CA1314552C - Preparation of quinolines - Google Patents
Preparation of quinolinesInfo
- Publication number
- CA1314552C CA1314552C CA000568488A CA568488A CA1314552C CA 1314552 C CA1314552 C CA 1314552C CA 000568488 A CA000568488 A CA 000568488A CA 568488 A CA568488 A CA 568488A CA 1314552 C CA1314552 C CA 1314552C
- Authority
- CA
- Canada
- Prior art keywords
- formula
- hydrogen
- sulfuric acid
- chloro
- quinoline
- 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 - Lifetime
Links
- 238000002360 preparation method Methods 0.000 title claims description 8
- 229940111121 antirheumatic drug quinolines Drugs 0.000 title abstract description 10
- 150000003248 quinolines Chemical class 0.000 title abstract description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims abstract description 38
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims abstract description 28
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims abstract description 14
- 238000000034 method Methods 0.000 claims abstract description 14
- 239000001257 hydrogen Substances 0.000 claims abstract description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 13
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 10
- 239000011630 iodine Substances 0.000 claims abstract description 10
- 150000001299 aldehydes Chemical class 0.000 claims abstract description 8
- 150000002576 ketones Chemical class 0.000 claims abstract description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 7
- 230000003197 catalytic effect Effects 0.000 claims abstract description 6
- 229910052736 halogen Chemical group 0.000 claims abstract description 3
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 3
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims abstract 4
- 150000002367 halogens Chemical group 0.000 claims abstract 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 39
- 238000006243 chemical reaction Methods 0.000 claims description 15
- 235000013350 formula milk Nutrition 0.000 claims description 11
- HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 239000007800 oxidant agent Substances 0.000 claims description 3
- 238000011065 in-situ storage Methods 0.000 claims description 2
- 230000036647 reaction Effects 0.000 claims description 2
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 21
- 229940032330 sulfuric acid Drugs 0.000 description 15
- ZUVPLKVDZNDZCM-UHFFFAOYSA-N 3-chloro-2-methylaniline Chemical compound CC1=C(N)C=CC=C1Cl ZUVPLKVDZNDZCM-UHFFFAOYSA-N 0.000 description 14
- 239000000243 solution Substances 0.000 description 12
- 229940039407 aniline Drugs 0.000 description 11
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 7
- 235000009518 sodium iodide Nutrition 0.000 description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- FUSUHKVFWTUUBE-UHFFFAOYSA-N buten-2-one Chemical compound CC(=O)C=C FUSUHKVFWTUUBE-UHFFFAOYSA-N 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- 238000004821 distillation Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 238000004817 gas chromatography Methods 0.000 description 4
- PZAXENZUGIIHBG-UHFFFAOYSA-N 7-chloro-3,8-dimethylquinoline Chemical compound CC1=C(Cl)C=CC2=CC(C)=CN=C21 PZAXENZUGIIHBG-UHFFFAOYSA-N 0.000 description 3
- NKWDCLXGUJHNHS-UHFFFAOYSA-N 7-chloro-8-methylquinoline Chemical compound C1=CN=C2C(C)=C(Cl)C=CC2=C1 NKWDCLXGUJHNHS-UHFFFAOYSA-N 0.000 description 3
- -1 Z-methylaniline Chemical compound 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 2
- JLIDVCMBCGBIEY-UHFFFAOYSA-N 1-penten-3-one Chemical compound CCC(=O)C=C JLIDVCMBCGBIEY-UHFFFAOYSA-N 0.000 description 2
- MLPVBIWIRCKMJV-UHFFFAOYSA-N 2-ethylaniline Chemical compound CCC1=CC=CC=C1N MLPVBIWIRCKMJV-UHFFFAOYSA-N 0.000 description 2
- MUDSDYNRBDKLGK-UHFFFAOYSA-N 4-methylquinoline Chemical compound C1=CC=C2C(C)=CC=NC2=C1 MUDSDYNRBDKLGK-UHFFFAOYSA-N 0.000 description 2
- FXDITTUYSNDPFH-UHFFFAOYSA-N 7-chloro-2,8-dimethylquinoline Chemical compound C1=CC(Cl)=C(C)C2=NC(C)=CC=C21 FXDITTUYSNDPFH-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- STNJBCKSHOAVAJ-UHFFFAOYSA-N Methacrolein Chemical compound CC(=C)C=O STNJBCKSHOAVAJ-UHFFFAOYSA-N 0.000 description 2
- COHDHYZHOPQOFD-UHFFFAOYSA-N arsenic pentoxide Chemical compound O=[As](=O)O[As](=O)=O COHDHYZHOPQOFD-UHFFFAOYSA-N 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- MLUCVPSAIODCQM-NSCUHMNNSA-N crotonaldehyde Chemical compound C\C=C\C=O MLUCVPSAIODCQM-NSCUHMNNSA-N 0.000 description 2
- MLUCVPSAIODCQM-UHFFFAOYSA-N crotonaldehyde Natural products CC=CC=O MLUCVPSAIODCQM-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- JTHNLKXLWOXOQK-UHFFFAOYSA-N hex-1-en-3-one Chemical compound CCCC(=O)C=C JTHNLKXLWOXOQK-UHFFFAOYSA-N 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 229940083608 sodium hydroxide Drugs 0.000 description 2
- 235000011121 sodium hydroxide Nutrition 0.000 description 2
- 239000012485 toluene extract Substances 0.000 description 2
- MBDOYVRWFFCFHM-SNAWJCMRSA-N (2E)-hexenal Chemical compound CCC\C=C\C=O MBDOYVRWFFCFHM-SNAWJCMRSA-N 0.000 description 1
- YKOLZVXSPGIIBJ-UHFFFAOYSA-N 2-Isopropylaniline Chemical compound CC(C)C1=CC=CC=C1N YKOLZVXSPGIIBJ-UHFFFAOYSA-N 0.000 description 1
- IFLLHNMCIXRVEC-UHFFFAOYSA-N 2-butyl-3-chloroaniline Chemical compound CCCCC1=C(N)C=CC=C1Cl IFLLHNMCIXRVEC-UHFFFAOYSA-N 0.000 description 1
- HDVUPIFFKAHPJY-UHFFFAOYSA-N 2-butylaniline Chemical compound CCCCC1=CC=CC=C1N HDVUPIFFKAHPJY-UHFFFAOYSA-N 0.000 description 1
- RWNBRROKBLKJDU-UHFFFAOYSA-N 2-ethyl-3-fluoroaniline Chemical compound CCC1=C(N)C=CC=C1F RWNBRROKBLKJDU-UHFFFAOYSA-N 0.000 description 1
- WKURVXXDGMYSDP-UHFFFAOYSA-N 2-propyl-aniline Chemical compound CCCC1=CC=CC=C1N WKURVXXDGMYSDP-UHFFFAOYSA-N 0.000 description 1
- AEIOZWYBDBVCGW-UHFFFAOYSA-N 2-tert-butylaniline Chemical compound CC(C)(C)C1=CC=CC=C1N AEIOZWYBDBVCGW-UHFFFAOYSA-N 0.000 description 1
- YNFNCYIUPQLIEX-UHFFFAOYSA-N 3-bromo-2-ethylaniline Chemical compound CCC1=C(N)C=CC=C1Br YNFNCYIUPQLIEX-UHFFFAOYSA-N 0.000 description 1
- IILVSKMKMOJHMA-UHFFFAOYSA-N 3-bromo-2-methylaniline Chemical compound CC1=C(N)C=CC=C1Br IILVSKMKMOJHMA-UHFFFAOYSA-N 0.000 description 1
- OMZRDBSLAGVDMI-UHFFFAOYSA-N 3-chloro-2-ethylaniline Chemical compound CCC1=C(N)C=CC=C1Cl OMZRDBSLAGVDMI-UHFFFAOYSA-N 0.000 description 1
- BLLIICMFQDJIES-UHFFFAOYSA-N 3-chloro-2-propan-2-ylaniline Chemical compound CC(C)C1=C(N)C=CC=C1Cl BLLIICMFQDJIES-UHFFFAOYSA-N 0.000 description 1
- WPYGEGUIGYISJW-UHFFFAOYSA-N 3-chloro-2-propylaniline Chemical compound CCCC1=C(N)C=CC=C1Cl WPYGEGUIGYISJW-UHFFFAOYSA-N 0.000 description 1
- SLDLVGFPFFLYBM-UHFFFAOYSA-N 3-fluoro-2-methyl-aniline Chemical compound CC1=C(N)C=CC=C1F SLDLVGFPFFLYBM-UHFFFAOYSA-N 0.000 description 1
- XYYHROWBTBFMBY-UHFFFAOYSA-N 3-fluoro-2-propylaniline Chemical compound CCCC1=C(N)C=CC=C1F XYYHROWBTBFMBY-UHFFFAOYSA-N 0.000 description 1
- FKYHSWFYBFHXKN-UHFFFAOYSA-N 7-chloro-3-methylquinoline Chemical compound C1=C(Cl)C=CC2=CC(C)=CN=C21 FKYHSWFYBFHXKN-UHFFFAOYSA-N 0.000 description 1
- HUSFLDKRAODFGV-UHFFFAOYSA-N 7-chloro-4,8-dimethylquinoline Chemical compound ClC1=CC=C2C(C)=CC=NC2=C1C HUSFLDKRAODFGV-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- UNMYWSMUMWPJLR-UHFFFAOYSA-L Calcium iodide Chemical compound [Ca+2].[I-].[I-] UNMYWSMUMWPJLR-UHFFFAOYSA-L 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 229940046413 calcium iodide Drugs 0.000 description 1
- 229910001640 calcium iodide Inorganic materials 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 230000002363 herbicidal effect Effects 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 150000002497 iodine compounds Chemical class 0.000 description 1
- LIKBJVNGSGBSGK-UHFFFAOYSA-N iron(3+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Fe+3].[Fe+3] LIKBJVNGSGBSGK-UHFFFAOYSA-N 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910001511 metal iodide Inorganic materials 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- LABTWGUMFABVFG-UHFFFAOYSA-N methyl propenyl ketone Chemical compound CC=CC(C)=O LABTWGUMFABVFG-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical compound OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- MBDOYVRWFFCFHM-UHFFFAOYSA-N trans-2-hexenal Natural products CCCC=CC=O MBDOYVRWFFCFHM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/04—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/18—Halogen atoms or nitro radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Quinoline Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Plural Heterocyclic Compounds (AREA)
- Catalysts (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE:
Quinolines of the formula (I):
where R is C1-C5-alkyl, R1, R2 and R3 are each hydrogen or C1-C5-alkyl and X is hydrogen or halogen, with the proviso that R may furthermore be hydrogen if X is hydrogen, are prepared by reacting an aniline of the formula (II):
(II) with an .alpha.,.beta.-unsaturated aldehyde or ketone of the formula (III):
Quinolines of the formula (I):
where R is C1-C5-alkyl, R1, R2 and R3 are each hydrogen or C1-C5-alkyl and X is hydrogen or halogen, with the proviso that R may furthermore be hydrogen if X is hydrogen, are prepared by reacting an aniline of the formula (II):
(II) with an .alpha.,.beta.-unsaturated aldehyde or ketone of the formula (III):
Description
~31~52 - 1 - O.z. OOS0/39235 Preparation of quinolines The present invention relates to a process for the preparation of quinolines by reacting an aniline with an ~,B-unsaturated aldehyde or ketone in sulfuric acid in the presence of a catalytic amount of iodine at elevated temperatures.
It is known ~hat quinolines can be prepared by the Skraup method by reacting an aniline with glycerol or an ~,~-unsaturated aldehyde or ~,B-unsaturated ke-tone in the presence of an oxidizing agent, such as nitro-benzene, arsenic pentoxide, iron(III) oxide or picric acid, in concentrated sulfuric acid (A. Weissberger and E.C. Taylor, Heterocyclic Compounds, Vol~ 32, I, pages 100-117). The yields obtained are moderate. Furthermore, the use of these oxidi~ing agents causes considerable pollution of ~astewater, so that this procedure is unsuit-able for an industrial process.
GB-A-549 502, moreover, discloses the use of iodine as an oxidizing agent in ~he reaction of an anil-ine ~ith glycerol in concentrated sulfuric acid. Inthis case too, the yields obtained are only ~oderate.
Another disadvantage is that a large excess of glycerol is required here.
It is an object of the present invention to pro-vide a process which can be carried out on a large indus-trial scale and gives quinolines in high yields.
~ e have found that this object is achieved by a process for the preparation of quinolines of the formula XJ~XR 1 where R is C1-Cs-alkyl, R1, R2 and R3 are each hydro-gen or C1-Cs-alkyl and X is hydrogen or h,3logen, with the proviso that R may further~ore be hydrogen if X is 1~4~52 - 2 - o.Z. 0050/39235 hydrogen, by reacting an aniline of the formuta X~NHz ( I I ) R
with an ~ unsaturated aldehyde or ketone of the for-mula R i--CH=C--i--R3 t I 11 ) in sulfuric acid in the presence of a catalytic amount of iodine at elevated temperatures, wherein the reaction is carried out in about 70-85X strength by weight sulfuric acid.
The reaction can be carried out as follo~s:
The aldehyde or ketone III ;s added to a solution, pre-heated to 100-140C~ of aniline II in sulfuric acid and a catalytic amount of iodine in the course of from oO to 90 minutes, the temperature of the reaction mixture as far as possible being prevented from falling belQw 100C.
The temperature is about 100-150C, prefer-ably 115-130C. After the end of the addition, the reac-tion solution is neutralized by adding an aqueous alkali, for example sodium hydroxid~ solution, at from 70 to 100C, the desired product separating from the aqueous phase in the form of an organic phase. ~orking up is then carried out in a conventional manner, for example by ex~raction.
The concentration of the sulfuric acid may vary from about 70 to about 85% by ~eight. Advantageously, the sulfuric acid used has a concentrat;on of about 7û-80X
by weight.
The starting materials are advantageously used in a molar ratio of aniline II to aldehyde or ketone III of from about 1 : 1 to 1 : 1.5, preferably from about 1 : 1.1 ~.; .,~ .
.~, ~ 31~5~2 - 3 - O.Z~ 0050/39235 to 1 : 1.3. The molar amount of sulfuric acid is from 2 to 8, preferably from 2.5 to 6, moles per mole of aniline II.
The catalytic amounts of iodine required in the reaction can be added to the reaction mixture ir the form of inorganic iodine compounds, for example ele~ental iodine, hydriodic acid or a metal iodide, such as calcium iodide or sodium iodide, in solicl or liquid form, for example in the form of an aqueous solution. The amount of iodine used is from 0.1 to 2, preferably from 0.2 to 1.5, mol %, based on aniline II.
It is surprising that the novel process gives the quinolines I in high yield and purity, since under the drastic reaction conditions side reactions of the unsaturated starting compounds III with iodine were to be expected (Houben-Weyl, Methoden der org. Chemie, Vol. 5/4, pages 530 and 535).
The process according to the invention can be very advantageously carried out if glycerol is used instead of the starting compounds III, the starting compound III
twhere R1, R2 and R3 are each hydrogen) being formed in situ from a glycerol. ~here glycerol is used, the novel process can be carried out in the same way as when alde-hydes or ketones III are employed. In this case, however, it is extremely advantageous if, after the addition of the glycerol, the mixture is stirred at about 100-150C, advan-tageously 130-145C, the resulting water of reaction being distilled off si~ultaneously. It is advisable to distill off not less than 60 - 70~ of the ~ater of reaction formed.
It is sufficient to continue stirring for a few hours, for example from 2 to 4 hours. In this procedure, ~ith an ex-cess of glycerol of 1.2, preferably 1.1, moles per mole of aniline II, the quinoline I is obtainable in high yield.
~ t was not to be expected that the reaction would give quinolines in h;gh yield and purity starting from a s~all molar excess of glycerol and using dilute sul-furic acid, since G~-A-549 50Z discloses that, despite a large excess of glycerol, carrying out the reaction in 13145~2 - 4 - O.Z. ~050/39235 dilute sulfuric acid results in very low yields. More-over, the measure of distilling off water of reaction, in which more than 90~ of the iodine used leaves the reaction mixture, would likewise have been expected to lead to a reduction in the yield or extension of the reaction times.
Examples of starting compounds II are aniline, Z-methylaniline, 2-ethylaniline, 2-propylaniline, 2-iso-propylaniline, 2-butylaniline, Z-pentylaniline, 2-tert-butylaniline, 3-chloro-2-methylaniline, 3-chloro-2-ethyl-aniline, 3-chloro-2-propylaniline, 3-chloro-2-isopropyl-aniline, 3-chloro-2-butylaniline, 3-fluoro 2-methylanil-ine, 3-fluoro-2-ethylaniline, 3-fluoro-2-propylaniline, 3-bromo-2-methylaniline and 3-bromo-2-ethylaniline.
Examples of suitable starting compounds III, in addition to glycerol, are acrolein, methacrolein, croton-aldehyde, penten-2-al, hexen-2-al, methyl vinyl ketone, ethyl vinyl ketone and propyl vinyl ketone.
The alkyl substituents R, R1, R2 and R3 in the formulae I, II and III may be straight-chain or branched and are, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl and tert-butyl. Suitable halogen sub-stituents R are chlorine, bromine and fluorine, preferably chlorine.
The quinolines of the formula I are used as inter-mediates for herbicidal active ingredients (DE-A-3 108 873 and DE-A-3 233 089).
7-chloro-8-methylquinoline a) 72~8 9 (1030 moles) of acrolein are added to a solution of 6Z5 9 of 80~ strength sulfuric acid (5.0 moles), 141.5 9 (1.0 mole) of 3-chloro-2-methylaniline and 2 9 (0.013 mole) of sodium iodide in the course of 60 minutes at from 115 to 120C. Stirring is continued for 10 minutes, after which the pH is brought to 7-8 with 25~ strength sodium hydroxide solution and extraction is carried out with 200 ml of toluene at from 70 to 90C.
13145~2 - 5 - O.Z. 3050/39235 Evaporating down the toluene extract gives 164.6 9 (yield 86.1%) of 7-chloro-3-methylquinoline having a purity of ~2.9% according to gas chromatography.
b) 101.3 9 (1.1 moles) of g~ycerol are added to a S solution of 550 9 of 80% strength sulfuric acid (4.5 moles), 141.5 9 (1.0 mole) of 3-chloro-2-methylaniline and 1 9 (0.007 mole) of sodium iodide in the course of 90 minutes at 140C. Thereafter, stirring is carried out for 2 hours at from 140 to 145C, 60 ml of water be-ing distilled off simultaneously. The reaction solution is then brought to pH 7-8 ~ith 25X strength sodium hydrox-ide solution and extracted with 200 ml of toluene at from 70 to 90C. Evaporating down the toluene extract gives 180.0 9 (yield 95.9%) of a product which, according to gas chromatography, contains 94.6% of 7-chloro-8-methyl-quinoline and 0.25% of 3-chloro-2-methylaniline.
Distillation of the crude product gives 166 9 (yield 92.8~) of 7-chloro-8-methylquinoline having a purity of 99.2X; bp1: 96-98C; mp.: 40-42C.
EXAMPLE Z
7-chloro-4,8-dimethylquinoline 91 9 ~1.30 moles) of methyl vinyl ketone are ad-ded to a solution of 840 9 of 70% strength sulfuric acid t6.0 moles), 141.5 9 (1 mole) of 3-chloro-2-methylaniline and 4 9 tO.027 mole) of sodium iodide in the course of 60 minutes at from 115 to 125C. Stirring is carried out for 2 hours, 35 described in Example 1a), after ~hich the mixture is ~orked up. 179 9 of crude product are ob-tained. Distillation of crude product gives 167.2 g (yield 86.8%) of 7-chloro-4,3-dimethylquinoline having a purity of 99.5%; mp.: 51C.
4-methylquinoline 91 9 (1.30 moles) of methyl vinyl ketone are ad-ded to a solution of 840 g of 70% strength sulfuric acid (6.0 moles), 93 9 (t mole) of aniline and 4 9 (0.027 mole) of sodium iodide in the course of 60 minutes at from 115 ~ 1 3 ~ 2 - 6 - O.Z. 0050/39235 to 125C. Stirring is carried out for 10 minutes, as des-cribed in E~ample 1a), after which the mixture is worked up. 146.4 9 of a brown oil are obtained. Distillation of the crude product gives 107.3 9 (yield 75%) of 4-methyl-S quinoline having a purity of 99.3%; bp1: 80C.
It is known ~hat quinolines can be prepared by the Skraup method by reacting an aniline with glycerol or an ~,~-unsaturated aldehyde or ~,B-unsaturated ke-tone in the presence of an oxidizing agent, such as nitro-benzene, arsenic pentoxide, iron(III) oxide or picric acid, in concentrated sulfuric acid (A. Weissberger and E.C. Taylor, Heterocyclic Compounds, Vol~ 32, I, pages 100-117). The yields obtained are moderate. Furthermore, the use of these oxidi~ing agents causes considerable pollution of ~astewater, so that this procedure is unsuit-able for an industrial process.
GB-A-549 502, moreover, discloses the use of iodine as an oxidizing agent in ~he reaction of an anil-ine ~ith glycerol in concentrated sulfuric acid. Inthis case too, the yields obtained are only ~oderate.
Another disadvantage is that a large excess of glycerol is required here.
It is an object of the present invention to pro-vide a process which can be carried out on a large indus-trial scale and gives quinolines in high yields.
~ e have found that this object is achieved by a process for the preparation of quinolines of the formula XJ~XR 1 where R is C1-Cs-alkyl, R1, R2 and R3 are each hydro-gen or C1-Cs-alkyl and X is hydrogen or h,3logen, with the proviso that R may further~ore be hydrogen if X is 1~4~52 - 2 - o.Z. 0050/39235 hydrogen, by reacting an aniline of the formuta X~NHz ( I I ) R
with an ~ unsaturated aldehyde or ketone of the for-mula R i--CH=C--i--R3 t I 11 ) in sulfuric acid in the presence of a catalytic amount of iodine at elevated temperatures, wherein the reaction is carried out in about 70-85X strength by weight sulfuric acid.
The reaction can be carried out as follo~s:
The aldehyde or ketone III ;s added to a solution, pre-heated to 100-140C~ of aniline II in sulfuric acid and a catalytic amount of iodine in the course of from oO to 90 minutes, the temperature of the reaction mixture as far as possible being prevented from falling belQw 100C.
The temperature is about 100-150C, prefer-ably 115-130C. After the end of the addition, the reac-tion solution is neutralized by adding an aqueous alkali, for example sodium hydroxid~ solution, at from 70 to 100C, the desired product separating from the aqueous phase in the form of an organic phase. ~orking up is then carried out in a conventional manner, for example by ex~raction.
The concentration of the sulfuric acid may vary from about 70 to about 85% by ~eight. Advantageously, the sulfuric acid used has a concentrat;on of about 7û-80X
by weight.
The starting materials are advantageously used in a molar ratio of aniline II to aldehyde or ketone III of from about 1 : 1 to 1 : 1.5, preferably from about 1 : 1.1 ~.; .,~ .
.~, ~ 31~5~2 - 3 - O.Z~ 0050/39235 to 1 : 1.3. The molar amount of sulfuric acid is from 2 to 8, preferably from 2.5 to 6, moles per mole of aniline II.
The catalytic amounts of iodine required in the reaction can be added to the reaction mixture ir the form of inorganic iodine compounds, for example ele~ental iodine, hydriodic acid or a metal iodide, such as calcium iodide or sodium iodide, in solicl or liquid form, for example in the form of an aqueous solution. The amount of iodine used is from 0.1 to 2, preferably from 0.2 to 1.5, mol %, based on aniline II.
It is surprising that the novel process gives the quinolines I in high yield and purity, since under the drastic reaction conditions side reactions of the unsaturated starting compounds III with iodine were to be expected (Houben-Weyl, Methoden der org. Chemie, Vol. 5/4, pages 530 and 535).
The process according to the invention can be very advantageously carried out if glycerol is used instead of the starting compounds III, the starting compound III
twhere R1, R2 and R3 are each hydrogen) being formed in situ from a glycerol. ~here glycerol is used, the novel process can be carried out in the same way as when alde-hydes or ketones III are employed. In this case, however, it is extremely advantageous if, after the addition of the glycerol, the mixture is stirred at about 100-150C, advan-tageously 130-145C, the resulting water of reaction being distilled off si~ultaneously. It is advisable to distill off not less than 60 - 70~ of the ~ater of reaction formed.
It is sufficient to continue stirring for a few hours, for example from 2 to 4 hours. In this procedure, ~ith an ex-cess of glycerol of 1.2, preferably 1.1, moles per mole of aniline II, the quinoline I is obtainable in high yield.
~ t was not to be expected that the reaction would give quinolines in h;gh yield and purity starting from a s~all molar excess of glycerol and using dilute sul-furic acid, since G~-A-549 50Z discloses that, despite a large excess of glycerol, carrying out the reaction in 13145~2 - 4 - O.Z. ~050/39235 dilute sulfuric acid results in very low yields. More-over, the measure of distilling off water of reaction, in which more than 90~ of the iodine used leaves the reaction mixture, would likewise have been expected to lead to a reduction in the yield or extension of the reaction times.
Examples of starting compounds II are aniline, Z-methylaniline, 2-ethylaniline, 2-propylaniline, 2-iso-propylaniline, 2-butylaniline, Z-pentylaniline, 2-tert-butylaniline, 3-chloro-2-methylaniline, 3-chloro-2-ethyl-aniline, 3-chloro-2-propylaniline, 3-chloro-2-isopropyl-aniline, 3-chloro-2-butylaniline, 3-fluoro 2-methylanil-ine, 3-fluoro-2-ethylaniline, 3-fluoro-2-propylaniline, 3-bromo-2-methylaniline and 3-bromo-2-ethylaniline.
Examples of suitable starting compounds III, in addition to glycerol, are acrolein, methacrolein, croton-aldehyde, penten-2-al, hexen-2-al, methyl vinyl ketone, ethyl vinyl ketone and propyl vinyl ketone.
The alkyl substituents R, R1, R2 and R3 in the formulae I, II and III may be straight-chain or branched and are, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl and tert-butyl. Suitable halogen sub-stituents R are chlorine, bromine and fluorine, preferably chlorine.
The quinolines of the formula I are used as inter-mediates for herbicidal active ingredients (DE-A-3 108 873 and DE-A-3 233 089).
7-chloro-8-methylquinoline a) 72~8 9 (1030 moles) of acrolein are added to a solution of 6Z5 9 of 80~ strength sulfuric acid (5.0 moles), 141.5 9 (1.0 mole) of 3-chloro-2-methylaniline and 2 9 (0.013 mole) of sodium iodide in the course of 60 minutes at from 115 to 120C. Stirring is continued for 10 minutes, after which the pH is brought to 7-8 with 25~ strength sodium hydroxide solution and extraction is carried out with 200 ml of toluene at from 70 to 90C.
13145~2 - 5 - O.Z. 3050/39235 Evaporating down the toluene extract gives 164.6 9 (yield 86.1%) of 7-chloro-3-methylquinoline having a purity of ~2.9% according to gas chromatography.
b) 101.3 9 (1.1 moles) of g~ycerol are added to a S solution of 550 9 of 80% strength sulfuric acid (4.5 moles), 141.5 9 (1.0 mole) of 3-chloro-2-methylaniline and 1 9 (0.007 mole) of sodium iodide in the course of 90 minutes at 140C. Thereafter, stirring is carried out for 2 hours at from 140 to 145C, 60 ml of water be-ing distilled off simultaneously. The reaction solution is then brought to pH 7-8 ~ith 25X strength sodium hydrox-ide solution and extracted with 200 ml of toluene at from 70 to 90C. Evaporating down the toluene extract gives 180.0 9 (yield 95.9%) of a product which, according to gas chromatography, contains 94.6% of 7-chloro-8-methyl-quinoline and 0.25% of 3-chloro-2-methylaniline.
Distillation of the crude product gives 166 9 (yield 92.8~) of 7-chloro-8-methylquinoline having a purity of 99.2X; bp1: 96-98C; mp.: 40-42C.
EXAMPLE Z
7-chloro-4,8-dimethylquinoline 91 9 ~1.30 moles) of methyl vinyl ketone are ad-ded to a solution of 840 9 of 70% strength sulfuric acid t6.0 moles), 141.5 9 (1 mole) of 3-chloro-2-methylaniline and 4 9 tO.027 mole) of sodium iodide in the course of 60 minutes at from 115 to 125C. Stirring is carried out for 2 hours, 35 described in Example 1a), after ~hich the mixture is ~orked up. 179 9 of crude product are ob-tained. Distillation of crude product gives 167.2 g (yield 86.8%) of 7-chloro-4,3-dimethylquinoline having a purity of 99.5%; mp.: 51C.
4-methylquinoline 91 9 (1.30 moles) of methyl vinyl ketone are ad-ded to a solution of 840 g of 70% strength sulfuric acid (6.0 moles), 93 9 (t mole) of aniline and 4 9 (0.027 mole) of sodium iodide in the course of 60 minutes at from 115 ~ 1 3 ~ 2 - 6 - O.Z. 0050/39235 to 125C. Stirring is carried out for 10 minutes, as des-cribed in E~ample 1a), after which the mixture is worked up. 146.4 9 of a brown oil are obtained. Distillation of the crude product gives 107.3 9 (yield 75%) of 4-methyl-S quinoline having a purity of 99.3%; bp1: 80C.
7-chloro-Z,8-dimethylquinoline 91 9 (1.30 moles) crotonaldehyde are added to a solution of 840 9 of 70~ strength sulfuric acid (6.0 moles), 141.5 9 (1 mole) of 3-chloro-2-methylaniline and 3 9 (0.02 mole) of sodium iodide in the course of 60 minutes at 110C.
After working up has been carried out as described in Example 1a), 190.2 g of 7-chloro-2,8-dimethylquinoline are obtained. Distillation of the crude product gives 146.8 9 (yield 75.7%) of 7-chloro-2,8-dimethylquinoline having a purity of 98.8~ according to gas chromatography;
bp1: 102C.
7-chloro-3,8-dimethylquinoline 91 9 (1.30 moles) of methacrolein are added to a solution of 840 9 of 70X strength sulfuric acid (6.0 moles), 141.5 9 (1 mole) of 3-chloro-2-methylaniline and 4 9 (0.027 mole) of sodium iodide in the course of 60 minutes at 12QCO
After ~lorking up has been carried out as des-cribed in Exa~ple 1a), 198.4 9 of 7-chloro-3,8-dimethyl-quinoline are obtained. Distillation of the crude pro-duct gives 180.7 9 ~yield 90.7X) of 7-chloro-3,8-dimethyl-quinoline having a purity of 96.1% according to gaschromatography; mp. 75-78C.
After working up has been carried out as described in Example 1a), 190.2 g of 7-chloro-2,8-dimethylquinoline are obtained. Distillation of the crude product gives 146.8 9 (yield 75.7%) of 7-chloro-2,8-dimethylquinoline having a purity of 98.8~ according to gas chromatography;
bp1: 102C.
7-chloro-3,8-dimethylquinoline 91 9 (1.30 moles) of methacrolein are added to a solution of 840 9 of 70X strength sulfuric acid (6.0 moles), 141.5 9 (1 mole) of 3-chloro-2-methylaniline and 4 9 (0.027 mole) of sodium iodide in the course of 60 minutes at 12QCO
After ~lorking up has been carried out as des-cribed in Exa~ple 1a), 198.4 9 of 7-chloro-3,8-dimethyl-quinoline are obtained. Distillation of the crude pro-duct gives 180.7 9 ~yield 90.7X) of 7-chloro-3,8-dimethyl-quinoline having a purity of 96.1% according to gaschromatography; mp. 75-78C.
Claims (4)
1. A process for the preparation of a quinoline of the formula (I) where R is C1-C5-alkyl, R1, R2 and R3 are each hydro-gen or C1-C5-alkyl and X is hydrogen or halogen, with the proviso that R may furthermore be hydrogen if X is hydrogen, by reacting an aniline of the formula (II) with an .alpha.,.beta.-unsaturated aldehyde or ketone of the for-mula (III) in sulfuric acid in the presence of an oxidizing agent at temperatures of about 100-150°C, wherein the reaction is car-ried out in about 70-85% strength by weight sulfuric acid in the presence of a catalytic amount of iodine.
2. A process for the preparation of a quinoline of the formula I as claimed in claim 1, wherein the ketone of the formula III is acrolein formed in situ from glycerol.
3. A process for the preparation of a quinoline of the formula I as claimed in claim 1, wherein the molar ratio of glycerol to aniline of the formula II is from about 1 : 1 to 1.2 : 1.
4. A process for the preparation of a quinoline of - 8 - O.Z. 0050/39235 the formula I as claimed in claim 2, wherein the water formed in the reaction is distilled off during the reac-tion.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19873719014 DE3719014A1 (en) | 1987-06-06 | 1987-06-06 | METHOD FOR PRODUCING CHINOLINES |
| DEP3719014.8-44 | 1987-06-06 |
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| Publication Number | Publication Date |
|---|---|
| CA1314552C true CA1314552C (en) | 1993-03-16 |
Family
ID=6329209
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000568488A Expired - Lifetime CA1314552C (en) | 1987-06-06 | 1988-06-02 | Preparation of quinolines |
Country Status (9)
| Country | Link |
|---|---|
| EP (1) | EP0294685B1 (en) |
| JP (1) | JP2569126B2 (en) |
| KR (1) | KR950014790B1 (en) |
| CN (1) | CN1028170C (en) |
| AT (1) | ATE125797T1 (en) |
| CA (1) | CA1314552C (en) |
| DE (2) | DE3719014A1 (en) |
| ES (1) | ES2074988T3 (en) |
| GR (1) | GR3017158T3 (en) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3930167A1 (en) * | 1989-09-09 | 1991-03-14 | Basf Ag | METHOD FOR PRODUCING 3-METHYLCHINOLIN-8-CARBONIC ACID |
| FR2672596B1 (en) * | 1991-02-07 | 1995-07-13 | Roussel Uclaf | NEW NITROGEN BICYCLIC DERIVATIVES, THEIR PREPARATION PROCESS, THE NEW INTERMEDIATES OBTAINED, THEIR APPLICATION AS MEDICAMENTS AND THE PHARMACEUTICAL COMPOSITIONS CONTAINING THEM. |
| US5126456A (en) * | 1991-10-17 | 1992-06-30 | Merck & Co., Inc. | 7-chloroquinaldine synthesis |
| US6103904A (en) * | 1997-07-17 | 2000-08-15 | Basf Corporation | Skraup reaction process for synthesizing quinolones |
| JP4969099B2 (en) * | 2005-12-21 | 2012-07-04 | エア・ウォーター株式会社 | 6-Quinolinol Production Method |
| CN101555225B (en) * | 2009-05-22 | 2011-10-12 | 北京欧凯纳斯科技有限公司 | Method for preparing poly-substituted quinoline compound |
| CN101851197B (en) * | 2010-06-07 | 2011-03-23 | 江苏绿利来股份有限公司 | Method for synthesizing and refining quinclorac |
| CN102464613B (en) * | 2010-11-10 | 2015-07-01 | 中国石油大学(北京) | Synthetic method of quinoline derivative |
| CN102060761B (en) * | 2011-01-11 | 2012-10-17 | 浙江大学 | A kind of method for preparing quinoline derivative |
| CN102070521B (en) * | 2011-01-19 | 2012-10-03 | 北京成宇化工有限公司 | Method for preparing quinoline derivative |
| CN107698503A (en) * | 2017-11-22 | 2018-02-16 | 金凯(辽宁)化工有限公司 | A kind of preparation method of 8 fluorine quinoline and the preparation method of the fluorine quinoline of 3 iodine 8 |
| CN111377859B (en) * | 2018-12-28 | 2022-12-16 | 北京颖泰嘉和生物科技股份有限公司 | Preparation method of 7-chloro-8-methylquinoline |
| CN109912503B (en) * | 2019-04-01 | 2022-04-08 | 江南大学 | Synthetic method of 2, 3-diacyl quinoline compound |
| CN115894357A (en) * | 2022-11-18 | 2023-04-04 | 山东兴文工业技术研究院有限公司 | Skraup method for synthesizing 3, 8-dimethyl-7-chloroquinoline |
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| US2358162A (en) * | 1941-09-01 | 1944-09-12 | Stafford Allen And Sons Ltd | Process for the preparation of compounds containing fused pyridine rings |
| US3787418A (en) * | 1971-02-17 | 1974-01-22 | American Cyanamid Co | 6-alkyl-3-methylquinaldinic acids |
| DE3326255A1 (en) * | 1983-07-21 | 1985-01-31 | Basf Ag, 6700 Ludwigshafen | METHOD FOR PRODUCING CHINOLINES |
-
1987
- 1987-06-06 DE DE19873719014 patent/DE3719014A1/en active Granted
-
1988
- 1988-05-31 ES ES88108661T patent/ES2074988T3/en not_active Expired - Lifetime
- 1988-05-31 DE DE3854245T patent/DE3854245D1/en not_active Expired - Lifetime
- 1988-05-31 AT AT88108661T patent/ATE125797T1/en not_active IP Right Cessation
- 1988-05-31 EP EP88108661A patent/EP0294685B1/en not_active Expired - Lifetime
- 1988-06-02 CA CA000568488A patent/CA1314552C/en not_active Expired - Lifetime
- 1988-06-04 KR KR1019880006737A patent/KR950014790B1/en not_active Expired - Lifetime
- 1988-06-06 JP JP63137611A patent/JP2569126B2/en not_active Expired - Lifetime
- 1988-06-06 CN CN88104315A patent/CN1028170C/en not_active Expired - Lifetime
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Also Published As
| Publication number | Publication date |
|---|---|
| DE3719014C2 (en) | 1989-03-30 |
| ES2074988T3 (en) | 1995-10-01 |
| EP0294685A2 (en) | 1988-12-14 |
| CN1030231A (en) | 1989-01-11 |
| KR950014790B1 (en) | 1995-12-14 |
| JPS63310868A (en) | 1988-12-19 |
| EP0294685A3 (en) | 1990-05-09 |
| EP0294685B1 (en) | 1995-08-02 |
| JP2569126B2 (en) | 1997-01-08 |
| CN1028170C (en) | 1995-04-12 |
| ATE125797T1 (en) | 1995-08-15 |
| KR890000426A (en) | 1989-03-14 |
| DE3719014A1 (en) | 1988-12-15 |
| DE3854245D1 (en) | 1995-09-07 |
| GR3017158T3 (en) | 1995-11-30 |
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