NO151039B - Utgangsmateriale for fremstilling av 5(6)-thio-benzimidazolderivater - Google Patents
Utgangsmateriale for fremstilling av 5(6)-thio-benzimidazolderivater Download PDFInfo
- Publication number
- NO151039B NO151039B NO824114A NO824114A NO151039B NO 151039 B NO151039 B NO 151039B NO 824114 A NO824114 A NO 824114A NO 824114 A NO824114 A NO 824114A NO 151039 B NO151039 B NO 151039B
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- Norway
- Prior art keywords
- disulfide
- formula
- bis
- benzimidazol
- carbon atoms
- Prior art date
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- 238000002360 preparation method Methods 0.000 title description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 239000007858 starting material Substances 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 239000000203 mixture Substances 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 238000000034 method Methods 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- WXIVZWNTQNCPGM-UHFFFAOYSA-N methyl n-[6-[[2-(methoxycarbonylamino)-3h-benzimidazol-5-yl]disulfanyl]-1h-benzimidazol-2-yl]carbamate Chemical compound C1=C2N=C(NC(=O)OC)NC2=CC(SSC2=CC=C3N=C(NC3=C2)NC(=O)OC)=C1 WXIVZWNTQNCPGM-UHFFFAOYSA-N 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- WKOURAGCEZGDCW-UHFFFAOYSA-N 6-[(2-amino-3h-benzimidazol-5-yl)disulfanyl]-1h-benzimidazol-2-amine Chemical compound C1=C2N=C(N)NC2=CC(SSC2=CC=C3N=C(NC3=C2)N)=C1 WKOURAGCEZGDCW-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- KJKAXLRDKURQNZ-UHFFFAOYSA-N methyl 4-amino-5-[(4-amino-2-methoxycarbonyl-1h-benzimidazol-5-yl)disulfanyl]-1h-benzimidazole-2-carboxylate Chemical compound C1=C2NC(C(=O)OC)=NC2=C(N)C(SSC=2C(N)=C3N=C(NC3=CC=2)C(=O)OC)=C1 KJKAXLRDKURQNZ-UHFFFAOYSA-N 0.000 description 2
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 2
- 239000012429 reaction media Substances 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- FPXQABNVPCVWQU-UHFFFAOYSA-N 3,4-diaminobenzenethiol Chemical compound NC1=CC=C(S)C=C1N FPXQABNVPCVWQU-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- QLBSTGSEKPJQNX-UHFFFAOYSA-N CSC(N)=N.CCOC(N)=O.CCOC(N)=O Chemical compound CSC(N)=N.CCOC(N)=O.CCOC(N)=O QLBSTGSEKPJQNX-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- IEJIGPNLZYLLBP-UHFFFAOYSA-N dimethyl carbonate Chemical compound COC(=O)OC IEJIGPNLZYLLBP-UHFFFAOYSA-N 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 150000002541 isothioureas Chemical class 0.000 description 1
- BBWBKSPQCKQTBM-UHFFFAOYSA-N methyl 4-amino-5-[(4-amino-6-butyl-2-methoxycarbonyl-1h-benzimidazol-5-yl)disulfanyl]-6-butyl-1h-benzimidazole-2-carboxylate Chemical compound C1=C2NC(C(=O)OC)=NC2=C(N)C(SSC2=C(N)C=3N=C(NC=3C=C2CCCC)C(=O)OC)=C1CCCC BBWBKSPQCKQTBM-UHFFFAOYSA-N 0.000 description 1
- ICVMKEPGXJYFEE-UHFFFAOYSA-N methyl 4-amino-5-[(4-amino-6-fluoro-2-methoxycarbonyl-1h-benzimidazol-5-yl)disulfanyl]-6-fluoro-1h-benzimidazole-2-carboxylate Chemical compound C1=C2NC(C(=O)OC)=NC2=C(N)C(SSC=2C(N)=C3N=C(NC3=CC=2F)C(=O)OC)=C1F ICVMKEPGXJYFEE-UHFFFAOYSA-N 0.000 description 1
- VYVMCWKLJJHGGO-UHFFFAOYSA-N methyl 4-amino-5-[(4-amino-6-methoxy-2-methoxycarbonyl-1h-benzimidazol-5-yl)disulfanyl]-6-methoxy-1h-benzimidazole-2-carboxylate Chemical compound C1=C2NC(C(=O)OC)=NC2=C(N)C(SSC=2C(N)=C3N=C(NC3=CC=2OC)C(=O)OC)=C1OC VYVMCWKLJJHGGO-UHFFFAOYSA-N 0.000 description 1
- WRBLLIRXIRJBDG-UHFFFAOYSA-N methyl 4-amino-5-[[4-amino-2-methoxycarbonyl-6-(trifluoromethyl)-1h-benzimidazol-5-yl]disulfanyl]-6-(trifluoromethyl)-1h-benzimidazole-2-carboxylate Chemical compound FC(F)(F)C=1C=C2NC(C(=O)OC)=NC2=C(N)C=1SSC(C(=C1)C(F)(F)F)=C(N)C2=C1NC(C(=O)OC)=N2 WRBLLIRXIRJBDG-UHFFFAOYSA-N 0.000 description 1
- JOQIVCYSHYMHKL-UHFFFAOYSA-N methyl 6-[(2-methoxycarbonyl-3h-benzimidazol-5-yl)disulfanyl]-1h-benzimidazole-2-carboxylate Chemical compound C1=C2N=C(C(=O)OC)NC2=CC(SSC2=CC=C3N=C(NC3=C2)C(=O)OC)=C1 JOQIVCYSHYMHKL-UHFFFAOYSA-N 0.000 description 1
- FAFLKYRQRSFXPI-UHFFFAOYSA-N methyl n-[5-[[2-(methoxycarbonylamino)-6-(trifluoromethyl)-1h-benzimidazol-5-yl]disulfanyl]-6-(trifluoromethyl)-1h-benzimidazol-2-yl]carbamate Chemical compound C1=C2NC(NC(=O)OC)=NC2=CC(C(F)(F)F)=C1SSC(C(=C1)C(F)(F)F)=CC2=C1N=C(NC(=O)OC)N2 FAFLKYRQRSFXPI-UHFFFAOYSA-N 0.000 description 1
- BPKWSJBNXIDMCU-UHFFFAOYSA-N methyl n-[5-[[2-(methoxycarbonylamino)-6-methyl-1h-benzimidazol-5-yl]disulfanyl]-6-methyl-1h-benzimidazol-2-yl]carbamate Chemical compound C1=C2NC(NC(=O)OC)=NC2=CC(C)=C1SSC(C(=C1)C)=CC2=C1N=C(NC(=O)OC)N2 BPKWSJBNXIDMCU-UHFFFAOYSA-N 0.000 description 1
- IGAIXLLJRUPDMT-UHFFFAOYSA-N methyl n-[6-bromo-5-[[6-bromo-2-(methoxycarbonylamino)-1h-benzimidazol-5-yl]disulfanyl]-1h-benzimidazol-2-yl]carbamate Chemical compound C1=C2NC(NC(=O)OC)=NC2=CC(Br)=C1SSC(C(=C1)Br)=CC2=C1N=C(NC(=O)OC)N2 IGAIXLLJRUPDMT-UHFFFAOYSA-N 0.000 description 1
- DXTKSYNNIGAORH-UHFFFAOYSA-N methyl n-[6-chloro-5-[[6-chloro-2-(methoxycarbonylamino)-1h-benzimidazol-5-yl]disulfanyl]-1h-benzimidazol-2-yl]carbamate Chemical compound C1=C2NC(NC(=O)OC)=NC2=CC(Cl)=C1SSC(C(=C1)Cl)=CC2=C1N=C(NC(=O)OC)N2 DXTKSYNNIGAORH-UHFFFAOYSA-N 0.000 description 1
- HYIUTEQZHUSORI-UHFFFAOYSA-N methyl n-[6-fluoro-5-[[6-fluoro-2-(methoxycarbonylamino)-1h-benzimidazol-5-yl]disulfanyl]-1h-benzimidazol-2-yl]carbamate Chemical compound C1=C2NC(NC(=O)OC)=NC2=CC(F)=C1SSC(C(=C1)F)=CC2=C1N=C(NC(=O)OC)N2 HYIUTEQZHUSORI-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 150000004987 o-phenylenediamines Chemical class 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M thiocyanate group Chemical group [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D235/30—Nitrogen atoms not forming part of a nitro radical
- C07D235/32—Benzimidazole-2-carbamic acids, unsubstituted or substituted; Esters thereof; Thio-analogues thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/10—Anthelmintics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/30—Oxygen or sulfur atoms
- C07D233/32—One oxygen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D235/30—Nitrogen atoms not forming part of a nitro radical
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Tropical Medicine & Parasitology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Description
Foreliggende oppfinnelse angår utgangsmaterialer for fremstilling av 5(6)-thiobenzimidazolderivater med formelen:
og salter derav, hvor
R 2 er hydrogen, halogen, alkyl med 1-6 carbonatomer, tri-fluormethyl eller -OR 3,
3
R er alkyl med 1-4 carbonatomer,
R 4er alkyl med 1-6 carbonatomer, cycloalkyl med
3-7 carbonatomer, alkenyl med 3-6 carbonatomer, alkynyl med 3-6 carbonatomer, fenyl eller benzyl,
R^ er alkyl med 1-4 carbonatomer.
Fremgangsmåten for fremstilling av 5(6)-thiobenzimidazol-derivatene av formel I er beskrevet og eksemplifisert i ålment tilgjengelig norsk patentsøknad 781630 hvorfra foreliggende søk-nad er avdelt.
De nye utgangsmaterialer ifølge oppfinnelsen er kjenne-tegnet ved at de har formelen:
hvor R og R er som ovenfor angitt.-
Særlig nyttige utgangsmaterialer med formel VI er de følg-ende derivater: bis -(2-methoxycarbonylamino-benzimidazol-5-yl)-disulf id; bis-(2-methoxycarbonylamino-6-methyl-benzimidazol-5-yl)-disulfid; bis - ( 2 -met hoxyca rbonylamino -6 -butyl -benzimidazol -5-y 1) -disu,lf id; bis -(2-methoxycarbonylamino-6-brom-benzimidazol-5-yl)-disulf id; bis -(2-methoxycarbonylamino-6-klor-benzimidazol-5-y1)-disulf id; bis-(2-methoxycarbonylamino-6-fluor-benzimidazol-5-y1)-disulfid; bis -( 2-methoxycarbonylamino-6-trifluormethyl-benzimidazol-5-yl)-disulf id;
bis-(2-methoxycarbony lamino-6-methoxy-benzimidazol-5-yl)-disulfid-Forbindelsene med formel VI kan fremstilles som følger:
En forbindelse med formel:
omsettes med en forbindelse med formelen: eller hvor R^ er som ovenfor angitt , eller ved å omsette en forbindelse med formel VI, som i 2-stilling bare inneholder amino, med et middel egnet for innføring av gruppen med formelen -COOR<5>, slik som en forbindelse med formelen:
hvor R"' er som ovenfor angitt, og X er halogen.
I henhold til en utførelsesform av fremgangsmåten omsettes en forbindelse med formel VII med et isothiourea-derivat med formel XII. Fremgangsmåten utføres fortrinnsvis ved å oppvarme forbindelsene i et protisk oppløsningsmiddel i nærvær av en syre. Som reaksjonsmedium kan vann, eller organiske oppløsningsmidler eller en blanding av vann og et organisk oppløsningsmiddel (f.eks. vann-ethanol-blanding) anvendes. Reaksjonen utføres fortrinnsvis ved en pH på 3 - 6, særlig i et intervall på 3,5 - 5- pH inn-stilles med en uorganisk syre (f.eks. saltsyre, svovelsyre, fosforsyre) eller en organisk syre, f.eks. maursyre, eddiksyre, propionsyre, etc, fortrinnsvis eddiksyre. Reaksjonstearperaturen er fortrinnsvis 50 - 100°C, og der kan med fordel arbeides ved kokepunktet for reaksjonsblandingen.
I henhold til en annen utførelsesform av fremgangsmåten omsettes en forbindelse med formel VII med et carbalkoxy-cyanamid med formel XIII i et med vann blandbart organisk oppløsningsmiddel (f.eks. methanol, ethanol, aceton, dioxan, pyridin) eller en blanding av vann og et organisk oppløsningsmiddel. Reaksjonen utføres fortrinnsvis ved en temperatur mellom 20°C og kokepunktet for reaksjonsblandingen.
En forbindelse med formel VI som i 2-stilling bare inneholder amino, kan overføres til den tilsvarende forbindelse med formel VI ved omsetning med et middel som er i stand til å inn-føre en carbalkoxygruppe. Reaksjonen utføres fortrinnsvis i et basisk organisk oppløsningsmiddel (f.eks. pyridin) ved en temperatur på 0 - 100°C. Som middel som er i stand til å innføre en> carbalkoxygruppe som vanligvis anvendes til dette formål, kan f.eks. alkylhalogen-formiater med formel XIV anvendes.
Forbindelsene med formel VI som i 2-stilling bare inneholder amino, kan også overføres til forbindelser med formel VI ved omsetning med et dialkylcarbonat med formel XV i nærvær av en ekvimolar mengde av et alkalialkoholat. Som oppløsningsmiddel anvendes fortrinnsvis en alkanol. Man kan fortrinnsvis som reaksjonsmedium anvende en alkohol som svarer til R<5->alkylgruppen av alkalialkoholatet. Reaksjonstemperaturer er fra 20 til 120°C, fortrinnsvis kokepunktet for det anvendte alkohol-oppløsnings-middel.
Det vil være åpenbart for en fagmann at forbindelsene som
er vist i eksemplene, kan betegnes på to måter avhengig av det forhold om nummereringen begynner fra N-atomet eller NH-gruppen. Således kan bis -(2-methoxycarbony1amino-benzimidazol-5-yl)-disulf id også betegnes som bis-(2-methoxycarbonylamino-benzimidazol-6-yl)-disulfid.
Alle forbindelsene med formel VII er nye unntatt derivatet hvor R 2er hydrogen. Ifølge teknikkens stand er angitt en meget komplisert og omstendelig syv-trinns-syntese for fremstilling av denne forbindelse ifølge hvilken en thiocyanatgruppe innføres i anilin, aminogruppen beskyttes ved innføring av en acylgruppe, produktet underkastes nitrering og hydrolyse, hvorpå det erholdte produkt overføres til et disulfid, som så spaltes i 2-amino-4-mercapto-anilin, og til slutt dannes et disulfid [Ber. 59, 190
(1926); J. Chem. Soc. 1928, 1364; Pharmazie 3, 151 (1948); Arzneimittelforschung 2, 455 (1952)]. I lys av de kompliserte trinn og det lave utbytte er denne fremgangsmåte uegnet for produksjon i industriell målestokk. Forbindelsen med formel VII, hvor R 2er hydrogen, var bare kjent som et laboratorieprodukt av teoretisk interesse.
Forbindelsene med formel VII kan fremstilles ved å oppvarme
en forbindelse med formelen:
Reaksjonen kan utføres fortrinnsvis ved å oppvarme utgangsmateri-alet med formel XVI i et passende oppløsningsmiddel i nærvær av en katalysator.
Videre detaljer ved foreliggende oppfinnelse vil fremgå av eksemplene.
Eksempel 1
2,78 g 3,3',4>4'-tetraamino-difenyl-disulfid og 6,0 g S-methyl-isothiourea-diurethan oppløses i lOO ml 50 volum%-ig alkohol og 1 ml eddiksyre tilsettes, blandingen kokes inntil methyl-mercaptanutviklingen opphører (ca. 3 timer), hvorefter det utfelte bis -(2-methoxycarbony1-benzimidazol-5-yl)-disulfid f raf ilt reres, vaskes og tørres. Man får 4>2 g av produktet (95%)» med smp. 328°C (spaltning).
Eksempel 2
8,8 g natriumhydroxyd oppløses i 50 ml vann, og 4>2 g cyanamid tilsettes. Blandingen avkjøles til 10°C, og 9>4 g klormaursyre-methylester tilsettes dråpevis i løpet av 30-45 minutter. Blandingen omrøres i ytterligere en halv time og tilsettes så til en oppløsning av 13>9 g 3,3',4,4'-tetraamino-difenyl-disulfid i 200 ml 75 volum%-ig alkohol. Reaksjonsblandingen kokes, og pH holdes mellom 3 og 4 ved periodisk tilsetning av konsentrert saltsyre. Efter kokning i 90 minutter avkjøles blandingen til værelse-temperatur, og det utfelte produkt isoleres ved filtrering. Man får 19,0 g bis-(2-methoxycarbonylamino-benzimidazol-5-yl)-disulfid med smp. 325°C (spaltning).
Eksempel 3 til n
Man går frem som i eksempel 1-2 ved å anvende de følg-ende o-fenylendiamin-derivater: 2,2'-dimethyl-4,4',5,5'-tetraamino-difenyl-disulfid, 2,2'-dibutyl-4,4',5,5'-tetraamino-difenyl-disulfid, 2,2*-dibrom-4,4', 5, 5'-tetraamino-difenyl-disulfid, 2,2"-diklor-4,4*, 5, 5'-tetraamino-difenyl-disulfid, 2,2'-difluor-4,4<*>,5,5'-tetraamino-difenyl-disulfid, 2,2'-di-(trifluormethyl)-4,4', 5, 5'-tetraamino-difenyl-disulfid, 2,2'-dimethoxy-4,4', 5, 5'-tetraamino-difenyl-disulfid, 2,2'-difenoxy-4,4', 5, 5'-tetraamino-difenyl-disulfid, 2,2*-dibenzyloxy-4,4', 5, 5'-tetraamino-difenyl-disulfid.
På denne måte fåes de følgende produkter: bis-(2-raethoxycarbonyl-amino-6-methyl-benzimidazol-5-yl)-
disulfid, smp. 305-31O°C;
bis-(2-methoxycarbony1-amino-6-butyl-benzimidazol- 5- yl)-disulfid, smp. 295-298°C;
bis-(2-methoxycarbonyl-amino-6-brom-benzimidazol-5-yl)-
disulfid, smp. 310°C (spaltn.)
bis -(2-methoxycarbonyl-amino-6-klor-benzimidazol-5-yl)-
disulfid, smp. 305-310°C (spaltn.)
bis -(2-methoxycarbonyl-amino-6-fluor-benzimidazol-5-yl)-disulfid, smp. 285-288°C
bis -(2-methoxycarbony1-amino-6-t rifluormet hy1-benzimidazol-5-yl)-disulfid, smp. over 340°C
bis -(2-methoxycarbonyl-amino-6-methoxy-benzimidazol-5-yl)-disulfid, smp. 297-300°C (spaltn.).
Eksempel 12
3,32 g bis-(2-amino-benzimidazol-5-yl)-disulfid oppløses i 300 ml pyridin, og 2,0 g klormaursyre-methylester tilsettes under avkjøling. Blandingen hensettes over natten, hvorefter den opp-varmes på et varmt vannbad i 90-120 minutter. Pyridinet avdestil-leres under vakuum, og vann helles på residuet og de utfelte krystaller frafiltreres, vaskes og tørres. Man får 3,4 g bis-(2-methoxy-carbony1-amino-benzimidazol-5-yl)-disulfid. Utbytte: 78%• Smeltepunkt: 325°C (spaltning).
Eksempel 13
3,32 g bis-(2-amino-benzimidazol-5-yl)-disulfid oppløses i 30 ml methylalkohol, og til denne oppløsning tilsettes 1,80 g dimethylcarbonat og 0,46 g metallisk natrium oppløst i 30 ml methylalkohol. Blandingen kokes i 1 time. Derefter surgjøres blandingen med eddiksyre (pH mellom 5,5 og 6), og det utfelte bis-(2-methoxycarbony1-amino-benzimidazol-5-yl)-disulfid frafiltreres. Vekt: 4,1 g (92,5%). Smeltepunkt: 325°C (spaltning).
Claims (1)
- Utgangsmaterialer for fremstilling av 5(6)-thiobenzimidazolderivater med formelen:og salter derav, hvorR 2 er hydrogen, halogen, alkyl med 1-6 carbonatomer, tri-fluormethyl eller -OR3,R 3 er alkyl med 1-4 carbonatomer,R 4er alkyl med 1-6 carbonatomer, cycloalkyl med 3-7 carbonatomer, alkenyl med 3-6 carbonatomer, alkynyl med 3-6 carbonatomer, fenyl eller benzyl,R 5 er alkyl med 1-4 carbonatomer, karakterisert ved at de har formelen: 2 5 hvor R og R er som ovenfor angitt.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU77CI1735A HU177182B (hu) | 1977-05-10 | 1977-05-10 | Eljárás tetraamino- difenil diszulfid származékok előállítására |
| HU77CI1736A HU176937B (hu) | 1977-05-11 | 1977-05-11 | Sposob poluchenija proizvodnykh diamino-tiocianato-benzola |
| HUCI001738 HU177416B (en) | 1977-05-16 | 1977-05-16 | Process for preparing benzimidazolyl-disulphides |
| HUCI001759 HU177418B (en) | 1977-07-29 | 1977-07-29 | Process for preparing benzimidazole derivatives containing sulphur |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO824114L NO824114L (no) | 1978-11-13 |
| NO151039B true NO151039B (no) | 1984-10-22 |
| NO151039C NO151039C (no) | 1985-01-30 |
Family
ID=27452003
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO781630A NO150156C (no) | 1977-05-10 | 1978-05-09 | Fremgangsmaate ved fremstilling av 5(6)-thio-benzimidazolderivater |
| NO824114A NO151039C (no) | 1977-05-10 | 1982-12-07 | Utgangsmateriale for fremstilling av 5(6)-thio-benzimidazolderivater |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO781630A NO150156C (no) | 1977-05-10 | 1978-05-09 | Fremgangsmaate ved fremstilling av 5(6)-thio-benzimidazolderivater |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US4259344A (no) |
| JP (1) | JPS53149948A (no) |
| AR (1) | AR224110A1 (no) |
| AT (1) | AT365175B (no) |
| CH (3) | CH647237A5 (no) |
| DE (2) | DE2858737C2 (no) |
| DK (1) | DK203178A (no) |
| ES (2) | ES469671A1 (no) |
| FI (1) | FI71557C (no) |
| FR (1) | FR2401144A1 (no) |
| GB (2) | GB1604164A (no) |
| GR (1) | GR64937B (no) |
| IN (1) | IN149802B (no) |
| IT (1) | IT1094815B (no) |
| NL (1) | NL7805019A (no) |
| NO (2) | NO150156C (no) |
| SE (2) | SE443977B (no) |
| SU (1) | SU1014473A3 (no) |
| YU (1) | YU40704B (no) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4152522A (en) * | 1978-01-03 | 1979-05-01 | Ethyl Corporation | Process for the preparation of 2-benzimidazole carbamates |
| JPS54104837A (en) * | 1978-02-03 | 1979-08-17 | Nippon Denso Co Ltd | Controller of copying machines |
| IT1100788B (it) * | 1978-12-06 | 1985-09-28 | Montedison Spa | Benzimidazol-carbammati |
| HU182782B (en) * | 1979-12-04 | 1984-03-28 | Chinoin Gyogyszer Es Vegyeszet | Process for producing alkylthio-benzimidazoles |
| EP0028455A1 (en) * | 1979-10-12 | 1981-05-13 | Imperial Chemical Industries Plc | 5-Phenylselenobenzimidazole derivatives, their preparation and anthelmintic or fasciolicidal compositions containing them |
| HU182763B (hu) * | 1979-10-19 | 1984-03-28 | Chinoin Gyogyszer Es Vegyeszet | Eljárás 5(6)-alkiltio-benzimidazolil-alkil-karbamátok előállítására |
| HU196185B (en) * | 1984-12-19 | 1988-10-28 | Chinoin Gyogyszer Es Vegyeszet | Process for producing benzimidazol-thiol derivatives |
| SE8604566D0 (sv) * | 1986-10-27 | 1986-10-27 | Haessle Ab | Novel compunds |
| US7572460B2 (en) * | 2005-10-25 | 2009-08-11 | Rodrigo Rodriguez-Kabana | Hydrogen cyanamide pesticide formulations |
| US7968108B2 (en) * | 2005-10-25 | 2011-06-28 | Metbro Distributing L.P. | Hydrogen cyanamide pesticide formulations |
| US8197834B2 (en) * | 2007-09-28 | 2012-06-12 | Metbro Distributing L.P. | Solid formulations of hydrogen cyanamide for agricultural applications |
| US8507674B2 (en) * | 2007-11-13 | 2013-08-13 | The University Of Tokyo | Quorum sensing inhibitor |
| US20090275474A1 (en) * | 2008-04-30 | 2009-11-05 | Metbro Distributing L.P. | Pesticidal applications of dimethyl cyanamide |
| US9771483B2 (en) * | 2013-04-19 | 2017-09-26 | The Boeing Company | Systems, compositions, and methods for corrosion inhibition |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE666795A (no) * | 1964-08-04 | 1966-01-13 | ||
| BE793358A (fr) * | 1971-12-27 | 1973-06-27 | Hoechst Ag | Nouveaux derives de 2-carbalcoxy-amino-benzimidazole presentantune activite anthelmintique et leur procede de preparation |
| US3965113A (en) | 1972-12-29 | 1976-06-22 | Syntex (U.S.A.) Inc. | 5(6)-Benzene ring substituted benzimidazole-2-carbamate derivatives having anthelmintic activity |
| DE2348120A1 (de) * | 1973-09-25 | 1975-04-03 | Hoechst Ag | Anthelmintisch wirksame 2-carbalkoxyamino-benzimidazolyl-5(6)-amino-phenylaether und verfahren zu ihrer herstellung |
| US3929823A (en) * | 1973-11-21 | 1975-12-30 | Syntex Inc | 5(6)-Benzene ring substituted benzimidazole-2-carbamate derivatives having anthelmintic activity |
| US3915986A (en) * | 1974-06-19 | 1975-10-28 | Smithkline Corp | Methyl 5-propylthio-2-benzimidazolecarbamate |
-
1978
- 1978-05-08 SE SE7805230A patent/SE443977B/sv not_active IP Right Cessation
- 1978-05-08 YU YU1090/78A patent/YU40704B/xx unknown
- 1978-05-09 GB GB39354/80A patent/GB1604164A/en not_active Expired
- 1978-05-09 CH CH5024/78A patent/CH647237A5/de not_active IP Right Cessation
- 1978-05-09 NO NO781630A patent/NO150156C/no unknown
- 1978-05-09 GB GB18516/78A patent/GB1604163A/en not_active Expired
- 1978-05-09 DK DK203178A patent/DK203178A/da not_active Application Discontinuation
- 1978-05-10 ES ES469671A patent/ES469671A1/es not_active Expired
- 1978-05-10 IN IN505/CAL/78A patent/IN149802B/en unknown
- 1978-05-10 NL NL7805019A patent/NL7805019A/xx not_active Application Discontinuation
- 1978-05-10 AT AT0338078A patent/AT365175B/de not_active IP Right Cessation
- 1978-05-10 DE DE2858737A patent/DE2858737C2/de not_active Expired - Fee Related
- 1978-05-10 JP JP5456778A patent/JPS53149948A/ja active Granted
- 1978-05-10 AR AR272114A patent/AR224110A1/es active
- 1978-05-10 GR GR56196A patent/GR64937B/el unknown
- 1978-05-10 DE DE19782820375 patent/DE2820375A1/de active Granted
- 1978-05-10 IT IT23227/78A patent/IT1094815B/it active
- 1978-05-10 SU SU782615450A patent/SU1014473A3/ru active
- 1978-05-10 FR FR7813909A patent/FR2401144A1/fr active Granted
- 1978-05-10 FI FI781480A patent/FI71557C/fi not_active IP Right Cessation
-
1979
- 1979-02-24 ES ES478062A patent/ES478062A1/es not_active Expired
- 1979-06-22 US US06/051,247 patent/US4259344A/en not_active Expired - Lifetime
-
1982
- 1982-10-07 CH CH590982A patent/CH643242A5/de not_active IP Right Cessation
- 1982-10-07 CH CH590882A patent/CH646156A5/de not_active IP Right Cessation
- 1982-12-07 NO NO824114A patent/NO151039C/no unknown
-
1983
- 1983-10-27 SE SE8305918A patent/SE457956B/sv not_active IP Right Cessation
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