CA1112241A - Process for the rearrangement of 10,11-epoxy-10,11- dihydro-5h-dibenz¬b,f|azepine-5-carboxamide to 10- oxo-10,11-dihydro-5h-dibenz¬b,f|azepine-5- carboxamide - Google Patents
Process for the rearrangement of 10,11-epoxy-10,11- dihydro-5h-dibenz¬b,f|azepine-5-carboxamide to 10- oxo-10,11-dihydro-5h-dibenz¬b,f|azepine-5- carboxamideInfo
- Publication number
- CA1112241A CA1112241A CA325,802A CA325802A CA1112241A CA 1112241 A CA1112241 A CA 1112241A CA 325802 A CA325802 A CA 325802A CA 1112241 A CA1112241 A CA 1112241A
- Authority
- CA
- Canada
- Prior art keywords
- process according
- dihydro
- carboxamide
- dibenz
- azepine
- 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
Links
- 238000000034 method Methods 0.000 title claims abstract description 27
- 230000008707 rearrangement Effects 0.000 title claims abstract description 14
- ZFXVFMBOFIEPII-UHFFFAOYSA-N 1h-azepine-4-carboxamide Chemical compound NC(=O)C1=CC=CNC=C1 ZFXVFMBOFIEPII-UHFFFAOYSA-N 0.000 title description 10
- 239000002904 solvent Substances 0.000 claims abstract description 16
- 150000001875 compounds Chemical class 0.000 claims abstract description 9
- 239000011777 magnesium Substances 0.000 claims abstract description 9
- 239000000126 substance Substances 0.000 claims abstract description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 9
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229910052749 magnesium Inorganic materials 0.000 claims abstract description 8
- 150000004677 hydrates Chemical class 0.000 claims abstract description 5
- CTRLABGOLIVAIY-UHFFFAOYSA-N oxcarbazepine Chemical compound C1C(=O)C2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 CTRLABGOLIVAIY-UHFFFAOYSA-N 0.000 claims abstract description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims abstract description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims abstract description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims abstract description 3
- 239000011575 calcium Substances 0.000 claims abstract description 3
- 229910052791 calcium Inorganic materials 0.000 claims abstract description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229910052744 lithium Inorganic materials 0.000 claims abstract description 3
- ZRWWEEVEIOGMMT-UHFFFAOYSA-N carbamazepine-10,11-epoxide Chemical compound NC(=O)N1C2=CC=CC=C2C2OC2C2=CC=CC=C12 ZRWWEEVEIOGMMT-UHFFFAOYSA-N 0.000 claims abstract 3
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical group ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 12
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 8
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Substances ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 239000004215 Carbon black (E152) Substances 0.000 claims description 2
- 125000001931 aliphatic group Chemical group 0.000 claims description 2
- WUSJALRVWRGZMI-UHFFFAOYSA-L calcium;diiodide;tetrahydrate Chemical compound O.O.O.O.[Ca+2].[I-].[I-] WUSJALRVWRGZMI-UHFFFAOYSA-L 0.000 claims description 2
- 229930195733 hydrocarbon Natural products 0.000 claims description 2
- 150000002430 hydrocarbons Chemical class 0.000 claims description 2
- UPZGJLYTRBYTLM-UHFFFAOYSA-M lithium;iodide;dihydrate Chemical compound [Li+].O.O.[I-] UPZGJLYTRBYTLM-UHFFFAOYSA-M 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- MVPPADPHJFYWMZ-IDEBNGHGSA-N chlorobenzene Chemical group Cl[13C]1=[13CH][13CH]=[13CH][13CH]=[13CH]1 MVPPADPHJFYWMZ-IDEBNGHGSA-N 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 16
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical class CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 13
- HSZCZNFXUDYRKD-UHFFFAOYSA-M lithium iodide Chemical compound [Li+].[I-] HSZCZNFXUDYRKD-UHFFFAOYSA-M 0.000 description 10
- 229910001641 magnesium iodide Inorganic materials 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- -1 aliphatic epoxides Chemical class 0.000 description 5
- BLQJIBCZHWBKSL-UHFFFAOYSA-L magnesium iodide Chemical compound [Mg+2].[I-].[I-] BLQJIBCZHWBKSL-UHFFFAOYSA-L 0.000 description 5
- DHKHKXVYLBGOIT-UHFFFAOYSA-N 1,1-Diethoxyethane Chemical compound CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 229910001623 magnesium bromide Inorganic materials 0.000 description 4
- KXKVLQRXCPHEJC-UHFFFAOYSA-N methyl acetate Chemical compound COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- UNMYWSMUMWPJLR-UHFFFAOYSA-L Calcium iodide Chemical compound [Ca+2].[I-].[I-] UNMYWSMUMWPJLR-UHFFFAOYSA-L 0.000 description 3
- 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
- 229910001640 calcium iodide Inorganic materials 0.000 description 3
- 150000002148 esters Chemical class 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
- OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical compound [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 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
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-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
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N acetaldehyde dimethyl acetal Natural products COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 description 2
- 229910001622 calcium bromide Inorganic materials 0.000 description 2
- WGEFECGEFUFIQW-UHFFFAOYSA-L calcium dibromide Chemical compound [Ca+2].[Br-].[Br-] WGEFECGEFUFIQW-UHFFFAOYSA-L 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
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 2
- 150000001983 dialkylethers Chemical class 0.000 description 2
- NKDDWNXOKDWJAK-UHFFFAOYSA-N dimethoxymethane Chemical compound COCOC NKDDWNXOKDWJAK-UHFFFAOYSA-N 0.000 description 2
- WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 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
- MLFHJEHSLIIPHL-UHFFFAOYSA-N isoamyl acetate Chemical compound CC(C)CCOC(C)=O MLFHJEHSLIIPHL-UHFFFAOYSA-N 0.000 description 2
- GJRQTCIYDGXPES-UHFFFAOYSA-N isobutyl acetate Chemical compound CC(C)COC(C)=O GJRQTCIYDGXPES-UHFFFAOYSA-N 0.000 description 2
- 238000006317 isomerization reaction Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 2
- 238000007157 ring contraction reaction Methods 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
- 239000007858 starting material Substances 0.000 description 2
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 2
- HFVMEOPYDLEHBR-UHFFFAOYSA-N (2-fluorophenyl)-phenylmethanol Chemical compound C=1C=CC=C(F)C=1C(O)C1=CC=CC=C1 HFVMEOPYDLEHBR-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-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
- KNSPBSQWRKKAPI-UHFFFAOYSA-N 2,2-dimethylcyclohexan-1-one Chemical compound CC1(C)CCCCC1=O KNSPBSQWRKKAPI-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
- WDJHALXBUFZDSR-UHFFFAOYSA-N Acetoacetic acid Natural products CC(=O)CC(O)=O WDJHALXBUFZDSR-UHFFFAOYSA-N 0.000 description 1
- VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 description 1
- DKMROQRQHGEIOW-UHFFFAOYSA-N Diethyl succinate Chemical compound CCOC(=O)CCC(=O)OCC DKMROQRQHGEIOW-UHFFFAOYSA-N 0.000 description 1
- IYXGSMUGOJNHAZ-UHFFFAOYSA-N Ethyl malonate Chemical compound CCOC(=O)CC(=O)OCC IYXGSMUGOJNHAZ-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 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
- DLIJPAHLBJIQHE-UHFFFAOYSA-N butylphosphane Chemical compound CCCCP DLIJPAHLBJIQHE-UHFFFAOYSA-N 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- VZGDMQKNWNREIO-UHFFFAOYSA-N carbon tetrachloride Substances ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- ZWAJLVLEBYIOTI-UHFFFAOYSA-N cyclohexene oxide Chemical compound C1CCCC2OC21 ZWAJLVLEBYIOTI-UHFFFAOYSA-N 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 150000002118 epoxides Chemical class 0.000 description 1
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 1
- 150000004694 iodide salts 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
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000001384 succinic acid Substances 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)
- Epoxy Compounds (AREA)
- Other In-Based Heterocyclic 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
Process for the rearrangement of 10,11-epoxy-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide to 10-oxo-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide Abstract The invention relates to a process for the rearrange-ment of 10,11-epoxy-10,11-dihydro-5H-dibenz[b,f]azepine 5-carboxamide of the formula to 10-oxo-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide of the formula
Description
~ 2~
Case 4-11672/-Process for the rearrangement of 10,11-~oxy-10211-dihydro-dihydro-5H-dibenzlb,f]azeeine-5-carboxamide The present invention relates to a process for the rearrangement of 10,11-epoxy-10,11-dihydro-5H-dibenz[b,fl azepine-5-carboxamide of the formula ~` CONH2 to 10-oxo-10,11-dihydro-5H-dibenz~b,f]azepiQe-5-car-boxamide of the formula . O
= _ ~ (II).
The rearrangement, catalysed by lithium salts, of epoxides to carbonyl compounds is known from J. Amer.
Chem. Soc. 90, 4193 (1968). Thus, for example, cyclohexene ' ~
. . .. ..
, ;. : ~ ,~, ,, ,.. , , . . . :
f , ~ , ~ . ' : " ' ' - ", , '~ 2'~
oxide, or the l-methyl or 1,2-dimethyl derivative thereof, is rearranged with the aid of lithium bromide in benzene, in the presence of tri~n-butylphosphine oxide, by means of ring contraction to aldehydes or methyl ketones, which are derived from cyclopentane. The information is also given therein that l-methyl-cyclohexene oxide is rearranged in benzene in the presence of lithium perchlorate at 80 to 2-methyl-cyclohexanone with an 80%
yield, whilst under the same conditions 2,2-dimethyl-cyclohexanone is obtained with 10% yield from 1,2-dimethyl-cyclohexene oxide.
In J. Amer. Chem. Soc. 93, 1693-1700 (1971) is moreover `
described the conversion of cycloheptene oxide in the presence of lithium bromide and hexamethylphosphoric acid triamide in benzene at 80C, with cycloheptanone being obtained with 26% yield. Cycloheptanone is obtained with 17% yield with the use of lithium perchlorate. According to J. Org. Chem. 34, 2355-58 (1969), exo-bicyclo[4.2.0]-octene-7 oxide is rearranged, by the action of lithium iodide, by means of ring contraction to bicyclo[4.1.0]
heptane 7-carboxaldehyde.
From Acta Chemica Scandinavica 18, 1551-1552, (1964) is known the isomerisation of aliphatic epoxides by means of a mixture of methyl iodide and sodium iodide in dimethyl-formamide, by 4 hours' refluæing, in quantitative yield to the corresponding ketones. Finally, the isomerisation of epoxycyclohexane, dissolved in dimethyl sulfoxide~ by means of sodium iodide and n-propyl iodide to cyclohexanone in 90% yield is described in Chemical Communications 1968, 227-229. The analogous application of these ~wo reactions to the compound of the formula I yielded, according to the thin-layer chromatogram using silica gel plates with ethyl acetate as the eluant, in the first case a product which ':
:
..
-4~
contained only traces oF the compoun~ o-F the ~ormula Tl, whilst in the second case no corresponding compound was de~ec~able. I;urthermore, it was asc~rtained that the rearrangement, glven in the foregoing as being known, o~ l-me~hyl-cyclohexene oxide in benzene, in the -presence of lithium perchlorate, to
Case 4-11672/-Process for the rearrangement of 10,11-~oxy-10211-dihydro-dihydro-5H-dibenzlb,f]azeeine-5-carboxamide The present invention relates to a process for the rearrangement of 10,11-epoxy-10,11-dihydro-5H-dibenz[b,fl azepine-5-carboxamide of the formula ~` CONH2 to 10-oxo-10,11-dihydro-5H-dibenz~b,f]azepiQe-5-car-boxamide of the formula . O
= _ ~ (II).
The rearrangement, catalysed by lithium salts, of epoxides to carbonyl compounds is known from J. Amer.
Chem. Soc. 90, 4193 (1968). Thus, for example, cyclohexene ' ~
. . .. ..
, ;. : ~ ,~, ,, ,.. , , . . . :
f , ~ , ~ . ' : " ' ' - ", , '~ 2'~
oxide, or the l-methyl or 1,2-dimethyl derivative thereof, is rearranged with the aid of lithium bromide in benzene, in the presence of tri~n-butylphosphine oxide, by means of ring contraction to aldehydes or methyl ketones, which are derived from cyclopentane. The information is also given therein that l-methyl-cyclohexene oxide is rearranged in benzene in the presence of lithium perchlorate at 80 to 2-methyl-cyclohexanone with an 80%
yield, whilst under the same conditions 2,2-dimethyl-cyclohexanone is obtained with 10% yield from 1,2-dimethyl-cyclohexene oxide.
In J. Amer. Chem. Soc. 93, 1693-1700 (1971) is moreover `
described the conversion of cycloheptene oxide in the presence of lithium bromide and hexamethylphosphoric acid triamide in benzene at 80C, with cycloheptanone being obtained with 26% yield. Cycloheptanone is obtained with 17% yield with the use of lithium perchlorate. According to J. Org. Chem. 34, 2355-58 (1969), exo-bicyclo[4.2.0]-octene-7 oxide is rearranged, by the action of lithium iodide, by means of ring contraction to bicyclo[4.1.0]
heptane 7-carboxaldehyde.
From Acta Chemica Scandinavica 18, 1551-1552, (1964) is known the isomerisation of aliphatic epoxides by means of a mixture of methyl iodide and sodium iodide in dimethyl-formamide, by 4 hours' refluæing, in quantitative yield to the corresponding ketones. Finally, the isomerisation of epoxycyclohexane, dissolved in dimethyl sulfoxide~ by means of sodium iodide and n-propyl iodide to cyclohexanone in 90% yield is described in Chemical Communications 1968, 227-229. The analogous application of these ~wo reactions to the compound of the formula I yielded, according to the thin-layer chromatogram using silica gel plates with ethyl acetate as the eluant, in the first case a product which ':
:
..
-4~
contained only traces oF the compoun~ o-F the ~ormula Tl, whilst in the second case no corresponding compound was de~ec~able. I;urthermore, it was asc~rtained that the rearrangement, glven in the foregoing as being known, o~ l-me~hyl-cyclohexene oxide in benzene, in the -presence of lithium perchlorate, to
2-methylcyclohexanone yielded on analogous application to the compound of the formula I a product which, according to the thin-layer chromatogram using silica gel plates with ethyl acetate as the eluant, contained only traces of the compound of the formula II.
It has now been found that, surprisingly, the rearrangement of 10,11-epoxy-10,11-dihydro-5H-dibenz~b,f]azepine-5-carboxamide of the formula I to 10-oxo-10,11-dihydro-51-1-dibenzLb,f]azepin-5-carboxamide of the formula II can be performed by means of a bromide or iodide of lithium, magnesium ; or calcium, without an addition of methyl iodide or n-propyl iodide being ; necessary. The iodides of the stated metals are preferred for the purpose.
The salts mentioned correspond accordingly to the formulae LiBr, LiI, MgBr2, ~lgI2~ CaBr2 and CaI2. These can be used in the dry form or as known compounds with water (hydrates) or with organic substances.
Hydrates to be mentioned are for example:
LiBr.H20, LiBr.2H20, LiBr.3}120, LiI.}120, LiI.21120, LiI.3H20, MgBr2.6H20, ~qgBr2 1H2, MgI2-8H20, MgIz.lOH20, CaBr2.61120, CaI2.~}120 and CaI2.6H20.
By organic substances in this connection are meant: lower alkanols, namely lower primary, secondary or tertiary alkanols, for instance methanol, ethanol, n-propanol, n-butanol, isopropanol or trimethylcarbinol; lower dialkyl ethers such as diethyl ether, also dioxane, lower ketonesg for example acetone, carboxylic acid esters, for example formic acid ethyl ester, acetic acid methyl ester, acetic acid ethyl ester, acetic acid isobutyl .~ - 3 -,, , : ~- , ,.,, , ;; ' :
.
t ' ~'' ~. ' :'~, '' ester, acetic acid et]lyl ester, acetic acid isobutyl ester or acetic acid isoamyl ester, acetoaCetic acid ethyl esterS nlalonic acld diethyl ester, orthoformic acid ethyl ester or succinic acid diet}lyl ester, also acetals such as formaldehyde dimethylacetal or acetaldehyde diethylacetal.
As compounds of the stated salts with organic substances are ` mentioned for example:
LiBr~methanol, LiBr.4 ethanol, LiBr.dioxane, LiBr.2 acetone, LiI.4 methanol, LiI 4 ethanol, LiI.4 n-propanol, LiI.2 ~ioxane, Mg~r2.6 ethanol, MgBr2.4 isopropanol, MgBr2.4 trimethylcarbinol, MgBr2.2 diethyl ether, ~ MgBr2.2 orthoformic acid ethyl ester, `- MgBr2.acetoacetic acid ethyl ester.diethy] ether, MgBr2.malonic acid diethyl ester.diethyl ether, MgBr2.succinic acid diethyl ester, MgBr2.2 dioxane, MgBr2.2 formaldehyde dimethylacetal, MgI2.6 methanol, MgI2.6 isopropanol, MgI2.2 diethyl ether, MgI2.6 ~ormic acid ethyl ester, MgI2.6 acetic acid methyl ester, MgI2.6 acetic acid ethyl ester, MgI2.acetic acid isobutyl ester, MgI2.acetic acid isoamyl ester, MgI2.dioxane, MgI2.acetaldehyde diethylacetal, CaBr2.4 methanol, CaBr2.4 ethanol, CaBr2.3-n-propanol, CaBr2.3 n-butanol, CaBr2.2 acetone, CaBr2.2 dioxane, CaBr2.diethyl ether, CaI2.6 methanol, CaI2.3 acetone, CaI2.2 dioxane, CaI2.2 diethyl ether.
~; ~
.- . : , . . . .
. "
f.
' .
., . , . ' ~ , ' ' , `' . . ' ,: '' "'. '' .
Salts and hydrates thereof or co~npounds thcreof with organic substances which are ~entioned as being particularly suitable for the process according to the invent;on arc: LiBr, liI.21120, MgI2.diethyletherate and CaI2'4112 - 4a -: ' - .: , . ' ;, ~, ' ' " ' . ,, ' ' ' ; ' ,: . ', ; ::, ,, ~:: , , . : ~ , , :, .
The rearrangement according to the invention i5 performed in a solvent, for example in an unsubstituted or halogen-substituted hydrocarbon of aliphatic or aromatic character, such as in a halo-lower alkane such as chloro-lower alkane, ~or example methylene chloride, -carbon tetrachloride, ethylene chloride or difluoro-chloromethane, preferably however in chloroform. As solvents of aromatic character are mentioned for example benzene and chlorobenzene~ It can be advantageous to raise the solubility of the stated salts in the respective solvent by the addition of a further solvent. Suitable such solvents are preferably those of polar character, for instance tetrahydrofuran or dioxane, or a derivative of a phosphorus acid amide, for example hexamethyl-- phosphoric acid triamide. The amount of polar solvent added varies depending on the amount of salt used, and up to 1 mol of further solvent per mol of employed salt can be used.
Processing of the reaction mixture in the customary manner yields the rearrangement product in good yield and in an excellent degree of purity.
The reaction temperature is within a range of 20 -120C, preferably between 40 and 80C. The compounds of the formulae I and II are known.
The organic substances or the compoùnds of the stated salts with organic substances to be used in the process according to the invention are known, or, in the case where they are new, they can be obtained by methods known per se. Thus, for example, a magnesium salt-di-lower alkyl etherate, for example magnesium iodide diethyl etherate, to be used in the process according to the invention, can be obtained by reaction of magnesium chips in a lower dialkyl ether, for example diethyl ether, with iodine.
' , ,:
- 6~ Z9Ll The ollowing Examples serve to illustrate the invention. The temperatures are given in degrees Centigrade.
Example 1 5.0 g of lithium iodide dihydrate is added to a suspension of 5.0 g of 10,11-dihydro-10,11-epoxy-5H-dibenzlb 9 f]azepine-5-carboxamide in 50 ml of chloroform.
The suspension is heated to reflux temperature, and is stirred for 30 minutes at this temperature. The solution is subsequently cooled to room temperature, and washed with 50 ml of water and afterwards with 20 ml of water.
The chloroform solution is evaporated to dryness, and the residue is recrystallised from methanol. The yield after drying is 4.1 g (82% of theory) of 10,11-dihydro-10-oxo-5H-dibenz[b,f~azepine-5 carboxamide, m.p. ~14.
Example 2 6.2 g o~ magnesium iodide diethyl etherate is added to a suspension of 5.0 g of 10,11-dihydro-10,11-epoxy-SH-dibenz[b,f]azepine-S-carboxamide in 50 ml of chloroformO
The suspension is heated to reflux temperature, and is stirred for 30 minutes at this temperature. The solution is then cooled to room temperature, and washed with 50 ml of water and afterwards with 20 ml of water. The chloroform solution is evaporated to dryness, and the residue is recrystallised from methanol. The yield after drying is 4.0 g (80% of theory) of lO,ll~dihydro-10-oxo-SH-dibenz [b,f]azepine-5-carboxamide, m.p. 214.
The magnesium iodide diethyl etherate used as starting material is produced as follows:
4.0 g of iodine is added portionwise to 1.5 g of magnesium chips in 40 ml of absolute diethyl ether. The mixture is stirred under reflux for a further 60 minutes;
.
., ' . , , ' , ,. ~
,, - 7 ~ Z~ ~
it is then ~iltered off from the unconsumed magnesium, and concentrated by evaporation to thus yie].d the starting material in the form of viscous, slightly coloured oil.
Example 3 1.8 g of hexamethylphosphoric acid triamide and 1.7 g of lithium bromide are added to a suspension of 2.3 g of lo~ dihydro-lo~ll-epoxy-5H-dibenz~b~f]azepine-5-carboxamide in 20 ml of chlorobenzene. The suspension is heated to 70 and stirred for 30 minutes at this tempera-ture. The solution is then cooled to room temperature, and distributed between 50 ml of water and 50 ml of ethyl acetate, The ethyl acetate solution is evaporated to dryness, and the residue is recrystallised from me~hanol.
The yield after drying is l.S g (65% of theory) of 10,11-dihydro-10-oxo-5H-dibenz[b,f]azepine-5-carboxamide, m.p. 214.
5.0 g of calcium iodide tetrahydrate is added to a suspension of 10.0 g of 10,11-dihydro-10,11-epoxy-5H-dibenz~b,f]azepine-5-carboxamide in 25 ml of chloroform.
The suspension is heated to reflux temperature, and stirred for 60 minutes at this temperature. The solution is then cooled to 0; it is subsequently stirred with 25 ml of water and filtered off with suction from the precipitate which has separated out. The yield after drying is 7.8 g (78% of theory) of 10,11-dihydro-10-oxo~SH-dibenz[b,f]
azepine-5-carboxamide, m~p. 214.
.
- ~ '','~ ' ~' , ' . '. ' :' ~ ' :,
It has now been found that, surprisingly, the rearrangement of 10,11-epoxy-10,11-dihydro-5H-dibenz~b,f]azepine-5-carboxamide of the formula I to 10-oxo-10,11-dihydro-51-1-dibenzLb,f]azepin-5-carboxamide of the formula II can be performed by means of a bromide or iodide of lithium, magnesium ; or calcium, without an addition of methyl iodide or n-propyl iodide being ; necessary. The iodides of the stated metals are preferred for the purpose.
The salts mentioned correspond accordingly to the formulae LiBr, LiI, MgBr2, ~lgI2~ CaBr2 and CaI2. These can be used in the dry form or as known compounds with water (hydrates) or with organic substances.
Hydrates to be mentioned are for example:
LiBr.H20, LiBr.2H20, LiBr.3}120, LiI.}120, LiI.21120, LiI.3H20, MgBr2.6H20, ~qgBr2 1H2, MgI2-8H20, MgIz.lOH20, CaBr2.61120, CaI2.~}120 and CaI2.6H20.
By organic substances in this connection are meant: lower alkanols, namely lower primary, secondary or tertiary alkanols, for instance methanol, ethanol, n-propanol, n-butanol, isopropanol or trimethylcarbinol; lower dialkyl ethers such as diethyl ether, also dioxane, lower ketonesg for example acetone, carboxylic acid esters, for example formic acid ethyl ester, acetic acid methyl ester, acetic acid ethyl ester, acetic acid isobutyl .~ - 3 -,, , : ~- , ,.,, , ;; ' :
.
t ' ~'' ~. ' :'~, '' ester, acetic acid et]lyl ester, acetic acid isobutyl ester or acetic acid isoamyl ester, acetoaCetic acid ethyl esterS nlalonic acld diethyl ester, orthoformic acid ethyl ester or succinic acid diet}lyl ester, also acetals such as formaldehyde dimethylacetal or acetaldehyde diethylacetal.
As compounds of the stated salts with organic substances are ` mentioned for example:
LiBr~methanol, LiBr.4 ethanol, LiBr.dioxane, LiBr.2 acetone, LiI.4 methanol, LiI 4 ethanol, LiI.4 n-propanol, LiI.2 ~ioxane, Mg~r2.6 ethanol, MgBr2.4 isopropanol, MgBr2.4 trimethylcarbinol, MgBr2.2 diethyl ether, ~ MgBr2.2 orthoformic acid ethyl ester, `- MgBr2.acetoacetic acid ethyl ester.diethy] ether, MgBr2.malonic acid diethyl ester.diethyl ether, MgBr2.succinic acid diethyl ester, MgBr2.2 dioxane, MgBr2.2 formaldehyde dimethylacetal, MgI2.6 methanol, MgI2.6 isopropanol, MgI2.2 diethyl ether, MgI2.6 ~ormic acid ethyl ester, MgI2.6 acetic acid methyl ester, MgI2.6 acetic acid ethyl ester, MgI2.acetic acid isobutyl ester, MgI2.acetic acid isoamyl ester, MgI2.dioxane, MgI2.acetaldehyde diethylacetal, CaBr2.4 methanol, CaBr2.4 ethanol, CaBr2.3-n-propanol, CaBr2.3 n-butanol, CaBr2.2 acetone, CaBr2.2 dioxane, CaBr2.diethyl ether, CaI2.6 methanol, CaI2.3 acetone, CaI2.2 dioxane, CaI2.2 diethyl ether.
~; ~
.- . : , . . . .
. "
f.
' .
., . , . ' ~ , ' ' , `' . . ' ,: '' "'. '' .
Salts and hydrates thereof or co~npounds thcreof with organic substances which are ~entioned as being particularly suitable for the process according to the invent;on arc: LiBr, liI.21120, MgI2.diethyletherate and CaI2'4112 - 4a -: ' - .: , . ' ;, ~, ' ' " ' . ,, ' ' ' ; ' ,: . ', ; ::, ,, ~:: , , . : ~ , , :, .
The rearrangement according to the invention i5 performed in a solvent, for example in an unsubstituted or halogen-substituted hydrocarbon of aliphatic or aromatic character, such as in a halo-lower alkane such as chloro-lower alkane, ~or example methylene chloride, -carbon tetrachloride, ethylene chloride or difluoro-chloromethane, preferably however in chloroform. As solvents of aromatic character are mentioned for example benzene and chlorobenzene~ It can be advantageous to raise the solubility of the stated salts in the respective solvent by the addition of a further solvent. Suitable such solvents are preferably those of polar character, for instance tetrahydrofuran or dioxane, or a derivative of a phosphorus acid amide, for example hexamethyl-- phosphoric acid triamide. The amount of polar solvent added varies depending on the amount of salt used, and up to 1 mol of further solvent per mol of employed salt can be used.
Processing of the reaction mixture in the customary manner yields the rearrangement product in good yield and in an excellent degree of purity.
The reaction temperature is within a range of 20 -120C, preferably between 40 and 80C. The compounds of the formulae I and II are known.
The organic substances or the compoùnds of the stated salts with organic substances to be used in the process according to the invention are known, or, in the case where they are new, they can be obtained by methods known per se. Thus, for example, a magnesium salt-di-lower alkyl etherate, for example magnesium iodide diethyl etherate, to be used in the process according to the invention, can be obtained by reaction of magnesium chips in a lower dialkyl ether, for example diethyl ether, with iodine.
' , ,:
- 6~ Z9Ll The ollowing Examples serve to illustrate the invention. The temperatures are given in degrees Centigrade.
Example 1 5.0 g of lithium iodide dihydrate is added to a suspension of 5.0 g of 10,11-dihydro-10,11-epoxy-5H-dibenzlb 9 f]azepine-5-carboxamide in 50 ml of chloroform.
The suspension is heated to reflux temperature, and is stirred for 30 minutes at this temperature. The solution is subsequently cooled to room temperature, and washed with 50 ml of water and afterwards with 20 ml of water.
The chloroform solution is evaporated to dryness, and the residue is recrystallised from methanol. The yield after drying is 4.1 g (82% of theory) of 10,11-dihydro-10-oxo-5H-dibenz[b,f~azepine-5 carboxamide, m.p. ~14.
Example 2 6.2 g o~ magnesium iodide diethyl etherate is added to a suspension of 5.0 g of 10,11-dihydro-10,11-epoxy-SH-dibenz[b,f]azepine-S-carboxamide in 50 ml of chloroformO
The suspension is heated to reflux temperature, and is stirred for 30 minutes at this temperature. The solution is then cooled to room temperature, and washed with 50 ml of water and afterwards with 20 ml of water. The chloroform solution is evaporated to dryness, and the residue is recrystallised from methanol. The yield after drying is 4.0 g (80% of theory) of lO,ll~dihydro-10-oxo-SH-dibenz [b,f]azepine-5-carboxamide, m.p. 214.
The magnesium iodide diethyl etherate used as starting material is produced as follows:
4.0 g of iodine is added portionwise to 1.5 g of magnesium chips in 40 ml of absolute diethyl ether. The mixture is stirred under reflux for a further 60 minutes;
.
., ' . , , ' , ,. ~
,, - 7 ~ Z~ ~
it is then ~iltered off from the unconsumed magnesium, and concentrated by evaporation to thus yie].d the starting material in the form of viscous, slightly coloured oil.
Example 3 1.8 g of hexamethylphosphoric acid triamide and 1.7 g of lithium bromide are added to a suspension of 2.3 g of lo~ dihydro-lo~ll-epoxy-5H-dibenz~b~f]azepine-5-carboxamide in 20 ml of chlorobenzene. The suspension is heated to 70 and stirred for 30 minutes at this tempera-ture. The solution is then cooled to room temperature, and distributed between 50 ml of water and 50 ml of ethyl acetate, The ethyl acetate solution is evaporated to dryness, and the residue is recrystallised from me~hanol.
The yield after drying is l.S g (65% of theory) of 10,11-dihydro-10-oxo-5H-dibenz[b,f]azepine-5-carboxamide, m.p. 214.
5.0 g of calcium iodide tetrahydrate is added to a suspension of 10.0 g of 10,11-dihydro-10,11-epoxy-5H-dibenz~b,f]azepine-5-carboxamide in 25 ml of chloroform.
The suspension is heated to reflux temperature, and stirred for 60 minutes at this temperature. The solution is then cooled to 0; it is subsequently stirred with 25 ml of water and filtered off with suction from the precipitate which has separated out. The yield after drying is 7.8 g (78% of theory) of 10,11-dihydro-10-oxo~SH-dibenz[b,f]
azepine-5-carboxamide, m~p. 214.
.
- ~ '','~ ' ~' , ' . '. ' :' ~ ' :,
Claims (15)
PRIVILEGE OR PROPERTY IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A process for the rearrangement of 10,11-epoxy-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide of the formula (I) to 10-oxo-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide of the formula (II), which process comprises performing the rearrangement by means of a bromide or iodide of lithium, magnesium or calcium in a solvent.
2. A process according to claim 1, wherein the salts are used in dry form or in the form of their compounds with water (hydrates) or with organic substances.
3. A process according to claim 2, wherein the salt used is lithium iodide-dihydrate.
4. A process according to claim 2, wherein the salt used is magnesium iodide-diethyletherate.
5. A process according to claim 2, wherein the salt used is calciumiodide-tetrahydrate.
6. A process according to claim 1, wherein the salt used is lithium bromide.
7. A process according to claim 1, wherein the solvent used is an unsubstituted or halogen-substituted hydro-carbon of aliphatic or aromatic character.
8. A process according to claim 7 wherein the solvent is chloroform.
9. A process according to claim 7 wherein the solvent is chlorobenzene.
10. A process according to claim 1 wherein the solubility of the salts is increased by the addition of a further solvent.
11. A process according to claim 10 wherein a solvent of polar character is used.
12. A process according to claim 11 wherein hexamethyl-phosphoric acid triamide is used as a further solvent.
13. A process according to claim 11 wherein tetrahydro-furan is used as a further solvent.
14. A process according to claim 11 wherein dioxane is used as a further solvent.
15. A process according to claim 1, wherein the rear.rangement is performed within a temperature range of 20-120°C.
160 A process according to claim 15 wherein the rearrangement is performed within a temperature range of 40-80°C.
160 A process according to claim 15 wherein the rearrangement is performed within a temperature range of 40-80°C.
Applications Claiming Priority (2)
| 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 |
| CH4134/78-1 | 1978-04-18 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1112241A true CA1112241A (en) | 1981-11-10 |
Family
ID=4270467
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA325,802A Expired CA1112241A (en) | 1978-04-18 | 1979-04-12 | Process for the rearrangement of 10,11-epoxy-10,11- dihydro-5h-dibenz¬b,f|azepine-5-carboxamide to 10- oxo-10,11-dihydro-5h-dibenz¬b,f|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) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7125987B2 (en) | 2004-06-18 | 2006-10-24 | Apotex Pharmachem Inc. | Process for the preparation of oxcarbazepine and related intermediates |
Families Citing this family (2)
| 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 |
| 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 ES ES479600A patent/ES479600A1/en not_active Expired
- 1979-04-16 AR AR276195A patent/AR222329A1/en active
- 1979-04-16 BG BG7943253A patent/BG29282A3/en unknown
- 1979-04-17 HU HU79CI1926A patent/HU182477B/en unknown
- 1979-04-17 AT AT0288379A patent/AT373877B/en not_active IP Right Cessation
- 1979-04-17 PT PT69495A patent/PT69495A/en unknown
- 1979-04-17 FI FI791233A patent/FI70010C/en not_active IP Right Cessation
- 1979-04-17 SE SE7903328A patent/SE7903328L/en not_active Application Discontinuation
- 1979-04-17 PL PL21495479A patent/PL214954A1/xx unknown
- 1979-04-17 DK DK157779A patent/DK157779A/en not_active IP Right Cessation
- 1979-04-17 NO NO791274A patent/NO149776C/en unknown
- 1979-04-17 YU YU00917/79A patent/YU91779A/en unknown
- 1979-04-18 JP JP4680279A patent/JPS54138588A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7125987B2 (en) | 2004-06-18 | 2006-10-24 | Apotex Pharmachem Inc. | Process for the preparation of oxcarbazepine and related intermediates |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS54138588A (en) | 1979-10-27 |
| ATA288379A (en) | 1983-07-15 |
| NL7902811A (en) | 1979-10-22 |
| AT373877B (en) | 1984-02-27 |
| AR222329A1 (en) | 1981-05-15 |
| NO149776C (en) | 1984-06-20 |
| NO149776B (en) | 1984-03-12 |
| SE7903328L (en) | 1979-10-19 |
| FI70010C (en) | 1986-09-12 |
| NO791274L (en) | 1979-10-19 |
| ES479600A1 (en) | 1979-07-16 |
| GR72260B (en) | 1983-10-10 |
| DK157779A (en) | 1979-10-19 |
| FI70010B (en) | 1986-01-31 |
| YU91779A (en) | 1983-01-21 |
| PL214954A1 (en) | 1980-07-01 |
| BG29282A3 (en) | 1980-10-15 |
| HU182477B (en) | 1984-01-30 |
| PT69495A (en) | 1979-05-01 |
| FI791233A (en) | 1979-10-19 |
| CH633271A5 (en) | 1982-11-30 |
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