NO791576L - THIOL DERIVATIVES OF IMIDAZOLE - Google Patents
THIOL DERIVATIVES OF IMIDAZOLEInfo
- Publication number
- NO791576L NO791576L NO791576A NO791576A NO791576L NO 791576 L NO791576 L NO 791576L NO 791576 A NO791576 A NO 791576A NO 791576 A NO791576 A NO 791576A NO 791576 L NO791576 L NO 791576L
- Authority
- NO
- Norway
- Prior art keywords
- imidazole
- accordance
- formula
- methylenethiol
- salts
- Prior art date
Links
- -1 THIOL DERIVATIVES OF IMIDAZOLE Chemical class 0.000 title claims description 5
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 16
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 16
- 150000001875 compounds Chemical class 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 11
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 5
- 229910052700 potassium Inorganic materials 0.000 claims description 5
- 150000007522 mineralic acids Chemical class 0.000 claims description 4
- 150000007524 organic acids Chemical class 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
- 150000001298 alcohols Chemical class 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 230000020477 pH reduction Effects 0.000 claims description 3
- 230000002378 acidificating effect Effects 0.000 claims description 2
- 150000007513 acids Chemical class 0.000 claims description 2
- 230000001476 alcoholic effect Effects 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 229910052788 barium Inorganic materials 0.000 claims description 2
- 229910052791 calcium Inorganic materials 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 229910052976 metal sulfide Inorganic materials 0.000 claims description 2
- 229910052712 strontium Inorganic materials 0.000 claims description 2
- 150000003573 thiols Chemical class 0.000 claims 4
- 150000001242 acetic acid derivatives Chemical class 0.000 claims 1
- 150000003840 hydrochlorides Chemical class 0.000 claims 1
- 235000005985 organic acids Nutrition 0.000 claims 1
- HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical compound [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 0.000 claims 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 claims 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 3
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 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 2
- 229960000583 acetic acid Drugs 0.000 description 2
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 229910017053 inorganic salt Inorganic materials 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 150000003568 thioethers Chemical class 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 1
- 229940122957 Histamine H2 receptor antagonist Drugs 0.000 description 1
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- LYBCHMBMGSZNOA-UHFFFAOYSA-N dichloromethane;formic acid;methanol Chemical compound OC.OC=O.ClCCl LYBCHMBMGSZNOA-UHFFFAOYSA-N 0.000 description 1
- 150000002019 disulfides Chemical class 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- UNHKSXOTUHOTAB-UHFFFAOYSA-N sodium;sulfane Chemical compound [Na].S UNHKSXOTUHOTAB-UHFFFAOYSA-N 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 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)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Cephalosporin Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Description
Tiolderivater av imidazol samt frem-Thiol derivatives of imidazole as well as
gangsmåte til fremstilling av samme.procedure for manufacturing the same.
Den foreliggende oppfinnelse vedrører tiolderivater av imidazol, og deres salter med organiske og uorganiske syrer. The present invention relates to thiol derivatives of imidazole, and their salts with organic and inorganic acids.
Oppfinnelsen vedrører også en fremgangsmåte til fremstilling av samme. The invention also relates to a method for producing the same.
Derivatene kjennetegnes ved at de har formelenThe derivatives are characterized by having the formula
hvor R er en alkylrest med høyst 4 karbonatomer i kjeden. where R is an alkyl residue with no more than 4 carbon atoms in the chain.
Fremgangsmåten ifølge oppfinnelsen kjennetegnes ved at forbindelser med formelen hvor R har samme betydning som i formelen I og X er et halogen-atom, omsettes med et surt sulfid med den generelle formel MeHS, hvor Me er Na, K, Ca, Ba, Sr, Mg eller NH4- Det kan også anvendes andre sure sulfider, men disse er for tiden økonomisk ikke av interesse, noe som begrenser deres anvendelse. Idet praktisk talt alle sure sulfider er løselige i lavere alkoholer, som også forbindelsene med den generelle .formel II er løselige i, arbeides det fortrinnsvis i absolutt metanol, etanol eller propanol. Andre alkoholer, som f.eks. isopropanol, amylalkohol eller allylalkohol, kan også anvendes. Utbyttet er imidlertid generelt fra 10 til 15% lavere enn ved anvendelse av metanol eller etanol. Andre løsnings-midler, som f.eks. dimetylsulfoksyd (DMSO), er ikke gunstige idet disse enten virker oksydative eller løser betydelige mengder oksygen fra luften, noe som kan føre til dannelse av disulfider. The method according to the invention is characterized by the fact that compounds with the formula where R has the same meaning as in formula I and X is a halogen atom are reacted with an acidic sulphide of the general formula MeHS, where Me is Na, K, Ca, Ba, Sr, Mg or NH4- Other acid sulphides can also be used, but these are currently economically not of interest, which limits their use. As practically all acid sulphides are soluble in lower alcohols, in which the compounds of the general formula II are also soluble, the work is preferably carried out in absolute methanol, ethanol or propanol. Other alcohols, such as isopropanol, amyl alcohol or allyl alcohol can also be used. However, the yield is generally from 10 to 15% lower than when using methanol or ethanol. Other solvents, such as e.g. dimethylsulfoxide (DMSO), are not favorable as these either have an oxidative effect or dissolve significant amounts of oxygen from the air, which can lead to the formation of disulphides.
Forbindelsene med den generelle formel I er i basiske medier temmelig ubestandige, særlig ved høyere temperatur, idet de oksy-deres meget hurtig til disulfidforbindelser. For å hindre oksy-dasjonen utføres reaksjonen under gjennomstrømning av tørr i^S The compounds with the general formula I are rather unstable in basic media, particularly at higher temperatures, as they oxidize very quickly to disulphide compounds. In order to prevent the oxidation, the reaction is carried out under a flow of dry i^S
og ved temperaturer på mellom 0 og 20°C.and at temperatures between 0 and 20°C.
Det er kjent at sure metallsulfider er meget ubestandigeIt is known that acid metal sulphides are very unstable
og at de hydrolyseres lett med luftfuktighet og lar seg oksydere med oksygen i luften. Av den grunn er det fordelaktig å arbeide med friskt tilberedet kalium- eller natriumhydrogensulfid. Dette fremstiller man vanligvis av kalium- eller natriumalkoholater i absolutt alkohol med gassformet, tørt svovelvannstoff. Forbindelsene med den generelle formel I i form av de frie baser er meget ubestandige. Av den grunn isoleres de med fordel i form av salter med organiske eller uorganiske syrer. Disse salter oppnås f.eks. enkelt ved surgjøring av reaksjonsmediet med alkoholiske løsninger av de tilsvarende syrer. For isolering har gassformig HCl i isopropanol (35 prosentig løsning), 96 prosentig svovelsyre i isopropanol (40 prosentig løsning) og iseddik i butanol (50 prosentig løsning) vist seg best egnet. and that they are easily hydrolyzed by humidity and can be oxidized by oxygen in the air. For that reason, it is advantageous to work with freshly prepared potassium or sodium hydrogen sulphide. This is usually prepared from potassium or sodium alcoholates in absolute alcohol with gaseous, dry hydrogen sulphide. The compounds with the general formula I in the form of the free bases are very unstable. For that reason, they are advantageously isolated in the form of salts with organic or inorganic acids. These salts are obtained, e.g. simply by acidifying the reaction medium with alcoholic solutions of the corresponding acids. For isolation, gaseous HCl in isopropanol (35 percent solution), 96 percent sulfuric acid in isopropanol (40 percent solution) and glacial acetic acid in butanol (50 percent solution) have proven to be most suitable.
Ved fremgangsmåten ifølge oppfinnelsen er følgende nye forbindelser blitt fremstilt: 4(5)-metyl-5(4)-metylentiol-imidazol i form av hydroklorid. 4(5)-etyl-5(4)-metylentiol-imidazol i form av sulfat. 4(5)-butyl-5(4)-metylentiol-imidazol i form av acetat. By the method according to the invention, the following new compounds have been prepared: 4(5)-methyl-5(4)-methylenethiol-imidazole in the form of hydrochloride. 4(5)-ethyl-5(4)-methylenethiol-imidazole in the form of sulfate. 4(5)-butyl-5(4)-methylenethiol-imidazole in the form of acetate.
Fremgangsmåten ifølge oppfinnelsen er utledet av den kjente fremgangsmåte til fremstilling av tioalkoholer, som er beskrevet i Houben-Weyl "Methoden der organischen Chemie", bind IX, sider 7-11 (1955). Denne fremgangsmåte kan på grunn av den store ube-standighet til forbindelsene med formelen I ikke umiddelbart anvendes, idet den gir en blanding av forbindelsene med den generelle formel I og deres disulfider. Bare ved senkning av temperaturen til 0-5°C og under dråpevis tilsetning av løsningen av forbindelsene II samt under stadig gjennomstrømning av tørr H 2S gjennom reaksjonsblandingen kan forbindelsene med formel I oppnås med høye utbytter (over 90% av det teoretiske). The method according to the invention is derived from the known method for the preparation of thioalcohols, which is described in Houben-Weyl "Methoden der organischen Chemie", volume IX, pages 7-11 (1955). Due to the great instability of the compounds of the formula I, this method cannot be immediately used, as it gives a mixture of the compounds of the general formula I and their disulfides. Only by lowering the temperature to 0-5°C and during the dropwise addition of the solution of the compounds II as well as during constant flow of dry H 2S through the reaction mixture can the compounds of formula I be obtained with high yields (over 90% of the theoretical).
Forbindelsene med formel I tjener som mellomprodukter ved fremstillingen av forskjellige antihystaminika, som er kjent somH2-reseptor-blokkerere. The compounds of formula I serve as intermediates in the preparation of various antihistamines, which are known as H 2 -receptor blockers.
Oppfinnelsen vil bli illustrert ved hjelp av følgende eksem-pler.. The invention will be illustrated using the following examples.
Eksempel 1Example 1
4( 5)- metyl- 5( 4)- metylentio- imidazolhydroklorid4( 5)- methyl- 5( 4)- methylenethio-imidazole hydrochloride
5,86 g (0,15 mol) kalium ble løst i 100 ml absolutt metanol. Løsningen ble deretter mettet med H2S ved 0-5°C. Ved samme temperatur, i en strøm av f^S, ble det i løpet av to timer dråpevis tilsatt en løsning av 10,0 g (0,06 mol) 4(5)-klormetyl-5(4)-metylimidazolhydroklorid i 50 ml absolutt metanol. Etter til-setningen ble det omrørt i ytterligere 3 0 minutter, hvoretter det utskilte uorganiske salt ble avfiltrert. Den filtrerte løs-ning ble surgjort med 10 ml 34 prosentig HCl i isopropanol, hvoretter det ble tilsatt 0,5 g aktivkull og filtrert. Filtratet ble inndampet til et lite volum og i varme tynnet med 3 0-4 0 ml isopropyleter, hvoretter krystallisasjon' begynte. Det ble oppnådd 8,8-9,5 g produkt (dvs. 90-95% av det teoretiske), med et smeltepunkt på 226-227°C. IR (KBr): 3100-2600, 1630, 820 cm<-1>. NMR (DMSO-d6) 6 i ppm: 2,31 (s,3H), 3,86 (s,2H), 9,00 (s,lH), Rf: -0,50, på silikagelplate eluert med CH2Cl2/MeOH/HCOOH (8:2:0,5) og gjort synlig med joddamper. 5.86 g (0.15 mol) of potassium was dissolved in 100 ml of absolute methanol. The solution was then saturated with H2S at 0-5°C. At the same temperature, in a stream of f^S, a solution of 10.0 g (0.06 mol) 4(5)-chloromethyl-5(4)-methylimidazole hydrochloride in 50 ml was added dropwise over the course of two hours absolute methanol. After the addition, it was stirred for a further 30 minutes, after which the separated inorganic salt was filtered off. The filtered solution was acidified with 10 ml of 34% HCl in isopropanol, after which 0.5 g of activated carbon was added and filtered. The filtrate was evaporated to a small volume and diluted in heat with 30-40 ml of isopropyl ether, after which crystallization began. 8.8-9.5 g of product was obtained (ie 90-95% of the theoretical), with a melting point of 226-227°C. IR (KBr): 3100-2600, 1630, 820 cm<-1>. NMR (DMSO-d6) 6 in ppm: 2.31 (s,3H), 3.86 (s,2H), 9.00 (s,1H), Rf: -0.50, on silica gel plate eluted with CH2Cl2/ MeOH/HCOOH (8:2:0.5) and made visible with iodine vapors.
Analyse for: C5HgClN2SAnalysis for: C5HgClN2S
beregnet: C: 36,47; H: 5,50; N: 17,01; S: 19,47% calcd: C: 36.47; H: 5.50; N: 17.01; S: 19.47%
funnet : C: 37,00; H: 5,66; N: 16,48; S: 20,02% found : C: 37.00; H: 5.66; N: 16.48; S: 20.02%
Eksempel 2Example 2
4( 5)- metyl- 5( 4)- metylentiol- imidazolhydroklorid4( 5)- methyl- 5( 4)- methylenethiol- imidazole hydrochloride
5,0 g (0,21 mol) natrium ble løst i 100 ml etanol. Løsningen ble mettet med H2S under kjøling (0-5°C). Til denne løsning ble 5.0 g (0.21 mol) of sodium was dissolved in 100 ml of ethanol. The solution was saturated with H2S under cooling (0-5°C). To this solution was
det i løpet av 2 timer under gjennomstrømning av I^S tilsatt 25,5 g (0,10 mol) 4(5)-brommetyl-5(4)-metylimidazol løst i 50 ml absolutt etanol. Deretter ble det omrørt i ytterligere 30 minutter, og det uorganiske salt ble avfiltrert. Filtratet ble 25.5 g (0.10 mol) of 4(5)-bromomethyl-5(4)-methylimidazole dissolved in 50 ml of absolute ethanol were added over the course of 2 hours while flowing through I^S. It was then stirred for a further 30 minutes and the inorganic salt was filtered off. The filtrate was
surgjort med 20 ml 34 prosentig HCl/isopropylalkohol, og det ble tilsatt 0,5 g aktivkull og filtrert. Filtratet ble inndampet til ca. 4 0 ml, og til den varme løsning ble det tilsatt diisopropyl-eter inntil begynnelse av krystallisasjon. Etter avkjøling til acidified with 20 ml of 34 percent HCl/isopropyl alcohol, and 0.5 g of activated carbon was added and filtered. The filtrate was evaporated to approx. 40 ml, and to the hot solution was added diisopropyl ether until the beginning of crystallization. After cooling to
0°C ble det avfiltrert, og bunnfallet ble spylt med eniblanding av metanol og isopropyleter (1:1). Produktet ble oppnådd med et smeltepunkt på 225-226°C (fra metanol) med et utbytte på 93-97%. IR (KBr): 3100-2600, 1630, 820 cm<-1>. NMR (DMSO-dg): 6 i ppm: 2,31 (s,3H), 3,86 (s,2H), 9,00 (s,lH). NMR (CD3OD): 2,33 (s,3H), 3,85 (s,2H), 8,80 (s,lH). 0°C, it was filtered off, and the precipitate was rinsed with a mixture of methanol and isopropyl ether (1:1). The product was obtained with a melting point of 225-226°C (from methanol) with a yield of 93-97%. IR (KBr): 3100-2600, 1630, 820 cm<-1>. NMR (DMSO-dg): 6 in ppm: 2.31 (s,3H), 3.86 (s,2H), 9.00 (s,1H). NMR (CD 3 OD): 2.33 (s,3H), 3.85 (s,2H), 8.80 (s,1H).
Analyse for C5HgClN2SAnalysis for C5HgClN2S
beregnet: C: 36,47; H: 5,50; N: 17,01; S: 19,47% calcd: C: 36.47; H: 5.50; N: 17.01; S: 19.47%
funnet : C: 36,90; H: 5,96; N: 16,68; S: 20,00% found : C: 36.90; H: 5.96; N: 16.68; S: 20.00%
Rf~0,5 med metylenklorid-metanol-maursyre (8,0:2,0:0,5). Rf~0.5 with methylene chloride-methanol-formic acid (8.0:2.0:0.5).
Eksempel 3Example 3
4( 5)- etyl- 5( 4)- metylentiol- imidazolsulfat4( 5)- ethyl- 5( 4)- methylenethiol- imidazole sulfate
Det ble arbeidet på samme måte som i eksempel 2, men det ble løst 6,5 g Ca(HS)2i 100 ml butanol, og 8,0 g 4(5)-etyl-5(4)-brommetylimidazol ble tilsatt. Surgjøring ble foretatt med 4 0 prosentig svovelsyre i isopropanol. Den ovenfor angitte forbindelse ble oppnådd i 88-90 prosentig utbytte og hadde smeltepunkt på 208-210°C. IR (KBr): 3200-2750, 1635, 915 og 820 cm<-1>. The procedure was the same as in example 2, but 6.5 g of Ca(HS) 2 were dissolved in 100 ml of butanol, and 8.0 g of 4(5)-ethyl-5(4)-bromomethylimidazole was added. Acidification was carried out with 40 percent sulfuric acid in isopropanol. The above compound was obtained in 88-90 percent yield and had a melting point of 208-210°C. IR (KBr): 3200-2750, 1635, 915 and 820 cm<-1>.
Analyse for C6H12<N>204S2Analysis for C6H12<N>204S2
beregnet: C: 29,99; H: 5,04; N: 11,55; S: 26,68% calculated: C: 29.99; H: 5.04; N: 11.55; S: 26.68%
funnet : C: 29,71; H: 5,26; N: 11,80; S: 26,35% found : C: 29.71; H: 5.26; N: 11.80; S: 26.35%
Eksempel 4Example 4
4( 5) - butyl- 5( 4)- metylentiol- imidazolacetat4(5)-butyl-5(4)-methylenethiol-imidazole acetate
Det ble arbeidet på samme måte som beskrevet i eksempel 2, men som utgangsmateriale ble det anvendt 6 g 4(5)-butyl-5(4)-brommetyl-imidazol og 10 g NH^SH, som begge var løst i isopropanol ved 15°C. Surgjøringen ble foretatt med 50 prosentig eddiksyre i butanol. Det ble oppnådd den ovenfor angitte forbindelse med smeltepunkt på 126-128°C og i utbytte på 85-90%. The work was carried out in the same way as described in example 2, but as starting material 6 g of 4(5)-butyl-5(4)-bromomethyl-imidazole and 10 g of NH^SH, both of which were dissolved in isopropanol at 15 °C. The acidification was carried out with 50 percent acetic acid in butanol. The above-mentioned compound was obtained with a melting point of 126-128°C and in a yield of 85-90%.
IR (KBr): 3150-2600, 1635, 910 og 820 cm"<1>. IR (KBr): 3150-2600, 1635, 910 and 820 cm"<1>.
Analyse for: ci0H18N2°2SAnalysis for: ci0H18N2°2S
beregnet: C: 52,15; H: 7,88; N: 12,16; S: 13,92% calcd: C: 52.15; H: 7.88; N: 12.16; S: 13.92%
funnet : C: 51,89; H: 7,99; N: 12,01; S: 13,65% found : C: 51.89; H: 7.99; N: 12.01; S: 13.65%
Claims (8)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH523678 | 1978-05-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO791576L true NO791576L (en) | 1979-11-13 |
Family
ID=4290219
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO791576A NO791576L (en) | 1978-05-12 | 1979-05-11 | THIOL DERIVATIVES OF IMIDAZOLE |
Country Status (18)
| Country | Link |
|---|---|
| JP (2) | JPS5440548B1 (en) |
| BE (1) | BE875994A (en) |
| CS (1) | CS213375B2 (en) |
| DE (1) | DE2919147A1 (en) |
| DK (1) | DK190379A (en) |
| FI (1) | FI791405A7 (en) |
| FR (1) | FR2425434A1 (en) |
| GB (1) | GB2024206B (en) |
| GR (1) | GR68392B (en) |
| HU (1) | HU178707B (en) |
| IT (1) | IT1166783B (en) |
| LU (1) | LU81178A1 (en) |
| NL (1) | NL7903731A (en) |
| NO (1) | NO791576L (en) |
| PL (1) | PL215534A1 (en) |
| SE (1) | SE7904060L (en) |
| SU (1) | SU784765A3 (en) |
| YU (1) | YU110279A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113234018B (en) * | 2021-05-11 | 2022-08-23 | 石家庄市普力制药有限公司 | Production method of cimetidine |
Family Cites Families (3)
| 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 |
| GR65283B (en) * | 1977-12-30 | 1980-08-01 | Crc Ricerca Chim | Method for the alkyliosis of 4(5)-merka ptomethyl-imidazoles with aziridin derivatives |
-
1979
- 1979-04-23 LU LU81178A patent/LU81178A1/en unknown
- 1979-04-27 CS CS792954A patent/CS213375B2/en unknown
- 1979-04-28 GR GR58978A patent/GR68392B/el unknown
- 1979-05-02 FI FI791405A patent/FI791405A7/en not_active Application Discontinuation
- 1979-05-02 BE BE0/194955A patent/BE875994A/en unknown
- 1979-05-08 IT IT22446/79A patent/IT1166783B/en active
- 1979-05-09 SE SE7904060A patent/SE7904060L/en not_active Application Discontinuation
- 1979-05-09 DK DK190379A patent/DK190379A/en not_active Application Discontinuation
- 1979-05-10 FR FR7911900A patent/FR2425434A1/en active Pending
- 1979-05-10 YU YU01102/79A patent/YU110279A/en unknown
- 1979-05-10 SU SU792761900A patent/SU784765A3/en active
- 1979-05-11 NL NL7903731A patent/NL7903731A/en not_active Application Discontinuation
- 1979-05-11 NO NO791576A patent/NO791576L/en unknown
- 1979-05-11 DE DE19792919147 patent/DE2919147A1/en not_active Ceased
- 1979-05-11 HU HU79RI711A patent/HU178707B/en unknown
- 1979-05-12 PL PL21553479A patent/PL215534A1/xx unknown
- 1979-05-12 JP JP5855779A patent/JPS5440548B1/ja active Pending
- 1979-05-14 GB GB7916706A patent/GB2024206B/en not_active Expired
-
1982
- 1982-02-04 JP JP57017396A patent/JPS57150666A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JPS57150666A (en) | 1982-09-17 |
| SU784765A3 (en) | 1980-11-30 |
| NL7903731A (en) | 1979-11-14 |
| IT1166783B (en) | 1987-05-06 |
| BE875994A (en) | 1979-09-03 |
| SE7904060L (en) | 1979-11-13 |
| GB2024206B (en) | 1982-11-10 |
| PL215534A1 (en) | 1980-12-01 |
| IT7922446A0 (en) | 1979-05-08 |
| GB2024206A (en) | 1980-01-09 |
| DK190379A (en) | 1979-11-13 |
| FI791405A7 (en) | 1981-01-01 |
| CS213375B2 (en) | 1982-04-09 |
| JPS5440548B1 (en) | 1979-12-04 |
| HU178707B (en) | 1982-06-28 |
| DE2919147A1 (en) | 1979-11-15 |
| FR2425434A1 (en) | 1979-12-07 |
| LU81178A1 (en) | 1979-09-10 |
| YU110279A (en) | 1983-01-21 |
| GR68392B (en) | 1981-12-29 |
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