HU187289B - Process for preparing 4-//2-amino-ethyl/-thiomethyl/-5-methyl-imidazole - Google Patents
Process for preparing 4-//2-amino-ethyl/-thiomethyl/-5-methyl-imidazole Download PDFInfo
- Publication number
- HU187289B HU187289B HU8171A HU7181A HU187289B HU 187289 B HU187289 B HU 187289B HU 8171 A HU8171 A HU 8171A HU 7181 A HU7181 A HU 7181A HU 187289 B HU187289 B HU 187289B
- Authority
- HU
- Hungary
- Prior art keywords
- thiomethyl
- formula
- methyl
- reaction
- aminoethyl
- Prior art date
Links
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 title abstract 3
- 238000004519 manufacturing process Methods 0.000 title abstract 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 8
- 150000003839 salts Chemical class 0.000 claims abstract description 5
- 239000002253 acid Substances 0.000 claims abstract description 4
- 150000004714 phosphonium salts Chemical group 0.000 claims abstract description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 3
- 239000001257 hydrogen Substances 0.000 claims abstract description 3
- 239000012074 organic phase Substances 0.000 claims abstract description 3
- 239000003444 phase transfer catalyst Substances 0.000 claims abstract description 3
- 125000001453 quaternary ammonium group Chemical group 0.000 claims abstract 3
- 229910052783 alkali metal Chemical group 0.000 claims abstract 2
- 150000001340 alkali metals Chemical group 0.000 claims abstract 2
- 239000007864 aqueous solution Substances 0.000 claims abstract 2
- 239000002585 base Substances 0.000 claims abstract 2
- 238000000034 method Methods 0.000 claims description 14
- 238000006243 chemical reaction Methods 0.000 claims description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 8
- JEOZNMMOIBLWLV-UHFFFAOYSA-N 2-[(5-methyl-1h-imidazol-4-yl)methylsulfanyl]ethanamine Chemical compound CC=1N=CNC=1CSCCN JEOZNMMOIBLWLV-UHFFFAOYSA-N 0.000 claims description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- VKPPFDPXZWFDFA-UHFFFAOYSA-N 2-chloroethanamine Chemical group NCCCl VKPPFDPXZWFDFA-UHFFFAOYSA-N 0.000 claims description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 4
- 150000001298 alcohols Chemical class 0.000 claims description 2
- 235000019270 ammonium chloride Nutrition 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- RYVBINGWVJJDPU-UHFFFAOYSA-M tributyl(hexadecyl)phosphanium;bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[P+](CCCC)(CCCC)CCCC RYVBINGWVJJDPU-UHFFFAOYSA-M 0.000 claims description 2
- IZQAUUVBKYXMET-UHFFFAOYSA-N 2-bromoethanamine Chemical compound NCCBr IZQAUUVBKYXMET-UHFFFAOYSA-N 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 239000003960 organic solvent Substances 0.000 claims 1
- 239000000243 solution Substances 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 abstract description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 2
- 125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 abstract 2
- 125000001246 bromo group Chemical group Br* 0.000 abstract 1
- 125000001309 chloro group Chemical group Cl* 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical group NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 description 5
- 229960003151 mercaptamine Drugs 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 239000012467 final product Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- AXJZCJSXNZZMDU-UHFFFAOYSA-N (5-methyl-1h-imidazol-4-yl)methanol Chemical group CC=1N=CNC=1CO AXJZCJSXNZZMDU-UHFFFAOYSA-N 0.000 description 2
- XLSZMDLNRCVEIJ-UHFFFAOYSA-N 4-methylimidazole Chemical compound CC1=CNC=N1 XLSZMDLNRCVEIJ-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- XKBGEWXEAPTVCK-UHFFFAOYSA-M methyltrioctylammonium chloride Chemical compound [Cl-].CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC XKBGEWXEAPTVCK-UHFFFAOYSA-M 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- MXTPRJXPLFGHEE-UHFFFAOYSA-N 1-amino-2-sulfosulfanylethane Chemical compound NCCSS(O)(=O)=O MXTPRJXPLFGHEE-UHFFFAOYSA-N 0.000 description 1
- PUIDZZJQDCILKY-UHFFFAOYSA-N 1-cyano-2-methyl-1-[2-[(5-methyl-1h-imidazol-4-yl)methylsulfanyl]ethyl]guanidine Chemical compound CN=C(N)N(C#N)CCSCC=1N=CNC=1C PUIDZZJQDCILKY-UHFFFAOYSA-N 0.000 description 1
- VFWUYASTZCOUKN-UHFFFAOYSA-N 2-[(5-methyl-1h-imidazol-4-yl)methylsulfanyl]ethanamine;dihydrochloride Chemical compound Cl.Cl.CC=1N=CNC=1CSCCN VFWUYASTZCOUKN-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- ZOHLKTFCEUOOOQ-UHFFFAOYSA-N 4-(methoxymethyl)-5-methyl-1h-imidazole Chemical compound COCC=1N=CNC=1C ZOHLKTFCEUOOOQ-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- USFRYJRPHFMVBZ-UHFFFAOYSA-M benzyl(triphenyl)phosphanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)CC1=CC=CC=C1 USFRYJRPHFMVBZ-UHFFFAOYSA-M 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- CCGSUNCLSOWKJO-UHFFFAOYSA-N cimetidine Chemical compound N#CNC(=N/C)\NCCSCC1=NC=N[C]1C CCGSUNCLSOWKJO-UHFFFAOYSA-N 0.000 description 1
- 229960001380 cimetidine Drugs 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical group 0.000 description 1
- 238000006698 hydrazinolysis reaction Methods 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000005544 phthalimido group Chemical group 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical compound [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- MJRPMUINYAOXRW-UHFFFAOYSA-N tributylphosphane;hydrochloride Chemical compound [Cl-].CCCC[PH+](CCCC)CCCC MJRPMUINYAOXRW-UHFFFAOYSA-N 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
- C07D233/64—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 substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Catalysts (AREA)
Abstract
Description
A találmány tárgya új eljárás a 4-((2-amino-etil)tiometil]-5-metil-imidazol és savaddíciós sói előállítására. Az (I) képletű célvegyület gyógyászatilag hatásos vegyületek, például a H2-receptorokra gyakorolt hisztamin-antagonista hatásáról ismert és „cimetidin” néven forgalmazott N-ciano-N'-metilN-{2-[(5-metil-4-imidazolil)-metil-tio]-etil}-guanidin előállításánakl értékes köztiterméke. Az (I) képletű vegyületet és előállítási eljárását elsőzör az 1 338 169 számú nagy-britanniai szabadalmi leírásban ismertették.The present invention relates to a novel process for the preparation of 4 - ((2-aminoethyl) thiomethyl] -5-methylimidazole and its acid addition salts. The target compound of formula (I) is a pharmacologically active compound, such as a histamine antagonist at H 2 receptors. N-cyano-N'-methyl-N- {2 - [(5-methyl-4-imidazolyl) methylthio] ethyl} guanidine, known as Cimetidine, is a valuable intermediate. The process for its preparation was first described in British Patent No. 1,338,169.
Az ismert eljárás egy (II) általános képletű 4-halogén-metil-, 4-hidroxi-metil- vagy 4-metoxi-metil5-metil-imidazol illetve hidrohalogenidje - a képletben Q jelentése halogénatom, hidroxilcsoport vagy metoxiesoport és a ciszteamin illetve annak hidrogén-halogenidje reagáltatásán alapul. Ha Q halogénatomot jelent, a reagáltatást lúgos közegben, például nátrium-etoxid vagy nátrium-hidroxid jelenlétében végzik. Mivel a ciszteamin egy primer amin, az aminocsoportot védeni kell, például egy ftálimidocsoporttal, amely a reagáltatás befejeztével savas hidrolízissel vagy hidrazinolízissel eltávolítható.The known process is a 4-halomethyl, 4-hydroxymethyl or 4-methoxymethyl-5-methylimidazole or a hydrohalide thereof, wherein Q is halogen, hydroxy or methoxy and cysteamine or its hydrogen. based on the reaction of its halide. When Q represents a halogen atom, the reaction is carried out in an alkaline medium, for example in the presence of sodium ethoxide or sodium hydroxide. Since cysteamine is a primary amine, the amino group must be protected, for example, by a phthalimido group, which can be removed at the end of the reaction by acid hydrolysis or hydrazinolysis.
Ha Q hidroxilcsoportot vagy metoxiesoportot jelent, a reakció savas közegben, 48%-os vizes hidrogén-bromid oldat vagy jégecet jelenlétében játszódik le. A kitermelés ezeknél a reakcióknál 70-90%, a reakcióidő 10-18 óra, 100-120 ’C reakcióhőmérséklet mellett.When Q is hydroxy or methoxy, the reaction takes place in an acidic medium in the presence of 48% aqueous hydrobromic acid or glacial acetic acid. The yield of these reactions is 70-90%, the reaction time is 10-18 hours at a reaction temperature of 100-120 ° C.
A 2 814 355 sz. NSZK-beli közrebocsátási iratNo. 2,814,355. Disclosure document in the Federal Republic of Germany
4-metil-5-[(2-amino-etil)-tiometil]-imidazol-dihidroklorid 4-metil-imidazoIból, formaldehidből és ciszteaminból koncentrált sósavban történő előállítását ismerteti. A reakciót autoklávban 110 és 170 ’C közötti hőmérsékleten hajtják végre. Az eljárás hátránya, hogy ipari méretekben nehezen hajtható végre (magas hőmérséklet, nyomás, zárt rendszer) és drága ciszteamint alkalmaz reaktánsként.Discloses the preparation of 4-methyl-5 - [(2-aminoethyl) thiomethyl] imidazole dihydrochloride from 4-methylimidazole, formaldehyde and cysteamine in concentrated hydrochloric acid. The reaction is carried out in an autoclave at a temperature between 110 and 170 ° C. The disadvantage of the process is that it is difficult to carry out on an industrial scale (high temperature, pressure, closed system) and uses expensive cysteamine as a reactant.
A 2 919 131 sz. NSZK-beli közrebocsátási irat szintén 4-metil-5-[(2-amino-etil)-tiometil]-imidazol előállítását ismerteti. 4-metil-5-hidroxi-metilimidazolból és 2-amino-etán-tiol-kénsavból kiindulva. Az eljárás hátránya, hogy a nagyszámú melléktermék miatt a kitermelés csekély, továbbá melléktermékként kénsav képződik, ami a végtermék izolálását igen megnehezíti.No. 2,919,131. The disclosure of the Federal Republic of Germany also discloses the preparation of 4-methyl-5 - [(2-aminoethyl) thiomethyl] imidazole. Starting from 4-methyl-5-hydroxymethylimidazole and 2-aminoethane-thiol-sulfuric acid. The disadvantage of the process is that due to the large number of by-products the yield is low and sulfuric acid is formed as a by-product which makes the isolation of the final product very difficult.
A találmány célkitűzése olyan eljárás létrehozása, amellyel a 4-[(2-amino-etil)-tiometiI]-5-metilimidazol jó kitermeléssel, szobahőmérsékleten, rövid idő alatt előállítható, és nagy tisztaságú termékként izolálható.It is an object of the present invention to provide a process for the preparation of 4 - [(2-aminoethyl) thiomethyl] -5-methylimidazole in good yield, at room temperature, in a short time, and isolated as a high purity product.
Azt találtuk, hogy a kitűzött cél úgy valósítható meg, hogy a (III) képletű 4(5)-tiometil-5(4)-metilimidazolt egy 2-halogén-etil-aminnal - ahol a halogénatom klór- vagy brómatom lehet - szelektíven alkilezzük. A reagáltatást szobahőmérséklet és 50 ’C közötti hőmérsékleten erős bázis 50%-os oldatából és egy szerves fázisból álló rendszerben, kvaterner ammónium- vagy foszfónium-só fázisátvivő katalizátor jelenlétében végezzük. Katalizátorként például metil-trikaprilil-ammónium-klorid, benziltrietil-ammónium-klorid, benzil-trifenil-foszfónium-klorid, hexadecil-tributil-foszfónium-bromid használható. A találmány szerinti eljárás egyik előnye a 4-[(2-amino-etil)-tiometil]-5-metil-imidazol előállítására eddig ismert eljárással összehasonlítva abban áll, hogy a találmány szerinti eljárásban nem használunk fel ciszteamin-hidrogm-halogenidet. Ezt a rendkívül drága vegyi anyagot egy 2-halogénetil-aminnal, előnyösen 2-klór-etil-aminnal helyettesítjük, amely elfogadhatóbb áru és könnyen hozzáférhető vegyület. Ennél a vegyületnél nincs szükség az aminocsoport előzetes levédésére sem.It has now been found that the object of the present invention can be achieved by selectively alkylating 4 (5) -thiomethyl-5 (4) -methylimidazole of formula (III) with a 2-haloethylamine where the halogen atom may be chlorine or bromine. . The reaction is carried out at room temperature to 50 ° C in a system consisting of a 50% strength base solution and an organic phase in the presence of a quaternary ammonium or phosphonium salt phase transfer catalyst. The catalysts used are, for example, methyl tricapryryl ammonium chloride, benzyltriethylammonium chloride, benzyl triphenylphosphonium chloride, hexadecyl tributylphosphonium bromide. An advantage of the process according to the invention in the preparation of 4 - [(2-aminoethyl) thiomethyl] -5-methylimidazole is that it does not use cysteamine hydrogen halide in the process according to the invention. This extremely expensive chemical is replaced by 2-haloethylamine, preferably 2-chloroethylamine, which is a more acceptable commodity and a readily available compound. This compound does not require any prior protection of the amino group.
Oldószerként olyan poláris oldószerek jönnek számításba, amelyekben a kiindulási vegyület oldódik, így például rövidszénláncú alkoholok vagy acetonitril. Az (I) képletű végtermék 85-90%-os kitermeléssel állítható elő.Suitable solvents are polar solvents in which the starting compound is soluble, such as lower alcohols or acetonitrile. The final product of formula (I) can be obtained in 85-90% yield.
A 4(5)-tiometil-5(4)-metil-imidazol kiindulási anyag és előállítási eljárása a 875 845 számú belga szabadalmi leírásban került bemutatásra.The starting material and the process for the preparation of 4 (5) -thiomethyl-5 (4) -methylimidazole are described in Belgian Patent No. 875,845.
Miután a tiolok nem túlságosan stabil vegyületek, a reagáltatást előnyösen inért atmoszférában végezzük.Since the thiols are not very stable compounds, the reaction is preferably carried out in an inert atmosphere.
Egy másik módszer szerint kiindulási anyagként 5(4)-metil-4(5)-tiometil-imidazol-alkáli-merkaptidot használunk, amely stabil vegyület. A reakciókörülmények hasonlóak az előbb ismertetettekhez,Alternatively, starting material is 5 (4) -methyl-4 (5) -thiomethyl-imidazole alkaline mercaptide which is a stable compound. The reaction conditions are similar to those described above,
A találmány szerinti eljárás előnye, hogy az átalakítást szobahőmérséklet és 50 ’C közötti hőmérsékleten, olcsó 2-halogén-etil-amin alkalmazásával katalizátor jelenlétében lehet végezni. A végtermék jó kitermeléssel, melléktermékek képződése nélkül állítható elő, és a végtermék egyszerűen izolálható.An advantage of the process according to the invention is that the conversion can be carried out at room temperature to 50 ° C using a cheap 2-haloethylamine in the presence of a catalyst. The final product can be obtained in good yield without formation of by-products, and the final product is easily isolated.
Találmányunk további részleteit a következő példákkal szemléltetjük, anélkül, hogy a példákra kívánnánk korlátozni.Further details of the present invention are illustrated by the following examples, but are not intended to be limiting.
1. példaExample 1
6,4 g (0,05 mól) 5-metiI-4-tiometil-imidazolt feloldunk 80 ml etanolban, majd az oldatot 10 ml 50%-os vizes nátrium-hidroxid oldattal és 1,16 g (0,0025 mól) hexadecil-tributil-foszfónium-kloriddal elegyítjük és 10 percen át szobahőmérsékleten, inért atmoszférában keverjük. Ezután 15 perc alatt hozzáadjuk 4,0 g 2-klór-etil-amin 30 ml etanollal készült oldatát, majd a reakcióelegyet 30 percen át szobahőmérsékleten, majd további 30 percen át 50 ’C-on keverjük. Ezután az oldószert lepároljuk, és a maradékot izopropanollal extraháljuk. A szervetlen sókat kiszűrjük és az izopropanolos fázist hidrogén-klorid gáz bevezetésével 1 pH-értékig megsavanyítjuk. A reakcióelegyet szárazra pároljuk és a maradékot etanolból átkristályosítjük. 10,9 g (89,3%) 4-[(2-amino-etil)-tiometil]-5-metil-imidazolt kapunk, dihidroklorid formájában, amelynek olvadáspontja 189-191 ’C.6.4 g (0.05 mol) of 5-methyl-4-thiomethylimidazole are dissolved in 80 ml of ethanol, followed by 10 ml of 50% aqueous sodium hydroxide solution and 1.16 g (0.0025 mol) of hexadecyl. mixed with tributylphosphonium chloride and stirred for 10 minutes at room temperature under inert atmosphere. A solution of 2-chloroethylamine (4.0 g) in ethanol (30 ml) was added over 15 minutes, and the reaction mixture was stirred at room temperature for 30 minutes and then at 50 ° C for an additional 30 minutes. The solvent was evaporated and the residue was extracted with isopropanol. The inorganic salts are filtered off and the isopropanol phase is acidified to pH 1 by the addition of hydrogen chloride gas. The reaction mixture was evaporated to dryness and the residue was recrystallized from ethanol. 10.9 g (89.3%) of 4 - [(2-aminoethyl) thiomethyl] -5-methylimidazole are obtained in the form of the dihydrochloride, m.p. 189-191 ° C.
187.289187 289
2. példaExample 2
Az 1. példával analóg módon, de katalizátorként 580 mg (2,5 mmól) benzil-trietil-ammónium-klori- 5 dót (TEBA) használva 10,8 g (88%) terméket kapunk.In analogy to Example 1, but using 580 mg (2.5 mmol) of benzyltriethylammonium chloride (TEBA) as a catalyst, 10.8 g (88%) of product are obtained.
3. példaExample 3
Az 1. példával analóg módon, de katalizátorként 1,04 (2,5 mmól) trikaprilil-metil-ammónium-kloridot (Aliquat 336) használva 10,9 g (89,3%) terméket kapunk. 15In analogy to Example 1, but using 1.04 (2.5 mmol) of tricaprylmethylammonium chloride (Aliquat 336) as a catalyst, 10.9 g (89.3%) of product are obtained. 15
4. példaExample 4
1,5 g (0,01 mól) 5-metil-4-tiometil-imidazolt nát- 20 rium-merkaptid formájában feloldunk 20 ml vízben, majd az oldatot 70 mg (0,3 mmól) benzil-trietil-ammónium-kloriddal elegyítjük és 10 percen át szobahőmérsékleten keverjük. A reakcióelegyhez 10 perc alatt 8,0 g 2-klór-etil-amin 8 ml etanollal 25 készült elegyét adjuk, és az elegyet 1,5 órán át keverjük. Az elegyet szárazra pároljuk, majd az 1. példában leírt módon dolgozzuk fel. 2,2 g (90,3%) terméket kapunk, amelynek olvadáspontja 190-192 ’C. 305-Methyl-4-thiomethylimidazole (1.5 g, 0.01 mol) was dissolved in sodium mercaptide (20 ml) and the solution was mixed with benzyl triethylammonium chloride (70 mg, 0.3 mmol). and stirred for 10 minutes at room temperature. A mixture of 2-chloroethylamine (8.0 g) in ethanol (8 mL) was added over 10 minutes and the mixture was stirred for 1.5 hours. The mixture was evaporated to dryness and worked up as described in Example 1. 2.2 g (90.3%) of product are obtained, m.p. 190-192 ° C. 30
Claims (4)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| YU80/80A YU41689B (en) | 1980-01-14 | 1980-01-14 | Process for preparing imidazole derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HU187289B true HU187289B (en) | 1985-12-28 |
Family
ID=25548243
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU8171A HU187289B (en) | 1980-01-14 | 1981-01-13 | Process for preparing 4-//2-amino-ethyl/-thiomethyl/-5-methyl-imidazole |
Country Status (10)
| Country | Link |
|---|---|
| JP (1) | JPS56127361A (en) |
| CA (1) | CA1154023A (en) |
| CS (1) | CS214847B2 (en) |
| FI (1) | FI804056L (en) |
| HU (1) | HU187289B (en) |
| NO (1) | NO810083L (en) |
| PL (1) | PL129291B1 (en) |
| SE (1) | SE8100127L (en) |
| SU (1) | SU969159A3 (en) |
| YU (1) | YU41689B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS58188860A (en) * | 1982-04-27 | 1983-11-04 | Fujimoto Seiyaku Kk | Preparation of imidazole derivative |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5440547A (en) * | 1977-09-07 | 1979-03-30 | Seikosha Kk | Device for adjusting output frequency of frequency divider |
| IL56265A (en) * | 1977-12-28 | 1982-08-31 | Om Lab Sa | Process for preparing imidazolyl methylthio guanidine derivatives and a novel intermediate therefor |
-
1980
- 1980-01-14 YU YU80/80A patent/YU41689B/en unknown
- 1980-12-30 FI FI804056A patent/FI804056L/en not_active Application Discontinuation
-
1981
- 1981-01-12 CS CS81233A patent/CS214847B2/en unknown
- 1981-01-12 CA CA000368285A patent/CA1154023A/en not_active Expired
- 1981-01-12 PL PL1981229185A patent/PL129291B1/en unknown
- 1981-01-12 SE SE8100127A patent/SE8100127L/en not_active Application Discontinuation
- 1981-01-12 NO NO810083A patent/NO810083L/en unknown
- 1981-01-13 HU HU8171A patent/HU187289B/en unknown
- 1981-01-13 SU SU813230706A patent/SU969159A3/en active
- 1981-01-13 JP JP275181A patent/JPS56127361A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| PL129291B1 (en) | 1984-04-30 |
| PL229185A1 (en) | 1981-09-18 |
| NO810083L (en) | 1981-07-15 |
| JPS56127361A (en) | 1981-10-06 |
| YU41689B (en) | 1987-12-31 |
| CA1154023A (en) | 1983-09-20 |
| YU8080A (en) | 1983-10-31 |
| SE8100127L (en) | 1981-07-15 |
| CS214847B2 (en) | 1982-06-25 |
| SU969159A3 (en) | 1982-10-23 |
| FI804056L (en) | 1981-07-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US3711498A (en) | N-trityl-imidazoles | |
| CA1096873A (en) | Tertiary imidazolyl alcohols, a process for their production and their use as medicaments | |
| ZA200203859B (en) | Method for production of a triazolinethione derivative. | |
| JP2003503409A (en) | Preparation of nitroguanidine- and nitroenamine-derivatives | |
| HU187289B (en) | Process for preparing 4-//2-amino-ethyl/-thiomethyl/-5-methyl-imidazole | |
| EP0046635B1 (en) | Process for the preparation of cimetidine | |
| EP1001947A1 (en) | Process for manufacturing fluconazole | |
| US6211379B1 (en) | Process for preparing heterocyclic compounds | |
| US4384118A (en) | 4-(3-Iodopropargyloxy) pyrimidine derivatives | |
| NO147838B (en) | INTERMEDIATE FOR USE IN PREPARATION OF THE HYPOTENSIVE AGENT 2- (4- (2-FUROYL) PIPERAZIN-1-YL) -4-AMINO-6,7-DIMETOXYKINAZOLINE | |
| KR100740983B1 (en) | Method for producing heterocyclic compounds | |
| JPS6296481A (en) | Manufacture of n-sulfamyl-3- (2-guanidino-thiazole-4-yl-methylthio)-propioneamidine | |
| JPS6317837B2 (en) | ||
| US4200761A (en) | Process for preparing N-cyano-N'methyl-N"-{2-[(4-methyl-5-imidazolyl)-methylthio]-ethyl} guanidine | |
| KR870001539B1 (en) | Preparing process for 4-methyl-5 thio amino-dimethyl imidazole dihydrochloro | |
| KR100351743B1 (en) | Process for preparation of the n,n-dicyclohexyl-2-benzothiazole sulfenamide | |
| US6248888B1 (en) | Process for the preparation of terazosin hydrochloride dihydrate | |
| EP0066440B1 (en) | Chemical process | |
| US6118006A (en) | Method for preparing a tetrahydropyridin derivative | |
| CZ170697A3 (en) | Process for preparing £(5,6-dicarboxy-3-pyridyl)methyl|ammonium halide | |
| KR900003882B1 (en) | Process for the preparation of compounds with h2 antihistamine activity | |
| JPH0344376A (en) | Production of imidazole derivative | |
| JPS62108872A (en) | Production of dilutiazem | |
| HU204514B (en) | Process for producing (azolyl-phenoxy-methyl)-keton derivatives | |
| JPS58188860A (en) | Preparation of imidazole derivative |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| HU90 | Patent valid on 900628 |