HU182477B - Process for transforming 10,11-epoxy-10,11-dihydro-5h-dibenzo-square bracket-b,f-square bracket closed-azepine -5-carboxamide for producing 10-oxo-10,11-dihydro-5h-dibenz-square bracket-b,f-square bracket closed-azepine-5-carboxamide - Google Patents
Process for transforming 10,11-epoxy-10,11-dihydro-5h-dibenzo-square bracket-b,f-square bracket closed-azepine -5-carboxamide for producing 10-oxo-10,11-dihydro-5h-dibenz-square bracket-b,f-square bracket closed-azepine-5-carboxamide Download PDFInfo
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- HU182477B HU182477B HU79CI1926A HUCI001926A HU182477B HU 182477 B HU182477 B HU 182477B HU 79CI1926 A HU79CI1926 A HU 79CI1926A HU CI001926 A HUCI001926 A HU CI001926A HU 182477 B HU182477 B HU 182477B
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- azepine
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- 238000000034 method Methods 0.000 title claims abstract description 18
- 230000001131 transforming effect Effects 0.000 title 1
- 239000002904 solvent Substances 0.000 claims abstract description 10
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims abstract description 5
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims abstract description 4
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims abstract description 3
- 239000011777 magnesium Substances 0.000 claims abstract description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical group ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 13
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Inorganic materials [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 7
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 6
- ZRWWEEVEIOGMMT-UHFFFAOYSA-N carbamazepine-10,11-epoxide Chemical compound NC(=O)N1C2=CC=CC=C2C2OC2C2=CC=CC=C12 ZRWWEEVEIOGMMT-UHFFFAOYSA-N 0.000 claims description 5
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical group CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 claims description 4
- 239000002798 polar solvent Substances 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 2
- 229910001622 calcium bromide Inorganic materials 0.000 claims 1
- WGEFECGEFUFIQW-UHFFFAOYSA-L calcium dibromide Chemical compound [Ca+2].[Br-].[Br-] WGEFECGEFUFIQW-UHFFFAOYSA-L 0.000 claims 1
- 229940046413 calcium iodide Drugs 0.000 claims 1
- 229910001623 magnesium bromide Inorganic materials 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 8
- 150000001875 compounds Chemical class 0.000 abstract description 6
- ZFXVFMBOFIEPII-UHFFFAOYSA-N 1h-azepine-4-carboxamide Chemical compound NC(=O)C1=CC=CNC=C1 ZFXVFMBOFIEPII-UHFFFAOYSA-N 0.000 abstract description 5
- 150000004677 hydrates Chemical class 0.000 abstract description 4
- 230000008707 rearrangement Effects 0.000 abstract description 4
- 239000011575 calcium Substances 0.000 abstract description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 abstract description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 abstract description 2
- 229910052791 calcium Inorganic materials 0.000 abstract description 2
- 229910052744 lithium Inorganic materials 0.000 abstract description 2
- 229910052749 magnesium Inorganic materials 0.000 abstract description 2
- 239000000126 substance Substances 0.000 abstract 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000000725 suspension Substances 0.000 description 8
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- 238000001035 drying Methods 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-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
- MHCFAGZWMAWTNR-UHFFFAOYSA-M lithium perchlorate Chemical compound [Li+].[O-]Cl(=O)(=O)=O MHCFAGZWMAWTNR-UHFFFAOYSA-M 0.000 description 3
- 229910001486 lithium perchlorate Inorganic materials 0.000 description 3
- 229910001641 magnesium iodide Inorganic materials 0.000 description 3
- CTRLABGOLIVAIY-UHFFFAOYSA-N oxcarbazepine Chemical compound C1C(=O)C2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 CTRLABGOLIVAIY-UHFFFAOYSA-N 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- LFSAPCRASZRSKS-UHFFFAOYSA-N 2-methylcyclohexan-1-one Chemical compound CC1CCCCC1=O LFSAPCRASZRSKS-UHFFFAOYSA-N 0.000 description 2
- FIEKVYPYFQSFTP-UHFFFAOYSA-N 6-methyl-7-oxabicyclo[4.1.0]heptane Chemical compound C1CCCC2OC21C FIEKVYPYFQSFTP-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- -1 aliphatic epoxides Chemical class 0.000 description 2
- CGZZMOTZOONQIA-UHFFFAOYSA-N cycloheptanone Chemical compound O=C1CCCCCC1 CGZZMOTZOONQIA-UHFFFAOYSA-N 0.000 description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
- ZWAJLVLEBYIOTI-UHFFFAOYSA-N cyclohexene oxide Chemical class C1CCCC2OC21 ZWAJLVLEBYIOTI-UHFFFAOYSA-N 0.000 description 2
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 238000006317 isomerization reaction Methods 0.000 description 2
- HSZCZNFXUDYRKD-UHFFFAOYSA-M lithium iodide Chemical compound [Li+].[I-] HSZCZNFXUDYRKD-UHFFFAOYSA-M 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 235000009518 sodium iodide Nutrition 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- WNEUNPWLVWPBGB-UHFFFAOYSA-N 1,6-dimethyl-7-oxabicyclo[4.1.0]heptane Chemical compound C1CCCC2(C)OC21C WNEUNPWLVWPBGB-UHFFFAOYSA-N 0.000 description 1
- MNZAKDODWSQONA-UHFFFAOYSA-N 1-dibutylphosphorylbutane Chemical compound CCCCP(=O)(CCCC)CCCC MNZAKDODWSQONA-UHFFFAOYSA-N 0.000 description 1
- MLOZFLXCWGERSM-UHFFFAOYSA-N 8-oxabicyclo[5.1.0]octane Chemical compound C1CCCCC2OC21 MLOZFLXCWGERSM-UHFFFAOYSA-N 0.000 description 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical class CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 1
- VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 150000001348 alkyl chlorides Chemical class 0.000 description 1
- 150000005215 alkyl ethers Chemical class 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 239000003849 aromatic solvent Substances 0.000 description 1
- MIOWCLFTUUSRGK-UHFFFAOYSA-N bicyclo[4.1.0]heptane-7-carbaldehyde Chemical compound C1CCCC2C(C=O)C21 MIOWCLFTUUSRGK-UHFFFAOYSA-N 0.000 description 1
- WUSJALRVWRGZMI-UHFFFAOYSA-L calcium;diiodide;tetrahydrate Chemical compound O.O.O.O.[Ca+2].[I-].[I-] WUSJALRVWRGZMI-UHFFFAOYSA-L 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 125000001511 cyclopentyl group Chemical class [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 150000002118 epoxides Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 229910003002 lithium salt Inorganic materials 0.000 description 1
- 159000000002 lithium salts Chemical class 0.000 description 1
- UPZGJLYTRBYTLM-UHFFFAOYSA-M lithium;iodide;dihydrate Chemical compound [Li+].O.O.[I-] UPZGJLYTRBYTLM-UHFFFAOYSA-M 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 150000008039 phosphoramides Chemical class 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/18—Dibenzazepines; Hydrogenated dibenzazepines
- C07D223/22—Dibenz [b, f] azepines; Hydrogenated dibenz [b, f] azepines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F3/00—Compounds containing elements of Groups 2 or 12 of the Periodic Table
- C07F3/02—Magnesium compounds
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Epoxy Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
Description
A találmány tárgya eljárás a (I) képletű 10,11-epoxi-10,ll-dihidro-5H-dibenz[b,f]azepin-5-karboxamid (II) képletű 10-oxo-10,11.-dihidro-5H-dibenz[b,f]azepin-5-karboxamiddá történő átalakítására.The present invention relates to a process for the preparation of 10,11-epoxy-10,11-dihydro-5H-dibenz [b, f] azepine-5-carboxamide 10-oxo-10,11-dihydro-5H of formula (I). to convert dibenz [b, f] to azepine-5-carboxamide.
A J. Amer. Chem. Soc. 90, 4193 (1968) cikke ismerteti epoxidoknak lítiumsókkal katalizált átalakítását karbonilvegyületekké. így például ciklohexen-oxidokat vagy azok I-metil- vagy 1,2-dimetil-származékait lítium-bromiddal benzolban tri-n-butil-foszfin-oxid jelenlétében gyűrűszűkítésmellett aldehidekké vagy metil-ketonokká rendeznek át, melyek ciklopentán-származékok. Ugyancsak megemlítik, hogy az 1-metil-ciklohexen-oxid benzolban lítium-perklorát jelenlétében 80° hőmérsékleten 80%-os kitermeléssel 2-metil-ciklohexanonná rendezhető át, míg ugyanilyen körülmények között az 1,2-dimetil-ciklohexen-oxidból a 2,2-dimetil-ciklohexanon 10%-os kitermeléssel nyerhető.J. Amer. Chem. Soc. 90, 4193 (1968) describes the conversion of epoxides to carbonyl compounds by catalysis with lithium salts. For example, cyclohexene oxides or their I-methyl or 1,2-dimethyl derivatives with lithium bromide in benzene in the presence of tri-n-butylphosphine oxide are rearranged to aldehydes or methyl ketones which are cyclopentane derivatives. It is also mentioned that 1-methylcyclohexene oxide in benzene can be converted to 2-methylcyclohexanone in 80% yield in 80% yield in the presence of lithium perchlorate, while under the same conditions, 1,2-dimethylcyclohexenoxide can be converted to 2-Dimethylcyclohexanone was obtained in 10% yield.
A J. Amer. Chem. Soc. 93, 1693—1700 (1971) cikke ezenkívül ismerteti ciklohepten-oxidnak lítium-bromid és hexametil-foszforsav-triamid jelenlétében benzolban 80°-on végzett átrendezését, melynek során a cikloheptanon 26%-os kitermeléssel keletkezik. Lítium-perklorát alkalmazása esetén a cikloheptanon 17%-os kitermeléssel keletkezik. A J. Org. Chem. 34, 2355—2358 (1969) cikke szerint az exo-biciklo[4.2.O]loktén-7-oxid lítium-jodid hatására gyűrűszűkítés közben biciklo[4.1.0] heptán-7-karboxaldehiddé alakítható.J. Amer. Chem. Soc., 93, 1693-1700 (1971) also discloses the rearrangement of cycloheptene oxide in the presence of lithium bromide and hexamethylphosphoric triamide in benzene at 80 ° to give cycloheptanone in a 26% yield. produced. When lithium perchlorate is used, cycloheptanone is formed in 17% yield. J. Org. Chem. 34, 2355-2358 (1969), lithium iodide exo-bicyclo [4.2.0] can be converted to bicyclo [4.1.0] heptane-7-carboxaldehyde by ring reduction.
Az Acta Chemica Scandinavica 18, 1551—1552 (1964) cikkéből az alifás epoxidok metil-jodiddal és nátrium-jodiddal dimetil-formamidban 4 órás viszszafolyatás közben végzett izomerizálása ismeretes, melynek során a megfelelő keton kvantitatív kitermeléssel keletkezik. A Chem. Comm. 1968 227—229oldalaindimetil-szulfoxidban oldott epoxiciklohexán izomerizációját ismerteti, nátrium-jodiddal, és n-propiljodiddal, melynek során 90%-os kitermeléssel ciklo-hexanon keletkezik. E két utóbbi eljárást az (I) képletű vegyidet esetén alkalmazva az első esetben a vékonyrétegkromatográfiás vizsgálat szerint (szilikagél-lemezek, futtatószer etil-acetát) olyan termék keletkezett, mely a (II) képletű vegyületnek csak nyomnyi mennyiségét tartalmazta, míg a második esetben a megfelelő végtermék egyáltalán nem volt kimutatható. Megállapítottuk azt is, hogy ha a fentiekben ismertetett eljárást alkalmaztuk az (I) képletű vegyület esetén, mely szerint 1-metil-ciklohexen-oxidot benzolban lítium-perklorát jelenlétében alakítottak 2-metil-ciklohexanonná, olyan termék keletkezett, mely szilikagél-lemezeken etil-acetát futtatószert használva vékonyrétegkromatográfiásan csak a (II) képletű vegyület nyomnyi mennyiségét mutatta.Acta Chemica Scandinavica 18, 1551-1552 (1964) discloses isomerization of aliphatic epoxides with methyl iodide and sodium iodide in dimethylformamide for 4 hours to give the corresponding ketone in quantitative yield. Chem. Comm. 1968 discloses the isomerization of epoxycyclohexane in 227-229 pages of dimethylsulfoxide, with sodium iodide and n-propyl iodide to give cyclohexanone in 90% yield. Applying the latter two methods to the compound of formula (I) in the first case by thin layer chromatography (silica gel plates, ethyl acetate as eluent) yielded a product containing only trace amounts of the compound of formula (II). no suitable end product could be detected at all. It was also found that using the above procedure for the compound of formula (I) to convert 1-methylcyclohexene oxide in benzene to 2-methylcyclohexanone in the presence of lithium perchlorate, the product formed on silica gel plates with ethyl TLC showed only trace amounts of the compound of formula (II).
Meglepő módon úgy találtuk, hogy a 10,11-epoxi-10,1 l-dihidro-5H-dibenz [b,f ]azepin-5-karboxamid 10-oxo-10,ll-dihidro-5H-dibenz[b,f]-azepin-5karboxamiddá történő átalakítása a lítium, magnézium vagy kalcium bromidja vagy jodidja alkalmazásával végrehajtható anélkül, hogy szükség volna metil-jodid vagy η-ρτορίΐ-jodid hozzáadására. Az eljárás során előnyös a fenti fémek jodidjának alkalmazása. Az alkalmazott sók képlete ezek szerint az LiBr, Lil, MgBr2, Mgl2 CaBr2 és Cal2.Surprisingly, it has been found that 10,11-epoxy-10,11-dihydro-5H-dibenz [b, f] azepine-5-carboxamide 10-oxo-10,11-dihydro-5H-dibenz [b, f] conversion of] -azepine-5-carboxamide to bromide or iodide of lithium, magnesium or calcium without the need for the addition of methyl iodide or η-ρτορίΐ-iodide. In the process, the use of iodide of the above metals is preferred. The salts used are thus defined as LiBr, Lil, MgBr 2 , Mgl 2 CaBr 2 and Cal 2 .
E sókat vízmentes formában vagy önmagában ismert, vízzel (hidrátok) vagy dietil-éterrel (dietiléterát) alkotott formájukban használhatjuk.These salts may be used in anhydrous form or in their known form with water (hydrates) or diethyl ether (diethyl etherate).
A hidrátok például a következők: LiBr-H2O, LiBr -2H2O, LiBr-3H2O, LiI H20, LiI 2H2O,LiI• 3H2O, MgBr2 · 6H2O, MgBr2 10H2O, Mgla · 8H2O, Mgl2 · 10H2O, CaBr2 -6H2O, Cal2 -4H2O, Cal2 ·6Η2Ο.Examples of hydrates are: LiBr-H 2 O, LiBr- 2 H 2 O, LiBr-3 H 2 O, Li I H 2 O, Li I 2 H 2 O, Li I • 3 H 2 O, MgBr 2 · 6H 2 O, MgBr 2 10H 2 O, Mgl a · 8H 2 O, Mgl 2 · 10H 2 O, CaBr 2 -6H 2 O, Cal 2 -4H 2 O, Cal 2 · 6Η 2 Ο.
A találmány szerinti eljárás során előnyösen alkalmazható sók, ezek hidrátjai illetve dietil-éterátjai a következők: LiBr, LiI-2H2O, Mgl2-(dietil-éterát) és CaI2-4H2O.The preferred salts, hydrates and diethyl ethers of the process according to the invention are LiBr, LiI-2H 2 O, Mgl 2 - (diethyl etherate) and Ca 2 4 -4H 2 O.
A találmány szerinti reakciót valamely oldószerben, például egy adott esetben halogénezett alifás vagy aromás szénhidrogénben, például valamely halogén-, például klór-alkánban, például metilén-kloridban, szén-tetrakloridban, etilén-kloridban v. difluor-klór-metánban, előnyösen azonban kloroformban végezzük. Aromás jellegű oldószer például a benzol vagy klór-benzol. Előnyös lehet egy további oldószer adagolása, hogy elősegítsük a lenti sóknak az alkalmazott oldószerben való oldódását. Ilyen szempontból elsősorban poláros oldószerek jönnek számításba, például a tetrahidrofurán, dioxán, vagy egy foszforamid-származék, például hexametil-foszforsav-triamid. Az alkalmazandó poláros oldószer mennyisége az alkalmazott só minőségétől függ, általában az adalék felső határa 1 mól oldószer 1 mól sóra vonatkoztatva.The reaction of the invention is carried out in a solvent such as an optionally halogenated aliphatic or aromatic hydrocarbon such as a halogen such as chloroalkane such as methylene chloride, carbon tetrachloride, ethylene chloride or the like. in difluorochloromethane, but preferably in chloroform. An aromatic solvent is, for example, benzene or chlorobenzene. It may be advantageous to add an additional solvent to facilitate the dissolution of the salts below in the solvent used. Polar solvents, for example, tetrahydrofuran, dioxane, or a phosphoramide derivative such as hexamethylphosphoric triamide, are preferred. The amount of polar solvent to be used will depend on the nature of the salt used, usually with an upper limit of 1 mole of solvent per mole of salt.
A reakcióelegy szokásos módon történő feldolgozásával a végterméket jó kitermeléssel és tisztán kapjuk.Workup of the reaction mixture in the usual manner affords the final product in good yield and purity.
A reakció hőmérséklete 20—120°, előnyösen 40— 80°. Az (I) és (II) képletű vegyületek egyaránt ismertek. Az eljárás során alkalmazandó szerves anyagok illetve a sóknak azokkal alkotott formái ismertek vagy amennyiben újak, önmagukban ismert módszerekkel könnyen előállíthatok. így például az eljárás egyik kiviteli alakjában használt magnézium-jodid-dietil-éterátot magnéziumforgács és jód rövidszénláncú díalkil-éterben, például dietil-éterben végzett reakciójával állítjuk elő.The reaction temperature is 20-120 °, preferably 40-80 °. Both compounds of formula (I) and (II) are known. The organic materials to be used in the process or the salt forms thereof are known or, if new, can be readily prepared by methods known per se. For example, magnesium iodide diethyl etherate used in one embodiment of the process is prepared by reaction of magnesium turnings and iodine in lower alkyl ether, such as diethyl ether.
Az alábbi példákban a találmány szerinti eljárást részletesen mutatjuk be. A hőmérsékleti értékeket Celsius fokban adjuk meg.The following examples illustrate the process of the invention in detail. Temperatures are given in degrees Celsius.
1. példaExample 1
5,0 g 10,ll-dihidro-10,ll-epoxi-5H-dibenz[b,f] -azepin-5-karboxamid 50 ml kloroformmal készített szuszpenziójához 5,0 g lítium-jodid-dihidrátot adunk. A-szuszpenziót visszafolyási hőmérsékletre melegítjük és ezen a hőmérsékleten 30 percen át ke vertet j ük. Ezután az oldatot szobahőmérsékletre hűtjük, 50 ml vízzel majd 20 ml vízzel mossuk, a kloroformos oldatot szárazra pároljuk és a maradékot metanolból átkristályosítjuk. Szárítás utánTo a suspension of 5.0 g of 10,11-dihydro-10,11-epoxy-5H-dibenz [b, f] -azepine-5-carboxamide in 50 ml of chloroform was added 5.0 g of lithium iodide dihydrate. A - The suspension was heated to reflux for 30 minutes and s j vert this temperature in uk. The solution was cooled to room temperature, washed with water (50 mL) and water (20 mL), the chloroform solution was evaporated to dryness and the residue was recrystallized from methanol. After drying
1,1 g (82%) 10,ll-dihidro-10-oxo-5H-dibenz[b,f]-azepin-5-karboxamidot kapunk, op.: 214°.1.1 g (82%) of 10,11-dihydro-10-oxo-5H-dibenz [b, f] -azepine-5-carboxamide are obtained, m.p.
2. példaExample 2
5,0 g 10,ll-dihidro-10,ll-epoxi-5H-dibenz[b,f]-azepin-5-karboxamid 50 ml kloroformmal készített szuszpenziójához 6,2 g magnézium-jodid-die1 il-éterátot adunk. A szuszpenziót visszafolyási hőmérsékletre melegítjük és ezen a hőmérsékleten 30 3 percen át kevertetjük. Ezután az oldatot szobahőmérsékletre hűtjük, 50 ml vízzel majd 20 ml vízzel mossuk, a kloroformos oldatot szárazra pároljuk és a maradékot metanolból átkristályosítjuk. Szárítás után 4,0 g (80%) 10,ll-dihidro-10-oxo-5H-dibenz[b,f]azepin -5-karhoxamidot kapunk, melynek olvadáspontja 214°.To a suspension of 5.0 g of 10,11-dihydro-10,11-epoxy-5H-dibenz [b, f] -azepine-5-carboxamide in 50 ml of chloroform was added 6.2 g of magnesium iodide diethyl etherate. The suspension was heated to reflux and stirred at this temperature for 30 minutes. The solution was cooled to room temperature, washed with water (50 mL) and water (20 mL), the chloroform solution was evaporated to dryness and the residue was recrystallized from methanol. After drying, 4.0 g (80%) of 10,11-dihydro-10-oxo-5 H -dibenz [b, f] azepine-5-carboxamide is obtained, m.p. 214 DEG.
A kiindulási anyagként használt magnézium-jodid-dietil-éterátot a következőképpen állíthatjuk elő: 10 ml vízmentes dietil-éterben 1,5 g magnéziumforgácshoz kis részletekben 4,0 g jódot adunk. Az elegyet 60 percen át visszafolyatás közben kevertetjük, majd a maradék magnéziumforgácsot kiszűrjük és a szűrletet bepároljuk, mikoris a kiin- 15 dulási anyag sűrűn folyó enyhén elszíneződött olajként marad vissza.The starting magnesium iodide diethyl etherate was prepared as follows: In 10 ml of anhydrous diethyl ether, 4.0 g of iodine was added in small portions. After stirring for 60 minutes at reflux, the remaining magnesium turnings were filtered off and the filtrate was evaporated to leave the starting material as a dense, slightly colored oil.
3. példaExample 3
2,3 g 10,ll-dihidro-10,ll-epoxi-5H-dibenz[b,f]- 20 -azepin-5-karboxamid 20 ml klór-benzollal készített szuszpenziójához 1,8 g hexametilfoszforsav-triamidot és 1,7 g lítium-bromidot adunk. A szuszpenziót 70°-ra melegítjük és 30 percen át ezen a hőmérsékleten kevertetjük. Ezután az oldatot szó- 25 bahőmérsékletre hűtjük, és a terméket 50 ml víz és 50 ml etil-acetát között megoszlatjuk. Az etilacetátos oldatot szárazra pároljuk és a maradékot metanolból átkristályosítjuk. Szárítás után 1,5 g (65%) 10,ll-dihidro-10-oxo-5H-dihenz[b,f]-azepin- 30 -5-karboxamidot kapunk, melynek olvadáspontja 214°.To a suspension of 2.3 g of 10,11-dihydro-10,11-epoxy-5H-dibenz [b, f] -20-azepine-5-carboxamide in 20 ml of chlorobenzene, 1.8 g of hexamethylphosphoric triamide and 1.7 g of g of lithium bromide was added. The suspension is heated to 70 ° and stirred at this temperature for 30 minutes. The solution was then cooled to room temperature and the product was partitioned between water (50 mL) and ethyl acetate (50 mL). The ethyl acetate solution was evaporated to dryness and the residue was recrystallized from methanol. After drying, 1.5 g (65%) of 10,11-dihydro-10-oxo-5H-dihenz [b, f] -azepine-30-5-carboxamide is obtained, m.p. 214 ° C.
4. példaExample 4
10,0 g 10,ll-dihidro-10,ll-epoxi-5H-dibenz[b,f]- 35 -azepin-5-karboxamid 25 ml kloroformmal készített szuszpenziójához 5,0 g kalcium-jodid-tetrahidrátot adunk. A szuszpenziót a visszafolyás hőmérsékletére melegítjük és 60 percen át ezen a hőmérsékleten kevertetjük. Ezután az oldatot 0°-ra 5 hűtjük, 25 ml vízzel elkeverjük és a kivált csapadékot leszívatjuk. Szárítás után 7,8 g (78%) 10,11-dihidro-10-oxo-5H-dibenz[b,f]azepin-5-karboxamidot kapunk, melynek olvadáspontja 214°.To a suspension of 10.0 g of 10,11-dihydro-10,11-epoxy-5H-dibenz [b, f] -35-azepine-5-carboxamide in 25 ml of chloroform was added 5.0 g of calcium iodide tetrahydrate. The suspension was warmed to reflux and stirred at this temperature for 60 minutes. The solution is then cooled to 0 ° C, stirred with 25 ml of water and the precipitate is filtered off with suction. After drying, 7.8 g (78%) of 10,11-dihydro-10-oxo-5H-dibenz [b, f] azepine-5-carboxamide, m.p. 214 DEG C., are obtained.
Claims (5)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH413478A CH633271A5 (en) | 1978-04-18 | 1978-04-18 | Process for the rearrangement of 10,11-epoxy-10,11-dihydro-5H-dibenz[b,f]azepines to give 10-oxo-10,11-dihydro-5H-dibenz(b,f)azepines |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HU182477B true HU182477B (en) | 1984-01-30 |
Family
ID=4270467
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU79CI1926A HU182477B (en) | 1978-04-18 | 1979-04-17 | Process for transforming 10,11-epoxy-10,11-dihydro-5h-dibenzo-square bracket-b,f-square bracket closed-azepine -5-carboxamide for producing 10-oxo-10,11-dihydro-5h-dibenz-square bracket-b,f-square bracket closed-azepine-5-carboxamide |
Country Status (17)
| Country | Link |
|---|---|
| JP (1) | JPS54138588A (en) |
| AR (1) | AR222329A1 (en) |
| AT (1) | AT373877B (en) |
| BG (1) | BG29282A3 (en) |
| CA (1) | CA1112241A (en) |
| CH (1) | CH633271A5 (en) |
| DK (1) | DK157779A (en) |
| ES (1) | ES479600A1 (en) |
| FI (1) | FI70010C (en) |
| GR (1) | GR72260B (en) |
| HU (1) | HU182477B (en) |
| NL (1) | NL7902811A (en) |
| NO (1) | NO149776C (en) |
| PL (1) | PL214954A1 (en) |
| PT (1) | PT69495A (en) |
| SE (1) | SE7903328L (en) |
| YU (1) | YU91779A (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0112812D0 (en) * | 2001-05-25 | 2001-07-18 | Portela & Ca Sa | Mthd for preparation of 10, 11-dihydro-10-hydroxy-5H-dibenz/B,F/azepine-5-c arboxamide and 10,11-dihydro-10-oxo-5H-dibenz/B,F/azepine-5-carb oxamide therefrom |
| CA2471666C (en) | 2004-06-18 | 2009-10-13 | Apotex Pharmachem Inc. | An improved process for the preparation of oxcarbazepine and related intermediates |
| GB2422149A (en) | 2005-01-14 | 2006-07-19 | Portela & Ca Sa | Process for the preparation of 10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide |
-
1978
- 1978-04-18 CH CH413478A patent/CH633271A5/en not_active IP Right Cessation
-
1979
- 1979-04-07 GR GR58835A patent/GR72260B/el unknown
- 1979-04-10 NL NL7902811A patent/NL7902811A/en not_active Application Discontinuation
- 1979-04-12 CA CA325,802A patent/CA1112241A/en not_active Expired
- 1979-04-16 BG BG043253A patent/BG29282A3/en unknown
- 1979-04-16 AR AR276195A patent/AR222329A1/en active
- 1979-04-16 ES ES479600A patent/ES479600A1/en not_active Expired
- 1979-04-17 NO NO791274A patent/NO149776C/en unknown
- 1979-04-17 YU YU00917/79A patent/YU91779A/en unknown
- 1979-04-17 HU HU79CI1926A patent/HU182477B/en unknown
- 1979-04-17 PT PT69495A patent/PT69495A/en unknown
- 1979-04-17 AT AT0288379A patent/AT373877B/en not_active IP Right Cessation
- 1979-04-17 SE SE7903328A patent/SE7903328L/en not_active Application Discontinuation
- 1979-04-17 FI FI791233A patent/FI70010C/en not_active IP Right Cessation
- 1979-04-17 PL PL21495479A patent/PL214954A1/xx unknown
- 1979-04-17 DK DK157779A patent/DK157779A/en not_active IP Right Cessation
- 1979-04-18 JP JP4680279A patent/JPS54138588A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| PT69495A (en) | 1979-05-01 |
| NO149776C (en) | 1984-06-20 |
| FI70010B (en) | 1986-01-31 |
| FI791233A (en) | 1979-10-19 |
| ATA288379A (en) | 1983-07-15 |
| SE7903328L (en) | 1979-10-19 |
| ES479600A1 (en) | 1979-07-16 |
| FI70010C (en) | 1986-09-12 |
| CH633271A5 (en) | 1982-11-30 |
| GR72260B (en) | 1983-10-10 |
| DK157779A (en) | 1979-10-19 |
| YU91779A (en) | 1983-01-21 |
| NO791274L (en) | 1979-10-19 |
| NL7902811A (en) | 1979-10-22 |
| BG29282A3 (en) | 1980-10-15 |
| AR222329A1 (en) | 1981-05-15 |
| AT373877B (en) | 1984-02-27 |
| PL214954A1 (en) | 1980-07-01 |
| JPS54138588A (en) | 1979-10-27 |
| NO149776B (en) | 1984-03-12 |
| CA1112241A (en) | 1981-11-10 |
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