EP0146610A4 - Substituted benzopentathiepins, process therefor and intermediates. - Google Patents

Substituted benzopentathiepins, process therefor and intermediates.

Info

Publication number
EP0146610A4
EP0146610A4 EP19840902416 EP84902416A EP0146610A4 EP 0146610 A4 EP0146610 A4 EP 0146610A4 EP 19840902416 EP19840902416 EP 19840902416 EP 84902416 A EP84902416 A EP 84902416A EP 0146610 A4 EP0146610 A4 EP 0146610A4
Authority
EP
European Patent Office
Prior art keywords
compound
aryl
benzothiadiazole
compound according
substituted
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP19840902416
Other languages
German (de)
French (fr)
Other versions
EP0146610A1 (en
Inventor
Bertrand Leo Chenard
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
EIDP Inc
Original Assignee
EI Du Pont de Nemours and Co
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by EI Du Pont de Nemours and Co filed Critical EI Du Pont de Nemours and Co
Publication of EP0146610A1 publication Critical patent/EP0146610A1/en
Publication of EP0146610A4 publication Critical patent/EP0146610A4/en
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
    • C07D285/01—Five-membered rings
    • C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
    • C07D285/14—Thiadiazoles; Hydrogenated thiadiazoles condensed with carbocyclic rings or ring systems
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
    • A01N43/24—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with two or more hetero atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D341/00—Heterocyclic compounds containing rings having three or more sulfur atoms as the only ring hetero atoms

Definitions

  • This, invention concerns substituted benzopentathiepins, intermediate 1,2.3-benzothiadiazoles and the process: for malcing. the former by reacting the latter with elemental sulfur.
  • Uhsubstituted benzopentathiepin is known (Feher et al., Z. Anorcr. Alia. Chem.. 452,. 37 to 42 (1979): Feher et al., Tet. Lett., 2125, to 2126 (1971). It, is prepared from 1,2-benzenedithiol and S 3 Cl 2 . No utility is described, Feher et al., in Z. Naturforsch. B, 27, 1006. (1972). describe preparation of the 7,8-dimethyl derivative by a similar method. A reduced hexahydr ⁇ benzopentathiepin was prepared by Feher et al., according to the method of Feher et al. described above: Angew. Chem. Int.
  • Watkins et al., J. Her. Chem.. 19. 459 to 462 (1982) describe the x-ray crystal structure of a complex indene pentathiepin. Synthesis and utility are not described.
  • R H, C 1 -C 6 alkyl, C 5 -C 6 cycloalkyl.
  • the 1,2-benzenedithiols can. be prepared by pyrolysis of benzothiadiazoles in the presence of carbon disulfide and alkaline hydrolysis of the intermediate trithiocarbonate: Hunig et al., Liebigs Ann. Chem. , 738, 192 to 194 (1970). The process requires a pressure vessel and temperatures of 220°C.
  • R 1 , R 2 and R 3 are the same or different substituents that do not react with sulfur at elevated temperatures and are selected from H (no more than two of R 1 , R 2 and R 3 being H), X,
  • R 4 is selected from aryl. substituted aryl and substituted and unsubstituted branched or straight chain C 1 to C 6 alkyl;
  • X is selected from Cl, Br and F.
  • R 1 , R 2 and R 3 substituents are selected from X, CX 3 , OR, SR,
  • benzopentathiepins of this invention are those wherein: (1)
  • R 1 and R 3 are both H and R 2 is selected from X,
  • R 1 is selected from X, CX 3 , SR 4 , OR 4 , NR 4 2 , COOR 4 , aryl and substituted aryl; and (3) R 1 and, R 2 are both NR 4 2 and R 3 is H.
  • Especially preferred compounds are those in category (1) wherein R 2 is N(CH 3 ) 2 , OCH 3 , CF 3 or Cl; those in category (2) wherein R 1 is CF 3 or Br; and the compound in category (3) wherein R 4 is methyl.
  • the latter compound is named
  • This invention also concerns the method for making benzopentathiepins by the following reaction:
  • the reaction is typically carried out in an inert solvent at temperatures between about 140o to 200°C, with about 160o to 190oC being preferred.
  • Suitable solvents are those which are inert to elemental sulfur and are tolerant of temperature and pressure combinations required to meet the temperature, range described.
  • the solvents include but are not limited to decahydronaphthalene, nitrobenzene, dichlorobenzenes. dimethylformamide and dimethyl sulfoxide.
  • the reaction is normally carried out in an inert atmosphere such as nitrogen, argon, helium and the like.
  • the molar ratio of elemental sulfur (calculated as S 8 ) to benzothiadiazole can range from about 1:2 to 2:1; the preferred ratio is about 1:1.
  • This invention also concerns the method for making said benzopentathiepins in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO):
  • the molar ratio of DABCO to benzothiadiazole is about 0.1:1 to 2:1; the preferred ratio is about 1:1.
  • Employing DABCO in the process of the invention has been found to increase product yields substantially. This invention also concerns these novel benzothiadiazoles:
  • This invention also concerns the method for making substituted 1,2-benzenedithiols by reduction of benzopentathiepins according to the reaction:
  • Suitable reducing agents for said process include but are not limited to sodium borohydride. lithium aluminum hydride, trialkyl phosphites, zinc/ aqueous acid, and the like. Sodium borohydride and lithim aluminum hydride are preferred.
  • the reaction temperature can be about 0o to 60oC; the preferred range for sodium borohydride, for reasons of ease of reactivity, is about 20o to 40o C; the preferred range for lithium aluminum hydride is about 0o to 35oC.
  • the molar ratio of sodium borohydride or lithium aluminum hydride to benzopentathiepia can range from about 2:1 to 6:1; a ratio of about 4:1 is preferred.
  • the process employing lithium aluminum hydride should be run in the absence of water.
  • the reaction process initially gives a dithiolate salt which caa be further reacted with aqueous acid to give the 1,2-benzenedithiols ⁇ or with alkylating agents such as methyl iodide to give di-thioethers.
  • alkylating agents such as methyl iodide
  • An additional aspect of this invention concerns the use of selected benzopentathiepins as anti-fungal and anti-viral agents.
  • the compounds of Table 1 were found to be effective against the recited fungus and virus types. Details concerning formulations and control methodology follow the Table.
  • CPM cucumber powdery mildew
  • BPM barley powdery mildew
  • CMV cucumber mosaic virus
  • WLR wheat leaf rust
  • benzopentathiepins caa be prepared in conventional ways. They include dusts, suspensions, emulsions, wettable powders, emulsifiable concentrates and the like. Many of them caa be applied directly. Sprayable formulations can be extended in suitable media and used at spray volumes of from a few liters to several hundred liters per hectare. High strength compositions can be used primarily as concentrates which are to be diluted prior to ultimate use.
  • the formulations broadly, contain about 1% to 99% by weight of active ingredient(s) and at least one of (a) about 0.1% to
  • surfactaat(s) and (b) about 1% to 99% solid or liquid diluent(s). More specifically, they will contain these ingredients in the approximate proportions set forth in Table 2 with the active ingredient plus at least one surfactant or diluent being equal to 100 weight percent.
  • Agricultural formulations that contain the compounds of this invention as active ingredient can also contain other active ingredients.
  • the additional agricultural chemicals are employed in mixtures or combinations in amounts ranging from 0.05 to 25 parts by weight for each part by weight of the compound or compounds of this invention. The proper choice of amounts is readily made by one skilled in the art of protecting plants from pests.
  • Fungicides methyl 2-benzimidazolecarbamate (carbendazim) tetramethylthiuram disulfide (thiuram) n-dodecylguanidine acetate (dodine) manganese ethylenebisdithiocarbamate (maneb) 1,4-dichloro-2.5-dimethoxybenzene (chloroneb) methyl 1-(butylcarbamoyl)-2-benzimidazolecarbamate
  • Fine solid compositions are made by blending and. usually, grinding as in a hammer or fluid energy mill.
  • Suspensions are prepared by wet milling.
  • Granules and pellets can be made by spraying the active material on preformed granular carriers or by agglomeration techniques.
  • Disease control is accomplished by applying the compounds of this invention to the portion of the plant to be protected.
  • the compounds can be applied as preventive treatments prior to inoculation with the pathogen, or after inoculation as a curative post-infection treatment. Rates of application for compounds of this invention will be influenced by specific host plants, fungal pathogens, and many factors of the environment must be determined under use conditions. Foliage sprayed with concentrations ranging from 1 to 500 ppm of active ingredient can be protected from disease under suitable conditions.
  • the benzopentathiepins of this invention have generic utility as intermediates in the preparation of substituted 1,2-benzenedithiols which are free of the 1,3-and 1,4-dithiol isomers.
  • substituted 1,2-benzenedithiols are known intermediates to pharmaceuticals (U.S. 4,242,510; Sindelar et al., Collect. Czech. Chem. Comm., 47, 72 to 87 (1982), pesticides (U.S. 3,746,707). and rubber crosslinking agents (U.S. 3,979,369).
  • Examples 1 to 7 and 16 illustrate the process of the invention for preparation of benzopentathiepins.
  • Examples 2 to 7 and 16 illustrate novel benzopentathiepins.
  • Examples 8 to 10 illustrate the yield enhancement of the process by employing DABCO.
  • Examples 11, 12 and 15 illustrate the novel benzothiadiazole compounds.
  • Examples 13 and 14 illustrate the process for conversion of benzopentathiepins to dithiols. In both Examples 13 and 14, the dithiols obtained are isolated as bismethylthioethers to prevent aerobic oxidation. These bismethylthioethers can be converted back to the benzenedithiols by treatment with, for example, sodium in liquid ammonia.
  • Decalin® (20 mL) was heated to 175°C for 1.25 h and nitrogen was evolved. The mixture was cooled and the solvent was removed by Kugelrohr distillation. The residue was preadsorbed and chromatographed (300 g) on Silica Woelm® TSC (1%. ether-hexane) to give first sulfur and then 2.2 g of a sulfur-product mixture.
  • the above salt was slurried in 5% aqueous HCl (100 mL) and chilled to 0°C.
  • a solution of sodium nitrite (3.22 g) in water (15 mL) was added dropwise over 20 min to the stirred mixture; then it was neutralized to pH 9 with 20% aqueous sodium hydroxide.
  • the reaction was extracted with ether (3 x100 mL) and the organic phase was washed with water and brine and then filtered through a cone of sodium sulfate.
  • This Example illustrates the making of a compound useful (as the unprotected dithiol) as a rubber cross-linking agent.
  • This Example illustrates the making of a compound useful as an intermediate (as the unprotected dithiol) to a tricyclic psychotropic agent.
  • 7-chlorobenzopentathiepin (0.32 g, 1.18 mmol) was dissolved in tetrahydrofuran (30 mL) and ethanol (30 mL) was added.
  • Sodium borohydride (0.22 g, 5.91 mmol) was added over 5 min in portions at ambient temperature causing the solution to evolve hydrogen gas and warm slightly. After gas evolution had ceased in about 15 min, water (10 mL) was added and the mixture was heated to about 50°C for 5 min and cooled to ambient temperature.
  • Methyl iodide (0.44 mL, 7.0 mmol) was added and the solution was stirred. The solvents were removed and the residue was partitioned between ether and water. The phases were separated and the organic layer was washed with brine and dried through a cone of sodium sulfate.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Agronomy & Crop Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Dentistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

Substituted benzopentathiepins, their preparation from 1, 2, 3-benzothiadiazoles and elemental sulfur, selected 1, 2, 3-benzothiadiazoles; the benzopentathiepins being useful as intermediates to 1, 2-benzenedithiols or as agricultural anti-viral and anti-fungal agents.

Description

TITLE
SUBSTITUTED BENZOPENTATHIEPINS. PROCESS
THEREFOR AND INTERMEDIATES CROSS-REFERENCE TO RELATED APPLICATION This is a continuation-in-part of copending Application Serial No. 502,231 filed on June 8, 1983.
BACKGROUND OF THE INVENTION This, invention; concerns substituted benzopentathiepins, intermediate 1,2.3-benzothiadiazoles and the process: for malcing. the former by reacting the latter with elemental sulfur.
Uhsubstituted benzopentathiepin is known (Feher et al., Z. Anorcr. Alia. Chem.. 452,. 37 to 42 (1979): Feher et al., Tet. Lett., 2125, to 2126 (1971). It, is prepared from 1,2-benzenedithiol and S3Cl2. No utility is described, Feher et al., in Z. Naturforsch. B, 27, 1006. (1972). describe preparation of the 7,8-dimethyl derivative by a similar method. A reduced hexahydrαbenzopentathiepin was prepared by Feher et al., according to the method of Feher et al. described above: Angew. Chem. Int. Ed.. 6., 703 (1967). NametKin et al., in Izv. Alcad. Nauk. SSSR, Ser. Khim., 12, 2841 (1980). describe a method for making said reduced pentathiepins by use of an organoiron complex.
Watkins et al., J. Her. Chem.. 19. 459 to 462 (1982) describe the x-ray crystal structure of a complex indene pentathiepin. Synthesis and utility are not described.
A variety of heterocyclic pentathiepins are known. For instance, U.S. 4,094,985 describes the following as fungicides:
ώ where X is CN or -CQ, et cetera. U.S. 4.275.073 describes these pyrazolopentathiepins as fungicides:
where R = H, C1-C6 alkyl, C5-C6 cycloalkyl.
-CH2∅, -Ar. Both of the patents describe processes employing a thiol or dithiol and S2Cl2. The substituted benzopentathiepins of this invention cannot be made by literature techniques.
Certain 1,2.3-benzothiadiazoles. are known, their syntheses being reviewed by Kurzer in "Org. Cmpd. of Sulphur, Selenium. Tellurium", Royal Society of Chemistry, London, Vols. 1 to 6 (1970 to 1980). A typical synthesis is diazotization of an o-aminobenzenethiol as follows:
In Oae, "Organic Chemistry of Sulfur", at pages 346 to 348, Plenum Press. N.Y. (1977), are reviewed the various means of reducing disulfides to give thiols. Reagents for these reductions include sodium borohydride. lithium aluminum hydride, sodium amalgam, zinc or tin with aqueous acid, phosphines and phosphites.
Cairns et al., J. Am. Chem. Soc., 74, 3982 to 3989 (1952), describe the reductioa of a linear tetrasulfide by lithium aluminum hydride. There is no known art, however, that describes reductioa of a pentathiepin. to give a dithiol.
The 1,2-benzenedithiols can. be prepared by pyrolysis of benzothiadiazoles in the presence of carbon disulfide and alkaline hydrolysis of the intermediate trithiocarbonate: Hunig et al., Liebigs Ann. Chem. , 738, 192 to 194 (1970). The process requires a pressure vessel and temperatures of 220°C.
SUMMARY OF THE INVENTION This invention: concerns novel substituted benzopentathiepins of the formula:
wherein
R1, R2 and R3 are the same or different substituents that do not react with sulfur at elevated temperatures and are selected from H (no more than two of R1, R2 and R3 being H), X,
CX3, NO2, SR4, OR4, NR4 2, OCR4, COR4, CR4, CNR2 4, aryl and substituted aryl;
R4 is selected from aryl. substituted aryl and substituted and unsubstituted branched or straight chain C1 to C6 alkyl; and
X is selected from Cl, Br and F.
The primary requirement of the R 1, R2 and R3 substituents is that they be substantially unreactive with sulfur at reaction temperatures. Several groups of such substituents are given as examples with no intent that the invention be limited thereto. The substituents on substituted R 4 aryl and alkyl groups are selected from X, CX3, OR, SR,
OCR, and COOR, wherein R is aryl or C1 to C4
straight or branched alkyl. Preferred benzopentathiepins of this invention, are those wherein: (1)
R 1 and R3 are both H and R2 is selected from X,
CX3, SR4, OR4, NR4 2, COOR4, aryl and substituted aryl; (2) R 2 and R3 are both H and
R1 is selected from X, CX3, SR4, OR4, NR4 2, COOR4, aryl and substituted aryl; and (3) R1 and, R2 are both NR4 2 and R3 is H. Especially preferred compounds are those in category (1) wherein R2 is N(CH3)2, OCH3, CF3 or Cl; those in category (2) wherein R1 is CF3 or Br; and the compound in category (3) wherein R 4 is methyl. The latter compound is named
6,7 bis(dimethylamino)benzopentathiepin.
This invention also concerns the method for making benzopentathiepins by the following reaction:
The reaction is typically carried out in an inert solvent at temperatures between about 140º to 200°C, with about 160º to 190ºC being preferred. The R1, R 2 and R 3 substituents are as defined heretofore except that the novel process also includes the making of compounds wherein R 1 = R2 = R3 = H.
Suitable solvents are those which are inert to elemental sulfur and are tolerant of temperature and pressure combinations required to meet the temperature, range described. The solvents include but are not limited to decahydronaphthalene, nitrobenzene, dichlorobenzenes. dimethylformamide and dimethyl sulfoxide. The reaction is normally carried out in an inert atmosphere such as nitrogen, argon, helium and the like. The molar ratio of elemental sulfur (calculated as S8) to benzothiadiazole can range from about 1:2 to 2:1; the preferred ratio is about 1:1.
This invention also concerns the method for making said benzopentathiepins in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO):
The molar ratio of DABCO to benzothiadiazole is about 0.1:1 to 2:1; the preferred ratio is about 1:1. Employing DABCO in the process of the invention has been found to increase product yields substantially. This invention also concerns these novel benzothiadiazoles:
This invention also concerns the method for making substituted 1,2-benzenedithiols by reduction of benzopentathiepins according to the reaction:
wherein R 1, R2 and R3 are as defined above including R 1 = R2 = R3 = H.
Suitable reducing agents for said process include but are not limited to sodium borohydride. lithium aluminum hydride, trialkyl phosphites, zinc/ aqueous acid, and the like. Sodium borohydride and lithim aluminum hydride are preferred. The reaction temperature can be about 0º to 60ºC; the preferred range for sodium borohydride, for reasons of ease of reactivity, is about 20º to 40º C; the preferred range for lithium aluminum hydride is about 0º to 35ºC.
DETAILS OF THE INVENTION la the matter of making 1,2-benzenedithiols, the following informatioa will guide one skilled in the art regarding choice of solvents. The process employing sodium borohydride is run with a protic solvent, with or without non-protic solvents as diluent. Solvents suitable for the sodium borohydride process include but are not limited to methanol. ethanol, isopropanol, butanol and water. Non-protic diluents include tetrahydrofuran. Other solvents caa be selected empirically depending on the type of reducing agent selected. Thus, lithium aluminum hydride requires non-protic solvents such as diethyl ether or tetrahydrofuran. The molar ratio of sodium borohydride or lithium aluminum hydride to benzopentathiepia can range from about 2:1 to 6:1; a ratio of about 4:1 is preferred. The process employing lithium aluminum hydride should be run in the absence of water. The reaction process initially gives a dithiolate salt which caa be further reacted with aqueous acid to give the 1,2-benzenedithiolsγ or with alkylating agents such as methyl iodide to give di-thioethers. The second choice gives materials which are protected against aerobic oxidation.
An additional aspect of this invention concerns the use of selected benzopentathiepins as anti-fungal and anti-viral agents. For example, the compounds of Table 1 were found to be effective against the recited fungus and virus types. Details concerning formulations and control methodology follow the Table.
(1) AS=apple scab RB=rice blast
CPM=cucumber powdery mildew BPM=barley powdery mildew CMV=cucumber mosaic virus WLR=wheat leaf rust
PLANT DISEASE CONTROL FORMULATIONS Useful formulations of benzopentathiepins caa be prepared in conventional ways. They include dusts, suspensions, emulsions, wettable powders, emulsifiable concentrates and the like. Many of them caa be applied directly. Sprayable formulations can be extended in suitable media and used at spray volumes of from a few liters to several hundred liters per hectare. High strength compositions can be used primarily as concentrates which are to be diluted prior to ultimate use. The formulations. broadly, contain about 1% to 99% by weight of active ingredient(s) and at least one of (a) about 0.1% to
20% surfactaat(s) and (b) about 1% to 99% solid or liquid diluent(s). More specifically, they will contain these ingredients in the approximate proportions set forth in Table 2 with the active ingredient plus at least one surfactant or diluent being equal to 100 weight percent.
Lower or higher levels of active ingredient can be present, depending on the intended use and the physical properties of the compound. Higher ratios of surfactant to active ingredient are sometimes desirable and are achieved by incorporation into the formulation, or by tank mixing.
Some typical solid diluents are described in Watkins et al., "Handbook of Insecticide Dust Diluents and Carriers", 2nd Ed., Dorland Books, Caldwell, N.J. but other solids, either mined or manufactured, can be used. The more absorptive diluents are preferred for wettable powders and the denser ones for dusts. Typical liquid diluents and solvents are described in Marsden, "Solvents Guide", 2nd Ed., Interscience. N.Y., 1950. Solubility under 0.1% is preferred for suspension concentrates; solution concentrates are preferably stable against phase separation at 0ºC. "McCutcheon's Detergents and Emulsifiers Annual", MC Publishing Corp., Ridgewood, N.J., as well as Sisely and Wood, "Encyclopedia of Surface Active Agents", Chemical Publishing Co., Inc., N.Y., 1964, list surfactants and recommended uses. All formulations can contain minor amounts of additives to reduce foaming, caking, corrosion, microbiological growth, and the like.
Agricultural formulations that contain the compounds of this invention as active ingredient can also contain other active ingredients. The additional agricultural chemicals are employed in mixtures or combinations in amounts ranging from 0.05 to 25 parts by weight for each part by weight of the compound or compounds of this invention. The proper choice of amounts is readily made by one skilled in the art of protecting plants from pests. The following are illustrative of the agricultural chemicals that can be included in compositions or added to sprays containing one or more of the active compounds of this invention: Fungicides: methyl 2-benzimidazolecarbamate (carbendazim) tetramethylthiuram disulfide (thiuram) n-dodecylguanidine acetate (dodine) manganese ethylenebisdithiocarbamate (maneb) 1,4-dichloro-2.5-dimethoxybenzene (chloroneb) methyl 1-(butylcarbamoyl)-2-benzimidazolecarbamate
(benomyl) 2-cyano-N-ethylcarbamoyl-2-methoxyiminoacetamide (cymoxanil) N-trichloromethylthiotetrahydrophthalimide (captan) N-trichloromethylthiophthalimide (folpet) dimethyl 4,4'-(o-phenylene)bis(3-thioallophanate) (thiophanate-methyl) 2-Cthiazol-4-yl)benzimidazole (thiabendazole) aluminum tris(o-ethyl phosphonate) (Aliette®) tetrachloroisophthalonitrile (chlorothalonil) 2,6-dichloro-4-nitroaniline (dichloran) N-(2,6-dimethylphenyl)-N-(methoxyacetyl)alanine methyl ester (metalaxyl) cis-N-[(1,1,2,2-tetrachloroethyl)thio] cyclohex4-ene-1,2-dicarbioximide (captafol) 3-(3,5-dichlorophenyl)-N-(1-methylethyl)- 2,4-dioxo-1-imidazolidine carboxaraide (iprodione)
3-(3.5-dichlorophenyl)-5-ethenyl-5-methyl-2,4oxazolidinedione (vinclozolia) kasugamycin o-ethyl-S,S-diphenylphosphorodithioate (edifenphos) Bactericides: tribasic copper sulfate streptomycin sulfate oxytetracycline Acaricides: senecioic acid, ester with 2-sec-butyl-4.6dinitrophenol (binapacryl) 6-methyl-1,3-dithiolo [2,3-B] quinonolin-2-one (oxythioquinox) 2.2,2-trichloro-1,1-bis(4-chlorophenyl)ethanol
(dicofol) bis(pentachloro-2,4-cyclopentadien-1-yl) (dienochlor) tricyclohexyltin hydroxide (cyhexatin) hexakis(2-methyl-2-phenylpropyl)distannoxane (fenbutin oxide) Nematicides:
2-[diethoxyphosphinylimino]-1,3-dithietane (fosthietan)
S-methyl-1-(dimethylcarbamoyl)-N-(methγlcarbamoyloxy)thioformimidate (oxamoyl) S-methyl-1-carbamoyl-N-(methylcarbamoyloxy)thioformimidate N-isopropylphosphoramidic acid, o-ethyl-o'[4-(methγlthio)-m-tolyl] diester (fenamiphos) Insecticides:
3-hydroxγ-N-methylcrotonamide(diraethylphosphate)- ester (monocrotophos) methylcarbamic acid, ester with 2,3-dihydro-2,2dimethyl-7-benzofuranol (carbofuran) o-[2,4.5-trichloro-α-(chloromethyl)benzyl] phosphoric acid, o',o,-dimethyl ester (tetrachlorvinphos) 2-mercaptosuccinic acid, diethyl ester,
S-ester with thionophosphoric acid, dimethyl ester (malathion) phosphorothioic acid, o,o-dimethyl, o-p-nitrophenyl ester (methyl parathion) methylcarbamic acid, ester with α-naphthol (carbaryl) methyl N-[[(methylamino)carbonyl]oxy] ethanimidothioate (methornyl) N'-(4-chloro-o-tolyl)-N,N-dimethylformamidine (chloridimeform) o. o-diethyl-o- (2-isopropyl-4-methyl-6-pyrimidyl ) phosphorothioate (diazinon) octachlorocamphene (toxaphene) o-ethyl o-p-nitrophenyl phenylphosphononthioate (EPN) cyano(3-ρhenoxyphenyl)-methyl 4-chloro-α-(1methylethyl)benzeneacetate (fenvalerate) (3-phenoxyphenyl)methyl (+)-cis.trans-3-(2,2dichloroethenyl)-2.2-dimethylcyclopropanecarboxylate (permethrin) dimethyl N,N'-Cthiobis](N-methylimino)carbonyloxy]]-bis[ethanimidothioate] (thiodicarb) phosphorothiolothionic acid, o-ethγl-o-[4-(methγlthio)phenyl]-S-n-propγl ester (sulprofos) α-cyano-3-phenoxybenzyl[3-(2,2-dichlorovinyl)-2,2dimethylcyσlopropane]carboxylate (cypermethrin) cyano(3-phenoxyphenyl)methyl 4-(difluoromethoxy-α(methylethyl)benzeneacetate (Payoff®) o,o-diethyl-o-(3,5.6-trichloro-2-pyridyl)phoshorothioate (chlorpyrifos) o.o-dimethyl-S-[(4-oxo-1,2,3-benzotriazin-3-(4H)yl)-methyl]phosphorodithioate (azinphos-methyl) 5,6-dimethyl-2-dimethylamino-4-pyrimidinyl dimethyl carbamate (Pirimor®)
S-(N-formyl-N-methylcarbamoylmethyl)-o,o-dimethyl phosphorodithioate (formothion) S-2-(ethylthioethyl)-o,o-dimethyl phosphiorothioate (demeton-S-methyl) α-cyano-3-phenoxybenzyl cis-3-(2.2-dibromovinyl)2.2-dimethylcyclopropane carboxylate (deltamethrin) cyano(3-phenoxyphenyl)methyl ester of N-(2-chloro4-trifluoromethylphenyl)alanine (Mavrik®). The methods for making such compositions are well known. Solutions are prepared by simply mixing the ingredients. Fine solid compositions are made by blending and. usually, grinding as in a hammer or fluid energy mill. Suspensions are prepared by wet milling. Granules and pellets can be made by spraying the active material on preformed granular carriers or by agglomeration techniques.
Disease control is accomplished by applying the compounds of this invention to the portion of the plant to be protected. The compounds can be applied as preventive treatments prior to inoculation with the pathogen, or after inoculation as a curative post-infection treatment. Rates of application for compounds of this invention will be influenced by specific host plants, fungal pathogens, and many factors of the environment must be determined under use conditions. Foliage sprayed with concentrations ranging from 1 to 500 ppm of active ingredient can be protected from disease under suitable conditions.
The "% Control" in Table 1 was calculated according to this formula: disease rating
100 - on treated plants x 100 = percent disease rating control on untreated plants
The benzopentathiepins of this invention have generic utility as intermediates in the preparation of substituted 1,2-benzenedithiols which are free of the 1,3-and 1,4-dithiol isomers. Such substituted 1,2-benzenedithiols are known intermediates to pharmaceuticals (U.S. 4,242,510; Sindelar et al., Collect. Czech. Chem. Comm., 47, 72 to 87 (1982), pesticides (U.S. 3,746,707). and rubber crosslinking agents (U.S. 3,979,369). Reduction of the benzopentathiepins with, for example, sodium borohydride gives solutions of disodium benzene dithiolates which can be neutralized to give the dithiol or alkylated with methyl iodide to give 1,2-bis(alkylthio) benzene derivatives. It would be possible to react the dithiolates with anhydrides; acid halides; esters; isocyanates; sulfonyl halides; tri- and pentavalent phosphorous esters, halides and anhydrides to make other useful materials. In the following Examples the inert atmosphere was N2. Kugelrohr distillation refers to a bulb-to-bulb microdistillation assembly. Examples 1 to 7 and 16 illustrate the process of the invention for preparation of benzopentathiepins. Examples 2 to 7 and 16 illustrate novel benzopentathiepins. Examples 8 to 10 illustrate the yield enhancement of the process by employing DABCO. Examples 11, 12 and 15 illustrate the novel benzothiadiazole compounds. Examples 13 and 14 illustrate the process for conversion of benzopentathiepins to dithiols. In both Examples 13 and 14, the dithiols obtained are isolated as bismethylthioethers to prevent aerobic oxidation. These bismethylthioethers can be converted back to the benzenedithiols by treatment with, for example, sodium in liquid ammonia.
EXAMPLE 1 Benzopentathiepin
Sulfur (1.88 g, 7.3 mmol), 1,2.3-benzothiadiazole (1.0 g, 7.3 mmol) and Decalin®, i.e., decahydronaphthalene (10 mL) were combined and heated to 170°C for 1.45 h. The resulting mixture was taken up in carbon disulfide and chromatographed on Silica Woelm® TSC (250 g, hexane). After a 340 mL forerun, 50 mL fractions were taken. Fractions 4 to 16 contained 1.61 g of oily solid. This residue was triturated with hexane (30 mL) while methylene chloride (15 mL) was added slowly. Sulfur, 0.47 g was left as residue. The yellow solution was purified ia 3x15 mL portions by medium pressure liquid chromatography (MPLC) (Lobar® Silica gel 60 size C, hexane) to give 0.60 g (34%) of benzopentathiepin as a light yellow solid, mp 56° to 58ºC. A sample recrystallized once from hexane had a mp Of 58º to 60ºC; 1H-NMR(CDCl3. 90 MHz) δ 7.85-7.7 and 7.45-7.2 (AA'BB' multiplet) in agreement with the literature. The mass spectrum from a sample prepared similarly but not purified by MPLC had Mass spec.: m/e 235.8914; calcd m/e for
C6H4S55 235.8917,
EXAMPLE 2 7-Chlorobenzopentathiepin
A mixture of sulfur (4.5 g. 17.6 mmol), 6-chloro-1,2,3-benzothiadiazole (3.0 g, 17.6 mmol) and Decalin® (12 mL) was heated to 170ºC for 1 h and nitrogen evolved steadily. The mixture was then heated to 180ºC for 1 h. The solution was cooled and the solvent was removed in a stream of nitrogen overnight. The yellow residue was dissolved in carbon disulfide and absorbed onto Silica Woelm® TSC (20 g) and chromatographed on 250 g of the same silica (hexane eluent). After a 300 mL forerun, sulfur and residual decalin were eluted in 100 mL, then 4.59 g of sulfur and product were obtained in 750 mL. A 0.3 g sample was partially dissolved in hexane (10 mL) with stirring and portionwise addition of methylene chloride (10 mL). After 10 min, 0.07 g sulfur was decanted. The solution was purified by medium pressure liquid chromatography (Lobar® Silica gel 60, size C, hexane eluent) to give 0.07 g of 7-chlorobenzopentathiepin corresponding to a 22.5% yield. A 0.05 g sample was recrystallized from boiling hexane (20 mL concentrated to 5 mL, cooling and seeding) to give 40 mg of off-white solid, rap 87.5° to 89°C. A sample from a similar preparation had 1H-NMR (CDCl3, 80 MHz) δ 7.9-7.7 (d, 2H), 7.4-7.2 (m. lH); IR (KBr) 1095, 822 cm-1; Mass spec.: m/e 269.8517; m/e calcd for C6H3ClS5 269.8527.
Anal. Calcd for C6H3ClS5: C, 26.61; H. 1.12, S, 59.19. Found: C, 26.84; H, 1.22; S, 65.7, 56.01.
56.79 The difference between the calculated and found values for sulfur was ascribed to a temporary difficulty with the analysis.
EXAMPLE 3
7-Trifluoromethylbenzopentathiepin
A mixture of sulfur (1.34 g, 4.9 mmol). 6-trifluoromethyl-1,2,3-benzothiadiazole (1.0 g, 4.9 mmol) and Decalin® (10 mL) was heated to 190°C for 45 min while nitrogen evolved. The mixture was cooled and stored overnight, then it was preadsorbed and chromatographed on Silica Woelm® TSC (400 g. hexane) to give 1.36 g of a sulfur-product mixture. This mixture was triturated with hexane (40 mL), decanting from sulfur. The solution was purified by medium pressure liquid chromatography (Lobar® Silica gel 60, size C) in 2 portions to give 0.46 g, 31% of 7-trifluoromethylbenzopentathiepin as a yellow oil which solidified on standing. A sample prepared by a similar procedure melted at 44° to 50ºC. A sample recrystallized from hexane had mp 59° to 60°C; 1H-NMR (CDCl3) δ 8.18 (d. J=2Hz. 1H), 8.0 (d. J=8Hz, lH), 7.55 (dd, J=2, 8Hz, 1H); IR(KBr) 1320 cm-1; Mass spec: m/e 303.8788; calcd m/e for C7H3F3S5 303.8790.
Anal, calcd for C7H3F3S5: C, 27.62; H, 0.99; S, 52.66. Found : C, 27 .92 ; H. 0.94 ; S . 51.75
C. 28 . 14 ; H, 1. 10 ; S , 51 . 98 EXAMPLE 4
7-Dimethylaminobenzopentathiepin
A mixture of sulfur (0.72 g, 2.79 mmol). 5-dimethylamino-1.2,3-benzothiadiazole (0.5 g, 2.79 mmol) and Decalin® (5 mL) was heated to 170°C for 1.5 h with steady evolution of nitrogen. The solution was cooled and the Decalin® was removed by Kugelrohr distillation at 50ºC (0.3 mm). The residue was preadsorbed (5 g) and chromatographed (100 g) on Silica Woelm® TSC (1% ether-hexane) giving first sulfur and then 0.32 g (40%) of 7-dimethylaminobenzo pentathiepin, mp 115° to 118°C; Hl-NMR (CDCl3. 80 MHz) δ 7.55 (d. J=8.5 Hz. 1H), 7.0 (d. J=2.7Hz, lH), 6.5 (dd. J=8.5,2.7Hz. 1H), 3.0 (s, 6H);
IR(KBr)1583 cm-1; Mass spec.: m/e 278.9343, calcd m/e for C8H9NS5 278.9338. An 80 mg sample was recrystallized from boiling ethanol (50 mL filtered and concentrated to 20 mL) to give 70 mg of bright yellow crystals, mp 121.5° to 122.5°C.
Anal, calcd for C8H9NS5: C.34.38; H. 3.25; S, 57.36.
Found: C, 34.21; H, 3.42; S, 56.99.
EXAMPLE 5 7-Methoxybenzopentathiepin
A mixture of sulfur (0.77 g, 3.01 mmol), 5-methoxy-1,2,3-benzothiadiazole (0.5 g, 3.01 mmol) and Decalin® (5 mL) was heated to 170ºC for 1.5 h. The solution was cooled and the Decalin® was removed by Kugelrohr distillation at 50°C (0.3 mm). The residue was preadsorbed (5 g) and chromatographed (100 g) on Silica Woelm® TSC (1% ether-hexane) to give first sulfur and then 0.27 g of 7-methoxybenzopentathiepin as a light yellow solid, mp 90° to 95°C. The sample was further purified by high pressure liquid chromatography (Zorbax® Sil, 25% methylene chloride-hexane) to give 0.17 g, 21% of the product, mp 97° to 98ºC; IR(KBr) 1577, 1291, 1229, 1037 cm-1; Mass spec: m/e 265.9011, m/e calcd for C7H6OS5 265.9022. A sample prepared by a similar procedure had H-NMR (CDCl3, 80 MHz) δ 7.75 (d, J=8.3Hz, 1H), 7.3 (d, J=2.7Hz, 1H). 6.8 (dd, J=2.7, 8.3Hz, 1H), 3.85 (s, 3H).
EXAMPLE 6
6-Bromobenzopentathiepin
A mixture of sulfur (2.4 g, 9.3 mmol), 4-bromo-1,2,3-benzothiadizole (2.0 g, 9.3 mmol) and
Decalin® (20 mL) was heated to 175°C for 1.25 h and nitrogen was evolved. The mixture was cooled and the solvent was removed by Kugelrohr distillation. The residue was preadsorbed and chromatographed (300 g) on Silica Woelm® TSC (1%. ether-hexane) to give first sulfur and then 2.2 g of a sulfur-product mixture.
The mixture was purified by high pressure liquid chromatography (Zorbax® Sil, hexane) to give 0.43 g,
14.6% of 6-bromobenzopentathiepin. retention time = 5.12 min. mp 93° to 98°C; IR(KBr) 788 cm-1; Mass spec: m/e 313.8036, m/e calcd for C6H3BrS5
313.8021.
A compound prepared similarly and recrystallized from hexane had a mp of 101° to 101.5°C; NMR (CDCl3, 360 MHz) δ 7.78 (dd, J=1.3,
8.0 Hz, 1H) 7.66 (dd, J=1.3, 8.0Hz, 1H) 7.12 (t,
J=8.0Hz, 1H).
Anal. calcd for C 6H3BrS5: C=22.86;
H=0.96 Found: C=23.53; H, 1.04
C=23.09; H, 0.94. EXAMPLE 7 6-Trifluoromethylbenzopentathiepin
A mixture of sulfur (0.65 g, 2.45 mmol), 4-trifluoromethyl-1,2,3-benzothiadiazole (0.5 g, 2.45 mmol) and Decalin® (5 mL) was heated to 180ºC for 3 h and nitrogen was slowly evolved. The mixture was cooled and the solvent was removed by Kugelrohr distillation. The residue was preadsorbed and chromatographed (100 g) on Silica Woelm® TSC (1% ether-hexane) giving first sulfur and then 0.55 g of a sulfur-product mixture. The mixture was purified by high pressure liquid chomatography (Zorbax® sil, hexane) to give 0.15 g, 20% of 6-trifluoromethylbenzopentathiepin as a light yellow solid, mp 55º to 60°C. retention time = 5.26 min, IR(KBr) 1310, 1137, 1129, 1119 cm-1; Mass spec.: m/e 303.8748, m/e calcd for C7H3F3S5 303.8791. A compound prepared similarly and recrystallized from hexane had a mp of 61° to 62°C. Anal. Calcd for C7H3F3S5: C=27.62; H=0.99
Found: C, 27.89; H, 1.06 C, 27.65; H, 1.03.
EXAMPLE 8
A mixture of sulfur (1.88 g, 7.3 mmol), 1,2,3-benzothiadiazole (1.0 g. 7.3 mmol), 1,4-diazabicγclo[2.2.2]octane (0.82 g, 7.3 mmol) and Decalin® (10 mL) was heated to 170°C for 1.5 h while nitrogen was evolved. The mixture was cooled and the solvent was removed by Kugelrohr distillation. The residue was chromatographed on Silica Woelm® TSC (200 g, 1% ether-hexane). The fraction containing the product was further purified by high pressure liquid chromatography to give 0.94 g, 54%, of benzopentathiepin.
EXAMPLE 9
A mixture of sulfur (1.2 g, 4.65 mmol), 4-bromo-1,2,3-benzothiadiazole (1.0 g, 4.65 mmol), 1,4-diazacyclo[2.2.2]octane (0.52 g. 4.65 mmol), and Decalin® (10 mL) was heated at 170°C for 1.25 h. The mixture was cooled and the solvent was removed by Kugelrohr distillation. The residue was chromatographed on silica Woelm® TSC (200 g, 1% ether-hexane). The fraction containing a sulfur-product mixture was further purified by high pressure liquid chromatography (Zorbax® Sil, hexane) to give 0.33 g, 22.6%, of 6-bromobenzopentathiepin. EXAMPLE 10
A mixture of sulfur (0.77 g, 3.01 mmol), 5-methoxy-1,2,3-benzothiadiazole (0.5 g. 3.01 mmol), 1,4-diazabicyclo[2.2.2]octane (0.34 g. 3.01 mmol) and Decalin® (5 mL) was heated to 170°C for 1.25 h. The mixture was cooled and the solvent was removed by Kugelrohr distillation. The residue was chromatographed on Silica Woelm® TSC (200 g, 1% ether-hexane) to give first sulfur and then 0.46 g, 57%, of 7-methoxybenzopentathieρin.
EXAMPLE 11 4-Trifluoromethyl-1,2,3-Benzothiadiazole
First, 4-bromo-1,2,3-benzothiadiazole (5.0 g, 23.2 mmol) was dissolved in N-methylpyrrolidinone (200 mL) and then sodium trifluoroacetate (8.5 g. 62.5 mmol) and cuprous iodide (8.75 g, 46 mmol) were added. The mixture was heated to 160ºC for 4 h (gentle CO2 evolution), cooled, and diluted carefully with water (300 mL). The slurry was filtered through Celite® (diatomaceous earth) and the pad was rinsed with ether (3x250 mL). The filtrate phases were separated and the organic layer was washed with water and brine; then it was filtered through a cone of calcium sulfate and concentrated. The crude product was chromatographed on Silica Woelm® TSC (500 g, 15% ether-hexane) to give first a mixture of 4-bromo and 4-iodo and 4-trifluoromethyl1,2,3-benzothiadiazoles followed by pure
4-trifluoromethyl-1,2,3-benzothiadiazole. The mixed fraction was rechromatographed on the same column to give additional pure product. In this manner. 3.19 g. 67%. of 4-trifluoromethyl-1,2,3-benzothiadiazole was obtained as an off-white solid. A sample prepared by a similar procedure had mp 41° to 44°C; 19F NMR (CDCl3) -58.78 (s). A sample further purified by sublimation at 45°C (35-50 mm-water aspirator) had mp 49° to 51°C; 1H-NMR (CDCl3) δ 8.35 (d, J=8Hz, 1H), 8.0 (d, J=8Hz, IH), 7.8 (t, J=8Hz, 1H); IR(KBr) 1319, 1152, 1122, 1089 cm-1.
Anal, calcd for C7H3F3N2S: C, 41.18; H, 1.48; N, 13.72.
Found: C. 41.13; H, 1.37; N, 13.96. EXAMPLE 12
6-Trifluoromethyl-1,2,3-Benzothiadiazole
First, 2-chloro-4-trifluoromethylnitrobenzene (20 g, 88.6 mmol) was dissolved in dimethylsulfoxide (100 mL, dried over molecular sieves) under a nitrogen atmosphere and then anhydrous sodium sulfide (6.92 g, 88.6 mmol) was added all at once. The mixture warmed to about 40°C and was stirred for 2 h. The red mixture was poured into a solution of brine (300 mL) and 6N HCl (100 mL) and extracted with methylene chloride (3x100 mL). The combined organic phase was filtered through a cone of sodium sulfate and concentrated to leave 18.46 g of yellow solid.
Nitrogen was bubbled through deionized water (400 mL) for 15 min. then the above yellow solid and ammonium hydroxide (90 mL) were added. Sodium hydrosulfite (90 g) was dissolved in deionized water (400 mL) and added to the mechanically stirred reaction over 10 to 15 min via an addition funnel. The resulting solution was warmed to 50°C for 3 h. then stirred overnight at ambient temperature. The mixture was acidified to pH 7 with acetic acid and extracted with ether (3x200 mL). The combined organic layer was washed with brine and filtered through a cone of calcium sulfate into a flask equipped with mechanical stirring and a gas inlet. Hydrogen chloride was bubbled through the stirred solution for 1.5 h. The solid was filtered, rinsed with dry ether and dried in vacuo to give 8.96 g of hydrochloride salt, mp 184° to 188°C; IR (KBr) 1330 cm-1.
The above salt was slurried in 5% aqueous HCl (100 mL) and chilled to 0°C. A solution of sodium nitrite (3.22 g) in water (15 mL) was added dropwise over 20 min to the stirred mixture; then it was neutralized to pH 9 with 20% aqueous sodium hydroxide. The reaction was extracted with ether (3 x100 mL) and the organic phase was washed with water and brine and then filtered through a cone of sodium sulfate. Concentration left 6.94 g of a brown oil which was chromatographed on Silica Woelm® TSC (250 g, 10% ether-hexane) to give (after a 350 mL forerun) a trace of impurity in 250 mL and then 2.35 g of 6-trifluoromethyl-1,2,3-benzothiadiazole in 150 mL of eluent. A sample sublimed at 25°C (0.15 mm) had mp 36° to 40°C; 1H-NMR (CDCl3, 90 MHz) δ 8.9 (m, IH). 8.25 (dd. IH). 7.9 (ddd, IH); IR (KBr) 1332. 1294. 1192, 1150. (sh) 1129 cm-1. A sample prepared by a similar procedure had mp 40° to 42°C.
Anal, calcd for C7H3F3N2S: C, 41.18; H. 1.48; N, 13.72.
Found: C, 41.31; H, 1.51; N, 13.56. 40.95 1.73 13.82. EXAMPLE 13
3.4-Bis(methylthio)-N-N-dimethylaniline
This Example illustrates the making of a compound useful (as the unprotected dithiol) as a rubber cross-linking agent. First,
7-dimethylaminobenzopentathiepin (0.5 g. 1.79 mmol) was dissolved in tetrahydrofuran (50 mL) and ethanol (50 mL) was added. Sodium borohydride (0.34 g, 8.96 mmol) was added to the stirred solution at ambient temperature over 5 min (after a short induction time hydrogen gas was evolved and the solution warmed slightly). When the foaming ceased in about 15 min, water (10 mL) was added and the mixture was warmed to 50°C for 5 min followed by cooling to ambient temperature and addition of methyl iodide (0.62 mL, 10 mmol). After stirring 30 min more, the solvent was removed and the residue was partitioned between water and ether. The phases were separated and the organic phase was washed with brine and dried through a cone of sodium sulfate. Concentration gave a yellow oil which was chromatographed on Silica Woelm® TSC (50 g, 20% ether-hexane) to give 0.33 g, 86%, of 3.4-bis(methylthio)-N,N-dimethylaniline as a yellow oil which crystallized on standing, mp 49° to 51°C; IR (neat) 1583 cm-1; 1H-NMR (CDCl3, 80 MHz) δ 7.22 (d. J=9.3 Hz, 1H). 6.49 (d. partially obscured. J=2.9Hz, 1H), 6.4 (dd. partially obscured, J=2.9. 9.3 Hz, 1H), 2.95 (s. 6H). 2.46 (s. 3H). 2.38 (s. 3H). Anal, calcd for C10H15NS2: C, 56.30; H, 7.09.
Found: C, 56.69; H, 6.93.
C. 56.72; H, 6.96. EXAMPLE 14 3,4-Bis(methylthio)-chlorobenzene
This Example illustrates the making of a compound useful as an intermediate (as the unprotected dithiol) to a tricyclic psychotropic agent. First, 7-chlorobenzopentathiepin (0.32 g, 1.18 mmol) was dissolved in tetrahydrofuran (30 mL) and ethanol (30 mL) was added. Sodium borohydride (0.22 g, 5.91 mmol) was added over 5 min in portions at ambient temperature causing the solution to evolve hydrogen gas and warm slightly. After gas evolution had ceased in about 15 min, water (10 mL) was added and the mixture was heated to about 50°C for 5 min and cooled to ambient temperature. Methyl iodide (0.44 mL, 7.0 mmol) was added and the solution was stirred. The solvents were removed and the residue was partitioned between ether and water. The phases were separated and the organic layer was washed with brine and dried through a cone of sodium sulfate. Concentration left an oil which was chromatographed on Silica Woelm® TSC (50 g, 10% ether-hexane) to give 0.16 g, 67%, of 3,4-bis(methylthio)chlorobenzene as a clear pale yellow oil; 1Η-NMR (CDCl3, 90 MHz) δ 7.1 (s, 3H), 2.46 (s, 3H), 2.44 (s, 3H), 1.4 (small impurity); IR (neat) 1448. 1430, 1029, 801 cm-1; Mass spec: m/e 203.9852, m/e calcd for C8H9ClS2 203.9834.
EXAMPLE 15 4,5-Bis(dimethylamino)-1,2,3-benzothiadiazole
A 3 necked round bottom flask fitted with magnetic stirrer, condenser, static nitrogen atmosphere and a septum was charged with sodium hydride (0.35 g, 50% mineral oil dispersion. 7.2 mmol). The oil was rinsed away with dry hexane (3 times using standard syringe technique) then dry tetrahydrofuran (20 mL) was added. To the slurry was added 4,5-diamino-1,2,3-benzothiadiazole (0.2 g, 1.2 mmol) neat over 5 min. Finally, methyl iodide (0.75 mL. 12 mmol) was added and the mixture was stirred at ambient temperature for 72 h. The mixture was cautiously quenched with water, the solvent was stripped off, and methylene chloride was added to the residue. After extraction of this organic phase with water and brine, it was filtered through a cone of sodium sulfate and concentrated onto silica gel.
Chromatography on silica gel (5% ether-hexane) gave
0.11 g (41%) of 4,5-bis(dimethylamino)-1,2,3benzothiadiazole as an orange oil: NMR (90 MHZ) δ 7.38 (ABq Δv1-3 = 18 Hz, J = 8Hz, 2H), 3.26 (s, 6H), 2.8 (s, 6H); IR (neat) 2980-2780 (multiplet. m) 1542, 1495 cm-1; exact mass calcd for
C10H14N4S; M/e 222.0939, observed M/e 222.0950.
EXAMPLE 16 6,7-Bis(dimethylamino)benzopentathiepin
A magnetically stirred mixture of 4,5-bis(dimethylamino)-1,2,3-benzothiadiazole (2.0 g. 9.0 mmol), sulfur (2.3 g, 9.0 mmol) and decalin (30 mL) was heated to 175°C under a static nitrogen atmosphere for 1.5 h. During this time, nitrogen-evolution was steady. The mixture was cooled to ambient temperature and the decalin was removed by kugelrohr distillation. The residue was chromatographed on silica gel (1% ether-hexane) to give 2.04 g (70%) of 6,7-bis(dimethylamino)benzopentathiepin. A 1 g sample was recrystallized from 100 mL of hexane by chilling to -78°C to give 0.7 g of bright orange solid: mp 59.5° to 61°C. Anal. Calcd for C10H14N2S5; C, 37-24; H, 4.38; Found: C, 37.45; H, 4.66. A sample prepared by a similar procedure had: NMR (80 mHz) δ 7.15 (ABq Δυ1- 3 - 59 Hz, J = 8.5Hz, 2H), 2.9 (s. 6H), 2.8 (s, 6H).

Claims

CLAIMS :
The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows: 1. A benzopentathiepin compound of the formula
wherein R 1, R2 and R3 are the same or different and are selected from H (provided no more than two of R 1, R2 and R3 are H), X, CX3,
NO , SR4, OR4, NR4 2, OCR4, COR4, CR4, CNR4 2, aryl and substituted aryl; R4 is selected from aryl, substituted aryl, and substituted and unsubstituted branched or straight chain Cl to C 6 alkyl; and
X is selected from Cl. Br and F.
2. A compound according to Claim 1 wherein R 1 and R3 are both H and R2 is selected from X, CX3, SR 4, OR4, NR4 2, COOR4, aryl and substituted aryl.
3. A compound according to Claim 2 wherein R2 is selected from N(CH3)2, OCH3, CF3, and Cl.
4. A compound according to Claim 1 wherein
R 2 and R3 are both H and R1 is selected from X. CX3, SR4, OR4, NR4 2, COOR4, aryl and substituted aryl.
5. A compound according to Claim 4 wherein
R1 is selected from CF3 and Br.
6. A compound according to Claim 3, 7-trifluoromethylbenzopentathiepin.
7. A compound according to Claim 3, 7-dimethylaminobenzopentathiepin. 8. A compound according to Claim 3,
7-methoxybenzopentathiepin.
9. A compound according to Claim 5, 6-trifluoromethylbenzopentathiepin.
10. A compound according to Claim 3, 7-chlorobenzopentathiepin.
11. A compound according to Claim 5, 6-bromobenzopentathiepin.
12. A compound,
4-trifluoromethyl-1,2,3-benzothiadiazole. 13. A compound,
6-trifluoromethyl-1,2,3-benzothiadiazole.
14. A method for making compounds of the formula
wherein R1, R 2 and R3 are the same or different and are selected from H, X, CX3, NO2, SR4, OR4, aryl and substituted aryl; R4 is selected from aryl. substituted aryl, and substituted and unsubstituted branched or straight chain C 1 to C 6 alkyl ; and X is selected from Cl , Br and F ; compris ing reacting a benzothiadiazole of the formula
with S8 at elevated temperature in a solvent inert to S8 at a molar ratio of S8 to benzothiadiazole of about 1:2 to 2:1.
15. A method according to Claim 14 wherein the solvent is selected from one or a mixture of decahydronaphthalene, nitrobenzene, dichlorobenzene, dimethylformamide, and dimethyl sulfoxide, and the temperature is about 140° to 200°C.
16. A method according to Claim 15 wherein the temperature is 160° to 190°C and the ratio of
S8 to benzothiazole is about 1:1. 17. A method according to Claim 14 conducted in the presence of 1,4-diazabicyclo[2.2.2]octane.
18. A method according to Claim 15 conducted in the presence of 1,4-diazabicyclo[2.2.2]octane.
19. A method according to Claim 16 conducted in the presence of 1,4-diazabicyclo[2.2.2]octane.
20. A method according to Claim 17 wherein the ratio of 1,4-diazabicyclo[2.2.2]octane to benzothiadiazole is 0.1:1 to 2:1.
21. A method according to Claim 18 wherein the ratio of 1,4-diazabicyclo[2.2.2]octane to benzothiadiazole is 0.1:1 to 2:1.
22. A method according to Claim 19 wherein the ratio of 1,4-diazabicyclo[2.2.2]octane to benzothiadiazole is 0.1:1 to 2:1.
23. A method for making a 1,2-benzenedithiol of the formula
comprising reducing a benzopentathiepin of the formula
wherein
R1, R2 and R3 are the same or different and are selected from H, X, CX3 NO 2, SR 4,
OR4, aryl and substituted aryl; R4 is selected from aryl, substituted aryl and substituted and unsubstituted branched or straight chain C1 to C6 alkyl; and
X is selected from Cl, Br and F.
24. A method according to Claim 23 wherein the reducing agent is selected, from at least one member of the group sodium borohydride, lithium aluminum hydride, trialkyl phosphite, and zinc/aqueous acid, the reaction conducted in the presence of a solvent at about 0° to 60°C.
25. A method according to Claim 24 wherein the reducing agent is sodium borohydride and the ratio thereof to benzopentathiepin is from about 2:1 to 6:1. 26. A method according to Claim 24 wherein the reducing agent is lithium aluminum hydride and the ratio thereof to benzopentathiepin is from about 2:1 to 6:1.
27. An anti-fungal formulation comprising an effective amount of a compound according to Claim 1.
28. A formulation according to Claim 27 wherein the compound is
7-trifluoromethylbenzopentathiepin.
29. A formulation according to Claim 27 wherein the compound is
7-dimethylaminobenzopentathiepin.
30. A formulation according to Claim 27 wherein the compound is 7-methoxybenzopentathieρin.
31. A formulation according to Claim 27 wherein the compound is
6-trifluoromethylbenzopentathiepin.
32. An anti-viral formulation comprising an effective amount of a compound according to Claim 1.
33. A formulation according to Claim 32 wherein the compound is
7-dimethylaminobenzopentathiepin.
34. A plant disease control formulation comprising an effective amount of a compound according to Claim 1. 35. A compound according to Claim 1 wherein R1 and R2 are both NR4 2 and R3 is H.
36. A compound according to Claim 35 wherein R4 is methyl.
37. A compound, 4,5-bis(dimethylamino)1,2,3-benzothiadiazole.
EP19840902416 1983-06-08 1984-06-07 Substituted benzopentathiepins, process therefor and intermediates. Withdrawn EP0146610A4 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US50223183A 1983-06-08 1983-06-08
US502231 1995-07-13

Publications (2)

Publication Number Publication Date
EP0146610A1 EP0146610A1 (en) 1985-07-03
EP0146610A4 true EP0146610A4 (en) 1986-02-20

Family

ID=23996915

Family Applications (1)

Application Number Title Priority Date Filing Date
EP19840902416 Withdrawn EP0146610A4 (en) 1983-06-08 1984-06-07 Substituted benzopentathiepins, process therefor and intermediates.

Country Status (7)

Country Link
EP (1) EP0146610A4 (en)
JP (1) JPS60501503A (en)
AU (1) AU3016084A (en)
DK (1) DK56985D0 (en)
FI (1) FI844675L (en)
HU (1) HUT35926A (en)
WO (1) WO1984004921A1 (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE496868A (en) * 1949-07-26
US4594453A (en) * 1984-06-11 1986-06-10 Ethyl Corporation Process for preparing (hydrocarbylthio)aromatic amines
JP2600122Y2 (en) * 1992-05-15 1999-10-04 株式会社アクロス Carbon fiber carbon composite firing chain
RU2581060C1 (en) * 2014-09-30 2016-04-10 Федеральное государственное бюджетное учреждение науки Институт химической биологии и фундаментальной медицины Сибирского отделения Российской академии наук (ИХБФМ СО РАН) Agent for inhibiting human tyrosyl-dna-phosphodiesterase 1 enzyme

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR1553701A (en) * 1967-05-19 1969-01-17
US3686329A (en) * 1969-11-25 1972-08-22 Stauffer Chemical Co Process for preparing organic thiols from polysulfides
US4104467A (en) * 1976-07-16 1978-08-01 E. R. Squibb & Sons, Inc. 1,3-Benzodithiolanes
US4094985A (en) * 1976-10-13 1978-06-13 E. I. Du Pont De Nemours And Company Fungicidal isothiazoles

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
No relevant documents have been disclosed *
See also references of WO8404921A1 *

Also Published As

Publication number Publication date
EP0146610A1 (en) 1985-07-03
AU3016084A (en) 1985-01-04
WO1984004921A1 (en) 1984-12-20
JPS60501503A (en) 1985-09-12
DK56985A (en) 1985-02-07
HUT35926A (en) 1985-08-28
FI844675A0 (en) 1984-11-28
FI844675A7 (en) 1984-12-09
FI844675L (en) 1984-12-09
DK56985D0 (en) 1985-02-07

Similar Documents

Publication Publication Date Title
US6541630B1 (en) Fungicides
EP0345775A1 (en) Oxa- or thia-zoline derivative
EP0238059A2 (en) 5H-1,3,4-Thiazole[3,2-a]pyrimidin-5-one derivatives and fungicidal compositions containing the same
EP0712853A1 (en) Pyrazole derivative
US4729986A (en) Fungicidal triazoles and imidazoles
EP0432892B1 (en) Imidazole fungicides
FR2460936A1 (en) PYRIDAZINE DERIVATIVES AND THEIR APPLICATION AS FUNGICIDES
WO1984004921A1 (en) Substituted benzopentathiepins, process therefor and intermediates
EP0517476B1 (en) Benzimidazole derivatives, a method for producing the same, agricultural and horticultural fungicides containing the same as an active ingredient and intermediate compounds thereof
US4786739A (en) Substituted benzopentathiepins, process therefor and intermediates
US3660421A (en) 1-carbamoyl-2-carbalkoxyamino-benzimidazoles
US4571404A (en) Substituted benzopentathiepins
EP0103114A2 (en) Thienopyridine derivatives, their preparation and insecticidal and acaricidal compositions containing them
EP0407621B1 (en) Benzothiazole derivatives as fungicide
GB1564182A (en) Benzothiazolone and benzoxazolone derivatives
EP0286006B1 (en) Thiadiazole derivative, and insecticidal and miticidal composition containing the derivative as the effective ingredient
EP0138622A2 (en) 8-substituted pyrazolopentathiepins and related compounds
EP0122761B1 (en) Herbicidal tetrahydrobenzothiazole derivatives
US4225615A (en) Insecticidal and nematicidal carbamates
EP0238997B1 (en) Agricultural-horticultural fungicide
US4795817A (en) 8-substituted pyrazolopentathiepins and related compounds
NO850249L (en) SUBSTITUTED BENZOPENTATE HYPINES, PROCEDURE FOR PRODUCING THESE AND INTERMEDIATES THEREOF
US2851391A (en) Processes and products
CA1110648A (en) Insecticidal and nematicidal carbamates
US4268520A (en) Insecticidal and nematicidal carbamates

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 19850121

AK Designated contracting states

Designated state(s): AT BE CH DE FR GB LI LU NL SE

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION HAS BEEN WITHDRAWN

A4 Supplementary search report drawn up and despatched

Effective date: 19860220

18W Application withdrawn

Withdrawal date: 19851120

RIN1 Information on inventor provided before grant (corrected)

Inventor name: CHENARD, BERTRAND, LEO