DE19618578C1 - Climbazole purificn. giving prod. of specification quality - Google Patents
Climbazole purificn. giving prod. of specification qualityInfo
- Publication number
- DE19618578C1 DE19618578C1 DE1996118578 DE19618578A DE19618578C1 DE 19618578 C1 DE19618578 C1 DE 19618578C1 DE 1996118578 DE1996118578 DE 1996118578 DE 19618578 A DE19618578 A DE 19618578A DE 19618578 C1 DE19618578 C1 DE 19618578C1
- Authority
- DE
- Germany
- Prior art keywords
- climbazole
- toluene
- purificn
- solution
- prod
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- OWEGWHBOCFMBLP-UHFFFAOYSA-N 1-(4-chlorophenoxy)-1-(1H-imidazol-1-yl)-3,3-dimethylbutan-2-one Chemical compound C1=CN=CN1C(C(=O)C(C)(C)C)OC1=CC=C(Cl)C=C1 OWEGWHBOCFMBLP-UHFFFAOYSA-N 0.000 title claims abstract description 22
- 229960003344 climbazole Drugs 0.000 title claims abstract description 20
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims abstract description 39
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims abstract description 10
- 239000013078 crystal Substances 0.000 claims abstract description 5
- 239000012065 filter cake Substances 0.000 claims abstract description 5
- 238000010992 reflux Methods 0.000 claims abstract description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 claims abstract description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims abstract description 5
- 239000012535 impurity Substances 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- 238000002425 crystallisation Methods 0.000 claims description 2
- 230000008025 crystallization Effects 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims 1
- 238000000746 purification Methods 0.000 claims 1
- 238000005406 washing Methods 0.000 abstract description 3
- 238000001035 drying Methods 0.000 abstract description 2
- 238000010438 heat treatment Methods 0.000 abstract description 2
- 238000010899 nucleation Methods 0.000 abstract description 2
- 238000010583 slow cooling Methods 0.000 abstract description 2
- 238000001914 filtration Methods 0.000 abstract 2
- 238000003756 stirring Methods 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 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 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-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
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- -1 B. xylene Chemical class 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 229960001701 chloroform Drugs 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000003495 polar organic solvent Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- HWNAEXPXQPQMQR-UHFFFAOYSA-N 1-(4-chlorophenoxy)-1-fluoro-3,3-dimethylbutan-2-one Chemical compound CC(C)(C)C(=O)C(F)OC1=CC=C(Cl)C=C1 HWNAEXPXQPQMQR-UHFFFAOYSA-N 0.000 description 1
- PUUKWAVTIJCRBR-UHFFFAOYSA-N 1-bromo-1-imidazol-1-yl-3,3-dimethylbutan-2-one;hydrobromide Chemical compound Br.CC(C)(C)C(=O)C(Br)N1C=CN=C1 PUUKWAVTIJCRBR-UHFFFAOYSA-N 0.000 description 1
- OCVXSFKKWXMYPF-UHFFFAOYSA-N 2-chloroimidazole Chemical compound ClC1=NC=CN1 OCVXSFKKWXMYPF-UHFFFAOYSA-N 0.000 description 1
- WXNZTHHGJRFXKQ-UHFFFAOYSA-N 4-chlorophenol Chemical compound OC1=CC=C(Cl)C=C1 WXNZTHHGJRFXKQ-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 229910000287 alkaline earth metal oxide Inorganic materials 0.000 description 1
- 150000003973 alkyl amines Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- XXBDWLFCJWSEKW-UHFFFAOYSA-N dimethylbenzylamine Chemical compound CN(C)CC1=CC=CC=C1 XXBDWLFCJWSEKW-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 150000003948 formamides Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 125000004971 nitroalkyl group Chemical group 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000003809 water extraction Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- 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
- C07D233/56—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 only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
Description
Die vorliegende Erfindung betrifft ein Verfahren zur Aufarbeitung bzw. Reinigung des Antimykotikums ClimbazolThe present invention relates to a method for working up or cleaning of the antifungal drug climbazole
1-(4-Chlorphenoxy)-1-(1H-imidazolyl)-3,3-dimethyl-2-butanon, indem dieses nach der Synthese in Toluol umkristallisiert und mit Toluol und Natriumhydrogen carbonat-Lösung gewaschen wird.1- (4-chlorophenoxy) -1- (1H-imidazolyl) -3,3-dimethyl-2-butanone by following this the synthesis recrystallized in toluene and with toluene and sodium hydrogen carbonate solution is washed.
In DE 21 05 490 werden drei Herstellungsverfahren, unter anderem auch für Climbazol beschrieben. Im dort beschriebenen Verfahren a) kommen vorzugsweise polare organische Lösungsmittel in Frage. Hierzu gehören vorzugsweise Nitrile, wie Acetonitril; Sulfoxide, wie Dimethylsulfoxid; Formamide, wie Dimethyl formamid; Keton, wie Aceton; Ether, wie Diethylether und Tetrahydrofuran; Nitroalkane, wie Nitromethan und unsymmetrische Chlorkohlenwasserstoffe, wie Methylenchlorid und Chloroform.DE 21 05 490 describes three manufacturing processes, including for Climbazol described. In process a) described there preferably come polar organic solvents in question. These preferably include nitriles, such as acetonitrile; Sulfoxides such as dimethyl sulfoxide; Formamides such as dimethyl formamide; Ketone such as acetone; Ethers such as diethyl ether and tetrahydrofuran; Nitroalkanes such as nitromethane and asymmetrical chlorinated hydrocarbons such as Methylene chloride and chloroform.
Die Umsetzung (Verfahren a) wird in Gegenwart eines Säurebinders vorge nommen. Vorzugsweise verwendet man einen entsprechenden Überschuß an Imid azol. Man kann jedoch auch alle übrigen üblicherweise verwendbaren organischen Säurebinder zugeben, wie niedere tertiäre Alkylamine oder Aralylamine, z. B. Triethylamin oder Dimethylbenzylamin.The reaction (process a) is carried out in the presence of an acid binder taken. An appropriate excess of imide is preferably used azole. However, it is also possible to use all the other organic compounds which can usually be used Add acid binders, such as lower tertiary alkyl amines or aralyl amines, e.g. B. Triethylamine or dimethylbenzylamine.
Zur Isolierung unter anderem von Climbazol wird das Lösungsmittel im Vakuum abgedampft und der Rückstand mit einem polaren organischen Solvens aufge nommen. Es schließt sich eine Wasserextraktion zur Entfernung des mitent standenen Imidazolylhydrochlorids und das Eindampfen der Lösung zur Trockne an. Aus dem Rückstand wird die Base durch Umkristallisieren, das Salz durch Behandeln mit der entsprechenden Säure nach den üblichen Methoden gewonnen. To isolate, among other things, climbazole, the solvent is used in vacuo evaporated and the residue with a polar organic solvent taken. This is followed by water extraction to remove the mitent standing imidazolyl hydrochloride and evaporating the solution to dryness on. The base is recrystallized from the residue, the salt by Treat with the appropriate acid obtained by the usual methods.
Als Verdünnungsmittel beim dort beschriebenen Verfahren b) kommen alle inerten hochsiedenden organischen Lösungsmittel in Frage. Hierzu gehören vorzugsweise aromatische Kohlenwasserstoffe, wie z. B. Xylol, oder halogenierte aromatische Kohlenwasserstoffe, wie z. B. Chlorbenzol. Mit Hilfe dieser Lösungsmittel kann das entstehende Reaktionswasser azeotrop abgetrennt werden. Das Verfahren b) kann auch ohne Lösungsmittel z. B. in der Schmelze durchgeführt werden.All inert are used as diluents in process b) described there high-boiling organic solvents in question. These preferably include aromatic hydrocarbons such as B. xylene, or halogenated aromatic Hydrocarbons such as B. chlorobenzene. With the help of these solvents can the water of reaction formed is separated off azeotropically. Procedure b) can also without solvent z. B. be carried out in the melt.
Es kann zweckmäßig sein, bei der Durchführung des Verfahrens b) zur Erleich terung der Wasserabspaltung wasserentziehende Mittel, vorzugsweise Erdalkali oxide, wie z. B. MgO, BaO, CaO oder Aluminiumoxid, zuzusetzen.It may be expedient to facilitate the implementation of method b) dehydration, preferably alkaline earth oxides such as B. MgO, BaO, CaO or aluminum oxide.
Als Verdünnungsmittel beim dort beschriebenen Verfahren c) kommen alle inerten organischen Lösungsmittel in Frage. Hierzu gehören vorzugsweise aromatische Kohlenwasserstoffe, wie z. B. Benzol, Toluol, Ether, wie z. B. Diethylether oder Tetrahydrofuran, chlorierte Kohlenwasserstoffe, wie z. B. Methylenchlorid, Chloro form und Tetrachlorkohlenstoff, und niedere Alkylnitrile, wie z. B. Acetonitril.All inert are used as diluents in process c) described there organic solvents in question. These preferably include aromatic ones Hydrocarbons such as As benzene, toluene, ether, such as. B. diethyl ether or Tetrahydrofuran, chlorinated hydrocarbons, such as. B. methylene chloride, chloro form and carbon tetrachloride, and lower alkyl nitriles, such as. B. acetonitrile.
Aus der EP 046 532 ist unter Beispiel a) ein Verfahren zur Herstellung des Climbazols aus 1-(4-Chlorphenoxy)-3,3-dimethyl-1-fluor-2-butanon mit Imidazol bekannt. Entsprechend den dort unter a) (Seite 6, Zeile 51 ff) beschriebenen Verfahren werden beide Substanzen für 3 Stunden auf 130°C erhitzt.From EP 046 532 under example a) is a method for producing the Climbazole from 1- (4-chlorophenoxy) -3,3-dimethyl-1-fluoro-2-butanone with imidazole known. Corresponding to those described there under a) (page 6, line 51 ff) Both substances are heated to 130 ° C for 3 hours.
Nach dem Erkalten wird der halbfeste Rückstand zwischen Methylenchlorid/ Wasser verteilt, die organische Phase abgetrennt und eingeengt. Das zurück bleib ende rohe Endprodukt wird über eine kleine Säule mit Siliciumdioxid chromatographiert.After cooling, the semi-solid residue is between methylene chloride / Distributed water, the organic phase separated and concentrated. That back The end raw end product is passed through a small column of silica chromatographed.
Schließlich wird in der DE 29 37 595 unter Beispiel 2 ein Verfahren zur Her stellung von Climbazol wie folgt beschrieben:Finally, in DE 29 37 595 under Example 2 a method for the manufacture position of climbazole as follows:
23,14 g (0,18 mol) 4-Chlorphenol werden in 200 ml absolutem Methanol gelöst und mit 4,14 g (0,18 mol) Natrium versetzt. Nach vollständiger Auflösung des Natriums wird die Lösung 30 Minuten unter Rückfluß erhitzt, dann werden bei leichtem Sieden 19,56 g (0,06 mol) 1-Brom-3,3-dimethyl-1-(imidazol-1-yl)-butan- 2-on-hydrobromid zugegeben. Die Reaktionsmischung wird über Nacht unter Rückfluß erhitzt und nach dem Abkühlen eingeengt. Der Rückstand wird zwischen Ether und Wasser verteilt, die organische Phase abgetrennt, dreimal mit 1n Natron lauge, zweimal mit Wasser und dreimal mit Natriumchloridlösung gewaschen und über Natriumsulfat getrocknet. Nach Abdestillieren des Lösungsmittels wird der Rückstand aus Cyclohexan umkristalliert. Man erhält 13,9 g (70% der Theorie) 1- (4-Chlorphenoxy)-3,3-dimethyl-1-(imidazol-1-yl)-butan-2-on vom Schmelzpunkt 95-97°C.23.14 g (0.18 mol) of 4-chlorophenol are dissolved in 200 ml of absolute methanol and 4.14 g (0.18 mol) of sodium were added. After the complete dissolution of the Sodium, the solution is heated under reflux for 30 minutes, then at gentle boiling 19.56 g (0.06 mol) of 1-bromo-3,3-dimethyl-1- (imidazol-1-yl) butane 2-on hydrobromide added. The reaction mixture is under overnight Reflux heated and concentrated after cooling. The backlog is between Distributed ether and water, the organic phase separated, three times with 1N sodium hydroxide lye, washed twice with water and three times with sodium chloride solution and dried over sodium sulfate. After the solvent has been distilled off, the Crystallized residue from cyclohexane. 13.9 g (70% of theory) 1- (4-chlorophenoxy) -3,3-dimethyl-1- (imidazol-1-yl) butan-2-one from the melting point 95-97 ° C.
Aufgrund der aus den Herstellprozessen resultierenden polaren und unpolaren Verunreinigungen wird Climbazol üblicherweise aus Isopropanol umkristallisiert. Dabei erhält man Climbazol in einer Ausbeute von ca. 80% der Theorie in spezi fikationsgerechter Qualität (98-100% Reinheit, Farbe und Geruch spezifikationsgerecht).Due to the polar and non-polar resulting from the manufacturing processes Climbazol is usually recrystallized from isopropanol. Climbazole is obtained in a yield of approx. 80% of theory in spec fictional quality (98-100% purity, color and smell according to specification).
Weniger polare Lösungsmittel wie z. B. Toluol liefern ca. 10% bessere Ausbeute, jedoch ist das Endprodukt stets durch stark riechende Nebenkomponenten, die u. a. aus Pivalinsäure bestehen, verunreinigt.Less polar solvents such as e.g. B. toluene yield about 10% better yield, however, the end product is always characterized by strong smelling secondary components that u. a. consist of pivalic acid, contaminated.
Überraschenderweise wurde gefunden, daß gute Ausbeute und gute Qualität erhal ten werden, wenn nach der Umkristallisation eine Wäsche aus verdünnter Natrium hydrogencarbonatlösung durchgeführt wird, wodurch die störenden Verunreini gungen völlig entfernt werden. Dies ist insbesondere deshalb überraschend, weil naturgemäß die organische toluolische Mutterlauge nicht mit wäßrigem Natriumhydrogencarbonat mischbar ist und so eine völlige Entfernung der Verunreinigungen nicht möglich erschien.Surprisingly, it was found that good yield and good quality when washing with dilute sodium after recrystallization Hydrogen carbonate solution is carried out, eliminating the troublesome impurities completely removed. This is particularly surprising because naturally not the organic toluene mother liquor with aqueous Sodium bicarbonate is miscible and so complete removal of the Impurities did not appear possible.
Nach dem erfinderischen Verfahren werden Ausbeuten um 90% in spezifikations gerechter Qualität erhalten.According to the inventive method, yields of around 90% are specified fair quality.
Im Lösebehälter werden 2,85 kg Toluol vorgelegt und 2,75 kg Climbazol (Reinheit 20%), 30 g Aktivkohle sowie 20 g Filterhilfsmittel dazugegeben.2.85 kg of toluene are placed in the dissolving container and 2.75 kg of climbazole (purity 20%), 30 g activated carbon and 20 g filter aid.
Der Ansatz wird zum Rückflußsieden erhitzt und bei dieser Temperatur eine vorgegebene Zeit gerührt. Das Climbazol geht bei dieser Temperatur vollständig in Lösung.The batch is heated to reflux and at this temperature a given time stirred. The climbazole is completely absorbed at this temperature Solution.
Die Suspension wird über Filter in den Kristallisierbehälter gepumpt. Aus dem klaren Filtrat wird durch langsames Abkühlen und Animpfen mit Climbazol- Kristallen das Climbazol aus der Lösung auskristallisiert. Die gewünschte End temperatur liegt bei ca. 0°C.The suspension is pumped through filters into the crystallization tank. From the clear filtrate is obtained by slow cooling and seeding with climbazole Crystals crystallized the climbazole from the solution. The desired end temperature is approx. 0 ° C.
Das kristalline Climbazol wird aus der erhaltenen Kristallsuspension auf einer Drucknutsche isoliert.The crystalline climbazole is obtained from the crystal suspension obtained on a Pressure filter isolated.
Zur Wäsche des Filterkuchens wird Toluol auf ca. 0°C abgekühlt und über die Sprühdüsen der Drucknutsche gleichmäßig auf den Filterkuchen verteilt. Nach Ab drücken des Toluols vom Feststoff mit Stickstoff wird eine weitere Wäsche mit ca. 5%iger Natriumhydrogencarbonat-Lösung durchgeführt. Anschließend wird der Filterkuchen in einem Trockner im Vakuum durch Mantelbeheizung getrocknet.To wash the filter cake, toluene is cooled to about 0 ° C and over the Spray nozzles of the pressure filter are evenly distributed on the filter cake. After Ab pressing the toluene from the solid with nitrogen, another wash with approx. 5% sodium bicarbonate solution performed. Then the Filter cake dried in a dryer in a vacuum by jacket heating.
Nach der Trocknung wird das Climbazol abgekühlt und über ein Passier-Sieb in
Gebinde abgefüllt.
Ausbeute: 2,215 kg (99%ig) Ware = 90%.After drying, the climbazole is cooled and filled into containers using a sieve.
Yield: 2.215 kg (99%) goods = 90%.
Claims (3)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE1996118578 DE19618578C1 (en) | 1996-05-09 | 1996-05-09 | Climbazole purificn. giving prod. of specification quality |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE1996118578 DE19618578C1 (en) | 1996-05-09 | 1996-05-09 | Climbazole purificn. giving prod. of specification quality |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE19618578C1 true DE19618578C1 (en) | 1997-01-23 |
Family
ID=7793762
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE1996118578 Expired - Fee Related DE19618578C1 (en) | 1996-05-09 | 1996-05-09 | Climbazole purificn. giving prod. of specification quality |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE19618578C1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002094817A1 (en) * | 2001-05-18 | 2002-11-28 | Basf Aktiengesellschaft | Method for the purification of triazolylmethylepoxides |
| EP1531152A1 (en) * | 2003-11-17 | 2005-05-18 | Symrise GmbH & Co. KG | Process for purification of climbazol |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2105490A1 (en) * | 1971-02-05 | 1972-08-10 | Farbenfabriken Bayer Ag, 5090 Leverkusen | Imidazole derivatives, processes for their preparation and their use as pharmaceuticals |
| DE2937595A1 (en) * | 1979-09-18 | 1981-04-02 | Bayer Ag, 5090 Leverkusen | METHOD FOR PRODUCING 1-AZOLYL-1-PHENOXY-ALKAN-2-ONES |
| EP0046532B1 (en) * | 1980-08-23 | 1983-09-14 | Bayer Ag | 3,3-dimethyl-1-fluoro-1-phenoxy-2-butanones(ols), process for their preparation and their use |
-
1996
- 1996-05-09 DE DE1996118578 patent/DE19618578C1/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2105490A1 (en) * | 1971-02-05 | 1972-08-10 | Farbenfabriken Bayer Ag, 5090 Leverkusen | Imidazole derivatives, processes for their preparation and their use as pharmaceuticals |
| DE2937595A1 (en) * | 1979-09-18 | 1981-04-02 | Bayer Ag, 5090 Leverkusen | METHOD FOR PRODUCING 1-AZOLYL-1-PHENOXY-ALKAN-2-ONES |
| EP0046532B1 (en) * | 1980-08-23 | 1983-09-14 | Bayer Ag | 3,3-dimethyl-1-fluoro-1-phenoxy-2-butanones(ols), process for their preparation and their use |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002094817A1 (en) * | 2001-05-18 | 2002-11-28 | Basf Aktiengesellschaft | Method for the purification of triazolylmethylepoxides |
| EP1531152A1 (en) * | 2003-11-17 | 2005-05-18 | Symrise GmbH & Co. KG | Process for purification of climbazol |
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Legal Events
| Date | Code | Title | Description |
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| 8100 | Publication of the examined application without publication of unexamined application | ||
| D1 | Grant (no unexamined application published) patent law 81 | ||
| 8364 | No opposition during term of opposition | ||
| 8339 | Ceased/non-payment of the annual fee |