C. 14. A composition for the control of nematodes com and 10° C. Subsequently, the temperature of the mix ture was raised to 18° C. and the mixture was poured 75 prising as an active ingredient 3-methylmercapto-5-chlo tries at room temperature, the reaction mixture was 3,090,721 8 r0-.1,2,4-thiadiazole in a nematocidal e?ective amount, a surface active material and a nematocide adjuvant there 23.- A method of combating nematodes comprising treating the habitat thereof with the composition of for. 15. A composition for the control of nematodes com prising as an active ingredient 3-(41-ch1orophenyl)-mer capto-S-chloro-1,2,4-thiadiazole in a nematocidal effec claim 12. 24. A method of combating nematodes comprising treating the habitat thereof with the composition of tive amount, a surface active material and a nematocide 25. A method of combating nematodes comprising treating the habitat thereof With; the composition of claim 13. adjuvant therefor. ' claim 14. V V 16. A composition for the control of nematodes com 26. A method of combating nematodes comprising prising as, an active ingredient 3-(41-methylpheny-D-mer 10 treating the habitat thereof with the composition of capto-S-chloro-l,2,4-thiadiazole in a nematocidal effective claim 15. 27. A method of combating nematodes comprising amount, a surface active material and a nematocide ad juvant therefor. treating the habitat 17. A composition for the control of nematodes com prising as an active ingredient S-benzylmercapto-5-chloro 15 claim 16. 28. A method of 1,2,4-thiadiazole in a nematocidal effective amount, a treating the habitat surface active material and a nematocide adjuvant there claim 17. for. 29. A method of 18. Acomposi-tion for the control of nematodes com prising-as an active ingredient 3-(41-henzylmercapto)-5 20 treating the habitat claim 18. chloro-1,2,4—thiadiazole in a nematocidal effective amount, thereof with the composition of combating nematodes comprising thereof with the composition of combating nematodes comprising thereof with the composition of a surface active material and a nematocide adjuvant therefor. 19. A method of treating the habitat claim 1. 20.- A method of treating the habitat claim 9. 21.»A- method of treating the habitat claim 10. 22. A method of treating the habitat claim 11. References Cited in the ?le of this patent combating nematodes comprising thereof with the composition of 25 combating nematodes comprising thereof with the composition of V a / combating nematodes comprising 30 thereof with the composition of UNITED STATES PATENTS 2,285,410 2,592,195 Bousquet et a1. ________ __ June 9, 1942 Schwarz _______ _'___V.___. Apr. 8, 1952 2,702,803 2,744,908 2,863,804 Ainsworth ___________ 2. Feb. 22, 1955. Young ______________ __ May 8, 1956 Benghiate et a1. _______ __ Dec. 9, 1958 ' combating nematodes comprising thereof with the composition of OTHER REFERENCES Agr. and Food Chem., vol. 5, pages 159-160, March CAD U! 1957.