NO770648L - PROCEDURES FOR THE PREPARATION OF 1-METHYL-2- (ALKYL SULPHONYL) - (PHENOXYMETHYL) -5-NITRO-IMIDAZOLES - Google Patents
PROCEDURES FOR THE PREPARATION OF 1-METHYL-2- (ALKYL SULPHONYL) - (PHENOXYMETHYL) -5-NITRO-IMIDAZOLESInfo
- Publication number
- NO770648L NO770648L NO770648A NO770648A NO770648L NO 770648 L NO770648 L NO 770648L NO 770648 A NO770648 A NO 770648A NO 770648 A NO770648 A NO 770648A NO 770648 L NO770648 L NO 770648L
- Authority
- NO
- Norway
- Prior art keywords
- methyl
- nitro
- phenoxymethyl
- imidazole
- imidazoles
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 8
- 238000002360 preparation method Methods 0.000 title claims description 5
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical class O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 title 1
- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical class [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 title 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 5
- BJNXOHUHVWNFLQ-UHFFFAOYSA-N 1-methyl-5-nitro-2-(phenoxymethyl)imidazole Chemical class C1=C([N+]([O-])=O)N(C)C(COC=2C=CC=CC=2)=N1 BJNXOHUHVWNFLQ-UHFFFAOYSA-N 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000006125 ethylsulfonyl group Chemical group 0.000 claims description 3
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 3
- 125000003375 sulfoxide group Chemical group 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- 230000001590 oxidative effect Effects 0.000 claims 1
- 238000002844 melting Methods 0.000 description 12
- 230000008018 melting Effects 0.000 description 12
- 238000007254 oxidation reaction Methods 0.000 description 9
- -1 nitro, cyano, methylsulphonyl Chemical group 0.000 description 8
- 230000003647 oxidation Effects 0.000 description 7
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
- 239000007800 oxidant agent Substances 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 239000007858 starting material Substances 0.000 description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- MWUXSHHQAYIFBG-UHFFFAOYSA-N nitrogen oxide Inorganic materials O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- MAGYJBIKZXSGHF-UHFFFAOYSA-N 2-[(4-ethyl-3-methylphenyl)sulfanylmethyl]-1-methyl-5-nitroimidazole Chemical compound CN1C(=NC=C1[N+](=O)[O-])CSC1=CC(=C(C=C1)CC)C MAGYJBIKZXSGHF-UHFFFAOYSA-N 0.000 description 2
- YNJSNEKCXVFDKW-UHFFFAOYSA-N 3-(5-amino-1h-indol-3-yl)-2-azaniumylpropanoate Chemical compound C1=C(N)C=C2C(CC(N)C(O)=O)=CNC2=C1 YNJSNEKCXVFDKW-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- WFPZPJSADLPSON-UHFFFAOYSA-N dinitrogen tetraoxide Chemical compound [O-][N+](=O)[N+]([O-])=O WFPZPJSADLPSON-UHFFFAOYSA-N 0.000 description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 150000003462 sulfoxides Chemical class 0.000 description 2
- MRLSLMCEWBURMB-UHFFFAOYSA-N 1-methyl-2-[(4-methylphenyl)sulfanylmethyl]-5-nitroimidazole Chemical compound CN1C(=NC=C1[N+](=O)[O-])CSC1=CC=C(C=C1)C MRLSLMCEWBURMB-UHFFFAOYSA-N 0.000 description 1
- HBDLZYHJBXDDJM-UHFFFAOYSA-N 1-methyl-2-[(4-methylsulfinylphenoxy)methyl]-5-nitroimidazole Chemical compound C1=C([N+]([O-])=O)N(C)C(COC=2C=CC(=CC=2)S(C)=O)=N1 HBDLZYHJBXDDJM-UHFFFAOYSA-N 0.000 description 1
- YMIAMMYJWRZXIX-UHFFFAOYSA-N 1-methyl-2-[(4-methylsulfonylphenoxy)methyl]-5-nitroimidazole Chemical compound C1=C([N+]([O-])=O)N(C)C(COC=2C=CC(=CC=2)S(C)(=O)=O)=N1 YMIAMMYJWRZXIX-UHFFFAOYSA-N 0.000 description 1
- XYPISWUKQGWYGX-UHFFFAOYSA-N 2,2,2-trifluoroethaneperoxoic acid Chemical compound OOC(=O)C(F)(F)F XYPISWUKQGWYGX-UHFFFAOYSA-N 0.000 description 1
- PDISGXFXQFGQFB-UHFFFAOYSA-N 2-(chloromethyl)-1-methyl-5-nitroimidazole Chemical compound CN1C(CCl)=NC=C1[N+]([O-])=O PDISGXFXQFGQFB-UHFFFAOYSA-N 0.000 description 1
- UCJSCNUJHUVGRG-UHFFFAOYSA-N 2-[(3,4-dimethylphenyl)sulfanylmethyl]-1-methyl-5-nitroimidazole Chemical compound CN1C(=NC=C1[N+](=O)[O-])CSC1=CC(=C(C=C1)C)C UCJSCNUJHUVGRG-UHFFFAOYSA-N 0.000 description 1
- IUJPNSGQTKWLRI-UHFFFAOYSA-N 2-[(4-ethylsulfinyl-3-methylphenoxy)methyl]-1-methyl-5-nitroimidazole Chemical compound C1=C(C)C(S(=O)CC)=CC=C1OCC1=NC=C([N+]([O-])=O)N1C IUJPNSGQTKWLRI-UHFFFAOYSA-N 0.000 description 1
- GXTVOQVRERBPSB-UHFFFAOYSA-N 2-[(4-ethylsulfinylphenoxy)methyl]-1-methyl-5-nitroimidazole Chemical compound C1=CC(S(=O)CC)=CC=C1OCC1=NC=C([N+]([O-])=O)N1C GXTVOQVRERBPSB-UHFFFAOYSA-N 0.000 description 1
- WKUBINCNXYCVEG-UHFFFAOYSA-N 2-[(4-ethylsulfonyl-3-methylphenoxy)methyl]-1-methyl-5-nitroimidazole Chemical compound CN1C(=NC=C1[N+](=O)[O-])COC1=CC(=C(C=C1)S(=O)(=O)CC)C WKUBINCNXYCVEG-UHFFFAOYSA-N 0.000 description 1
- QNVJMNNKCZIFIX-UHFFFAOYSA-N 2-[(4-ethylsulfonylphenoxy)methyl]-1-methyl-5-nitroimidazole Chemical compound C1=CC(S(=O)(=O)CC)=CC=C1OCC1=NC=C([N+]([O-])=O)N1C QNVJMNNKCZIFIX-UHFFFAOYSA-N 0.000 description 1
- ULQQGOGMQRGFFR-UHFFFAOYSA-N 2-chlorobenzenecarboperoxoic acid Chemical compound OOC(=O)C1=CC=CC=C1Cl ULQQGOGMQRGFFR-UHFFFAOYSA-N 0.000 description 1
- VMKYTRPNOVFCGZ-UHFFFAOYSA-N 2-sulfanylphenol Chemical class OC1=CC=CC=C1S VMKYTRPNOVFCGZ-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- XTEGARKTQYYJKE-UHFFFAOYSA-M Chlorate Chemical class [O-]Cl(=O)=O XTEGARKTQYYJKE-UHFFFAOYSA-M 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 150000008050 dialkyl sulfates Chemical class 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- WQYVRQLZKVEZGA-UHFFFAOYSA-N hypochlorite Chemical class Cl[O-] WQYVRQLZKVEZGA-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical class OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical class OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
Classifications
-
- 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
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members 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
- C07D233/91—Nitro radicals
- C07D233/92—Nitro radicals attached in position 4 or 5
- C07D233/94—Nitro radicals attached in position 4 or 5 with hydrocarbon radicals, substituted by oxygen or sulfur atoms, attached to other ring members
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Preventing Corrosion Or Incrustation Of Metals (AREA)
Description
Fremgangsmåte til fremstilling av Method for the production of
l-metyl-2-(alkylsulfonyl)-fenoksy-metyl)-5_nitro-imidazoler. 1-methyl-2-(alkylsulfonyl)-phenoxy-methyl)-5-nitro-imidazoles.
Gjenstand for søknad nr. 75 ^2 57 er l-alkyl-2-(fenoksymetyl)-5_nitro-iinidazoler med formel The subject of application no. 75 ^2 57 is 1-alkyl-2-(phenoxymethyl)-5-nitro-inidazoles of formula
1 2 hvori R betyr metyl eller etyl, R betyr trifluormetyl, tri-. klormetyl, nitro, cyan,.metylsulfonyl eller ■ etylsulfonyl og R betyr hydrogen, fluor, klor, brom, jod, trifluormetyl, tri-klormetyl, nitro eller cyan, fremgangsmåte til fremstilling av disse forbindelser, farmasøytiske"midler som inneholder dem og deres anvendelse. Gjenstand for tilleggssøknaden er l-metyl-2-(fenoksymetyl)-5_nitro-imidazoler med formel 1 2 in which R means methyl or ethyl, R means trifluoromethyl, tri-. chloromethyl, nitro, cyan,.methylsulfonyl or ■ ethylsulfonyl and R means hydrogen, fluorine, chlorine, bromine, iodine, trifluoromethyl, trichloromethyl, nitro or cyano, process for the preparation of these compounds, pharmaceuticals containing them and their use The subject matter of the supplementary application is 1-methyl-2-(phenoxymethyl)-5-nitro-imidazoles with the formula
hvori R betyr nitro, cyan, metylsulfonyl eller etylsulfonyl og R betyr metyl eller halogen samt fremgangsmåte til fremstilling av disse forbindelser, farmasøytiske "midler som inneholder dem og deres anvendelse. in which R means nitro, cyano, methylsulphonyl or ethylsulphonyl and R means methyl or halogen as well as processes for the preparation of these compounds, pharmaceutical "agents containing them and their use.
I videreutviklingen av gjenstanden for søknad nr. In the further development of the subject of application no.
75 ^2 57 er det nå funnet en fremgangsmåte til fremstilling av l-alkyl-2-(fenoksymetyl)-5-nitro-imidazoler med formel I 75 ^2 57 a process has now been found for the preparation of 1-alkyl-2-(phenoxymethyl)-5-nitro-imidazoles of formula I
1 2 hvori R betyr metyl, R betyr metylsulfonyl eller etylsulfonyl og R^ betyr hydrogen, metyl eller halogen som fluor, klor, brom eller jod, idet denne fremgangsmåte erkarakterisert vedat 1-■ metyl-2-(fenoksymetyl)-5-nitro-imidazoler med formel II 1 2 in which R means methyl, R means methylsulfonyl or ethylsulfonyl and R^ means hydrogen, methyl or halogen such as fluorine, chlorine, bromine or iodine, this method being characterized by 1-■ methyl-2-(phenoxymethyl)-5-nitro- imidazoles of formula II
hvori A betyr et svovelatoirr eller en sulfoksydgruppe (-S0-), where A means a sulfur atom or a sulfoxide group (-S0-),
R betyr metyl eller etyl, R"<*>"betyr metyl og R^ betyr hydrogen, metyl eller halogen,som fluor, klor, brom eller jod, oksyderes. R means methyl or ethyl, R"<*>" means methyl and R^ means hydrogen, methyl or halogen, such as fluorine, chlorine, bromine or iodine, is oxidized.
De som utgangsstoffer anvendte 1-mety1-2-(fenoksy-metyl )-5-nitro-imidazoler med formel II er gjenstand for søknad nr. 76 24 23. De kan fåes av l-metyl-2-klormetyl-5-nitro-imidazol (oppnåelig ifølge DOS 1.595-929 og DOS 1.470.'102) og eventuelt substituert alkylmerkaptofenoler eller alkylsulfinyl-fenoler (oppnåelig av de tilsvarende merkaptofenoler og dialkyl-sulfat og eventuelt deretter oksydasjon med perbenzosyre) i dimetylformamid og i nærvær av kaliumkarbonat.• The 1-methyl-2-(phenoxy-methyl)-5-nitro-imidazoles of formula II used as starting substances are the subject of application no. 76 24 23. They can be obtained from 1-methyl-2-chloromethyl-5-nitro- imidazole (obtainable according to DOS 1.595-929 and DOS 1.470.'102) and optionally substituted alkyl mercaptophenols or alkylsulfinyl phenols (obtainable from the corresponding mercaptophenols and dialkyl sulfate and optionally subsequent oxidation with perbenzoic acid) in dimethylformamide and in the presence of potassium carbonate.•
Som utgangsstoTfer med formel II kommer det eksempelvis på tale: 1-mety1-2-(4-metyltio-fenoksymetyl)-5-nitro-imidazol 1-mety1-2-(4-etyltio-fenoksymetyl)-5-nitro-imidazol 1-mety1-2-(3-metyl-4-metyltio-fenoksymetyl)-5-nitro-imidazol 1-mety1-2-(3~mety1-4-etyltio-fenoksymetyl)-5-nitro-imidazol l-metyl-2-(3~fluor-, -klor-, -brom-, -jod-4-metyltio-fenoksy-metyl )-5-nitro-imidazol Examples of starting materials with formula II include: 1-methyl-2-(4-methylthio-phenoxymethyl)-5-nitro-imidazole 1-methyl-2-(4-ethylthio-phenoxymethyl)-5-nitro-imidazole 1 -methyl-2-(3-methyl-4-methylthio-phenoxymethyl)-5-nitro-imidazole 1-methyl-2-(3-methyl-4-ethylthio-phenoxymethyl)-5-nitro-imidazole 1-methyl-2 -(3~fluoro-, -chloro-, -bromo-, -iodo-4-methylthio-phenoxy-methyl )-5-nitro-imidazole
l-metyl-2-(3~fluor-, -klor-, -brom-, -jod-4-etyltio-fenoksy-metyl ) -5-nitro-imidazol 1-methyl-2-(3-fluoro-, -chloro-, -bromo-, -iodo-4-ethylthio-phenoxy-methyl )-5-nitro-imidazole
l-metyl-2-(4-metylsulfinyl-fenoksymetyl)-5-nitro-imidazol l-metyl-2-(4-etylsulfinyl-fenoksymetyl)-5-nitro-imidazol l-metyl-2-(3-mety1-4-metylsulfinyl-fenoksymetyl)-5-nitroimidazol l-methyl-2-(4-methylsulfinyl-phenoxymethyl)-5-nitro-imidazole l-methyl-2-(4-ethylsulfinyl-phenoxymethyl)-5-nitro-imidazole l-methyl-2-(3-methyl-4 -methylsulfinyl-phenoxymethyl)-5-nitroimidazole
l-metyl-2- (3-mety1-4-etylsulf inyl-f enoksymetyl) - 5-nitro-imidazol l-metyl-2-(3~fluor-, -klor-, -brom-, -jod-4-metylsulfinyl-fenoksymetyl)-5-nitro-imidazol 1-methyl-2-(3-methyl-4-ethylsulfinyl-phenoxymethyl)-5-nitro-imidazole 1-methyl-2-(3-fluoro-, -chloro-, -bromo-, -iodo-4- methylsulfinyl-phenoxymethyl)-5-nitro-imidazole
l-metyl-2-(3-fluor-, -klor-, -brom-, -jod-4-etyIsulfinyl-fenoksymetyl)-5-nitro-imidazol. 1-methyl-2-(3-fluoro-, -chloro-, -bromo-, -iodo-4-ethylsulfinyl-phenoxymethyl)-5-nitro-imidazole.
Til oksydasjonen anvendes hensiktsmessig en- eller to ganger molare mengder av et oksydasjonsmiddel. Ofte kan det fortrinnsvis anvendes et overskudd av oksydasjonsmidlet. Anvender man som utgangsstoffer de tilsvarende sulfider (A = -S- One or two times molar quantities of an oxidizing agent are suitably used for the oxidation. Often, an excess of the oxidizing agent can preferably be used. The corresponding sulfides are used as starting materials (A = -S-
i formel II), så krever man minst to molekvivalenter oksydasjonsmiddel. Anvender man som utgangsstoff de tilsvarende sulfoksyder (A = -SO--i formel II), så trenger man en molekvi-valent oksydasjonsmiddel. in formula II), then at least two molar equivalents of oxidizing agent are required. If the corresponding sulfoxides (A = -SO-- in formula II) are used as starting materials, then a molecularly equivalent oxidizing agent is needed.
Som oksydasjonsmiddel kommer det eksempelvis påAs an oxidizing agent, it comes on, for example
tale hydrogenperoksyd eller persyrer, som f.eks. pereddiksyre, pertrifluoreddiksyre, klorperbenzosyre, spesielt 3-klorperbenzosyre, salpetersyre, kromsyre og deres salter, kromsyreanhydrid, permanganater, hypokloriter, klorater, perklorater, perjodater og nitrogenoksyder, spesielt dinitrogentetroksyd. say hydrogen peroxide or peracids, such as peracetic acid, pertrifluoroacetic acid, chloroperbenzoic acid, especially 3-chloroperbenzoic acid, nitric acid, chromic acid and their salts, chromic anhydride, permanganates, hypochlorites, chlorates, perchlorates, periodates and nitrogen oxides, especially dinitrogen tetroxide.
Oksydasjonsreaksjonene gjennomføres - fortrinnsvis iThe oxidation reactions are carried out - preferably in
et oppløsnings- eller fordelingsmiddel.a dissolving or dispersing agent.
Herved egner det seg spesielt slike .oppløsningsmidler som ikke angripes" av oksydasjonsmidlet, som f,eks. eddiksyre, trifluoreddiksyre. Ved anvendelse av perbenzosyre egner det seg også metylenklorid og kloroform som oppløsningsmiddel. Solvents which are not attacked by the oxidizing agent, such as, for example, acetic acid, trifluoroacetic acid, are particularly suitable. When using perbenzoic acid, methylene chloride and chloroform are also suitable as solvents.
OksydasJ onsreaksj onene gj ennomf øre.s vanligvis ved temperaturer mellom 0r-og 100°C, spesielt ved 40-60°C. Reaksjons-tidene utgjør.alt etter reaksjonsbetingelsene få minutter til noen timer. The oxidation reactions usually take place at temperatures between 0 and 100°C, especially at 40-60°C. Depending on the reaction conditions, the reaction times range from a few minutes to a few hours.
Isoleringen av fremgangsmåteproduktene foregår ved fortynning av reaksjonsoppløsningen med vann under samtidig utfelling eller ved inndampning av det organiske oppløsningsmiddel i vakuum.. Eventuelt kan det foregå en rensning ved omkrystalli-sering fra et egnet oppløsningsmiddel eller oppløsningsmiddel-blanding. The process products are isolated by diluting the reaction solution with water during simultaneous precipitation or by evaporating the organic solvent in a vacuum. Optionally, purification may take place by recrystallization from a suitable solvent or solvent mixture.
Eksempel 1. 1- me t y 1- 2 - ( 4 - me t y 1 su 1 f ony 1- f enoks yrne tyl) -' 5- ni ' tr o- imi' d' a' z" o' l, Example 1. 1- me t y 1- 2 - ( 4 - me t y 1 su 1 f ony 1- f enox yrne tyl) -' 5- ni ' tr o- imi' d' a' z" o' l,
27,9 g (0,1 mol) l-metyl-2-(4-metyltio-fenoksy-metyl)-5-nitro-imidazol (smeltepunkt ll6°C) oppløses i 250 ml iseddik og under omrøring tildryppes ved værelsestemperatur 27.9 g (0.1 mol) 1-methyl-2-(4-methylthio-phenoxy-methyl)-5-nitro-imidazole (melting point 116°C) are dissolved in 250 ml of glacial acetic acid and added dropwise at room temperature while stirring
24,3 g (0,25 mol) 35%-ig hydrogenperoksyd. Ved den eksoterme reaksjon foregår temperaturøkning "til ca. 45°C. Derved opp-varmes ennu 1 time ved 60°C under omrøring. Etter avkjøling til værelsestemperatur helles blandingen på 800 ml is/vann-blanding, utfellingen frasuges, vaskes med vann og omkrystalli-. seres fra isopropanol under aktivkulltilsetning. Man får så-ledes 29 g = 93% av det teoretiske l-metyl-2-(4-metyl-sulfonyl-fenoksymetyl)-5-nitro-imidazol i form av gulaktige krystaller med et smeltepunkt 157°C. 24.3 g (0.25 mol) 35% hydrogen peroxide. During the exothermic reaction, the temperature rises to approx. 45°C. The mixture is then heated for another 1 hour at 60°C with stirring. After cooling to room temperature, the mixture is poured into 800 ml of an ice/water mixture, the precipitate is suctioned off, washed with water and is recrystallized from isopropanol with the addition of activated carbon. This gives 29 g = 93% of the theoretical 1-methyl-2-(4-methyl-sulfonyl-phenoxymethyl)-5-nitro-imidazole in the form of yellowish crystals with a melting point 157°C.
Istedenfor utgangsstoffet l-metyl-2-(4-metyltio-fenoksymetyl)-5-nitro-imidazdl kan det også anvendes det tilsvarende sulfoksyd, l-metyl-2-(4-metylsulfinyl-fenoksymetyl)-5-nitro-imidazol (smeltepunkt 130°C). Det er da nødvendig med anvendelse av halve mengden hydrogenperoksyd.. Instead of the starting material 1-methyl-2-(4-methylthio-phenoxymethyl)-5-nitro-imidazdl, the corresponding sulfoxide, 1-methyl-2-(4-methylsulfinyl-phenoxymethyl)-5-nitro-imidazole can also be used (melting point 130°C). It is then necessary to use half the amount of hydrogen peroxide.
På samme måte kan det fremstilles: 1- metyl-2-(4-etylsulfonyl-fenoksymetyl)-5-nitro-imidazol, smeltepunkt 132°C ved oksydasj>on av l-metyl-2-(4-etyltio-fenoksy-metyl)-5-nitro-imidazol (smeltepunkt.90°C) eller l-metyl-2-(4-etylsulfinyl-fenoksymetyl)-5-nitro-imidazol (smeltepunkt 103°C). In the same way, it can be prepared: 1-methyl-2-(4-ethylsulfonyl-phenoxymethyl)-5-nitro-imidazole, melting point 132°C by oxidation of 1-methyl-2-(4-ethylthio-phenoxy-methyl) )-5-nitro-imidazole (melting point 90°C) or 1-methyl-2-(4-ethylsulfinyl-phenoxymethyl)-5-nitro-imidazole (melting point 103°C).
l-metyl-2- (3-me ty 1-4-metylsulf onyl-f enoksymetyl)-5-nitro-imidazol, smeltepunkt l4l°C ved oksydasjon av 1-metyl-2- (3-metyl-4-metyltio-fenoksymetyl)-5-nitro-imidazol (smeltepunkt 108°C) eller l-metyl-2-(3-metyl-4-metylsulfinyl-fenoksy-, metyl)-5-nitroimidazol (smeltepunkt 121°C). 1-methyl-2-(3-methyl 1-4-methylsulfonyl-phenoxymethyl)-5-nitro-imidazole, melting point 141°C by oxidation of 1-methyl-2-(3-methyl-4-methylthio- phenoxymethyl)-5-nitroimidazole (melting point 108°C) or 1-methyl-2-(3-methyl-4-methylsulfinyl-phenoxy-, methyl)-5-nitroimidazole (melting point 121°C).
l-metyl-2-(3-metyl-4-etylsulfonyl-fenoksymetyl)-5-nitroimidazol, smeltepunkt 115°C ved oksydasjon av l-metyl-2-(3-metyl-4-etyltio-fenoksymetyl)-5-nitro-imidazol (smeltepunkt 80°C) eller-l-metyl-2-(3-metyl-4-etylsulfinyl-fenoksymetyl)-5-nitroimidazol (smeltepunkt 95°C). 1-methyl-2-(3-methyl-4-ethylsulfonyl-phenoxymethyl)-5-nitroimidazole, melting point 115°C by oxidation of 1-methyl-2-(3-methyl-4-ethylthio-phenoxymethyl)-5-nitro -imidazole (melting point 80°C) or -1-methyl-2-(3-methyl-4-ethylsulfinyl-phenoxymethyl)-5-nitroimidazole (melting point 95°C).
l-metyl-2-(3-klor-4-metylsulfonyl-fenoksymetyl)-5-nitroimidazpl ved oksydasjon av l-metyl-2-(3-klor-4-metyl-tiofenoksymetyl)-5-nitro-imidazol eller l-metyl-2-(3-klor-4-metylsulfinyl-fenoksymetyl)-5-nitro-imidazol. l-methyl-2-(3-chloro-4-methylsulfonyl-phenoxymethyl)-5-nitroimidazpl by oxidation of l-methyl-2-(3-chloro-4-methyl-thiophenoxymethyl)-5-nitroimidazole or l- methyl-2-(3-chloro-4-methylsulfinyl-phenoxymethyl)-5-nitro-imidazole.
l-metyl-2-(3-klor-4-etylsulfonyl-fenoksymetyl)-5-nitroimidazol ved oksydasjon av l-metyl-2-(3-klor-4-etyltio-fenoksymetyl)-nitro-imidazol eller l-metyl-2-(3-klor-4-etyl-sulfinyl-fenoksy-metyl)-5-nitro-imidazol.. l-methyl-2-(3-chloro-4-ethylsulfonyl-phenoxymethyl)-5-nitroimidazole by oxidation of l-methyl-2-(3-chloro-4-ethylthio-phenoxymethyl)-nitro-imidazole or l-methyl- 2-(3-chloro-4-ethyl-sulfinyl-phenoxy-methyl)-5-nitro-imidazole..
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19762607789 DE2607789A1 (en) | 1974-12-16 | 1976-02-26 | PROCESS FOR THE PREPARATION OF 1-METHYL-2-(ALKYLSULFONYL)-PHENOXY-METHYL)-5-NITRO-IMIDAZOLE |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO770648L true NO770648L (en) | 1977-08-29 |
Family
ID=5970911
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO770648A NO770648L (en) | 1976-02-26 | 1977-02-25 | PROCEDURES FOR THE PREPARATION OF 1-METHYL-2- (ALKYL SULPHONYL) - (PHENOXYMETHYL) -5-NITRO-IMIDAZOLES |
Country Status (12)
| Country | Link |
|---|---|
| AT (1) | AT361468B (en) |
| CA (1) | CA1079738A (en) |
| CH (1) | CH624942A5 (en) |
| DK (1) | DK144524C (en) |
| EG (1) | EG13828A (en) |
| ES (1) | ES456117A2 (en) |
| FI (1) | FI770599A (en) |
| IT (1) | IT1115608B (en) |
| LU (1) | LU76834A1 (en) |
| NL (1) | NL7701838A (en) |
| NO (1) | NO770648L (en) |
| SE (1) | SE7702126L (en) |
-
1977
- 1977-02-21 ES ES456117A patent/ES456117A2/en not_active Expired
- 1977-02-21 NL NL7701838A patent/NL7701838A/en not_active Application Discontinuation
- 1977-02-23 EG EG111/77A patent/EG13828A/en active
- 1977-02-24 IT IT20658/77A patent/IT1115608B/en active
- 1977-02-24 LU LU76834A patent/LU76834A1/xx unknown
- 1977-02-24 CA CA272,551A patent/CA1079738A/en not_active Expired
- 1977-02-24 CH CH231377A patent/CH624942A5/en not_active IP Right Cessation
- 1977-02-24 FI FI770599A patent/FI770599A/fi not_active Application Discontinuation
- 1977-02-25 SE SE7702126A patent/SE7702126L/en unknown
- 1977-02-25 NO NO770648A patent/NO770648L/en unknown
- 1977-02-25 AT AT128477A patent/AT361468B/en not_active IP Right Cessation
- 1977-02-25 DK DK84177A patent/DK144524C/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| SE7702126L (en) | 1977-08-27 |
| AT361468B (en) | 1981-03-10 |
| DK144524C (en) | 1982-09-06 |
| ATA128477A (en) | 1980-08-15 |
| CH624942A5 (en) | 1981-08-31 |
| EG13828A (en) | 1982-09-30 |
| NL7701838A (en) | 1977-08-30 |
| DK144524B (en) | 1982-03-22 |
| LU76834A1 (en) | 1977-09-26 |
| FI770599A (en) | 1977-08-27 |
| ES456117A2 (en) | 1978-03-01 |
| CA1079738A (en) | 1980-06-17 |
| DK84177A (en) | 1977-08-27 |
| IT1115608B (en) | 1986-02-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| BRPI0515944B1 (en) | PROCESS FOR THE PREPARATION OF 4-{4-[({[4-CHLORINE-3-(TRIFLUOROMETHYL)PHEN]AMINO}CARBONYL) AMINO]PHENOXY}NMETHYLPYRIDINE-2-CARBOXAMIDE | |
| RU2284324C2 (en) | Method for preparing benzenesulfonyls | |
| FI59253C (en) | PROCEDURE FOR THERAPEUTIC PREPARATION OF THERAPEUTIC 4-HYDROXY-2H-THIENO (2,3-E) OCH (3,4-E) -1,2-THIAZINE-3-CARBOXAMIDE-1,1-DIOXIDE DERIVATIVES | |
| US4230873A (en) | Thiophene derivatives | |
| NO770161L (en) | THIAZOLIDINE DERIVATIVES AND PROCEDURES FOR THEIR PREPARATION. | |
| JPS58124758A (en) | Benzenesulfonamide derivative | |
| JPH01316379A (en) | Production of condensed heterocyclic rings | |
| NO770648L (en) | PROCEDURES FOR THE PREPARATION OF 1-METHYL-2- (ALKYL SULPHONYL) - (PHENOXYMETHYL) -5-NITRO-IMIDAZOLES | |
| Andersen et al. | 1, 2, 3-Benzoxathiazole 2, 2-dioxides: synthesis, mechanism of hydrolysis, and reactions with nucleophiles | |
| US4127585A (en) | Isoxazol amides of 4-hydroxy-6H-thieno[2,3-b]thiopyran-5-carboxylic acid-7,7-dioxide | |
| JPS62263177A (en) | Benzimidazole compound | |
| NO780202L (en) | PROCEDURE FOR PREPARING NEW ISOKINOLIN DERIVATIVES | |
| US3922277A (en) | (1-Alkyl-5-nitro-imidazolyl-2-alkyl)-pyridyl compounds | |
| GILMAN et al. | Some new N-substituted phenothiazine derivatives and their 5-oxides and 5, 5-dioxides | |
| SE436743B (en) | PROCEDURE FOR THE PREPARATION OF 2,1,3-THIADIAZIN-4-ON-2,2-DIOXIDE DERIVATIVES | |
| Sokolov et al. | Reactions of 2-(α-Haloalkyl) thiiranes with Nucleophilic Reagents: IV. Alkylation of Sulfonamides with 2-Chloromethylthiirane. Synthesis and Properties of 3-(Arylamino) thietanes | |
| US3696122A (en) | Thiophene derivatives | |
| KR800001147B1 (en) | Process for 1-alkyl-2-(phenoxyl methyl)-s-nitro-imidazole | |
| US4066656A (en) | [1,2,5,6]Tetrathiocino-[3,4-c; 7,8-c']diisothiazole-3,8-dicarbonitrile | |
| HU190228B (en) | Process for producing 17-qlpha-dihalogenoethenyl-adrostanes | |
| Deady et al. | On the synthesis of pyridinylthiobarbituric acids | |
| US6509470B2 (en) | Process for preparing tribromomethylsulfonylpyridine | |
| JAKOBSEN et al. | N “‐SULFONYLFORMAMIDRAZONES, METHYLATION, TOSYLATION, HYDROLYSIS AND REACTION WITH AMINES | |
| Pluta | The 1, 4-dithiin ring opening in isothioquinanthrene | |
| SU479282A3 (en) | The method of obtaining - (-chloroethyl) -dinitrotrifluoromethylanilines. |