NO850249L

NO850249L - SUBSTITUTED BENZOPENTATE HYPINES, PROCEDURE FOR PRODUCING THESE AND INTERMEDIATES THEREOF

Info

Publication number: NO850249L
Application number: NO850249A
Authority: NO
Inventors: Bertrand Leo Chenard
Original assignee: Du Pont
Priority date: 1983-06-08
Filing date: 1985-01-21
Publication date: 1985-01-21

Description

Kryssreferanse til beslektet søknadCross reference to related application

Foreliggende søknad er en continuation-in-part av US The present application is a continuation-in-part of US

patentsøknad 502 231 innlevert 8. juni 1983.patent application 502,231 filed June 8, 1983.

Foreliggende oppfinnelse angår substituerte benzopentathiepiner, 1,2,3-benzothiadiazol-mellomprodukter og fremgangsmåte for fremstilling av de førstnevnte ved omsetning av de sistnevnte med elementært svovel. The present invention relates to substituted benzopentathiepines, 1,2,3-benzothiadiazole intermediates and a method for producing the former by reacting the latter with elemental sulphur.

Usubstituert benzopentathiepin er kjent (Feher et al., Z. Anorg. Allg. Chem., 452, 37 til 42 (1979); Feher et al., Tet. Lett., 2125 til 2126 (1971). Det fremstilles fra 1,2-benzendithiol og S^C^. Ingen anvendelse er beskrevet. Unsubstituted benzopentathiepine is known (Feher et al., Z. Anorg. Allg. Chem., 452, 37 to 42 (1979); Feher et al., Tet. Lett., 2125 to 2126 (1971). It is prepared from 1, 2-benzenedithiol and S^C^ No application is described.

Feher et al., i Naturforsch. B, 27, 1006 (19 72), beskriver fremstilling av 7,8-dimethylderivatet ved en lignende metode. Feher et al., in Naturforsch. B, 27, 1006 (1972), describes the preparation of the 7,8-dimethyl derivative by a similar method.

Et redusert hexahydrobenzopentathiepin ble fremstilt av Feher et al. i henhold til metoden ifølge Feher et al. som ovenfor beskrevet: Angew. Chem. Int. Ed., 6, 703 (1967). Nametkin et al., i Izv. Akad. Nauk. SSSR, Ser. Khim., 12, 2841 (1980), beskriver en metode for fremstilling av angitte reduserte pentathiepiner ved anvendelse av et organo-jern-kompleks. A reduced hexahydrobenzopentathiepine was prepared by Feher et al. according to the method of Feher et al. as above described: Angew. Chem. Int. Ed., 6, 703 (1967). Nametkin et al., in Izv. Acad. Nauk. USSR, Ser. Khim., 12, 2841 (1980), describes a method for the preparation of indicated reduced pentathiepines using an organo-iron complex.

Watkins et al., J. Het. Chem., 19, 459 til 462 (1982), beskriver røntgenkrystallstrukturen av et komplekst inden-pentathiepin. Syntese og anvendelse er ikke beskrevet. Watkins et al., J. Het. Chem., 19, 459 to 462 (1982), describes the X-ray crystal structure of an indene-pentathiepine complex. Synthesis and application are not described.

Et utall av heterocycliske pentathiepiner er kjent. A number of heterocyclic pentathiepines are known.

Eksempelvis beskriver US patentskrift 4 094 985 følgende som For example, US patent document 4,094,985 describes the following as

fungicider: fungicides:

hvori X er CN eller etc. US patentskrift 4 275 073 beskriver disse pyrazolopentathiepiner som fungicider: wherein X is CN or etc. US Patent 4,275,073 describes these pyrazolopentathiepines as fungicides:

hvori R = H, C^Cg-alkyl, C^Cg-cycloalkyl,~CH20, -Ar. Begge patenter beskriver fremgangsmåter under anvendelse av en thiol eller dithiol og S2Cl2. De substituerte benzopentathiepiner ifølge oppfinnelsen kan ikke fremstilles etter wherein R = H, C 1 -C 8 -alkyl, C 1 -C 8 -cycloalkyl, -CH 2 O, -Ar. Both patents describe methods using a thiol or dithiol and S2Cl2. The substituted benzopentathiepines according to the invention cannot be prepared after

teknikker kjente fra litteraturen.techniques known from the literature.

Visse 1,2,3-benzothiadiazoler er kjente, og deres syntese er blitt beskrevet av Kurzer i "Org. Cmpd. of Sulphur, Selenium, Tellurium", Royal Society of Chemistry, London, vol. 1 til 6 (1970 til 1980) . En typisk syntese er diazoter-ing av en o-aminobenzenthiol som følger: Certain 1,2,3-benzothiadiazoles are known and their synthesis has been described by Kurzer in "Org. Cmpd. of Sulphur, Selenium, Tellurium", Royal Society of Chemistry, London, vol. 1 to 6 (1970 to 1980). A typical synthesis is the diazotization of an o-aminobenzenethiol as follows:

I Oae, "Organic Chemistry of Sulfur", side 346 til 348, Plenum Press, N.Y. (1977), er det beskrevet forskjellige måter for å redusere disulfider til thioler. Reagenser for disse reduksjoner innbefatter natriumborhydrid, lithiumaluminiumhydrid, natriumamalgam, sink eller tinn med vandig syre, fosfiner og fosfitter. In Oae, "Organic Chemistry of Sulphur", pages 346 to 348, Plenum Press, N.Y. (1977), various ways of reducing disulfides to thiols are described. 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 til 3989 Cairns et al., J. Am. Chem. Soc, 74, 3982 to 3989

(1952), beskriver reduksjonen av et lineært tetrasulfid med lithiumaluminiumhydrid. Det finnes imidlertid ingen kjent teknikk som beskriver reduksjon av et pentathiepin under dannelse av en dithiol. 1,2-benzendithiolene kan fremstilles ved pyrolyse av benzothiadiazoler i nærvær av carbondisulfid og alkalisk hydrolyse av trithiocarbonat-mellomproduktet: Hunig et al., Liebigs Ann. Chem., 738, 192 til 194 (1970). Fremgangsmåten krever et trykkar og temperaturer på 220°C. (1952), describes the reduction of a linear tetrasulfide with lithium aluminum hydride. However, there is no known technique that describes the reduction of a pentathiepine to form a dithiol. The 1,2-benzenedithiols can be prepared by pyrolysis of benzothiadiazoles in the presence of carbon disulfide and alkaline hydrolysis of the trithiocarbonate intermediate: Hunig et al., Liebigs Ann. Chem., 738, 192 to 194 (1970). The procedure requires a pressure vessel and temperatures of 220°C.

Sammendrag av oppfinnelsenSummary of the invention

Foreliggende oppfinnelse angår nye substituerte benzopentathiepiner av formel: The present invention relates to new substituted benzopentathiepines of the formula:

12 3 12 3

hvori R , R og R er like eller forskjellige substituenter som ikke reagerer med svovel ved forhøyede temperaturer og er valgt fra H (ikke mer enn to avR<1>, R<2>og R<3>er H), X, wherein R , R and R are the same or different substituents which 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> are H), X,

CX3. N02. SR4. OR4. NR4. CX3. N02. SR4. OR4. NR4.

og substituert aryl; and substituted aryl;

R 4er valgt fra aryl, substituert aryl og substituert og usubstituert, forgrenet eller rettkjedet C1 , - Cb,-alkyl; og X er valgt fra Cl, Br og F. R 4 is selected from aryl, substituted aryl and substituted and unsubstituted, branched or straight chain C 1 , - C 6 -alkyl; and X is selected from Cl, Br and F.

12 3 12 3

Det primære krav til R -, R -og R -substituentene er at disse er hovedsakelig ureaktive med svovel ved reaksjons-temperaturene. Flere grupper av slike substituenter er gitt som eksempler uten den hensikt at oppfinnelsen skal være begrenset dertil. The primary requirement for the R -, R - and R -substituents is that these are mainly unreactive with sulfur at the reaction temperatures. Several groups of such substituents are given as examples without the intention that the invention should be limited thereto.

Substituentene på substituerte R<4->aryl- og alkylgrupper The substituents on substituted R<4->aryl and alkyl groups

er valgt fra X, CX^, OR, SR, is selected from X, CX^, OR, SR,

og COOR hvori R er aryl eller C^- C^, rettkjedet eller forgrenet alkyl. Foretrukne benzopentathiepiner ifølge oppfinnelsen er de hvori: (1) R<1>og R<3>begge er H og R<2>er valgt fra X, CX , SR<4>, OR<4>, 4 4 2 3 and COOR wherein R is aryl or C₁-C₁, straight or branched alkyl. Preferred benzopentathiepines according to the invention are those in which: (1) R<1> and R<3> are both H and R<2> is selected from X, CX , SR<4>, OR<4>, 4 4 2 3

NR2, COOR , aryl og substituert aryl; (2) R og R er begge H, og R1 er valgt fra X, CX , SR4, OR4, NR4 COOR4, aryl og 12 4 3 substituert aryl; og (3) R og R er begge NR2og R er H. Spesielt foretrukne forbindelser er de innen kategori (1) hvori R<2>er N(CH3)2, OCH3, CF3eller Cl; de i kategori (2) hvori R^"er CF, eller Br; og forbindelsen i kategori (3) hvori R 4er methyl. Den sistnevnte forbindelse angis som 6,7-bis-(dimethylamino)-benzopentathiepin. NR 2 , COOR , aryl and substituted aryl; (2) R and R are both H, and R 1 is selected from X, CX , SR 4 , OR 4 , NR 4 COOR 4 , aryl and 12 4 3 substituted aryl; and (3) R and R are both NR 2 and R is H. Particularly preferred compounds are those within category (1) wherein R<2> is N(CH 3 ) 2 , OCH 3 , CF 3 or Cl; those in category (2) in which R 4 is CF, or Br; and the compound in category (3) in which R 4 is methyl. The latter compound is designated as 6,7-bis-(dimethylamino)-benzopentathiepine.

Oppfinnelsen angår også en fremgangsmåte for fremstilling av benzopentathiepinene ved følgende reaksjon: The invention also relates to a method for producing the benzopentathiepines by the following reaction:

Reaksjonen utføres typisk i et inert løsningsmiddel ved en temperatur mellom 140 og 200°C, med 160 til 190°C som foretrukket. R 1 -, R 2 - og R 3-substituentene er som tidligere definert bortsett fra at den nye fremgangsmåte også innbe-12 3 fatter fremstilling av forbindelser hvori R = R = R = H. The reaction is typically carried out in an inert solvent at a temperature between 140 and 200°C, with 160 to 190°C being preferred. The R 1 -, R 2 - and R 3 -substituents are as previously defined except that the new method also includes the preparation of compounds in which R = R = R = H.

Egnede løsningsmidler er de som er inerte overfor elementært svovel og som tåler de temperatur- og trykkombina-sjoner som er nødvendige for å oppfylle det beskrevne temp-era turområde . Løsningsmidlene innbefatter, men er ikke begrenset til, decahydronafthaien, nitrobenzen, diklorbenzener, dimethylformamid og dimethylsulfoxyd. Reaksjonen utføres normalt i en inert atmosfære slik som nitrogen, argon, helium og lignende. Molarforholdet mellom elementært svovel (beregnet som Sg) og benzothiadiazol kan variere fra 1:2 til 2:1, hvor det foretrukne forhold er 1:1. Suitable solvents are those which are inert to elemental sulfur and which withstand the temperature and pressure combinations necessary to fulfill the described temperature range. Solvents include, but are not limited to, decahydronaphthalene, nitrobenzene, dichlorobenzenes, dimethylformamide, and dimethylsulfoxide. The reaction is normally carried out in an inert atmosphere such as nitrogen, argon, helium and the like. The molar ratio between elemental sulfur (calculated as Sg) and benzothiadiazole can vary from 1:2 to 2:1, with the preferred ratio being 1:1.

Oppfinnelsen angår også en fremgangsmåte for fremstilling av angitte benzopentathiepiner i nærvær av 1,4-diaza-bicyclo[2.2.2]octan (DABCO): The invention also relates to a process for the production of specified benzopentathiepines in the presence of 1,4-diaza-bicyclo[2.2.2]octane (DABCO):

Molarforholdet mellom DABCO og benzothiadiazol er 0,1:1 til 2:1, hvor det foretrukne forhold er 1:1. Anvendelse av DABCO ved fremgangsmåten ifølge oppfinnelsen er blitt funnet å øke produktutbyttene betydelig. The molar ratio of DABCO to benzothiadiazole is 0.1:1 to 2:1, with the preferred ratio being 1:1. Use of DABCO in the method according to the invention has been found to increase product yields significantly.

Foreliggende oppfinnelse angår også disse nye benzothiadiazoler: The present invention also relates to these new benzothiadiazoles:

Oppfinnelsen angår også en fremgangsmåte for fremstilling av substituerte 1,2-benzendithioler ved reduksjon av benzopentathiepiner etter reaksjonsligningen: The invention also relates to a process for the production of substituted 1,2-benzenedithiols by reduction of benzopentathiepines according to the reaction equation:

hvori R 1, R 2 og R 3er som ovenfor definert, innbefattende 12 3 H. wherein R 1 , R 2 and R 3 are as defined above, including 12 3 H.

Egnede reduksjonsmidler for angitte fremgangsmåte innbefatter, men er ikke begrenset til, natriumborhydrid, lithiumaluminiumhydrid, trialkylfosfitter, sink/vandig syre og lignende. Natriumborhydrid og lithiumaluminiumhydrid er foretrukne. Reaksjonstemperaturen kan være fra 0 til 60°C, Suitable reducing agents for the stated process include, but are not limited to, sodium borohydride, lithium aluminum hydride, trialkyl phosphites, zinc/aqueous acid and the like. Sodium borohydride and lithium aluminum hydride are preferred. The reaction temperature can be from 0 to 60°C,

og det foretrukne område for natriumborhydrid av reaktivitets-grunner, er 20 til 40°C, og det foretrukne område for lithiumaluminiumhydrid er fra 0 til 35°C. and the preferred range for sodium borohydride for reactivity reasons is 20 to 40°C, and the preferred range for lithium aluminum hydride is from 0 to 35°C.

Detaljer ved oppfinnelsen Details of the invention

For fremstilling av 1,2-benzendithiolene vil den etter-følgende informasjon rettlede fagmannen når det gjelder valg av løsningsmidler. Fremgangsmåten under anvendelse av natriumborhydrid utføres med et protisk løsningsmiddel, med eller uten ikke-protiske løsningsmidler som fortynningsmiddel. Løsningsmidler egnet for natriumborhydridprosessen, innbefatter, men er ikke begrenset til, methanol, ethanol, iso-propanol, butanol og vann. Ikke-protiske fortynningsmidler innbefatter tetrahydrofuran. Andre løsningsmidler kan velges empirisk avhengig av typen av valgt reduksjonsmiddel. Således krever lithiumaluminiumhydrid ikke-protiske løsningsmidler slik som diethylether eller tetrahydrofuran. For the production of the 1,2-benzenedithiols, the following information will guide the person skilled in the art when it comes to the choice of solvents. The process using sodium borohydride is carried out 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, iso-propanol, butanol and water. Non-protic diluents include tetrahydrofuran. Other solvents can be chosen empirically depending on the type of reducing agent chosen. Thus, lithium aluminum hydride requires non-protic solvents such as diethyl ether or tetrahydrofuran.

Molarforholdet mellom natriumborhydrid eller lithiumaluminiumhydrid og benzopentathiepin kan variere fra 2:1 til 6:1, hvor et forhold på 4:1 er foretrukket. Prosessen som anvender lithiumaluminiumhydrid, skal utføres i fravær av vann. Reaksjonsprosessen gir i begynnelsen et dithiolatsalt som kan omsettes ytterligere med vandig syre under dannelse av 1,2-benzendithiolene, eller med alkyleringsmidler slik som methyljodid under dannelse av di-thioethere. Det andre valg gir materialer som er beskyttet mot aerob oxydasjon. The molar ratio between sodium borohydride or lithium aluminum hydride and benzopentathiepine can vary from 2:1 to 6:1, where a ratio of 4:1 is preferred. The process using lithium aluminum hydride must be carried out in the absence of water. The reaction process initially gives a dithiolate salt which can be reacted further with aqueous acid to form the 1,2-benzenedithiolene, or with alkylating agents such as methyl iodide to form di-thioethers. The second choice provides materials that are protected against aerobic oxidation.

En ytterligere side ved oppfinnelsen angår anvendelse av valgte benzopentathiepiner som antifungale og antivirale midler. Eksempelvis ble forbindelsene angitt i tabell 1, funnet å være effektive mot de angitte fungus og virus-typer. Detaljer vedrørende formuleringer og kontrollmetodo-logi følger tabellen. A further aspect of the invention relates to the use of selected benzopentathiepines as antifungal and antiviral agents. For example, the compounds indicated in Table 1 were found to be effective against the indicated fungus and virus types. Details regarding formulations and control methodology follow the table.

Plantesykdomskontrollformuleringer Plant Disease Control Formulations

Anvendbare formuleringer av benzopentathiepiner kan fremstilles på konvensjonell måte. Disse innbefatter støv, suspensjoner, emulsjoner, fuktbare pulvere, emulgerbare konsentrater og lignende. Mange av disse kan påføres direkte. Sprøytbare formuleringer kan fortynnes i egnede media og anvendes ved sprøytevolumer på fra noen få liter til flere hundre liter pr. hektar. Materialer med høy styrke kan anvendes primært som konsentrater som må fortynnes før endelig bruk. Formuleringene inneholder bredt angitt fra 1 til 99 vekt% aktiv bestanddel og minst én av (a) fra 0,1 til 20% overflateaktive midler og (b) fra 1 til 99% faste eller væske-formige fortynningsmidler. Nærmere bestemt vil de inneholde disse bestanddeler i de tilnærmede mengder som angitt i tabell 2 med den aktive bestanddel pluss minst ett overflateaktivt middel eller fortynningsmiddel som er lik 100 vekt%. Useful formulations of benzopentathiepines can be prepared by conventional means. These include dusts, suspensions, emulsions, wettable powders, emulsifiable concentrates and the like. Many of these can be applied directly. Sprayable formulations can be diluted in suitable media and used with spray volumes of from a few liters to several hundred liters per hectares. Materials with high strength can be used primarily as concentrates that must be diluted before final use. The formulations contain broadly stated from 1 to 99% by weight active ingredient and at least one of (a) from 0.1 to 20% surfactants and (b) from 1 to 99% solid or liquid diluents. More specifically, they will contain these ingredients in the approximate amounts indicated in Table 2 with the active ingredient plus at least one surfactant or diluent equal to 100% by weight.

Lavere eller høyere konsentrasjoner av aktiv bestanddel kan være tilstede, avhengig av den beregnede bruk og de fysikalske egenskaper av forbindelsen. Høyere forhold mellom overflateaktivt middel og aktiv bestanddel er enkelte ganger ønskelig og kan oppnås ved innarbeidelse i formuleringen eller ved tankblanding. Lower or higher concentrations of active ingredient may be present, depending on the intended use and the physical properties of the compound. A higher ratio between surfactant and active ingredient is sometimes desirable and can be achieved by incorporation in the formulation or by tank mixing.

Enkelte typiske faste fortynningsmidler er beskrevet i Watkins et al., "Handbook of Insecticide Dust Diluents and Some typical solid diluents are described in Watkins et al., "Handbook of Insecticide Dust Diluents and

Carriers", 2. utgave, Dorland Books, Caldwell, N.J., men andre faste materialer, enten utvunnet eller fremstilt, kan anvendes. De mer absorberende fortynningsmidler foretrekkes for fuktbare pulvere og de tettere for støv. Typiske væske-formige fortynningsmidler og løsningsmidler er beskrevet i Marsden, "Solvents Guide", 2. utg., Interscience, N.Y., 1950. En løselighet under 0,1% foretrekkes for suspensjonskonsen-trater, og løsningskonsentrater er fortrinnsvis stabile mot faseseparering ved 0°C. "McCutcheon's Detergents and Emulsifiers Annual", MC Publishing Corp., Ridgewood, N.J., såvel som Sisely and Wood, "Encyclopedia of Surface Active Agents", Chemical Publishing Co., Inc., N.Y., 1964, angir overflateaktive stoffer og anbefalt bruk. Alle formuleringer kan inneholde mindre mengder av additiver for å redusere skumming, sammenkakning, korrosjon, mikrobiologisk vekst o.l. Carriers", 2nd ed., Dorland Books, Caldwell, N.J., but other solid materials, either mined or manufactured, may be used. The more absorbent diluents are preferred for wettable powders and the denser for dusts. Typical liquid diluents and solvents are described in Marsden, "Solvents Guide", 2nd ed., Interscience, N.Y., 1950. A solubility below 0.1% is preferred for suspension concentrates, and solution concentrates are preferably stable to phase separation at 0°C. "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 may contain minor amounts of additives to reduce foaming, caking, corrosion, microbiological growth etc.

Landbruksformuleringer som inneholder forbindelsene ifølge oppfinnelsen som aktiv bestanddel, kan også inneholde andre aktive bestanddeler. De ytterligere landbrukskjemi-kalier anvendes i blandinger eller kombinasjoner i mengder varierende fra 0,05 til 25 vektdeler pr. vektdel av forbindelsen eller forbindelsene ifølge oppfinnelsen. Den riktige valg av mengder foretas lett av fagmannen når det gjelder beskyttelse av planter mot plantesykdommer. De etterfølgende er eksempler på landbrukskjcmikalier som kan innbefattes i preparatene eller tilsettes til spray inneholdende én eller flere av de aktive forbindelser ifølge oppfinnelsen: Fungicider: methyl-2-benzimidazolcarbamat (carbendazim) tetramethy1thiuream-disulfid (thiuram) Agricultural formulations containing the compounds according to the invention as active ingredient may also contain other active ingredients. The additional agricultural chemicals are used in mixtures or combinations in amounts varying from 0.05 to 25 parts by weight per weight part of the compound or compounds according to the invention. The correct choice of quantities is easily made by the person skilled in the art when it comes to the protection of plants against plant diseases. The following are examples of agricultural chemicals that can be included in the preparations or added to sprays containing one or more of the active compounds according to the invention: Fungicides: methyl-2-benzimidazole carbamate (carbendazim) tetramethylthiuream-disulfide (thiuram)

n-dodecylguanidinacetat (dodin) n-dodecylguanidine acetate (dodine)

mangan-ethylenbisdithiocarbamat (maneb) manganese ethylene bisdithiocarbamate (maneb)

1,4-diklor-2,5-dimethoxybenzen (klorneb) 1,4-dichloro-2,5-dimethoxybenzene (chloroneb)

methyl-1-(butylcarbamoyl)-2-benzimidazolcarbamat (benomyl) 2-cyano-N-ethylcarbamoyl-2-methoxyiminoacetamid (cymoxanil) N-triklormethylthiotetrahydrofthalimid (captan) N-triklormethylthiofthalimid (folpet) methyl 1-(butylcarbamoyl)-2-benzimidazole carbamate (benomyl) 2-cyano-N-ethylcarbamoyl-2-methoxyiminoacetamide (cymoxanil) N-trichloromethylthiotetrahydrophthalimide (captan) N-trichloromethylthiophthalimide (folpet)

dimethyl-4,4'-(o-fenylen)-bis-(3-thioallofanat) dimethyl-4,4'-(o-phenylene)-bis-(3-thioallophanate)

(thiofanat-methy1)(thiophanate-methyl1)

2- (thiazol-4-yl)-benzimidazol (thiabendazol) aluminium-tris- (O-ethylfosfonat) (Aliette^ tetraklorisofthalonitril (klorthalonil) 2,6-diklor-4-nitroanilin (dikloran) 2-(thiazol-4-yl)-benzimidazole (thiabendazole) aluminum tris-(O-ethylphosphonate) (Aliette^ tetrachloroisophthalonitrile (chlorothalonil) 2,6-dichloro-4-nitroaniline (dichloran)

N-(2,6-dimethylfenyl)-N-(methoxyacetyl)-alanin-methylester N-(2,6-dimethylphenyl)-N-(methoxyacetyl)-alanine methyl ester

(metalaxyl)(metalaxyl)

cis-N-[(1,1,2,2-tetraklorethyl)-thio]-cyclohex-4-en-l,2-dicarbioximid (captafol) cis-N-[(1,1,2,2-tetrachloroethyl)-thio]-cyclohex-4-ene-1,2-dicarboxiimide (captafol)

3- (3,5-diklorfenyl)-N-(1-methylethyl)-2,4-dioxo-l-imidazqlidin-carboxamid (iprodion) 3-(3,5-Dichlorophenyl)-N-(1-methylethyl)-2,4-dioxo-1-imidazqlidin-carboxamide (iprodione)

3-(3,5-diklorfenyl)-5-ethenyl-5-methyl-2,4-oxazolidindion 3-(3,5-dichlorophenyl)-5-ethenyl-5-methyl-2,4-oxazolidinedione

(vinclozolin)(vinclozolin)

kasugamycinkasugamycin

0-ethyl-S,S-difenylfosforodithioat (edifenfos) 0-ethyl-S,S-diphenylphosphorodithioate (edifenphos)

Baktericider; Bactericides;

tribasisk kobbersulfattribasic copper sulfate

streptomycinsulfatstreptomycin sulfate

oxytetracyclinoxytetracycline

Acarlcider:Acarlcides:

senecioinsyre, ester med 2-sek-butyl-4,6-dinitrofenol senecioic acid, ester with 2-sec-butyl-4,6-dinitrophenol

(binapacryl)(binapacryl)

6-methyl-l,3-dithiolo-[2,3-B]-kinonolin-2-on 6-methyl-1,3-dithiolo-[2,3-B]-quinonolin-2-one

(oxythiokinox)(oxythioquinox)

2,2,2-triklor-l,l-bis-(4-klorfenyl)-ethanol (dicofol) bis-(pentaklor-2,4-cyclopentadien-l-yl) (dienoklor) tricyclohexyl-tinn-hydroxyd (cyhexatinn) hexakis-(2-methyl-2-fenylpropyl)-distannoxan 2,2,2-trichloro-1,1-bis-(4-chlorophenyl)-ethanol (dicofol) bis-(pentachloro-2,4-cyclopentadien-1-yl) (dienochlor) tricyclohexyltin hydroxide (cyhexatinn) hexakis-(2-methyl-2-phenylpropyl)-distannoxan

(fenbutinnoxyd)(phenbutin oxide)

Nematicider:Nematicides:

2-[diethoxyfosfinylimino]-!,3-dithietan (fosthietan) S-methyl-1-(dimethylcarbamoyl)-N-(raethylcarbamoyloxy)- thioformimidat (oxamoyl) 2-[diethoxyphosphinylimino]-!,3-dithietane (phosthietane) S-methyl-1-(dimethylcarbamoyl)-N-(raethylcarbamoyloxy)- thioformimidate (oxamoyl)

S-methyl-l-carbamoyl-N-(methylcarbamoyloxy)-thioformimidat N-isopropylfosforamidinsyre, O-ethyl-0'-[4-(methylthio)-m-tolyl]-diester (fenamifos) S-methyl-1-carbamoyl-N-(methylcarbamoyloxy)-thioformimidate N-isopropylphosphoramidic acid, O-ethyl-0'-[4-(methylthio)-m-tolyl]-diester (fenamiphos)

Insekticider: 3-hydroxy-N-methylcrotonamid- (dimethylfosfat) -ester Insecticides: 3-hydroxy-N-methylcrotonamide (dimethyl phosphate) ester

(monocrotofos)(monocrotophos)

methylcarbaminsyfe, ester med 2,3-dihydro-2,2-dimethyl-7-benzofuranol (carbofuran) methylcarbamine syfe, ester with 2,3-dihydro-2,2-dimethyl-7-benzofuranol (carbofuran)

0-[2,4/5-triklor-a-(klormethyl)-benzyl]-fosforsyre, 0,0-dimethylester (tetraklorvinfos) 0-[2,4/5-trichloro-α-(chloromethyl)-benzyl]-phosphoric acid, 0,0-dimethyl ester (tetrachlorovinphos)

2-mercaptoravsyre, diethylester, S-ester med thionofosfor-syre, dimethylester (malathion) 2-mercaptosuccinic acid, diethyl ester, S-ester with thionophosphoric acid, dimethyl ester (malathion)

fosforthiosyre, 0,0-dimethyl, O-p-nitrofenylester phosphorothioic acid, 0,0-dimethyl, O-p-nitrophenyl ester

(methylparathion)(methylparathion)

methylcarbaminsyre, ester med a-nafthol (carbaryl) methyl-N-[[(methylamino)-carbonyl]-oxy]-ethanimido-thioat (methomyl) methylcarbamic acid, ester with α-naphthol (carbaryl) methyl-N-[[(methylamino)-carbonyl]-oxy]-ethanimido-thioate (methomyl)

N'-(4-klor-o-tolyl)-N,N-dimethylformamidin (kloridimeform) 0,0-diethyl-O-(2-isopropyl-4-methyl-6-pyrimidyl)-fosforothioat (diazinon) N'-(4-chloro-o-tolyl)-N,N-dimethylformamidine (chloridimeform) 0,0-diethyl-O-(2-isopropyl-4-methyl-6-pyrimidyl)-phosphorothioate (diazinon)

octaklorcamfen (toxafen) octachlorocamphene (toxaphene)

O-ethyl-O-p-nitrofenyl-fenylfosfononthioat (EPN) cyano-(3-fenoxyfenyl)-methyl-4-klor-a-(1-methylethyl)-benzenacetat (fenvalerat) O-ethyl-O-p-nitrophenyl-phenylphosphononethioate (EPN) cyano-(3-phenoxyphenyl)-methyl-4-chloro-a-(1-methylethyl)-benzeneacetate (fenvalerate)

(3-fenoxyfenyl)-methyl-(+)-cis,trans-3-(2,2-diklor-ethenyl)-2,2-dimethylcyclopropancarboxylat (permethrin) (3-phenoxyphenyl)-methyl-(+)-cis,trans-3-(2,2-dichloro-ethenyl)-2,2-dimethylcyclopropanecarboxylate (permethrin)

dimethyl-N,N'-[thiobis —(N-methylimino)-carbonyloxy]-bis-[ethanimidothioat] (thiodicarb) dimethyl-N,N'-[thiobis—(N-methylimino)-carbonyloxy]-bis-[ethanimidothioate] (thiodicarb)

fosforothiolothionsyre, O-ethyl-0-[4-(methylthio)-fenyl]-S-n-propylester (sulprofos) phosphorothiolothionic acid, O-ethyl-0-[4-(methylthio)-phenyl]-S-n-propyl ester (sulprofos)

d-cyano-3-fenoxybenzyl-[3-(2,2-diklorvinyl)-2,2-dimethyl-cyclopropan]-carboxylat (cypermethrin) d-cyano-3-phenoxybenzyl-[3-(2,2-dichlorovinyl)-2,2-dimethyl-cyclopropane]-carboxylate (cypermethrin)

cyano-(3-fenoxyfenyl)-methyl-4-(difluormethoxy)-a-(methyl-ethyl)-benzenacetat fPayoff") cyano-(3-phenoxyphenyl)-methyl-4-(difluoromethoxy)-a-(methyl-ethyl)-benzeneacetate fPayoff")

0,0-diethyl-O-(3,5,6-triklor-2-pyridyl)-fosforothioat 0,0-diethyl-O-(3,5,6-trichloro-2-pyridyl)-phosphorothioate

(klorpyrifos)(chlorpyrifos)

0,0-dimethyl-S-[(4-oxo-l,2,3-benzotriazin-3-(4H)-yl)-methyl] -fosforothioat (azinfos-methyl) 0,0-dimethyl-S-[(4-oxo-1,2,3-benzotriazin-3-(4H)-yl)-methyl]-phosphorothioate (azinfos-methyl)

5,6-dimethyl-2-dimethylamino-4-pyrimidinyl-dimethyl-carbamat (Pirimor^ 5,6-dimethyl-2-dimethylamino-4-pyrimidinyl-dimethyl-carbamate (Pirimor^

S-(N-formyl-N-methylcarbamoylmethyl)-0,O-dimethyl-fosfordithioat (formothion) S-(N-formyl-N-methylcarbamoylmethyl)-0,O-dimethyl phosphorodithioate (formothion)

S-2-(ethylthioethyl)-0,0-dimethylfosforthioat (demeton-S-methyl) S-2-(ethylthioethyl)-0,0-dimethylphosphorothioate (demeton-S-methyl)

a-cyano-3-fenoxybenzyl-cis-3-(2,2-dibromvinyl)-2,2-dimethylcyclopropancarboxylat (deltamethrin) α-cyano-3-phenoxybenzyl-cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylate (deltamethrin)

cyano-(3-fenoxyfenyl)-methylester av N-(2-klor-4-tri-fluormethylfenyl)-alanin fMavrik"). cyano-(3-phenoxyphenyl)-methyl ester of N-(2-chloro-4-tri-fluoromethylphenyl)-alanine fMavrik").

Metodene for fremstilling av slike preparater er vel-kjente. Oppløsninger fremstilles ved enkel blanding av bestanddelene. Finpartiklede, faste preparater fremstilles ved blanding, og vanligvis maling, slik som i en hammermølle eller fludiumdreven mølle. Suspensjoner fremstilles ved våt-maling. Granuler og pellets fremstilles ved sprøyting av det aktive materiale på fordannede granulære bærere eller ved agglomereringsteknikker. The methods for producing such preparations are well known. Solutions are prepared by simple mixing of the components. Fine-particle, solid preparations are produced by mixing, and usually grinding, such as in a hammer mill or fludium-driven mill. Suspensions are produced by wet painting. Granules and pellets are produced by spraying the active material on formed granular carriers or by agglomeration techniques.

Sykdomskontroll utføres ved å påføre forbindelsene ifølge oppfinnelsen på den del av planten som skal beskyttes. Forbindelsene kan påføres som preventive behandlinger før inokulering med patogenet, eller etter inokulering som en legende, post-infeksjonsbehandling. Disease control is carried out by applying the compounds according to the invention to the part of the plant to be protected. The compounds can be applied as preventive treatments before inoculation with the pathogen, or after inoculation as a therapeutic, post-infection treatment.

Påføringsmengdene av forbindelsene ifølge oppfinnelsen influeres av de spesifikke vertplanter, fungale patogener, og mange faktorer i miljøet må bestemmes under bruk. Bladverk sprøytet med konsentrasjoner varierende fra 1 til 500 ppm aktiv bestanddel, kan beskyttes mot sykdommer under egnede betingelser. The application amounts of the compounds according to the invention are influenced by the specific host plants, fungal pathogens, and many factors in the environment must be determined during use. Foliage sprayed with concentrations varying from 1 to 500 ppm of active ingredient can be protected against diseases under suitable conditions.

Angivelsen "% kontroll" i tabell 1 ble beregnet etter følgende formel: The indication "% control" in table 1 was calculated according to the following formula:

sykdomsgraddegree of illness

100-På behandlede planter x1QQ=%kontroll sykdomsgrad 100-On treated plants x1QQ=% control disease severity

på ubehandlede planter on untreated plants

Benzopentathiepinene ifølge oppfinnelsen har generisk anvendelse som mellomprodukter ved fremstilling av substi tuerte 1,2-benzendithioler som er frie for 1,3- og 1,4-dithiol-isomerer. Slike substituerte 1,2-benzendithioler er kjente mellomprodukter for legemidler (U.S. 4 242 510; Sindelar et al., Collect. Czech. Chem. Comm., 47, 72 til 87 The benzopentathiepines according to the invention have generic use as intermediates in the production of substituted 1,2-benzenedithiols which are free of 1,3- and 1,4-dithiol isomers. Such substituted 1,2-benzenedithiols are known pharmaceutical intermediates (U.S. 4,242,510; Sindelar et al., Collect. Czech. Chem. Comm., 47, 72 to 87

(1982), pesticider (U.S. 3 746 707) og gummi-tverrbindings-midler (U.S. 3 979 369) . (1982), pesticides (U.S. 3,746,707) and rubber cross-linking agents (U.S. 3,979,369).

Reduksjon av benzopentathiepinene med f.eks. natriumborhydrid gir løsninger av dinatriumbénzendithiolater som kan nøytraliseres under dannelse av dithiolen eller alkyleres med methyljodid under dannelse av 1,2-bis-(alkylthio)-benzen-derivater. Det vil være mulig å reagere dithiolatene med anhydrider; syrehalogenider; estere; isocyanater; sulfonyl-halogenider; tri- og pentavalente fosforestere, halogenider og anhydrider for fremstilling av andre anvendbare materialer. Reduction of the benzopentathiepines with e.g. sodium borohydride gives solutions of disodium benzene dithiolates which can be neutralized to form the dithiolene or alkylated with methyl iodide to form 1,2-bis-(alkylthio)-benzene derivatives. It will be possible to react the dithiolates with anhydrides; acid halides; esters; isocyanates; sulfonyl halides; tri- and pentavalent phosphorous esters, halides and anhydrides for the production of other applicable materials.

I de etterfølgende eksempler var den inerte atmosfære N2<Kulerørdestillasjon henviser til en boble-til-boble-mikrodestillasjonsmontasje. Eksempel 1 til 7 og 16 illustrerer fremgangsmåten ifølge oppfinnelsen for fremstilling av benzopentathiepiner. Eksempel 2 til 7 og 16 illustrerer nye benzopentathiepiner. Eksempel 8 til 10 illustrerer utbytteøkningen ved prosessen under anvendelse av DABCO. Eksempel 11, 12 og 15 illustrerer de nye benzothiadoazol-forbindelser. Eksempel 13 og 14 illustrerer fremgangsmåten for omdannelse av benzopentathiepiner til dithioler. I både eksempel 13 og 14 isoleres de erholdte dithioler som bismethylthioethere for å forhindre aerob oxydasjon. Disse bismethylthioethere kan omdannes tilbake til benzendithiolene ved behandling med f.eks. natrium i flytende ammoniakk. In the following examples, the inert atmosphere was N 2 < Ball tube distillation refers to a bubble-to-bubble micro-distillation setup. Examples 1 to 7 and 16 illustrate the process according to the invention for the production of benzopentathiepines. Examples 2 to 7 and 16 illustrate novel benzopentathiepines. Examples 8 to 10 illustrate the yield increase of the process using DABCO. Examples 11, 12 and 15 illustrate the new benzothiadoazole compounds. Examples 13 and 14 illustrate the process for converting benzopentathiepines 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 e.g. sodium in liquid ammonia.

Eksempel 1Example 1

BenzopentathiepinBenzopenthiepine

1,88 g (7,3 mmol) svovel, 1,0 g (7,3 mmol) 1,2,3-benzothiadiazol og"Decalin", , dvs. decahydronafthaien (10 ml)(ble blandet og oppvarmet til 170°C i 1,45 timer. Den resulterende blanding ble tatt opp i carbondisulfid og kromatografert på 250 g Silica"Woelra" TSC (hexan). Etter et 340 ml forløp ble 50 ml fraksjoner oppsamlet. Fraksjon 4 til 16 inneholdt 1,61 g av et oljeaktig, fast materiale. Dette residuum ble triturert med 30 ml hexan mens 15 ml methylenklorid ble langsomt tilsatt. 0,4 7 g svovel var tilbake som residuum. Den gule løsning ble renset i 3 x 15 ml porsjoner ved væskekromatografi ved middels trykk (MPLC) (Lobai<®>Silica gel 60 størrelse C, hexan) under dannelse av 0,60 g (34%) av benzopentathiepin som et lyst gult, fast materiale med smp. 56 til 58°C. En prøve omkrystallisert én gang fra hexan, hadde et smeltepunkt på 58 til 60°C;<1>H-NMR (CDC13, 90 MHz), S 7,85-7,7 og 7,45-7,2 (AA<?>BB' multiplett) i over-ensstemmelse med litteraturen. Massespektret fra en prøve fremstilt på lignende måte, men som ikke var renset ved MPLC, hadde et massespektrum: m/e 235,8914; beregnet m/e for CCH.SC235,8917. 6 4 5 1.88 g (7.3 mmol) of sulfur, 1.0 g (7.3 mmol) of 1,2,3-benzothiadiazole and "Decalin", i.e. the decahydronaphthalene (10 ml) (were mixed and heated to 170° C for 1.45 hours. The resulting mixture was taken up in carbon disulfide and chromatographed on 250 g Silica "Woelra" TSC (hexane). After a 340 ml run, 50 ml fractions were collected. Fractions 4 to 16 contained 1.61 g of an oily solid. This residue was triturated with 30 mL of hexane while 15 mL of methylene chloride was slowly added. 0.47 g of sulfur remained as a residue. The yellow solution was purified in 3 x 15 mL portions by medium pressure liquid chromatography ( MPLC) (Lobai<®>Silica gel 60 size C, hexane) to give 0.60 g (34%) of benzopentathiepine as a pale yellow solid, mp 56 to 58° C. A sample recrystallized once from hexane, had a melting point of 58 to 60°C;<1>H-NMR (CDCl 3 , 90 MHz), S 7.85-7.7 and 7.45-7.2 (AA<?>BB' multiplet) in agreement with the literature.The mass spectrum from a sample preparation t similarly but not purified by MPLC had a mass spectrum: m/e 235.8914; calculated m/e for CCH.SC235,8917. 6 4 5

Eksempel 2Example 2

7-klorbenzopentathiépin7-Chlorobenzopentathiépine

En blanding av 4,5 g (17,6 mmol) svovel, 3,0 g A mixture of 4.5 g (17.6 mmol) sulfur, 3.0 g

(17,6 mmol) 6-klor-l,2,3-benzothiadiazol og 12 ml"Decalin" ble oppvarmet til 170°C i 1 time, og nitrogen ble jevnt utviklet. Blandingen ble deretter oppvarmet til 180°C i 1 time. Løsningen ble avkjølt, og løsningsmidlet ble fjernet i en strøm av nitrogen over natten. Det gule residuum ble oppløst i carbondisulfid og absorbert på 20 g Silica"Woelm" TSC og kromatografert på 250 g av samme silica (hexanelueringsmiddel). Etter et 300 ml forløp ble svovel og rest- (17.6 mmol) of 6-chloro-1,2,3-benzothiadiazole and 12 mL of "Decalin" were heated to 170°C for 1 hour, and nitrogen was steadily evolved. The mixture was then heated to 180°C for 1 hour. 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 on 20 g of Silica "Woelm" TSC and chromatographed on 250 g of the same silica (hexane eluent). After a 300 ml course, sulfur and residual

decalin eluert i 100 ml, hvoretter 4,59 g svovel og produktet ble erholdt i 750 ml. En 0,3 g prøve ble delvis oppløst i 10 ml hexan under omrøring og porsjonsvis tilsetning av 10 ml methylenklorid. Etter 10 minutter ble 0,07 g svovel dekantert. Løsningen ble renset ved væskekromatografi under middels trykk (Lobai<®>Silica gel 60, størrelse C, hexanelueringsmiddel) under dannelse av 0,07 g 7-klorbenzopentathiepin svarende til et utbytte på 22,5%. En 0,05 g prøve ble omkrystallisert fra kokende hexan (20 ml konsen- decalin eluted in 100 ml, after which 4.59 g of sulfur and the product was obtained in 750 ml. A 0.3 g sample was partially dissolved in 10 ml of hexane with stirring and portionwise addition of 10 ml of methylene chloride. After 10 minutes, 0.07 g of sulfur was decanted. The solution was purified by liquid chromatography under medium pressure (Lobai<®>Silica gel 60, size C, hexane eluent) to give 0.07 g of 7-chlorobenzopentathiepine corresponding to a yield of 22.5%. A 0.05 g sample was recrystallized from boiling hexane (20 ml conc.

tert til 5 ml, avkjøling og poding) under dannelse av 40 g av et off-white, fast materiale med smp. 87,5 til 89°C. En prøve fra en lignende fremstilling hadde<1>H-NMR (CDC13, 80 MHz) tert to 5 ml, cooling and inoculation) to give 40 g of an off-white solid with m.p. 87.5 to 89°C. A sample from a similar preparation had<1>H-NMR (CDC13, 80 MHz)

S 7,9-7,7 (d, 2H), 7,4-7,2 (m, 1H); IR (KBr) 1095, 822 cm"<1>; S 7.9-7.7 (d, 2H), 7.4-7.2 (m, 1H); IR (KBr) 1095, 822 cm"<1>;

massespektrum: m/e 269,8517; m/e beregnet for CgH3ClS5 269,8527. mass spectrum: m/e 269.8517; m/e calculated for CgH3ClS5 269.8527.

Anal. beregn, for CgB^ClS: C 26,61; H 1,12; S 59,19Anal. calculate, for CgB^ClS: C 26.61; H 1.12; S 59,19

Funnet: C 26,84; H 1,22; S 65,7, 56,01, 56,79 Found: C 26.84; H 1.22; S 65.7, 56.01, 56.79

Forskjellen mellom de beregnede og fundne verdier for svovel tilskrives temporære problemer med analysen. The difference between the calculated and found values for sulfur is attributed to temporary problems with the analysis.

Eksempel 3Example 3

7- trifluormethylbenzopentathiepin 7- trifluoromethylbenzopentathiepine

En blanding av 1,34 g (4,9 mmol) svovel, 1,0 g (4,9 mmol) 6-trifluormethyl-1,2,3-benzothiadiazol og 10 ml"Decalin" ble-oppvarmet til 190°C i 45 minutter mens nitrogen ble utviklet. Blandingen ble avkjølt og lagret over natten og ble deretter preadsorbert og kromatografert på Silica"Woelm" TSC (400 g, hexan) under dannelse av 1,36 g av en svovel-, produktblanding. Denne blanding ble triturert med 40 ml hexan og ble dekantert fra svovel. Løsningen ble renset ved A mixture of 1.34 g (4.9 mmol) sulfur, 1.0 g (4.9 mmol) 6-trifluoromethyl-1,2,3-benzothiadiazole and 10 ml "Decalin" was heated to 190°C in 45 minutes while nitrogen was evolved. The mixture was cooled and stored overnight and was then 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 40 mL of hexane and decanted from sulfur. The solution was purified by

.væskekromatografi under middels trykk (Lobar^Silica gel 60, størrelse. C) i 2 porsjoner under dannelse av 0,46 g, 31% av .liquid chromatography under medium pressure (Lobar^Silica gel 60, size. C) in 2 portions to give 0.46 g, 31% of

7-trifluormethylbenzopentathiepin som en gul olje som stivnet ved henstand. En prøve fremstilt ved en lignende prosedyre, smeltet ved 44 til 50°C. En prøve omkrystallisert fra hexan hadde et smp. på 59 til 60°C; 1H-NMR (CDClg)- S8,18 7-trifluoromethylbenzopentathiepine as a yellow oil which solidified on standing. A sample prepared by a similar procedure melted at 44 to 50°C. A sample recrystallized from hexane had a m.p. at 59 to 60°C; 1 H-NMR (CDCl 2 )- S 8.18

(d, J=2Hz, 1H), 8,0 (d, J=8Hz, 1H), 7,55 (dd, J=2, 8Hz, 1H) ; IR(KBr) 1320 cm"<1>; massespek.: m/e 303,8788; beregn, m/e for C?H3F3S5303,8790. (d, J=2Hz, 1H), 8.0 (d, J=8Hz, 1H), 7.55 (dd, J=2, 8Hz, 1H) ; IR(KBr) 1320 cm"<1>; mass spec.: m/e 303.8788; calc., m/e for C?H3F3S5303.8790.

Anal. beregn, for C7H3F3S5: C 27,62; H 0,99; S 52,66. Funnet: C 27,92; H 0,94; S 51,75 Anal. calc, 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 C 28.14; H 1.10; S 51.98

Eksempel 4Example 4

7- dimethylamlnobenzopentathiepin7- dimethylamlnobenzopentathiepine

En blanding av 0,72 g (2,79 mmol) svovel, 0,5 g A mixture of 0.72 g (2.79 mmol) sulfur, 0.5 g

(2,79 mmol) 5-dimethylamino-l,2,3-benzothiadiazol og 5 ml "Decalin" ble oppvarmet til 170°C i 1,5 time med jevn utvik-ling av nitrogen. Løsningen ble avkjølt, og "Decalin" (2.79 mmol) of 5-dimethylamino-1,2,3-benzothiadiazole and 5 ml of "Decalin" were heated to 170° C. for 1.5 hours with steady evolution of nitrogen. The solution was cooled, and "Decalin"

ble fjernet ved kulerørdestillasjon ved 50°C (0,3 mm). Residuet ble preadsorbert (5 g) og kromatografert (100 g) på Silica "Woelm" TSC (1% ether-hexan) under dannelse først av svovel og deretter 0,32 g (40%) 7-dimethylaminobenzopenta-thiepin, smp.. 115 til 118°C; ^-NMR (CDC13, 80 MHz) , 5 7,55 (d, -J=8,5 Hz, 1H), 7,0 (d, J=2,7Hz, 1H), 6,5 (dd, J=8,5, 2,7Hz, 1H), 3,0 (s, 6H); IR(KBr) 1583 cm<-1>; massespek.: m/e 278,9343, beregn, m/e for CgHgNS5278,9338. En 80 mg prøve ble omkrystallisert fra kokende ethanol (50 ml filtrert og konsentrert til 20 ml) under dannelse av 70 mg av lysegule krystaller, smp. 121,5 til 122,5°C. was removed by bubble tube 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 0.32 g (40%) 7-dimethylaminobenzopenta-thiepine, m.p. 115 to 118°C; 3-NMR (CDC13, 80 MHz), δ 7.55 (d, -J=8.5 Hz, 1H), 7.0 (d, J=2.7Hz, 1H), 6.5 (dd, J =8.5, 2.7Hz, 1H), 3.0 (s, 6H); IR(KBr) 1583 cm<-1>; mass spec.: m/e 278.9343, calc., m/e for CgHgNS5278.9338. An 80 mg sample was recrystallized from boiling ethanol (50 mL filtered and concentrated to 20 mL) to give 70 mg of pale yellow crystals, m.p. 121.5 to 122.5°C.

Anal. beregn, for CgHgNS^ C 34,38; H 3,25; S 57,36. Funnet: C 34,21; H 3,42; S 56,99. Anal. calculate, for CgHgNS^ C 34.38; H 3.25; S 57,36. Found: C 34.21; H 3.42; S 56.99.

Eksempel 5 Example 5

7- me thoxyberizopéntathiepi n 7- me thoxyberizopéntathiepi n

En blanding av 0,77 g (3,01 mmol) svovel, 0,5 g A mixture of 0.77 g (3.01 mmol) sulfur, 0.5 g

(3,01 mmol) 5-methoxy-l,2,3-benzothladiazol og 5 ml "Decalin" ble oppvarmet til 170°C i 1,5 time. Løsningen ble avkjølt, og "Decalin" ble fjernet ved kulerørdestillasjon ved 50°C (0,3 mm). Residuet ble preadsorbert (5 g) og kromatografert (100 g) på Silica "Woelm" TSC (1% ether-hexan) under dannelse først av svovel og deretter 0,27 g 7-methoxybenzopentathiepin som et lysegult fast materiale, smp. 90 til 95°C. Prøven ble ytterligere renset ved høytrykks-væskekromatografi ("Zorbax" Sil, 25% methylenklorid-hexan) under dannelse av 0,17 g, 21% av produktet, smp. 97 til 98°C; IR(KBr) 1577, 1291, 1229, 1037 cm ^; massespek.: m/e 265,9011, m/e beregn, for C^HgOSj- 265,9022. En prøve fremstilt ved en lignende prosedyre, hadde ^H-NMR (CDC13, 80 MHz) 8 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). (3.01 mmol) of 5-methoxy-1,2,3-benzothladiazole and 5 ml of "Decalin" were heated to 170°C for 1.5 hours. The solution was cooled and the "Decalin" was removed by bubble tube 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-methoxybenzopentathiepine as a pale yellow solid, m.p. 90 to 95°C. The sample was further purified by high pressure liquid chromatography ("Zorbax" Sill, 25% methylene chloride-hexane) to give 0.17 g, 21% of the product, m.p. 97 to 98°C; IR(KBr) 1577, 1291, 1229, 1037 cm 2 ; mass spec.: m/e 265.9011, m/e calc., for C^HgOSj- 265.9022. A sample prepared by a similar procedure had 1 H-NMR (CDCl 3 , 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).

Eksempel 6Example 6

6-brombenzopentathle pin6-bromobenzopentathle pin

En blanding av 2,4 g (9,3 mmol) svovel, 2,0 g (9,3 mmol) 4-brom-l,2,3-benzothiadiazol og 20 ml "Decalin" ble oppvarmet til 175°C i 1,25 timer, og nitrogen ble utviklet. Blandingen ble avkjølt, og løsningsmidlet ble fjernet ved kulerør-destillas jon. Residuet ble preadsorbert og kromatografert (300 g) på Silica "Woelm" TSC (1% ether-hexan) under dannelse først av svovel og deretter 2,2 g av en svovel-produktblanding. Blandingen ble renset ved høytrykks-væskekromatografi ("Zorbax" Sil, hexan) under dannelse av 0,43 g, 14,6%, 6-brombenzopentathiepin, retensjonstid = 5,12 min, smp. 93 til 98°C; IR(KBr) 788 cm"<1>; massespek.: m/e 313,8036, A mixture of 2.4 g (9.3 mmol) of sulfur, 2.0 g (9.3 mmol) of 4-bromo-1,2,3-benzothiadiazole and 20 ml of "Decalin" was heated to 175°C for 1 .25 hours, and nitrogen was evolved. The mixture was cooled and the solvent was removed by bubble tube 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%, 6-bromobenzopentathiepine, retention time = 5.12 min, m.p. 93 to 98°C; IR(KBr) 788 cm"<1>; mass spec.: m/e 313.8036,

m/e beregn, for CgH3BrS5 313,8021.m/e calc., for CgH3BrS5 313.8021.

En forbindelse fremstilt på lignende måte og omkrystallisert fra hexan, hadde et smp. på 101 til 101,5°C; NMR (CDC13, 360 MHz) 6 7,78 (dd, J=l,3, 8,0 Hz, 1H), 7,66 (dd, J=l,3, 8,0Hz, 1H), 7,12 (t, J=8,0Hz, 1H). A compound prepared in a similar manner and recrystallized from hexane had a m.p. of 101 to 101.5°C; NMR (CDCl 3 , 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. beregn, for CgH3BrS5: C 22,86; H 0,96Anal. calculate, for CgH3BrS5: C 22.86; H 0.96

Funnet: C 23,53; H 1,04Found: C 23.53; H 1.04

C 23,09; H 0,94. C 23.09; H 0.94.

Eksempel 7Example 7

6- trifluormethylbenzopentathiepin6-trifluoromethylbenzopentathiepine

En blanding av 0,65 g (2,45 mmol) svovel, 0,5 g A mixture of 0.65 g (2.45 mmol) sulfur, 0.5 g

(2,45 mmol) 4-trifluormethyl-1,2,3-benzothiadiazol og 5 ml "Decalin" ble oppvarmet til 180°C i 3 timer, og nitrogen ble langsomt utviklet. Blandingen ble avkjølt, og løsningsmidlet ble fjernet ved kulerørdestillasjon. Residuet ble preadsorbert og kromatografert (100 g) på Silica "Woelm" TSC (1% (2.45 mmol) of 4-trifluoromethyl-1,2,3-benzothiadiazole and 5 mL of "Decalin" were heated to 180°C for 3 hours, and nitrogen was slowly evolved. The mixture was cooled and the solvent was removed by bubble tube distillation. The residue was preadsorbed and chromatographed (100 g) on Silica "Woelm" TSC (1%

ether-hexan) under dannelse først av svovel og deretter 0,55 g av en svovel-produktblanding. Blandingen ble renset ved høytrykks-væskekromatografi ("Zorbax" Sil, hexan) under dannelse av 0,15 g, 20% 6-trifluormethylbenzopentathiepin som et lysegult, fast materiale, smp. 55 til 60°C, retens jonstid = 5,26 min, IR(KBr) 1310, 1137, 1129, 1119 cm"<1>; massespek.: m/e 303,8748, m/e beregn, for<C>?H3F3S5303,8791. En forbindelse fremstilt på lignende måte og omkrystallisert fra hexan, hadde et smp. på 61 til 62°C. ether-hexane) forming first sulfur and then 0.55 g of a sulfur-product mixture. The mixture was purified by high pressure liquid chromatography ("Zorbax" Sil, hexane) to give 0.15 g, 20% 6-trifluoromethylbenzopentathiepine as a pale yellow solid, m.p. 55 to 60°C, retention ion time = 5.26 min, IR(KBr) 1310, 1137, 1129, 1119 cm"<1>; mass spec.: m/e 303.8748, m/e calc., for<C> ?H3F3S5303.8791 A compound prepared in a similar manner and recrystallized from hexane had a mp of 61 to 62°C.

Anal. beregn, for C7H3F3S5: C 27,62; H 0,99Anal. calc, for C7H3F3S5: C 27.62; H 0.99

Funnet: C 27,89; H 1,06Found: C 27.89; H 1.06

C 27,65; H 1,03 C 27.65; H 1.03

Eksempel 8 Example 8

En blanding av 1,88 g (7,3 mmol) svovel, 1,0 g A mixture of 1.88 g (7.3 mmol) sulfur, 1.0 g

(7,3 mmol) 1,2,3-benzothiadiazol, 0,82 g (7,3 mmol) 1,4-diazabicyclo-[2.2.2]-octan (0,82 g, 7,3 mmol) og 10 ml "Decalin" ble oppvarmet til 170°C i 1,5 timer, mens nitrogen ble utviklet. Blandingen ble avkjølt, og løsningsmidlet ble fjernet ved kulerørdestillasjon. Residuet ble kromatografert på Silica "Woelm" TSC (200 g, 1% ether-hexan). Fraksjonen inneholdende produktet ble ytterligere renset ved høytrykks-væskekromatografi under dannelse av 0,94 g, 54%, benzopentathiepin. (7.3 mmol) 1,2,3-benzothiadiazole, 0.82 g (7.3 mmol) 1,4-diazabicyclo-[2.2.2]-octane (0.82 g, 7.3 mmol) and 10 ml "Decalin" was heated to 170°C for 1.5 hours while nitrogen was evolved. The mixture was cooled and the solvent was removed by bubble tube 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%, benzopentathiepine.

Eksempel 9Example 9

En blanding av 1,2 g (4,65 mmol) svovel, 1,0 g A mixture of 1.2 g (4.65 mmol) of sulfur, 1.0 g

(4,65 mmol) 4-brom-l,2,3-benzothiadiazol, 0,52 g (4,65 mmol) 1,4-diazacyclo-[2.2.2]-octan og 10 ml "Decalin" ble oppvarmet til 170°C 1 1,25 timer. Blandingen ble avkjølt, og løsningsmidlet ble fjernet ved kulerørdestillasjon. Residuet ble kromatografert på Silica "Woelm" TSC (200 g, 1% ether-hexan). Fraksjonen inneholdende en svovel-produktblanding, ble ytterligere renset ved høytrykks-væskekromatografi ("Zorbax" Sil, hexan) under dannelse av 0,33 g, 22,6%, 6-brombenzopentathiepin. (4.65 mmol) of 4-bromo-1,2,3-benzothiadiazole, 0.52 g (4.65 mmol) of 1,4-diazacyclo-[2.2.2]-octane and 10 ml of "Decalin" were heated to 170°C 1 1.25 hours. The mixture was cooled and the solvent was removed by bubble tube 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%, 6-bromobenzopentathiepine.

Eksampe! IO Exam! IO

(3,01 mmol) 5-methoxy-l,2,3-benzothiadiazol, 0,34 g (3,01 mmol) 1,4-diazabicyclo-[2.2.2]-octan og 5 ml "Decalin" ble oppvarmet til 170°C i 1,25 timer. Blandingen ble avkjølt, og løsningsmidlet ble fjernet ved kulerørdestillasjon. Residuet ble kromatografert på Silica "Woelm" TSC (200 g, 1% ether-hexan) under dannelse først av svovel og deretter av 0,46 g, 57%, 7-methoxybenzopentathiepin. (3.01 mmol) 5-methoxy-1,2,3-benzothiadiazole, 0.34 g (3.01 mmol) 1,4-diazabicyclo-[2.2.2]-octane and 5 ml "Decalin" were heated to 170°C for 1.25 hours. The mixture was cooled and the solvent was removed by bubble tube distillation. The residue was chromatographed on Silica "Woelm" TSC (200 g, 1% ether-hexane) to give first sulfur and then 0.46 g, 57%, 7-methoxybenzopentathiepine.

Eksempel 11Example 11

4- trifluormethyl- 1, 2,3-benzothiadiazol4-trifluoromethyl-1,2,3-benzothiadiazole

5,0 g (23,2 mmol) 4-brom-l,2,3-benzothiadiazol ble oppløst i 200 ml N-methylpyrrolidinon, hvoretter 8,5 g (62,5 mmol) natriumtrifluoracetat og 8,75 g (46 mmol) kobber-jodid ble tilsatt. Blandingen ble oppvarmet til 160°C i 4 timer (svak C02~utvikling), avkjølt og fortynnet forsiktig med 300 ml vann. Oppslemmingen ble filtrert gjennom "Celite" (diatoméjord), og filterputen ble skylt med 3 x 250 ml ether. Filtratfåsene ble fraskilt, og det organiske lag ble vasket med vann og saltvann og ble deretter filtrert gjennom en konus av calciumsulfat og konsentrert. Det urene produkt ble kromatografert på Silica "Woelm" TSC (500 g, 15% ether-hexan) under dannelse først av en blanding av 4-brom og 4-jod og 4-trifluormethyl-1,2,3-bénzothiadiazol etterfulgt av ren 4-trifluormethyl-1,2,3-bénzothiadiazol. 5.0 g (23.2 mmol) of 4-bromo-1,2,3-benzothiadiazole was dissolved in 200 ml of N-methylpyrrolidinone, after which 8.5 g (62.5 mmol) of sodium trifluoroacetate and 8.75 g (46 mmol ) copper iodide was added. The mixture was heated to 160°C for 4 hours (slight CO 2 evolution), cooled and diluted carefully with 300 ml of water. The slurry was filtered through "Celite" (diatomaceous earth), and the filter pad was rinsed with 3 x 250 ml of ether. The filtrate fractions were separated and the organic layer was washed with water and brine and then 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-trifluoromethyl-1,2,3-benzothiadiazole followed by pure 4-trifluoromethyl-1,2,3-benzothiadiazole.

Den blandede fraksjon ble rekromatografert på samme kolonne under dannelse av ytterligere rent produkt. På denne måte ble det erholdt 3,19 g, 67%, av 4-trifluormethyl-1,2,3-benzothiadiazol som et off-white, fast materiale. En prøve fremstilt ved en lignende prosedyre, hadde et smp. på 41 til 44°C;<19>F NMR (CDC13> -58,78 (s). En prøve ytterligere renset ved sublimasjon ved 45°C (35-50 mm vannsug) hadde et smp. på 49 til 51°C;<1>H-NMR (CDC13) S8,35 (d, J=8Z, 1H), 8,0 (d, J=8Hz, 1H), 7,8 (t, J=8Hz, 1H) ; IR(KBr) 1319, 1152, 1122, 1089 cm"<1>. The mixed fraction was rechromatographed on the same column to give further pure product. In this way, 3.19 g, 67%, of 4-trifluoromethyl-1,2,3-benzothiadiazole were obtained as an off-white solid. A sample prepared by a similar procedure had a m.p. of 41 to 44°C; <19>F NMR (CDC13> -58.78 (s). A sample further purified by sublimation at 45°C (35-50 mm water suction) had a m.p. of 49 to 51°C ;<1>H-NMR (CDCl 3 ) S 8.35 (d, J=8Z, 1H), 8.0 (d, J=8Hz, 1H), 7.8 (t, J=8Hz, 1H) ;IR (KBr) 1319, 1152, 1122, 1089 cm"<1>.

Anal. beregn, for C^F^S: C 41,18?H 1,48; N 13,72. Funnet: C 41,13?. H 1,37; N 13,96. Anal. calculate, for C^F^S: C 41.18?H 1.48; N 13.72. Found: C 41.13?. H 1.37; N 13.96.

Eksempel 12Example 12

6- trifluormethyl- 1, 2, 3- benzothiadiazol6- trifluoromethyl- 1, 2, 3- benzothiadiazole

20 g (88,6 mmol) 2-klor-4-trifluormethylnitrobenzen ble oppløst i 100 ml dimethylsulfoxyd (tørket over molekyl-siler) under en nitrogenatmosfære, hvoretter 6,9 2 g (88,6 mmol) vannfritt natriumsulfid ble tilsatt alt på en gang. Blandingen ble oppvarmet til 40°C og ble omrørt i 2 timer. Den røde blanding ble helt over i en løsning av 20 g (88.6 mmol) of 2-chloro-4-trifluoromethylnitrobenzene was dissolved in 100 ml of dimethylsulfoxide (dried over molecular sieves) under a nitrogen atmosphere, after which 6.92 g (88.6 mmol) of anhydrous sodium sulfide was added all at once. The mixture was heated to 40°C and stirred for 2 hours. The red mixture was poured into a solution of

300 ml saltvann og 100 ml 6N HC1 og ble ekstrahert med300 ml of brine and 100 ml of 6N HCl and was extracted with

3 x 100 ml methylenklorid. Den kombinerte organiske fase ble 3 x 100 ml methylene chloride. The combined organic phase was

filtrert gjennom en konus av natriumsulfat og ble konsentrert under dannelse av 18,46 g av et gult, fast materiale. filtered through a cone of sodium sulfate and concentrated to give 18.46 g of a yellow solid.

Nitrogen ble boblet gjennom 400 ml avionisert vann iNitrogen was bubbled through 400 ml of deionized water i

15 minutter, hvoretter det ovenfor erholdte gule, faste materiale og 90 ml ammoniumhydroxyd ble tilsatt. 90 g natrium-hydrosulfitt ble oppløst i 400 ml avionisert vann og ble tilsatt til den mekanisk omrørte reaksjonsblanding i løpet av 10 til 15 minutter via en tilsetningstrakt. Den resulterende løsning ble oppvarmet til 50°C i 3 timer og deretter omrørt over natten ved omgivende temperatur.Blandingen ble sur-gjort til pH 7 med eddiksyre og ekstrahert med 3 x 200 ml ether. Det kombinerte organiske lag ble vasket med saltvann og filtrert gjennom en konus av calciumsulfat i en kolbe utstyrt med mekanisk omrører og et gassinnløpsrør. Hydrogen-klorid ble boblet gjennom den omrørte løsning i 1,5 timer. 15 minutes, after which the yellow solid material obtained above and 90 ml of ammonium hydroxide were added. 90 g of sodium hydrosulfite was dissolved in 400 ml of deionized water and was added to the mechanically stirred reaction mixture over 10 to 15 minutes via an addition funnel. The resulting solution was heated to 50°C for 3 hours and then stirred overnight at ambient temperature. The mixture was acidified to pH 7 with acetic acid and extracted with 3 x 200 ml of ether. The combined organic layer was washed with brine and filtered through a cone of calcium sulfate into a flask equipped with a mechanical stirrer and a gas inlet tube. Hydrogen chloride was bubbled through the stirred solution for 1.5 hours.

Det faste materiale ble filtrert, vasket med tørr ether og tørket i vakuum under dannelse av 8,9 6 g av hydrokloridsaltet med smp. 184 til 188°C; IR (KBr) 1330 cm<-1>. The solid material was filtered, washed with dry ether and dried in vacuo to give 8.96 g of the hydrochloride salt with m.p. 184 to 188°C; IR (KBr) 1330 cm<-1>.

Det ovenfor angitte salt ble oppslemmet i 100 ml 5%-ig vandig HC1 og ble avkjølt til 0°C. En løsning av 3,22 g natriumnitritt i 15 ml vann ble dråpevis tilsatt i løpet av 20 minutter til den omrørte blanding som deretter ble nøy-tralisert til pH 9 med 20%-ig vandig natriumhydroxyd. Reak-sjonsblandingen ble ekstrahert med 3 x 100 ml ether, og den organiske fase ble vasket med vann og saltvann og ble deretter filtrert gjennom en konus av natriumsulfat. Konsentrering ga 6,94 g av en brun olje som ble kromatografert på Silica "Woelm" TSC (250 g, 10% ether-hexan) under dannelse (etter et 350 ml forløp) av spor av forurensning i 250 ml og deretter 2,35 g 6-trifluormethyl-1,2,3-benzothiadiazol i 150 ml elueringsmiddel. En prøve sublimert ved 25°C The above salt was slurried in 100 ml of 5% aqueous HCl and cooled to 0°C. A solution of 3.22 g of sodium nitrite in 15 ml of water was added dropwise over 20 minutes to the stirred mixture which was then neutralized to pH 9 with 20% aqueous sodium hydroxide. The reaction mixture was extracted with 3 x 100 ml of ether, and the organic phase was washed with water and brine and then filtered through a cone of sodium sulfate. Concentration gave 6.94 g of a brown oil which was chromatographed on Silica "Woelm" TSC (250 g, 10% ether-hexane) giving (after a 350 ml run) traces of impurity in 250 ml and then 2.35 g 6-trifluoromethyl-1,2,3-benzothiadiazole in 150 ml eluent. A sample sublimed at 25°C

(0,15 mm) hadde et smp. på 36 til 40°C; ^H-NMR (CDC13, 90 MHz) S8,9 (m, 1H) , 8,25 (dd, 1H) , 7,9 (ddd, 1H) ; IR (KBr) 1332, 1294, 1192, 1150, (sh) 1129 cm<-1>. En prøve fremstilt ved en lignende prosedyre, hadde et smp. på 40 til 42°C. (0.15 mm) had a m.p. at 36 to 40°C; 1 H-NMR (CDCl 3 , 90 MHz) δ 8.9 (m, 1H), 8.25 (dd, 1H), 7.9 (ddd, 1H); IR (KBr) 1332, 1294, 1192, 1150, (sh) 1129 cm<-1>. A sample prepared by a similar procedure had a m.p. of 40 to 42°C.

Anal. beregn, for C^F^S: C 41,18; H 1,48; N 13,72. Funnet: C 41,31; H 1,51; N 13,56. Anal. calculate, for C^F^S: 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 40.95 1.73 13.82

Eksempel 13 Example 13

3, 4- bis-( methylthio)-N, N- dimethylariilin 3,4-bis-(methylthio)-N,N-dimethylaryline

Dette eksempel illustrerer fremstilling av en forbindelse som er anvendbar (som ubeskyttet dithiol) som gummi-tverrbindingsmiddel. 0,5 g (1,79 mmol) 7-dimethylaminobenzo-pentathiepin ble oppløst i 50 ml tetrahydrofuran, og 50 ml ethanol ble tilsatt. 0,34 g (8,96 mmol) natriumborhydrid ble tilsatt til den omrørte løsning ved omgivende temperatur i løpet av 5 minutter (etter en kort induksjonstid ble hydrogengass utviklet, og løsningen ble oppvarmet litt). Når skummingen avtok i løpet av 15 minutter, ble 10 ml vann tilsatt, og blandingen ble oppvarmet til 50°C i 5 minutter etterfulgt av avkjøling til omgivende temperatur, hvoretter 0,62 ml (10 mmol) methyljodid ble tilsatt. Etter ytterligere omrøring i 30 minutter ble løsningsmidlet fjernet, og residuet ble fordelt mellom vann og ether. Fasene ble fraskilt, og den organiske fase ble vasket med saltvann og tørket gjennom en konus av natriumsulfat. Konsentrering ga en gul olje som ble kromatografert på Silica "Woelm" TSC This example illustrates the preparation of a compound useful (as an unprotected dithiol) as a rubber cross-linking agent. 0.5 g (1.79 mmol) of 7-dimethylaminobenzo-pentathiepine was dissolved in 50 ml of tetrahydrofuran, and 50 ml of ethanol was added. 0.34 g (8.96 mmol) of sodium borohydride was added to the stirred solution at ambient temperature over 5 minutes (after a short induction time hydrogen gas was evolved and the solution was slightly warmed). When the foaming subsided within 15 minutes, 10 mL of water was added and the mixture was heated to 50°C for 5 minutes followed by cooling to ambient temperature, after which 0.62 mL (10 mmol) of methyl iodide was added. After further stirring for 30 minutes, 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-hexan) under dannelse av 0,33 g, 86%, av 3,4-bis-(methylthio)-N,N-dimethylanilin som en gul olje som krystalliserte ved henstand, smp. 49 til 51°C? IR (ren) (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, m.p. 49 to 51°C? IR (pure)

1583 cm<-1>;<1>H-NMR (CDCl3, 80 MHz) & 7,22 (d, J=9,3 Hz, 1H), 6,49 (d, delvis skjult, J=2,9 Hz, 1H), 6,4 (dd, delvis skjult, J= 2,9, 9,3 Hz, 1H), 2,95 (s, 6H), 2,46 (s, 3H), 2,38 (s, 3H). 1583 cm<-1>;<1>H-NMR (CDCl3, 80 MHz) & 7.22 (d, J=9.3 Hz, 1H), 6.49 (d, partially obscured, J=2.9 Hz, 1H), 6.4 (dd, partially hidden, J= 2.9, 9.3 Hz, 1H), 2.95 (s, 6H), 2.46 (s, 3H), 2.38 ( pp, 3H).

Anal. beregn, for ci0H15NS2:C 56'30; H 7/09Anal. calc., for ci0H15NS2:C 56'30; H 7/09

Funnet: C 56,69?H 6,93Found: C 56.69; H 6.93

C 56,72?H 6,96. C 56.72; H 6.96.

Eksempel 14 Example 14

3, 4- bis'- ( methylthio) - klorbenzen 3, 4-bis'-(methylthio)-chlorobenzene

Dette eksempel illustrerer fremstilling av en forbindelse som er anvendbar som et mellomprodukt (som ubeskyttet dithiol) for et tricyclisk psykotropt middel. This example illustrates the preparation of a compound useful as an intermediate (as an unprotected dithiol) for a tricyclic psychotropic agent.

0,32 g (1,18 mmol) 7-klorbenzopentathiepin ble oppløst i 30 ml tetrahydrofuran, og 30 ml ethanol ble tilsatt. 0,22 g (5,91 mmol) natriumborhydrid ble tilsatt i løpet av 5 minutter i porsjoner ved omgivende temperatur som bevirket at løsningen utviklet hydrogengass og ble svakt oppvarmet. 0.32 g (1.18 mmol) of 7-chlorobenzopentathiepine was dissolved in 30 ml of tetrahydrofuran, and 30 ml of ethanol was added. 0.22 g (5.91 mmol) of sodium borohydride was added over 5 minutes in portions at ambient temperature causing the solution to evolve hydrogen gas and to be slightly heated.

Etter at gassutviklingen hadde avtatt innen 15 minutter, ble 10 ml vann tilsatt, og blandingen ble oppvarmet til 50°C i After gas evolution had subsided within 15 minutes, 10 mL of water was added and the mixture was heated to 50°C in

5 minutter og ble deretter avkjølt til romtemperatur. 0,44 ml (7,0 mmol) methyljodid ble tilsatt, og løsningen ble omrørt. Løsningsmidlene ble fjernet, og residuet ble fordelt mellom ether og vann. Fasene ble fraskilt, og det organiske lag ble vasket med saltvann og tørket gjennom en konus av natrium-sulf at. Konsentrering ga en olje som ble kromatografert på Silica "Woelm" TSC (50 g, 10% ether-hexan) under dannelse av 0,16 g, 67%, 3,4-bis-(methylthio)-klorbenzen som en klar, lysegul olje; """H-NMR (CDC13, 90 MHz) & 7,1 (s, 3H) , 2,46 5 minutes and was then cooled to room temperature. 0.44 mL (7.0 mmol) of methyl iodide 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 gave an oil which was chromatographed on Silica "Woelm" TSC (50 g, 10% ether-hexane) to give 0.16 g, 67%, 3,4-bis-(methylthio)-chlorobenzene as a clear, pale yellow oil; """H-NMR (CDC13, 90 MHz) & 7.1 (s, 3H) , 2.46

(s, '3H) , 2,44 (s, 3H) , 1,4 (litt urenhet); IR (ren) 1448, 14 30, 1029, 801 cm"<1>; massespek.: m/e 203,9852, m/e beregn, for CgH9ClS2203,9834. (s, '3H) , 2.44 (s, 3H) , 1.4 (slight impurity); IR (pure) 1448, 14 30, 1029, 801 cm"<1>; mass spec.: m/e 203.9852, m/e calcd, for CgH9ClS2203.9834.

Eksempel 15 Example 15

4,5-bis-(dioréthylamino)-1,2, 3- berizothiadiazol 4,5-bis-(diorethylamino)-1,2,3-berizothiadiazole

En 3-hals rundkolbe utstyrt med magnetisk omrører, kjøler, statisk nitrogenatmosfære og en skillevegg, ble fylt med 0,35 g natriumhydrid (50% mineraloljedispersjon, A 3-neck round-bottomed flask equipped with a magnetic stirrer, condenser, static nitrogen atmosphere and a septum was charged with 0.35 g of sodium hydride (50% mineral oil dispersion,

7,2 mmol). Oljen ble skylt bort med tørt hexan (3 ganger under anvendelse av standard sprøyteteknikk), hvoretter 20 ml tørt tetrahydrofuran ble tilsatt. Til oppslemmingen ble tilsatt 0,2 g (1,2 mmol) 4,5-diamino-l,2,3-benzothiadiazol (ufortynnet) i løpet av 5 minutter. Til slutt ble 0,75 ml (12 mmol) methyljodid tilsatt, og blandingen ble omrørt ved omgivende temperatur i 72 timer. Blandingen ble forsiktig slukket med vann, løsningsmidlet ble avdrevet, og methylenklorid ble tilsatt til residuet. Etter ekstraksjon av denne organiske fase med vann og saltvann ble det filtrert gjennom en konus av natriumsulfat og konsentrert på silicagel. Kromatograf! på silicagel (5% ether-hexan) ga 0,11 g (41%) 4,5-bis-(dimethylamino)-1,2,3-benzothiadiazol som en orange olje; NMR (90 MHz) S 7,38 (ABq ^^.3= 18 Hz, J=8 Hz, 2H) , 3,26 (s, 6H), 2,8 (s, 6H); IR (ren) 2980-2780 (multiplett, m) , 1542, 1495 cm "*"; eksakt masse beregnet for<c>^qH14<N>4<S>' m/e 222,0939, observert m/e 222,0950. 7.2 mmol). The oil was washed away with dry hexane (3 times using standard spraying technique), after which 20 ml of dry tetrahydrofuran was added. To the slurry was added 0.2 g (1.2 mmol) of 4,5-diamino-1,2,3-benzothiadiazole (undiluted) over 5 minutes. Finally, 0.75 mL (12 mmol) of methyl iodide was added and the mixture was stirred at ambient temperature for 72 hours. The mixture was carefully quenched with water, the solvent was evaporated, 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 on silica gel. Chromatograph! on silica gel (5% ether-hexane) gave 0.11 g (41%) of 4,5-bis-(dimethylamino)-1,2,3-benzothiadiazole as an orange oil; NMR (90 MHz) S 7.38 (ABq 3 = 18 Hz, J=8 Hz, 2H), 3.26 (s, 6H), 2.8 (s, 6H); IR (pure) 2980-2780 (multiplet, m) , 1542, 1495 cm "*"; exact mass calculated for<c>^qH14<N>4<S>' m/e 222.0939, observed m/e 222.0950.

Eksempel 16Example 16

6, 7- bis-( dimethylamino)- benzopentathiepin6, 7-bis-(dimethylamino)-benzopentathiepine

En magnetisk omrørt blanding av 2,0 g (9,0 mmol) 4,5-bis-(dimethylamino)-1,2,3-benzothiadiazol, 2,3 g (9,0 mmol) svovel og 30 ml decalin ble oppvarmet til 175°C under en statisk nitrogenatmosfære i 1,5 timer. I dette tidsrom var nitrogenutvikiingen jevn. Blandingen ble avkjølt til omgivende temperatur, og decalinet ble fjernet ved kulerør-destillas jon. Residuet ble kromatografert på silicagel (1% ether-hexan) under dannelse av 2,04 g (70%) 6,7-bis-(dimethyl-amino) -benzopentathiepin. En 1 g prøve ble omkrystallisert fra 100 ml hexan ved avkjøling til -78°C under dannelse av 0,7 g av et lyst orange, fast materiale: smp. 59,5 til 61°C. A magnetically stirred mixture of 2.0 g (9.0 mmol) 4,5-bis-(dimethylamino)-1,2,3-benzothiadiazole, 2.3 g (9.0 mmol) sulfur and 30 ml decalin was heated to 175°C under a static nitrogen atmosphere for 1.5 hours. During this period, the nitrogen evolution was steady. The mixture was cooled to ambient temperature and the decalin was removed by ball tube distillation. The residue was chromatographed on silica gel (1% ether-hexane) to give 2.04 g (70%) of 6,7-bis-(dimethyl-amino)-benzopentathiepine. A 1 g sample was recrystallized from 100 ml of hexane on cooling to -78°C to give 0.7 g of a bright orange solid: m.p. 59.5 to 61°C.

Anal. beregn, for c10Hi4N2S5'C 37,24; H 4,38Anal. calc, for c10Hi4N2S5'C 37.24; H 4.38

Funnet: C 37,45; H 4,66Found: C 37.45; H 4.66

En prøve fremstilt ved lignende fremgangsmåte hadde:A sample prepared by a similar method had:

NMR (80 MHz) 5 7,15 (ABq A91-3= 59 Hz, J=8,5 Hz, 2H) , 2,9 (s, 6H), 2,8 (s, 6H). NMR (80 MHz) δ 7.15 (ABq A91-3 = 59 Hz, J=8.5 Hz, 2H), 2.9 (s, 6H), 2.8 (s, 6H).

i in

Claims

1. Benzopenthiepine compound of formula:

12 3 wherein R , R and R are the same or different and are selected 12 3 from H (provided that no more than two of R , R and R are H), X, CX-, N0„, SR4, OR4, NR4, OCR4, COR4, CR4, CNR4, aryl and J Z „ „ „ ii z 0 0 0 0 substituted aryl; R 4 is selected from aryl, substituted aryl, and substituted and unsubstituted, branched or straight chain C 1 -C 8 alkyl; and X is selected from Cl, Br and F.

2. Connection according to claim 1, 1 3 characterized in that R and R are both H, and R<2> is selected from X, CX3, SR<4>, OR<4>, NR<4>, COOR<4>, aryl and substituted aryl.

3. Compound according to claim 2, characterized in that R <2> is selected from N(CH3 )2 , 0CH3 , CF3 and Cl.

4. Compound according to claim 1, characterized in that R 2 and R 3 are both H, and R 1 is selected from X, CX 3 , SR 4 , OR 4 , NR 4 , COOR 4 , aryl and substituted aryl.

5. Compound according to claim 4, characterized in that R1 is selected from CF3 and Br.

6. Connection according to claim 3, characterized in that it is 7-trifluoromethylbenzopentathiepine.

7. Connection according to claim 3, characterized in that it is 7-dimethylamino-benzopentathiepine.

8. Connection according to claim 3, characterized in that it is 7-methoxybenzopentathiepine.

9. Connection according to claim 5, characterized in that it is 6-trifluoromethylbenzopentathiepine.

10. Connection according to claim 3, characterized in that it is 7-chlorobenzopentathiepine..

11. Connection according to claim 5, characterized in that it is 6-bromobenzopentathiepine.

12. Compound, characterized in that it is 4-trifluoromethyl-1,2,3-benzothiadiazole.

13. Compound, characterized in that it is 6-trifluoromethyl-1,2,3-benzothiadiazole.

14. Process for the preparation of compounds of formula:

,..12 3 wherein R , R and R are the same or different and are selected from H, X, CX3 , NO2 , SR <4> , OR <4> , NR <4> ,

aryl and substituted aryl; R 4 is selected from aryl, substituted aryl and substituted and unsubstituted, branched or straight chain C 1 -C 8 alkyl; and X is selected from Cl, Br and F; characterized in that a benzothiadiazole of formula:

is reacted with Sg at elevated temperature in a solvent which is inert to Sg in a molar ratio between Sg and benzothiadiazole of 1:2 to 2:1.

15. Method according to claim 14, characterized in that the solvent is selected from one or a mixture of decahydronaphthalene, nitrobenzene, dichlorobenzene, dimethylformamide and dimethylsulfoxide, and that the temperature is from 140 to 200°C.

16. Method according to claim 15, characterized in that the temperature is 160 to 190°C, and that the ratio between Sg and benzothiazole is 1:1.

17. Process according to claim 14, carried out in the presence of 1,4-diazabicyclo-[2.2.2]-octane.

18. Method according to claim 15, carried out in the presence of 1,4-diazabicyclo-[2.2.2]-octane.

19. Method according to claim 16, carried out in the presence of 1,4-diazabicyclo-[2.2.2]-octane.

20. Method according to claim 17, characterized in that the ratio between 1,4-diazabicyclo-[2.2.2]-octane and benzothiadiazole is 0.1:1 to 2:1.

21. Method according to claim 18, characterized in that the ratio between 1,4-diazabicyclo-[2.2.2]-octane and benzothiadiazole is 0.1:1 to 2:1.

22. Method according to claim 19, characterized in that the ratio between 1,4-diazabicyclo-[2.2.2]-octane and benzothiadiazole is 0.1:1 to 2:1.

23. Process for the preparation of a 1,2-benzenedithiol of formula:

characterized in that a benzopentathiepine of formula:

wherein R 1 , R 2 and R 3 are the same or different and are selected from H, X, CX3 , N02 , SR <4> , OR <4> ,

aryl and substituted aryl; R 4 is selected from aryl, substituted aryl and substituted and unsubstituted, branched or straight chain C, to C 8 alkyl; and X is selected from Cl, Br and F, is reduced.

24. Method according to claim 23, characterized in that the reducing agent is selected from at least one member of the group sodium borohydride, lithium aluminum hydride, trialkyl phosphite and zinc/aqueous acid, and that the reaction is carried out in the presence of a solvent at from 0 to 60°C.

25. Process according to claim 24, characterized in that the reducing agent is sodium borohydride and that the ratio thereof to benzopentathiepine is from 2:1 to 6:1.

26. Method according to claim 24, characterized in that the reducing agent is lithium aluminum hydride and that the ratio thereof to benzopentathiepine is from 2:1 to 6:1.

27. Antifungal formulation, characterized in that it comprises an effective amount of a compound according to claim 1.

28. Formulation according to claim 27, characterized in that the compound is 7-trifluoromethylbenzopentathiepine.

29. Formulation according to claim 27, characterized in that the compound is 7-dimethylaminobenzopentathiepine.

30. Formulation according to claim 27, characterized in that the compound is 7-methoxybenzopentathiepine.

31. Formulation according to claim 27, characterized in that the compound is 6-trifluoromethylbenzopentathiepine.

32. Antiviral formulation, characterized in that it comprises an effective amount of a compound according to claim 1.

33. Formulation according to claim 32, characterized in that the compound is 7-dimethylaminobenzopentathiepine.

34. Plant disease control formulation, characterized in that it comprises an effective amount of a compound according to claim 1.

35. Compound according to claim 1, characterized in that R 1 and R 2 are both NR 4 and R <3> is H.

36. Compound according to claim 35, characterized in that R 4 is methyl.

37. Compound, characterized in that it is 4,5-bis-(dimethylamino)-1,2,3-benzothiadiazole.