DK168335B1 - Fremgangsmåde til fremstilling af substituerede furanforbindelser og isoxazoliner til brug herved - Google Patents
Fremgangsmåde til fremstilling af substituerede furanforbindelser og isoxazoliner til brug herved Download PDFInfo
- Publication number
- DK168335B1 DK168335B1 DK608185A DK608185A DK168335B1 DK 168335 B1 DK168335 B1 DK 168335B1 DK 608185 A DK608185 A DK 608185A DK 608185 A DK608185 A DK 608185A DK 168335 B1 DK168335 B1 DK 168335B1
- Authority
- DK
- Denmark
- Prior art keywords
- general formula
- isoxazolines
- hydroxy
- preparation
- isoxazoline
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 14
- 150000002240 furans Chemical class 0.000 title claims description 11
- 238000002360 preparation method Methods 0.000 title claims description 9
- 150000002547 isoxazolines Chemical class 0.000 title description 10
- WEQPBCSPRXFQQS-UHFFFAOYSA-N 4,5-dihydro-1,2-oxazole Chemical compound C1CC=NO1 WEQPBCSPRXFQQS-UHFFFAOYSA-N 0.000 claims description 28
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 8
- 125000006239 protecting group Chemical group 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 claims description 2
- 238000005984 hydrogenation reaction Methods 0.000 claims description 2
- 230000002378 acidificating effect Effects 0.000 claims 1
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 1
- 125000003710 aryl alkyl group Chemical group 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 claims 1
- 125000004093 cyano group Chemical group *C#N 0.000 claims 1
- 125000004438 haloalkoxy group Chemical group 0.000 claims 1
- 125000001188 haloalkyl group Chemical group 0.000 claims 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 6
- 150000002825 nitriles Chemical class 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- -1 5-hydroxymethyl-substituted isoxazolines Chemical class 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 125000000623 heterocyclic group Chemical group 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- AFEOKIGLYCQHAZ-UHFFFAOYSA-N (5-benzylfuran-3-yl)methanol Chemical compound OCC1=COC(CC=2C=CC=CC=2)=C1 AFEOKIGLYCQHAZ-UHFFFAOYSA-N 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000000887 hydrating effect Effects 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- HXVNBWAKAOHACI-UHFFFAOYSA-N 2,4-dimethyl-3-pentanone Chemical compound CC(C)C(=O)C(C)C HXVNBWAKAOHACI-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 150000001336 alkenes Chemical class 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 150000001491 aromatic compounds Chemical class 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 150000002241 furanones Chemical class 0.000 description 2
- 230000036571 hydration Effects 0.000 description 2
- 238000006703 hydration reaction Methods 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- SEWWFHKIKWFJNV-GQCTYLIASA-N (E)-2-methylbutanal oxime Chemical compound CCC(C)\C=N\O SEWWFHKIKWFJNV-GQCTYLIASA-N 0.000 description 1
- CXISHLWVCSLKOJ-CLFYSBASSA-N (Z)-phenylacetaldehyde oxime Chemical compound O\N=C/CC1=CC=CC=C1 CXISHLWVCSLKOJ-CLFYSBASSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- BZKFMUIJRXWWQK-UHFFFAOYSA-N Cyclopentenone Chemical class O=C1CCC=C1 BZKFMUIJRXWWQK-UHFFFAOYSA-N 0.000 description 1
- 229910004809 Na2 SO4 Inorganic materials 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 239000005708 Sodium hypochlorite Substances 0.000 description 1
- 229910010068 TiCl2 Inorganic materials 0.000 description 1
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 1
- NYMIJZDIYZUPNM-UHFFFAOYSA-N [3-benzyl-5-(hydroxymethyl)-4h-1,2-oxazol-5-yl]methanol Chemical compound O1C(CO)(CO)CC(CC=2C=CC=CC=2)=N1 NYMIJZDIYZUPNM-UHFFFAOYSA-N 0.000 description 1
- UTPMWAHVXSSSPU-UHFFFAOYSA-N [5-(hydroxymethyl)-4h-1,2-oxazol-5-yl]methanol Chemical class OCC1(CO)CC=NO1 UTPMWAHVXSSSPU-UHFFFAOYSA-N 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- BKVVMFUJRYQWSL-UHFFFAOYSA-N acetic acid;2-methylprop-1-ene Chemical compound CC(C)=C.CC(O)=O.CC(O)=O BKVVMFUJRYQWSL-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- SWXVUIWOUIDPGS-UHFFFAOYSA-N diacetone alcohol Chemical compound CC(=O)CC(C)(C)O SWXVUIWOUIDPGS-UHFFFAOYSA-N 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 238000006266 etherification reaction Methods 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 150000002545 isoxazoles Chemical class 0.000 description 1
- 125000003971 isoxazolinyl group Chemical group 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- HVAMZGADVCBITI-UHFFFAOYSA-M pent-4-enoate Chemical compound [O-]C(=O)CCC=C HVAMZGADVCBITI-UHFFFAOYSA-M 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 150000003217 pyrazoles Chemical class 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 150000008318 pyrimidones Chemical class 0.000 description 1
- 150000003233 pyrroles Chemical class 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- ZWYDDDAMNQQZHD-UHFFFAOYSA-L titanium(ii) chloride Chemical compound [Cl-].[Cl-].[Ti+2] ZWYDDDAMNQQZHD-UHFFFAOYSA-L 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/40—Radicals substituted by oxygen atoms
- C07D307/42—Singly bound oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/56—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/04—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
- C07D307/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- 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
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6527—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having nitrogen and oxygen atoms as the only ring hetero atoms
- C07F9/653—Five-membered rings
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
Description
i DK 168335 B1
Den foreliggende opfindelse angår en særlig fremgangsmåde til fremstilling af indtil 4 gange substituerede furaner med den almene formel (I) '‘rf'l 111 hvori R1 til har den i krav l's indledning angivne 5 betydning. Endvidere angår opfindelsen isooxazoliner til brug ved fremgangsmåden.
Det er kendt, at furaner kan fremstilles af 1,4-diketoner ved cyclisering (Comprehensive Heterocyclic Chemistry bind 4 657 ff, (1984). Ved syntesen af især asymmetrisk 10 substituerede furaner (f.eks. 2,4-disubstitution ) er fremstillingen af de nødvendige udgangsprodukter vanskelig.
Af denne grund anbefales f.eks. til fremstilling af 2-benzyl-4-hydroxymethylfuran, der er et efterspurgt mellemprodukt til insekticidsynteser, forskellige fremgangs-15 måder (JCS (c) 1971, 2551; Wegler bind 7 (1981) S. 76; DOS 21 22 823). Alle disse fremgangsmåder har dog væsentlige ulemper (mangetrinssynteser med moderat totalt udbytte, sikkerhedsproblemer på grund af høje temperaturer, isomerdannelse).
20 Det er formålet med opfindelsen at fremstille substituerede furaner ved en særlig fremgangsmåde, der kan gennemføres med let tilgængelige udgangsmaterialer, og som er let at gennemføre.
Det har ifølge opfindelsen vist sig, at man med fordel 25 kan fremstille furaner af den før angivne art på den
måde, at man hydrerer et tilsvarende isoxazolin med formel II
R'K___✓'R2 I , (ID.
il
X
DK 168335 B1 2 1 4 hvori R til R har den i krav 1 angivne betydning, og X betyder hydroxy, halogen eller med en afspaltelig beskyttelsesgruppe, valgt blandt t-butyl, trimethylsilyl, acetyl og benzyl, termineret hydroxy.
5 Hydreringen af substituerede isoxazoliner er principielt kendt (J. Am. Chem. Soc. 104, 4024 (1982), Tetrahedron Lett. 23, 3123 (1982) og 24, 1337 (1983)) og blev også anvendt til syntese af heterocycler. På denne måde kan man således f.eks. på basis af på velegnet måde sub-10 stituerede isoxazoliner ved hydrerende spaltning fremstille pyroner (US-Pat 4 136 114). Pyridiner (J. Org.
Chem. 2784 (1971)), pyrimidiner eller pyrimidoner (J. Pharm. Soc. (Jap) ^3, 471 (1963) eller Ann. Chimica 60, 393 (1970)), pyrroler (Ann. Chimica 5_6, 858 (1966)), 15 pyrazoler (Chem. Ber. 106, 332 (1973) eller TH 29_, 4291 (1973)), imidazoler (Ann. Chemica j60, 343 (1970)) eller også furanoner (Tetrahedron Lett. (1983) 2079 eller (1966) 233 eller (1967) 327 eller Gazetta (1966) 1073).
Dannelsen af de furaner, der fremstilles ved fremgangs-20 måden ifølge opfindelsen, iagttages ikke ved nogen af de nævnte kendte hydreringer, skønt på egnet måde substituerede udgangsprodukter (dvs. 5-hydroxymethylsubsti-tuerede isoxazoliner - f.eks. J. Ann. Chem. Soc. 105, 5826 - 5833 (1983); forbindelse 18 a) i fuldt omfang 25 anvendtes ved denne reaktion. Kun en i Acta Chem. Scand.
B 36, 1-14 (1982) beskreven sur katalytisk omlejring af isoxazolin under ikke-hydrerende betingelser frembragte i forbindelse med en speciel subsitution via et di-ketonmellemtrin et furanderivat. Ved lidt afvigende sub-30 stitutionstyper fremkom der ikke mere noget furanderi-vat, men derimod furanoner eller cyclopentenoner.
Isoxazoliner med den almene formel II, med undtagelse o 1 3 af sadanne, hvori R eller R betyder hydrogen, er nye DK 168335 B1 3 stoffer. Det er klart, at der i de tilfælde, hvor det både gælder, at er en forethret eller forestret hydroxymethyl, og at X er termineret hydroxy, kan have fundet en forethring eller en forestring med en i hvert 5 tilfælde bifunktionel partner sted under ringdannelse.
Afhængigt af den specielle fremgangsmåde kan dette ske direkte, eller man kan isolere hydroxyketonen III
11111
OH I X
som mellemprodukt, hvorved man i et påfølgende trin kan fremstille det ønskede furanderivat I:
Riv._^R2 R1^-p'R2 R2""n-jj^R3 ^•r3 ”* I /R3 Rl^O^R1*
0 T OH T
X X
(II) (III) (U
10 I tilfælde af den før angivne 2-benzyl-4-hydroxymethyl- furan kan omsætningen gengives således: ΟΠ H2/Kat 0 I ROH/H© oh ί η
Det glatte forløb af denne reaktion er blandt andet også overraskende, fordi hydrering af specielt substituerede isoxazoler hidtil kun har været beskrevet i 15 forbindelse med syntesen af dihydrofuran-3-oner (THI
(1983) 2079,- THL (1966) 233,· THL (1967) 327,- Gazetta (1966) 1073).
DK 168335 B1 4 'T l H2/Kat JTlf0 N^O-^S_OH -> ^0^·
Desuden frembragte en speciel isoxazolinsubstitution ved reduktionen med TiCl^ 2,5-disubstituerede furaner (Acta Chem. Scand. B 36 (1982):
COOR
v li 1 :—► J~l ^0^\<^COOHe 0 I forbindelse med fremstilling af de nye mellemproduk-5 ter med formlen II skal især følgende bemærkes:
Isoxazolin (II) R1vn—rR2 1 ^R3 (II) N\
X
kan f.eks. fremstilles ved en metode beskrevet i Hetero-cycles, bind 12, s. 1243 ff. (1979) ved omsætning af nitriloxider med bestemte olefiner i henhold til skemaet:
Ri N R l's-'^t'NO i ,
\ /// \ Θ T
C 0 -> R2^-<R3 (Π) + R3 R2/r=rV-Rt> X 1
Ved den forløbne omsætning betyder X hydroxy eller med en afspaltelig beskyttelsesgruppe, f.eks. t-butyl, tri- DK 168335 B1 5 methylsilyl, acetyl, benzyl, termineret hydroxy. I øvrigt kan man fremstille mange af isoxazolinerne ud fra andre isoxazoliner, der er tilgængelige i henhold til den i det foregående angivne metode; f.eks. kan i 3-5 stilling substitueret 5,5-bis-hydroxymethylisoxazolin ved hydroxygrupperne være forsynet med de før angivne beskyttelsesgrupper, eller disse kan fraspaltes, eller f.eks. kan hydroxy og halogen eller halogen og en beskyttelsesgruppe udveksles med hinanden.
10 De som udgangsstoffer anvendte nitriloxider kan på sin side f.eks. fremstilles ud fra tilsvarende oximer eller af alifatiske nitroforbindelser.
I denne forbindelse skal der henvises til Heterocycles, I. c. og de der anførte litteraturhenvisninger, desuden 15 til Houben-Weyl, Methoden, 14. oplag, bind 10/3, s.
83) og til J. Org. Chem. 2Q_, 1150 (1963). Om specielle aspekter ved den asymmetriske induktion ved denne isoxa-zolinsyntese beretter Jager og Schohe (Tetrahedron Lett.
24, 5301 - 04 (1983).
20 Isoleringen af nitriloxiderne med formel II er ikke ubetinget nødvendig. De dannes med fordel straks i tilstedeværelse af de alkenyl forbindelser, med hvilke de umiddelbart omsætter sig til isoxazolinerne med formel II.
25 De til fremstilling af isoxazolinerne anvendte nitriloxi der og alkenyl forbindelserne kan anvendes i ækvimolære forhold, eller i hvert tilfælde kan en af reaktionspartnerne anvendes i overskud.
Som opløsningsmiddel for omsætningen egner sig f.eks.
30 den pågældende alkenylforbindelse selv, desuden aromatiske forbindelser (f.eks. benzen, toluen, xylen), halogenerede DK 168335 B1 6 aromatiske forbindelser, ketoner (f.eks. acetone, methyl-ethylketon, diisopropylketon), ethere (f.eks. dioxan, diethylether, THF), chlorerede alifatiske carbonhydrider (f.eks. dichlorethan, chloroform, methylenchlorid).
5 Der kan henvises til, at tillejringen af olefinerne til disse nitriloxider forløber i afhængighed af arten af substituenterne, og at man derfor under visse omstændigheder kan forvente isomere eller blandinger af isomere. Det kan som en almen regel antages, at den side af den 10 olefiniske binding, der er tillejret til nitriloxidets oxygenatom, er den, som bærer den i rumlig henseende største substituent.
Alle de i det foregående beskrevne omsætninger forløber sædvanligvis under ca. 150 °C med tilstrækkelig hastighed.
15 Fremstillinqseksempel 1 på et isoxazolin o I o o-c-ch3 159 g phenylacetaldoxim og 202,5 g isobutylendiacetat opløses i 500 ml diethylether og blandes under stærk omrøring ved 10 til 15 °C med 1 050 ml af 10S5 natrium-hypochloritopløsning. Efter flere timers omrøring udrys-20 tes den organiske fase med vand, tørres over natriumsul fat og befries for opløsningsmiddel.
Udbytte 333 g = 92,85ό af den beregnede mængde. Krystaller af ethanolpetrolether smelter ved 78 til 79 °C.
DK 168335 B1 7
Fremstillinqseksempel 2 på en isoxazolin
Til 200 g allylacetat og 242 g 2-methylbutyraldoxim i 600 g methylenchlorid tilsættes 1960 g af en 10/¾ NaOH-oplasning portionsvis, og der omrøres i 3 timer ved 5 stuetemperatur. Den organiske fase separeres, vaskes med vand, tørres over Na^SO^ og bliver efter filtrering befriet for opløsningsmiddel. Den tilbageblivende olie (339 g) er 3-sek.butyl-5-acetoxymethyl-isoxazol.
300-MHz-NMR-spektrum i CDClj (ppm): 0,95 (3H); 1,08 10 (3H); 1,2 - 1,3 (2H); 2,04 (3H); 2,3 (IH); 2,35 (IH); 3,0 (IH); 4,0 - 4,1 (2H); 4,4 (IH).
Fremstillinqseksempel 1 på en furan 88,4 g 3-benzyl-5,5-bis(hydroxymethyl)isoxazolin optages i 550 ml tetrahydrofuran, 40 ml vand og 80 ml iseddike 15 og blandes med 1,6 g platinoxid. Ved indføring af hydrogen begynder en let exotherm reaktion; efter afsluttet hydrogenoptagelse frafiltrerer man, der koncentreres, og remanensen sammenrøres med acetone. Det uopløste ammoniumacetat frafiltreres, filtratet bliver igen koncentreret 20 og derpå i 300 ml methylenchlorid sammenrørt i 1 time ved 20 °C med 300 ml 10¾ saltsyre. Derpå separeres opløsningen i methylenchlorid, vaskes med vand og koncentre res. Som remanens foreligger der 59,2 g 2-benzy1-4-hydro-xymethylfuran NMR-spektroskopisk praktisk rent (79¾ 25 beregnet på isoxazolin). Ved destillation (0,3 mm/125 - 128°) fremkommer 52,0 g af et stof med smeltepunkt 37 til 38 °C).
Fremstillinqseksempel 2 på en furan 100 g 3-sek.buty1-5-acetoxymethylisoxazol i 400 g methanol 30 og 27 g vand hydreres med 25 g Raney-nikkel ved 20 - DK 168335 B1 8 30°. Derpå filtreres, der befries for opløsningsmiddel og destilleres. Den ued 70 - 80 °C overdestillerende uæske er 2-sek.butyl-furan. 200 MHz-NMR-spektrum i CDCl^ (ppm): 0,9 (3H); 1,23 (2H) j 1,5 - 1,8 (2H); 2,78 (IH); 5 6,0 (IH); 6,3 (IH); 7,35 (IH).
I henhold til de ovenstående forskrifter kan man fremstille yderligere isoxazoliner på basis af tilsvarende udgangsstoffer. Således fremstilledes de i den efterfølgende tabel anførte stoffer, som frembringer en forestil-10 ling om de mangesidige muligheder ved fremgangsmåden ifølge opfindelsen og de dermed opnåelige aktive stoffer eller disses forprodukter.
Ri R2 R3 X
' 0 o Kp =133-136°; “ II II 0.25 CH3 H CH3-C-OCH2 H CH3-C-0 M =1,4572 _D25__ 0 0 80 MHz-NMR i: C0Cl3(ppml: II || 1.4I3H); 2,15 (6H); 3.212H); C2H5-OOC H CH3-C-OCH2 H CH3-C-O 4.2-4,6 (6H); /" "v o o O- 11 11
H CH3-C-OCH2 H CH3—C—0 smp. = 73-80° C
é \—ch2 II II n
H CH3-C-OCH2 H CH3—C—0 sip. = 78-79°C
^^—«2 H CH2-OH . H OH smp. = 68-74° C
5 “
CH3-OCH2 H CH3 Η II Kp =107-110° C
CH3-C-0 0.2
Cl -~0 0 200 MHz-NMR i COCI3 (ppm) y—i II II 2,06 (6H ); 2.8 (2H) ; 3.8H2H)
Cl—\ V-CH2 η CH3--C-OCH2 H CHa-C-O 4.16I4H); 7,25(2H); 7.43I1H).
P_^_CH2 η CH20H H OH smp. = 93-97° C
CF^ 0 300-HHz—NMR i C0C13 (ppm) y-, II II 2.OK6H): 2,8 (2H) ; (' V-CHo H CH3-C-OCH2 H CH3-C-O 3.7512H); 4.04-4.23 (6H); \=/ * 7.4-7.68I4H).
-OH-- 0 0 300-MHz—NMR i C0C13 (ppm) | II II 1.53(3HJ; 2.013H); v -CH H CH3-C-°CH2 H CH3-C-O 2.0313H); 2,71(2H); \=/ 3,82 (1H); 4,12(2H): ___4.15(2H )._
Claims (3)
1. Fremgangsmåde til fremstilling af furaner med den almene formel I, R1\-^R3 111' hvori r\ R^, R3 og R^ betyder usubstitueret eller med halogen, 5 halogenalky1, alkoxy, halogenalkoxy, nitro, cyano, dial- kylphosphonyl eller alkoxycarbonyl substitueret alkyl, ary1, aralkyl, alkoxycarbonyl eller dialkoxyphosphonyl, R og R desuden hydrogen og R også hydroxymethyl eller med en afspaltelig beskyttelsesgruppe, valgt blandt lø t-butyl, trimethylsilyl, acetyl og benzyl, termineret hydroxymethyl, kendetegnet ved, at man hydrerer en tilsvarende isoxazolin med den almene formel II _r-'R2 (II) , ^R3 N\ X hvori X 2 3 λ
15 R , R , R"5 og R4 har den ovennævnte betydning, og X er hydroxy, halogen eller med en afspaltelig beskyttelsesgruppe, valgt blandt t-butyl, trimethylsilyl, acetyl, og benzyl, termineret hydroxy. Fremgangsmåde ifølge krav 1, kendetegnet DK 168335 Bl ved, at man foretager hydreringen under ikke sure betingelser, at man udvinder en tilsvarende hydroxyketon med den almene formel III R1C0-CHR2-C(0H)R3-CH(X)R4 (III) 12 3 4 5 hvor R , R , R , R og X har den i krav 1 angivne be tydning, og at man overfører dette mellemprodukt til den ønskede furan ved syretilsætning,
3. Isoxazolin til brug ved fremgangsmåden ifølge krav 1 eller 2, kendetegnet ved, at den har den ID almene formel II R11 ;£!» 1111 x 12 3 4 hvori R , R , R , R og X har den i krav 1 angivne betydning.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE3447793 | 1984-12-29 | ||
| DE19843447793 DE3447793A1 (de) | 1984-12-29 | 1984-12-29 | Substituierte furane und deren vorprodukte |
| DE3514384 | 1985-04-20 | ||
| DE19853514384 DE3514384A1 (de) | 1985-04-20 | 1985-04-20 | Substituierte furane und deren vorprodukte |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DK608185D0 DK608185D0 (da) | 1985-12-30 |
| DK608185A DK608185A (da) | 1986-06-30 |
| DK168335B1 true DK168335B1 (da) | 1994-03-14 |
Family
ID=25827876
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK608185A DK168335B1 (da) | 1984-12-29 | 1985-12-30 | Fremgangsmåde til fremstilling af substituerede furanforbindelser og isoxazoliner til brug herved |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US4954633A (da) |
| EP (1) | EP0187345B1 (da) |
| AU (1) | AU579693B2 (da) |
| CA (1) | CA1268465A (da) |
| DE (1) | DE3565103D1 (da) |
| DK (1) | DK168335B1 (da) |
| HU (1) | HUT39734A (da) |
| IL (1) | IL77448A (da) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3546371A1 (de) * | 1985-12-31 | 1987-07-02 | Basf Ag | Pyrethroide, verfahren zu ihrer herstellung und ihre verwendung zur bekaempfung von schaedlingen sowie vorprodukte fuer die herstellung der pyrethroide |
| DE3809765A1 (de) * | 1988-03-23 | 1989-10-05 | Basf Ag | Isoxazoline, verfahren zu ihrer herstellung und ihre verwendung als herbizide |
| GB9110858D0 (en) * | 1991-05-20 | 1991-07-10 | Shell Int Research | Herbicidal compounds |
| ITMI20010914A1 (it) * | 2001-05-04 | 2002-11-04 | Endura Spa | Processo per la produzione di alcool 5-benzil-3-furfurilico |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3415821A (en) * | 1965-09-07 | 1968-12-10 | Norwich Pharma Co | 1-(5-substituted)furfurylideneamino hydantoins and imidazolidinones |
| DE2122823A1 (de) * | 1971-05-08 | 1972-11-23 | Badische Anilin- & Soda-Fabrik Ag, 6700 Ludwigshafen | Verfahren zur Herstellung von Furanderivaten |
| DE3514384A1 (de) * | 1985-04-20 | 1986-10-23 | Basf Ag, 6700 Ludwigshafen | Substituierte furane und deren vorprodukte |
| DE3447793A1 (de) * | 1984-12-29 | 1986-07-10 | Basf Ag, 6700 Ludwigshafen | Substituierte furane und deren vorprodukte |
| DE3546371A1 (de) * | 1985-12-31 | 1987-07-02 | Basf Ag | Pyrethroide, verfahren zu ihrer herstellung und ihre verwendung zur bekaempfung von schaedlingen sowie vorprodukte fuer die herstellung der pyrethroide |
-
1985
- 1985-12-20 DE DE8585116323T patent/DE3565103D1/de not_active Expired
- 1985-12-20 EP EP85116323A patent/EP0187345B1/de not_active Expired
- 1985-12-24 AU AU51679/85A patent/AU579693B2/en not_active Expired
- 1985-12-25 IL IL77448A patent/IL77448A/xx not_active IP Right Cessation
- 1985-12-27 HU HU854968A patent/HUT39734A/hu unknown
- 1985-12-27 CA CA000498662A patent/CA1268465A/en not_active Expired - Lifetime
- 1985-12-30 DK DK608185A patent/DK168335B1/da not_active IP Right Cessation
-
1989
- 1989-07-25 US US07/384,910 patent/US4954633A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US4954633A (en) | 1990-09-04 |
| IL77448A (en) | 1989-10-31 |
| AU579693B2 (en) | 1988-12-08 |
| HUT39734A (en) | 1986-10-29 |
| EP0187345A1 (de) | 1986-07-16 |
| EP0187345B1 (de) | 1988-09-21 |
| DK608185A (da) | 1986-06-30 |
| DK608185D0 (da) | 1985-12-30 |
| CA1268465A (en) | 1990-05-01 |
| AU5167985A (en) | 1986-07-03 |
| DE3565103D1 (en) | 1988-10-27 |
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Legal Events
| Date | Code | Title | Description |
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| B1 | Patent granted (law 1993) | ||
| PUP | Patent expired |