CN109503657A - A kind of synthetic method of bis- oxyl phosphono -2- methyl-2-butenoic acid hydrocarbyl carbonate of 4- - Google Patents
A kind of synthetic method of bis- oxyl phosphono -2- methyl-2-butenoic acid hydrocarbyl carbonate of 4- Download PDFInfo
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- CN109503657A CN109503657A CN201811531121.3A CN201811531121A CN109503657A CN 109503657 A CN109503657 A CN 109503657A CN 201811531121 A CN201811531121 A CN 201811531121A CN 109503657 A CN109503657 A CN 109503657A
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- Prior art keywords
- methyl
- butenoic acid
- synthetic method
- ester
- phosphono
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- -1 bis- oxyl phosphono -2- methyl-2-butenoic acid Chemical compound 0.000 title claims abstract description 58
- 238000010189 synthetic method Methods 0.000 title claims abstract description 24
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 title claims abstract description 20
- 125000001183 hydrocarbyl group Chemical group 0.000 title claims abstract description 20
- 238000006243 chemical reaction Methods 0.000 claims abstract description 42
- 239000002994 raw material Substances 0.000 claims abstract description 40
- 239000003054 catalyst Substances 0.000 claims abstract description 15
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 claims abstract description 14
- 150000002148 esters Chemical class 0.000 claims abstract description 12
- SXQCPXKZTFJHQI-UHFFFAOYSA-N 2-hydroxy-2-methylbut-3-enoic acid Chemical compound C=CC(O)(C)C(O)=O SXQCPXKZTFJHQI-UHFFFAOYSA-N 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims description 26
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 19
- 229910052740 iodine Inorganic materials 0.000 claims description 19
- 239000011630 iodine Substances 0.000 claims description 19
- 239000007788 liquid Substances 0.000 claims description 18
- 150000002500 ions Chemical class 0.000 claims description 17
- 229910001511 metal iodide Inorganic materials 0.000 claims description 17
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 claims description 13
- XYFCBTPGUUZFHI-UHFFFAOYSA-N phosphine group Chemical group P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 12
- 125000000304 alkynyl group Chemical group 0.000 claims description 10
- 125000003342 alkenyl group Chemical group 0.000 claims description 9
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 7
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 4
- 235000021466 carotenoid Nutrition 0.000 claims description 4
- 150000001747 carotenoids Chemical class 0.000 claims description 4
- 150000002460 imidazoles Chemical class 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 4
- KAIPKTYOBMEXRR-UHFFFAOYSA-N 1-butyl-3-methyl-2h-imidazole Chemical class CCCCN1CN(C)C=C1 KAIPKTYOBMEXRR-UHFFFAOYSA-N 0.000 claims description 3
- 239000004215 Carbon black (E152) Substances 0.000 claims description 3
- GHEPZQBYCKAOAB-UHFFFAOYSA-M P.[I-].C(CCC)[P+](C)(CCCC)CCCC Chemical compound P.[I-].C(CCC)[P+](C)(CCCC)CCCC GHEPZQBYCKAOAB-UHFFFAOYSA-M 0.000 claims description 3
- 229930195733 hydrocarbon Natural products 0.000 claims description 3
- 239000002608 ionic liquid Substances 0.000 claims description 3
- JNMIXMFEVJHFNY-UHFFFAOYSA-M methyl(triphenyl)phosphanium;iodide Chemical compound [I-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 JNMIXMFEVJHFNY-UHFFFAOYSA-M 0.000 claims description 3
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 2
- 150000003053 piperidines Chemical class 0.000 claims description 2
- 230000001681 protective effect Effects 0.000 claims description 2
- LLTNLMDJCYJOOR-UHFFFAOYSA-N [I].C(C)N1CN(C=C1)C Chemical compound [I].C(C)N1CN(C=C1)C LLTNLMDJCYJOOR-UHFFFAOYSA-N 0.000 claims 1
- LDHQCZJRKDOVOX-NSCUHMNNSA-N crotonic acid Chemical compound C\C=C\C(O)=O LDHQCZJRKDOVOX-NSCUHMNNSA-N 0.000 claims 1
- RLZMYANQLOCZOB-UHFFFAOYSA-M tributyl(methyl)phosphanium;iodide Chemical compound [I-].CCCC[P+](C)(CCCC)CCCC RLZMYANQLOCZOB-UHFFFAOYSA-M 0.000 claims 1
- 239000002699 waste material Substances 0.000 abstract description 6
- 230000008901 benefit Effects 0.000 abstract description 2
- 238000010438 heat treatment Methods 0.000 abstract 1
- 239000000047 product Substances 0.000 description 33
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 24
- 238000003786 synthesis reaction Methods 0.000 description 20
- 230000015572 biosynthetic process Effects 0.000 description 18
- DOSPXNJPDHTNGN-UHFFFAOYSA-M [P].[I-].C(CCC)[P+](C)(CCCC)CCCC Chemical compound [P].[I-].C(CCC)[P+](C)(CCCC)CCCC DOSPXNJPDHTNGN-UHFFFAOYSA-M 0.000 description 16
- 150000001875 compounds Chemical class 0.000 description 15
- 238000005654 Michaelis-Arbuzov synthesis reaction Methods 0.000 description 11
- 150000008282 halocarbons Chemical class 0.000 description 11
- 239000006227 byproduct Substances 0.000 description 9
- 239000007789 gas Substances 0.000 description 9
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 8
- 238000009835 boiling Methods 0.000 description 7
- UNSIKXJBHRTIOD-UHFFFAOYSA-N ethyl 2-hydroxy-2-methylbut-3-enoate Chemical compound CCOC(=O)C(C)(O)C=C UNSIKXJBHRTIOD-UHFFFAOYSA-N 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 150000008301 phosphite esters Chemical class 0.000 description 7
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 238000004821 distillation Methods 0.000 description 6
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 229910052736 halogen Inorganic materials 0.000 description 6
- 238000010907 mechanical stirring Methods 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 239000012299 nitrogen atmosphere Substances 0.000 description 6
- 230000005311 nuclear magnetism Effects 0.000 description 6
- 238000005070 sampling Methods 0.000 description 6
- 238000001577 simple distillation Methods 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- GRFXGVMQYVLZJJ-UHFFFAOYSA-N methyl 2-hydroxy-2-methylbut-3-enoate Chemical class COC(=O)C(C)(O)C=C GRFXGVMQYVLZJJ-UHFFFAOYSA-N 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 5
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Substances C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 235000019260 propionic acid Nutrition 0.000 description 4
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 150000001336 alkenes Chemical class 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 3
- CYTQBVOFDCPGCX-UHFFFAOYSA-N trimethyl phosphite Chemical compound COP(OC)OC CYTQBVOFDCPGCX-UHFFFAOYSA-N 0.000 description 3
- VNDYJBBGRKZCSX-UHFFFAOYSA-L zinc bromide Chemical compound Br[Zn]Br VNDYJBBGRKZCSX-UHFFFAOYSA-L 0.000 description 3
- IBZJNLWLRUHZIX-UHFFFAOYSA-N 1-ethyl-3-methyl-2h-imidazole Chemical class CCN1CN(C)C=C1 IBZJNLWLRUHZIX-UHFFFAOYSA-N 0.000 description 2
- XXRCUYVCPSWGCC-UHFFFAOYSA-N Ethyl pyruvate Chemical compound CCOC(=O)C(C)=O XXRCUYVCPSWGCC-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- QGBSISYHAICWAH-UHFFFAOYSA-N dicyandiamide Chemical compound NC(N)=NC#N QGBSISYHAICWAH-UHFFFAOYSA-N 0.000 description 2
- WDCCXADRWCXXOR-UHFFFAOYSA-N ethyl 2-methylbut-3-enoate Chemical compound CCOC(=O)C(C)C=C WDCCXADRWCXXOR-UHFFFAOYSA-N 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 238000006317 isomerization reaction Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- SJHCUXCOGGKFAI-UHFFFAOYSA-N tripropan-2-yl phosphite Chemical compound CC(C)OP(OC(C)C)OC(C)C SJHCUXCOGGKFAI-UHFFFAOYSA-N 0.000 description 2
- 125000001340 2-chloroethyl group Chemical class [H]C([H])(Cl)C([H])([H])* 0.000 description 1
- MJBPUQUGJNAPAZ-UHFFFAOYSA-N Butine Natural products O1C2=CC(O)=CC=C2C(=O)CC1C1=CC=C(O)C(O)=C1 MJBPUQUGJNAPAZ-UHFFFAOYSA-N 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- ATFVTAOSZBVGHC-UHFFFAOYSA-N Glycolaldehyde dimer Chemical compound OC1COC(O)CO1 ATFVTAOSZBVGHC-UHFFFAOYSA-N 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- 238000006130 Horner-Wadsworth-Emmons olefination reaction Methods 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- UPYKUZBSLRQECL-UKMVMLAPSA-N Lycopene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1C(=C)CCCC1(C)C)C=CC=C(/C)C=CC2C(=C)CCCC2(C)C UPYKUZBSLRQECL-UKMVMLAPSA-N 0.000 description 1
- 206010054949 Metaplasia Diseases 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- UAYWVJHJZHQCIE-UHFFFAOYSA-L Zinc iodide Inorganic materials I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 235000005473 carotenes Nutrition 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 229940117360 ethyl pyruvate Drugs 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 150000002431 hydrogen Chemical group 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 150000002496 iodine Chemical class 0.000 description 1
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 230000015689 metaplastic ossification Effects 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 125000004365 octenyl group Chemical group C(=CCCCCCC)* 0.000 description 1
- 125000005069 octynyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C#C* 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- 150000004714 phosphonium salts Chemical class 0.000 description 1
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- BKOOMYPCSUNDGP-UHFFFAOYSA-N trimethyl-ethylene Natural products CC=C(C)C BKOOMYPCSUNDGP-UHFFFAOYSA-N 0.000 description 1
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- NCYCYZXNIZJOKI-UHFFFAOYSA-N vitamin A aldehyde Natural products O=CC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-UHFFFAOYSA-N 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
Classifications
-
- 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
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4015—Esters of acyclic unsaturated acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C403/00—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone
- C07C403/20—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by carboxyl groups or halides, anhydrides, or (thio)esters thereof
-
- 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
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4071—Esters thereof the ester moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4075—Esters with hydroxyalkyl compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
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- 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)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a kind of synthetic methods of bis- oxyl phosphono -2- methyl-2-butenoic acid hydrocarbyl carbonate of 4-.The present invention mixes under gas shield and catalyst existence condition, by 2- methyl -2- hydroxyl -3-butenoic acid hydrocarbyl carbonate (I) with phosphorous acid trialkyl ester, and heating, which is reacted, is made bis- oxyl phosphono -2- methyl-2-butenoic acid hydrocarbyl carbonate of 4-.The raw material that the present invention uses is easy to get, cheap, has reaction step few and high income, waste discharge amount is few and is easily processed, it is easy to accomplish industrialized advantage.
Description
Technical field
The present invention relates to organic synthesis fields, in particular to a kind of bis- oxyl phosphono -2- methyl -2- fourth of 4-
The synthetic method of olefin(e) acid hydrocarbyl carbonate.
Background technique
Bis- oxyl phosphono -2- methyl-2-butenoic acid hydrocarbyl carbonate of 4- (structure such as Formula Il ' shown:) it is a kind of important organic synthesis intermediate, it is mainly used for through Horner-
Wadsworth-Emmons reacts synthesis of conjugate polyenoid carboxylic acid and its derivative, especially for the β-in carotenoid field
Apo- -8 '-carrotene acetoacetic ester and the synthesis of β-apo- -4 '-carrotene acetoacetic ester.
Due to the importance of compound (II '), people since the 1960s just to its synthetic method into
Row research.Synthesis for the compound, there are many method reported in the literature, but without exception, it is this to have phosphono base junction
The preparation of structure compound requires first to prepare corresponding halogenated hydrocarbons, then is obtained by Michaelis-Arbuzov reaction.Below
For representational four kinds of synthetic methods in the prior art:
(1) US4937308 reports a kind of synthetic method using 2- vinylpropionic acid ethyl ester as raw material, specific: 2-
Addition reaction occurs for vinylpropionic acid ethyl ester and halogen, then sloughs a molecular halides hydrogen under alkaline condition, obtains 2- methyl-
4- halogen -2- butenoic acid ethyl；It reacts to obtain target production finally, Michaelis-Arbuzov is occurred with triethyl phosphite in it
Object.Reaction route is as follows:
(2) US5717128 reports a kind of using 2- methyl -2- hydroxyl -3-butenoic acid ethyl ester as the synthesis side of intermediate
Method.Specific: isomerization halogenating reaction occurs for 2- methyl -2- hydroxyl -3-butenoic acid ethyl ester and phosphorus trihalide, obtains 2- methyl -
4- halogen -2- butenoic acid ethyl；Then, it is reacted to obtain target product with triethyl phosphite.The following institute of reaction route
Show:
(3) CN104513164 reports a kind of synthetic method using ethyl pyruvate as raw material.It is specific: pyruvic acid
Ethyl ester reacts to obtain 2- methyl -2- hydroxyl -3-butenoic acid ethyl ester with vinyl chloride Grignard Reagent；Then, it reacts to obtain with hydrogen halides
2- methyl -4- halogen -2- butenoic acid ethyl；Finally, reacting to obtain target product with triethyl phosphite.Reaction route is as follows
It is shown:
(4) CN103113404 reports a kind of synthetic method using bis- oxyl phosphono ethylhexanal of 2- as raw material.Specifically
: bis- oxyl phosphono ethylhexanal of 2- reacts to obtain target product with 2- triphenylphosphine ylide propionic acid hydrocarbyl carbonate.
Synthetic route in this method, which seems, requires no halogenated hydrocarbons and Michaelis-Arbuzov reaction.And in fact,
The bis- oxyl phosphono ethylhexanal of raw material 2- of the route is to need to be passed through with Haloacetaldehydes and corresponding phosphite ester
Michaelis-Arbuzov reacts to synthesize.Its synthetic route can refer to as follows:
It can be seen that in the existing method, Michaelis-Arbuzov reaction is that synthesis compound (II) is subjected to
The step of.And classical Michaelis-Arbuzov reaction there are problems that some being difficult to overcome: (1) must first prepare halogen
For hydrocarbon, the process of preparation inevitably generates by-product inorganic salts and phosphorous acid in more waste, such as above-mentioned route,
And halogen atom is finally discharged in the form of halogenated hydrocarbons as by-product, the not indispensable part of product；(2)
Michaelis-Arbuzov reacts the generation of the low boiling point halogenated hydrocarbons along with a molecule, and the halogenated hydrocarbons of this molecule also can be with
Side reaction occurs for phosphite ester raw material, constantly consumes phosphite ester raw material, and produce another phosphonate ester by-product.As a result,
While generating waste disagreeableness to environment, the consumption of phosphite ester raw material is also increased, improves the synthesis of product
Cost.
Above-mentioned Michaelis-Arbuzov react itself there are aiming at the problem that, be done a large amount of improvement
Research.One of them critically important direction is directly to be reacted with phosphite ester using alcohol compound as raw material, obtained phase
The phosphonate product (being not required to by halogenated hydrocarbons) answered.However, current most of methods reported in the literature, such as
J.Org.Chem.2011,76,2875-2879 and Org.Lett., 2011,13,1270-1273 etc., it requires using excessive
Activator (such as ZnBr2, ZnI2Deng), the halogenated hydrocarbons of a molecule can be similarly generated, can be generated largely disagreeableness to environment discarded
Object (such as zinc salt, phosphonate ester by-product), also will increase the consumption of phosphite ester raw material.So these methods are not from root
It is solved the problems, such as on this.
Document Green Chem., 2018,20,3408-3413 and patent CN106543221 report one kind with alcohols
Conjunction object is raw material, and using salt compounded of iodine as catalyst, the method for synthesis phosphonate ester is directly reacted with phosphite ester.This method salt compounded of iodine only needs
Satisfied effect can be obtained using 2mol% dosage, and the not generation of halogenated hydrocarbons, very good solution Michaelis-
Arbuzov reaction there are the problem of.But compound (II) is synthesized using this method, it needs with 4- hydroxy-2-methyl -2- fourth
(structure is as follows for olefin(e) acid hydrocarbyl carbonate (III)) it is used as raw material.Currently, the synthetic method of compound (III) compared with
It is few, mainly using glycolaldehyde dimer as raw material, with 2- triphenylphosphine ylide propionic acid hydrocarbyl carbonate by Wittig react come
It synthesizes (such as WO2006039685, US2008221377 and Angew.Chem.Int.Ed., 2018,57,7240-7244 etc.).
The preparation of 2- triphenylphosphine ylide propionic acid hydrocarbyl carbonate, which is reacted generally by 2- halogen propionic acid hydrocarbyl carbonate with triphenylphosphine, to be made
(Angew.Chem.Int.Ed.,2018,57,7240-7244).As it can be seen that the reaction is also to need to use halogenated hydrocarbons as raw material,
It reacts the triphenylphosphine oxide generated and inorganic salts is needed as offal treatment.Therefore, this method does not also solve fundamentally
The composition problem of compound (II)
In conclusion requiring to lead to using halogenated hydrocarbons as raw material at present in the synthetic method of compound (II) reported in the literature
Michaelis-Arbuzov reaction is crossed to synthesize, this method inevitably generates a molecule halogenated hydrocarbons, needs to handle more
Waste.Have in document using alcohol compound as raw material, salt compounded of iodine efficiently synthesizes the side of phosphonate ester as catalyst
Method.But while solving the problems, such as that Michaelis-Arbuzov reacts itself, and bring alcohol compound (III)
Composition problem.
In view of this, the present invention is specifically proposed.
Summary of the invention
The first object of the present invention is to provide a kind of bis- oxyl phosphono -2- methyl-2-butenoic acid hydrocarbyl carbonate of 4-
Synthetic method, the method for the present invention synthesis step is few, high income, waste discharge amount is few and is easily processed, is easily industrialized.
In order to realize above-mentioned purpose of the invention, the following technical scheme is adopted:
A kind of synthetic method of bis- oxyl phosphono -2- methyl-2-butenoic acid hydrocarbyl carbonate of 4-, comprising: in gas shield
And under catalyst existence condition, 2- methyl -2- hydroxyl -3-butenoic acid hydroxy ester is reacted with phosphorous acid trialkyl ester, obtains 4-
Two oxyl phosphono -2- methyl-2-butenoic acid hydrocarbyl carbonates.
Compared with prior art, the invention has the benefit that
(1) in the present invention, use quaternary phosphine salt compounded of iodine or salt compounded of iodine class ionic liquid as catalyst, while realizing three-level alkene
The isomerization and phosphine esterification of propyl alcohol.
(2) in the present invention, the synthesis technology of raw material alcohol compound is mature, cheap and easy to get, is advantageously implemented industrial metaplasia
It produces.
(3) present invention is not needed using transition metal and ligand, and by-product is alcohol, and waste discharge amount is few and easy place
Reason, effect on environment are small.
Specific embodiment
Embodiment of the present invention is described in detail below in conjunction with embodiment, but those skilled in the art will
Understand, the following example is merely to illustrate the present invention, and is not construed as limiting the scope of the invention.It is not specified in embodiment specific
Condition person carries out according to conventional conditions or manufacturer's recommended conditions.Reagents or instruments used without specified manufacturer is
The conventional products that can be obtained by commercially available purchase.
In view of present in existing bis- oxyl phosphono -2- methyl-2-butenoic acid hydrocarbyl carbonate compound synthesis of 4-
Reaction process is long, step is more, and the problems such as the halide by-product generation being difficult to avoid that/raw material application, the present invention provides
One kind is using 2- methyl -2- hydroxyl -3-butenoic acid hydroxy ester and phosphorous acid trialkyl ester as raw material, Jing quaternary phosphine salt compounded of iodine or iodine
The method that ionic liquid is catalyzed to prepare bis- oxyl phosphono -2- methyl-2-butenoic acid alkyl ester compounds of 4-.
The method of the present invention synthetic route is as follows:
By existing literature technical report it is found that 2- methyl -2- hydroxyl -3-butenoic acid hydrocarbyl carbonate (I) synthetic method more
Maturation, cost is relatively low, thus is more suitable as raw material application.It, can also be effective using formula (I) compound as raw material in the present invention
Reduce product preparation cost.
Meanwhile reaction process is prepared it is found that with compound (I) for the pair of Material synthesis compound (II) by the present invention as above
Product only has small molecular alcohol, and environmentally protective pollution is small, has very important significance.
Specifically, being with 2- methyl -2- hydroxyl -3-butenoic acid hydroxy ester in present invention reaction as aboveAnd phosphorous acid trialkyl esterFor raw material, the two is in catalyst (season
At least one of Phosphonium salt compounded of iodine or metal iodide ions liquid) effect under, obtain bis- oxyl phosphono -2- methyl -2- fourth of product 4-
Olefin(e) acid hydrocarbyl carbonateAnd by-product alcohol (R2OH)。
Wherein, raw material 2- methyl -2- hydroxyl -3-butenoic acid hydroxy esterIn, R1To replace
Or non-substituted C1-C20Linear or branched alkyl group, C2-C20Linear chain or branched chain alkenyl, C2-C20Linear chain or branched chain alkynyl,
C3-C7Naphthenic base, C5-C12Aryl, C5-C12Heteroaryl, (C1-C4Alkylidene)-C5-C12Aryl, or (C1-C4Alkylidene)-C5-
C12Any one of heteroaryl；
Preferably, R1For substituted or non-substituted C1-C6Linear or branched alkyl group, C2-C6Linear chain or branched chain alkenyl,
C2-C6Linear chain or branched chain alkynyl, C5-C12Aryl, C5-C12Heteroaryl, (C1-C4Alkylidene)-C5-C12Aryl, or (C1-C4It is sub-
Alkyl)-C5-C12Any one of heteroaryl.
Meanwhile raw material phosphorous acid trialkyl esterIn, substituted or non-substituted C1-C20Straight chain or branch
Alkyl group, C2-C20Linear chain or branched chain alkenyl, C2-C20Linear chain or branched chain alkynyl, C3-C7Naphthenic base, C5-C12Aryl, C5-
C12Heteroaryl, (C1-C4Alkylidene)-C5-C12Aryl, or (C1-C4Alkylidene)-C5-C12Any one of heteroaryl；
Preferably, R2For substituted or non-substituted C1-C6Linear or branched alkyl group, C2-C6Linear chain or branched chain alkenyl,
C2-C6Linear chain or branched chain alkynyl, C5-C12Aryl, C5-C12Heteroaryl, (C1-C4Alkylidene)-C5-C12Aryl, or (C1-C4It is sub-
Alkyl)-C5-C12Any one of heteroaryl；
Wherein, in phosphorous acid trialkyl ester, different R2Can respectively it is individually optional be same or different；It is preferred that
, in raw material phosphorous acid trialkyl ester, three R2It is all the same.
In two kinds of raw materials as above, " substituted " one or more indicated in given structure described in each raw material compound definition
It is a can substituted hydrogen atom replaced specific substituent group, one substitution group can have a substituent group each in group
Substitutive position is replaced, when more than one position can be taken by the one or more of specific group in given structural formula
Replaced Dai Ji, then substituent group can replace at various locations identical or differently.
Preferably, substituent group as described above is preferably C1-C20Linear or branched alkyl group, more preferably C1-C6Straight chain
Or branched alkyl (such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl group, amyl, octyl etc.).
Meanwhile in the present invention, described in each raw material compound definition: " C1-C6Linear or branched alkyl group " be indicate containing
The saturated alkyl of the linear chain or branched chain of 1 to 6 carbon atom, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl group, penta
Base, octyl etc.；"C2-C6Linear chain or branched chain alkenyl " is the ethylenic unsaturation for indicating the linear chain or branched chain containing 2 to 6 carbon atoms
Base, such as vinyl, acrylic, isopropenyl, cyclobutenyl, isobutenyl, pentenyl, octenyl etc.；"C2-C6Linear chain or branched chain
Alkynyl " is the unsaturated alkynyl for indicating the linear chain or branched chain containing 2 to 6 carbon atoms, such as acetenyl, propinyl, butine
Base, butynyl, pentynyl, octynyl etc.；"C3-C7Naphthenic base " is expressed as including 3-7 carbon atoms containing only hydrocarbon two kinds
The cyclic alkyl of element, such as cyclopropyl, 2- methylcyclopropyl groups, cyclopenta；"C5-C12Aryl " indicates to contain 5 to 12 carbon
Atom has the cyclic group of armaticity, such as phenyl ring；"C5-C12Heteroaryl " indicate containing 5 to 12 carbon atoms and 1 with
Upper hetero atom (including but not limited to oxygen atom (O), sulphur atom (S), nitrogen-atoms (N)) has the cyclic group of armaticity, such as pyrrole
Cough up alkyl, pyridine alkyl etc..
Raw material 2- methyl -2- hydroxyl -3-butenoic acid hydroxy ester of arbitrary structures as above With
And phosphorous acid trialkyl esterProtect gas and under the conditions of, via catalyst, obtain product 4- bis-
Oxyl phosphono -2- methyl-2-butenoic acid hydrocarbyl carbonateAnd by-product alcohol (R2OH)。
In product and by-product compounds, R1、R2Definition with defined in raw material compound it is identical；Preferably, product and pair
In product, each R2It is all the same；It is furthermore preferred that in the present invention, bis- oxyl phosphono -2- methyl-2-butenoic acid alkyl of product 4-
Ester are as follows: 4- dimethoxy phosphono -2- methyl-2-butenoic acid methyl esters (corresponds to R in raw material and product1、R2It is methyl), 4- bis-
Ethyoxyl phosphono -2- methyl-2-butenoic acid methyl esters (corresponds to R in raw material and product1For methyl, R2For ethyl), 4- diisopropyl oxygen
Base phosphono -2- methyl-2-butenoic acid methyl esters (corresponds to R in raw material and product1For methyl, R2For isopropyl), 4- dimethoxy phosphine
Acyl group -2- methyl-2-butene acetoacetic ester (corresponds to R in raw material and product1For ethyl, R2For methyl), 4- diethoxy phosphonium mesitoyl base-
2- methyl-2-butene acetoacetic ester (corresponds to R in raw material and product1、R2It is ethyl) or 4- diisopropoxy phosphono -2- first
Base -2- butenoic acid ethyl (corresponds to R in raw material and product1For ethyl, R2For isopropyl).
In certain embodiments of the present invention, as above in reaction, protection gas used is nitrogen or inert gas；Preferably
Nitrogen.
In certain embodiments of the present invention, as above in reaction, raw material phosphorous acid trialkyl ester
With 2- methyl -2- hydroxyl -3-butenoic acid hydroxy esterMolar ratio be (0.8~3): 1,
Such as 1:1,1.2:1,1.4:1,1.5:1,2:1,2.2:1,2.5:1 etc.；Preferably (1~1.4): 1.
In certain embodiments of the present invention, as above in reaction, used catalyst is quaternary phosphine salt compounded of iodine or iodine salt ion
At least one of liquid；
Wherein , quaternary phosphine salt compounded of iodine includes: at least one of tributyl methyl phosphonium iodide phosphine or methyl triphenyl phosphonium iodide；It is preferred that
, the quaternary phosphine salt compounded of iodine includes tributyl methyl phosphonium iodide phosphine；
Metal iodide ions liquid includes: imidazoles/alkyl imidazole metal iodide ions liquid, pyridine/alkyl pyridine metal iodide ions liquid,
At least one of piperidines/Alkylpiperidine metal iodide ions liquid or morpholine/alkyl morpholine metal iodide ions liquid；Preferably, described
Metal iodide ions liquid includes: at least one of imidazoles/alkyl imidazole metal iodide ions liquid；It is furthermore preferred that the metal iodide ions
Liquid includes at least one of 1- butyl -3- methylimidazole salt compounded of iodine or 1- ethyl-3-methylimidazole salt compounded of iodine.
In certain embodiments of the present invention, as above in reaction, catalyst and 2- methyl -2- hydroxyl -3-butenoic acid hydroxyl
Base esterMolar ratio be (0.0001~1): 1, for example, 0.001:1,0.005:1,
0.1:1,0.5:1 etc.；Preferably (0.001~0.1): 1.
In certain embodiments of the present invention, as above reaction can be carried out in dicyandiamide solution (that is, by stock dispersion in
Reacted in solvent), it can also be carried out under the conditions of non-solvent；Preferably, as above reaction carries out under the conditions of non-solvent；
Wherein, when reaction carries out in dicyandiamide solution, solvent for use is atent solvent, such as hexane, carbon tetrachloride, two
Chloroethanes etc..
In certain embodiments of the present invention, as above reaction in, reaction temperature be 70~150 DEG C, the reaction time be 1~
60h；Preferably, reaction temperature is 100~130 DEG C, and the reaction time is 8~30h.
Further, the bis- oxyl phosphono -2- methyl-2-butenoic acid hydrocarbyl carbonate of 4- as obtained by the present invention can be with
As raw material, and it is further used for the classes such as β-apo- -8 '-carrotene acetoacetic ester or β-apo- -4 '-carrotene acetoacetic ester
In the preparation of carotene compound.
In following specific example, raw material 2- methyl -2- hydroxyl -3-butenoic acid methyl esters and 2- methyl -2- hydroxyl -3-butenoic acid
Ethyl ester can refer to the synthesis of method provided by US4596889.
The synthesis of 1 4- dimethoxy phosphono -2- methyl-2-butenoic acid methyl esters of embodiment
Under nitrogen atmosphere, 2- methyl -2- hydroxyl -3-butenoic acid methyl esters is added into 1000ml three-necked flask
(260.28g, 2mol), Trimethyl phosphite (272.98g, 2.2mol) and tributyl methyl phosphonium iodide phosphorus (0.69g,
0.002mol), mechanical stirring and simple distillation device are installed.Stirring, revolving speed 600r/min are started, and is heated to 110 DEG C.
In reaction process, engler distillation and low-boiling point material is not collected.Meanwhile gas chromatographic analysis is done every 1h sampling.After 12h, 2- first
Base -2- hydroxyl -3-butenoic acid methyl esters converts completely.After reaction, product obtains 407.13g production by rectifying separating-purifying
Object, purity 98.2%, yield 90.0%.Reaction route is as follows:
Product 4- dimethoxy phosphono -2- methyl-2-butenoic acid methyl esters nuclear-magnetism and Mass Spectrometer Method result are as follows:
1H NMR(600MHz,CDCl3) δ 6.72-6.76 (m, 1H), 3.75 (d, J=11.2Hz, 6H), 3.73 (s, 3H),
2.77 (dd, J=23.8,8.0Hz, 2H), 1.88 (d, J=4.5Hz, 3H)
13C NMR(150MHz,CDCl3) 167.21 (d, J=3.1Hz), 130.71 (d, J=10.2Hz), 129.46 (d, J
=11.5Hz), 52.39 (d, J=7.0Hz), 51.37,26.01 (d, J=139.4Hz), 12.6 (d, J=3.1Hz)
ESI-MS:223.5(M+H)+,221.7(M-H)-.
Embodiment 2-14
The step of repeating embodiment 1, the dosage of fixed 2- methyl -2- hydroxyl -3-butenoic acid methyl esters, change reaction temperature,
The dosage of Trimethyl phosphite, the type and dosage of catalyst, obtained result are as shown in table 1 below.
The result of 1 embodiment 2-14 of table
| Embodiment | Temperature/DEG C | P(OMe)3Dosage | Catalyst type and dosage | Yield/% |
| 2 | 100 | 272.98g,2.2mol | Tributyl methyl phosphonium iodide phosphorus (0.69g, 0.002mol) | 85.3 |
| 3 | 120 | 272.98g,2.2mol | Tributyl methyl phosphonium iodide phosphorus (0.69g, 0.002mol) | 90.5 |
| 4 | 130 | 272.98g,2.2mol | Tributyl methyl phosphonium iodide phosphorus (0.69g, 0.002mol) | 88.4 |
| 5 | 110 | 297.79g,2.4mol | Tributyl methyl phosphonium iodide phosphorus (0.69g, 0.002mol) | 91.8 |
| 6 | 110 | 248.15g,2.0mol | Tributyl methyl phosphonium iodide phosphorus (0.69g, 0.002mol) | 84.2 |
| 7 | 110 | 272.98g,2.2mol | Tributyl methyl phosphonium iodide phosphorus (0.17g, 0.0005mol) | 80.7 |
| 8 | 110 | 272.98g,2.2mol | Tributyl methyl phosphonium iodide phosphorus (0.34g, 0.001mol) | 88.4 |
| 9 | 110 | 272.98g,2.2mol | Tributyl methyl phosphonium iodide phosphorus (1.36g, 0.004mol) | 92.1 |
| 10 | 110 | 272.98g,2.2mol | Tributyl methyl phosphonium iodide phosphorus (2.72g, 0.008mol) | 92.7 |
| 11 | 110 | 272.98g,2.2mol | Tributyl methyl phosphonium iodide phosphorus (5.44g, 0.016mol) | 93.1 |
| 12 | 110 | 272.98g,2.2mol | Methyl triphenyl phosphonium iodide (0.81g, 0.002mol) | 81.4 |
| 13 | 110 | 272.98g,2.2mol | 1- butyl -3- methylimidazole salt compounded of iodine (0.53g, 0.002mol) | 91.3 |
| 14 | 110 | 272.98g,2.2mol | 1- ethyl-3-methylimidazole salt compounded of iodine (0.48g, 0.002mol) | 92.7 |
The synthesis of 15 4- diethoxy phosphonium mesitoyl base -2- methyl-2-butenoic acid methyl esters of embodiment
Under nitrogen atmosphere, 2- methyl -2- hydroxyl -3-butenoic acid methyl esters is added into 1000ml three-necked flask
(260.28g, 2mol), triethyl phosphite (365.55g, 2.2mol) and tributyl methyl phosphonium iodide phosphorus (0.69g,
0.002mol), mechanical stirring and simple distillation device are installed.Stirring, revolving speed 600r/min are started, and is heated to 120 DEG C.
In reaction process, engler distillation and low-boiling point material is not collected.Meanwhile gas chromatographic analysis is done every 1h sampling.After 8h, 2- first
Base -2- hydroxyl -3-butenoic acid methyl esters converts completely.After reaction, product obtains 469.42g production by rectifying separating-purifying
Object, purity 98.5%, yield 92.4%.Reaction route is as follows:
Product 4- diethoxy phosphonium mesitoyl base -2- methyl-2-butenoic acid methyl esters nuclear-magnetism and Mass Spectrometer Method data are as follows:
1H NMR(600MHz,CDCl3)δ6.73-6.78(m,1H),4.08-4.15(m,4H),3.74(s,3H),2.74
(dd, J=23.2,8.1Hz, 2H), 1.89 (d, J=4.2Hz, 3H), 1.25-1.38 (m, 6H)
13C NMR(150MHz,CDCl3) 168.11 (d, J=3.2Hz), 131.71 (d, J=13.2Hz), 130.46 (d, J
=11.2Hz), 62.42 (d, J=6.7Hz), 52.39,27.71 (d, J=138.4Hz), 16.78 (d, J=6.0Hz), 12.74
(d, J=2.8Hz)
ESI-MS:251.6(M+H)+,249.7(M-H)-.
The synthesis of 16 4- diisopropoxy phosphono -2- methyl-2-butenoic acid methyl esters of embodiment
Under nitrogen atmosphere, 2- methyl -2- hydroxyl -3-butenoic acid methyl esters is added into 1000ml three-necked flask
(260.28g, 2mol), triisopropyl phosphite (458.13g, 2.2mol) and tributyl methyl phosphonium iodide phosphorus (0.69g,
0.002mol), mechanical stirring and simple distillation device are installed.Stirring, revolving speed 600r/min are started, and is heated to 120 DEG C.
In reaction process, engler distillation and low-boiling point material is not collected.Meanwhile gas chromatographic analysis is done every 1h sampling.After 10h, 2- first
Base -2- hydroxyl -3-butenoic acid methyl esters converts completely.After reaction, product obtains 528.64g production by rectifying separating-purifying
Object, purity 98.0%, yield 93.1%.Reaction route is as follows:
Product 4- diisopropoxy phosphono -2- methyl-2-butenoic acid methyl esters nuclear-magnetism and Mass Spectrometer Method data are as follows:
1H NMR(600MHz,CDCl3)δ6.63-6.68(m,1H),4.22-4.28(m,2H),3.72(s,3H),2.94
(dd, J=23.3,8.5Hz, 2H), 1.86 (d, J=4.7Hz, 3H), 1.37 (d, J=6.2Hz, 6H), 1.27 (d, J=
6.1Hz,6H).
13C NMR(150MHz,CDCl3) 167.61 (d, J=3.4Hz), 131.21 (d, J=13.5Hz), 129.86 (d, J
=12.2Hz), 83.44 (d, J=6.9Hz), 52.12,27.73 (d, J=128.4Hz), 17.98 (d, J=6.0Hz), 17.28
(d, J=6.3Hz), 12.91 (d, J=3.1Hz)
ESI-MS:279.5(M+H)+,277.3(M-H)-.
The synthesis of 17 4- dimethoxy phosphono -2- methyl-2-butene acetoacetic ester of embodiment
Under nitrogen atmosphere, 2- methyl -2- hydroxyl -3-butenoic acid ethyl ester is added into 1000ml three-necked flask
(288.34g, 2mol), Trimethyl phosphite (272.98g, 2.2mol) and tributyl methyl phosphonium iodide phosphorus (0.69g,
0.002mol), mechanical stirring and simple distillation device are installed.Stirring, revolving speed 600r/min are started, and is heated to 110 DEG C.
In reaction process, engler distillation and low-boiling point material is not collected.Meanwhile gas chromatographic analysis is done every 1h sampling.After 12h, 2- first
Base -2- hydroxyl -3-butenoic acid ethyl ester converts completely.After reaction, product obtains 427.18g production by rectifying separating-purifying
Object, purity 98.5%, yield 89.1%.Reaction route is as follows:
Product 4- dimethoxy phosphono -2- methyl-2-butene acetoacetic ester nuclear-magnetism and Mass Spectrometer Method data are as follows:
1H NMR(600MHz,CDCl3) δ 6.65-6.70 (m, 1H), 4.10 (q, J=7.7Hz, 2H), 3.64 (d, J=
10.7Hz, 6H), 2.98 (dd, J=23.1,8.8Hz, 2H), 1.85 (d, J=4.1Hz, 3H), 1.20 (t, J=7.4Hz, 3H)
13C NMR(150MHz,CDCl3) 167.35 (d, J=3.2Hz), 131.43 (d, J=13.2Hz), 130.01 (d, J
=12.0Hz), 61.27,52.58 (d, J=7.2Hz), 29.14 (d, J=138.4Hz), 17.10 (d, J=6.1Hz),
12.51.
ESI-MS:237.5(M+H)+,235.4(M-H)-.
The synthesis of 18 4- diethoxy phosphonium mesitoyl base -2- methyl-2-butene acetoacetic ester of embodiment
Under nitrogen atmosphere, 2- methyl -2- hydroxyl -3-butenoic acid ethyl ester is added into 1000ml three-necked flask
(288.34g, 2mol), triethyl phosphite (365.55g, 2.2mol) and tributyl methyl phosphonium iodide phosphorus (0.69g,
0.002mol), mechanical stirring and simple distillation device are installed.Stirring, revolving speed 600r/min are started, and is heated to 120 DEG C.
In reaction process, engler distillation and low-boiling point material is not collected.Meanwhile gas chromatographic analysis is done every 1h sampling.After 12h, 2- first
Base -2- hydroxyl -3-butenoic acid ethyl ester converts completely.After reaction, product obtains 510.85g production by rectifying separating-purifying
Object, purity 98.3%, yield 95.0%.Reaction route is as follows:
Product 4- diethoxy phosphonium mesitoyl base -2- methyl-2-butene acetoacetic ester nuclear-magnetism and Mass Spectrometer Method data are as follows:
1H NMR(600MHz,CDCl3) δ 6.75-6.79 (m, 1H), 4.21 (q, J=7.4Hz, 2H), 4.10-4.17 (m,
4H), 2.76 (dd, J=23.2,7.8Hz, 2H), 1.90 (d, J=4.2Hz, 3H), 1.24-1.41 (m, 9H)
13C NMR(150MHz,CDCl3) 167.38 (d, J=2.0Hz), 131.90 (d, J=13.5Hz), 130.07 (d, J
=12.0Hz), 62.20 (d, J=7.5Hz), 60.77,27.58 (d, J=138.0Hz), 16.43 (d, J=6.0Hz),
(14.23,12.60 d, J=1.5Hz)
ESI-MS:265.8(M+H)+,263.5(M-H)-。
The synthesis of 19 4- diisopropoxy phosphono -2- methyl-2-butene acetoacetic ester of embodiment
Under nitrogen atmosphere, 2- methyl -2- hydroxyl -3-butenoic acid ethyl ester is added into 1000ml three-necked flask
(288.34g, 2mol), triisopropyl phosphite (458.13g, 2.2mol) and tributyl methyl phosphonium iodide phosphorus (0.69g,
0.002mol), mechanical stirring and simple distillation device are installed.Stirring, revolving speed 600r/min are started, and is heated to 120 DEG C.
In reaction process, engler distillation and low-boiling point material is not collected.Meanwhile gas chromatographic analysis is done every 1h sampling.After 12h, 2- first
Base -2- hydroxyl -3-butenoic acid ethyl ester converts completely.After reaction, product obtains 545.12g production by rectifying separating-purifying
Object, purity 98.1%, yield 91.8%.Reaction route is as follows:
Product 4- diisopropoxy phosphono -2- methyl-2-butene acetoacetic ester nuclear-magnetism and Mass Spectrometer Method data are as follows:
1H NMR(600MHz,CDCl3) δ 6.70-6.77 (m, 1H), 4.27-4.35 (m, 2H), 4.20 (q, J=7.5Hz,
2H), 2.82 (dd, J=23.6,8.2Hz, 2H), 1.87 (d, J=4.6Hz, 3H), 1.38 (d, J=6.3Hz, 6H), 1.26 (d,
J=6.5Hz, 6H), 1.25 (t, J=7.9Hz, 3H)；
13C NMR(150MHz,CDCl3) 166.98 (d, J=2.4Hz), 131.76 (d, J=13.2Hz), 130.32 (d, J
=12.3Hz), 83.05 (d, J=6.3Hz), 61.11,27.67 (d, J=138.9Hz), 16.94 (d, J=6.5Hz), 17.73
(d, J=6.8Hz), 17.19 (d, J=6.5Hz), 14.52.
ESI-MS:293.4(M+H)+,292.5(M-H)-。
Although illustrate and describing the present invention with specific embodiment, it will be appreciated that without departing substantially from of the invention
Many other change and modification can be made in the case where spirit and scope.It is, therefore, intended that in the following claims
Including belonging to all such changes and modifications in the scope of the invention.
Claims (10)
1. a kind of synthetic method of bis- oxyl phosphono -2- methyl-2-butenoic acid hydrocarbyl carbonate of 4- characterized by comprising
Under protective atmosphere and catalyst existence condition, 2- methyl -2- hydroxyl -3-butenoic acid hydroxy ester and phosphorous acid trialkyl
Ester reaction, obtains bis- oxyl phosphono -2- methyl-2-butenoic acid hydrocarbyl carbonate of 4-.
2. synthetic method according to claim 1, which is characterized in that the 2- methyl -2- hydroxyl -3-butenoic acid hydroxy ester
Shown in structure such as following formula (I)；
In formula (I), R1For substituted or non-substituted C1-C20Linear or branched alkyl group, C2-C20Linear chain or branched chain alkenyl, C2-
C20Linear chain or branched chain alkynyl, C3-C7Naphthenic base, C5-C12Aryl, C5-C12Heteroaryl, (C1-C4Alkylidene)-C5-C12Virtue
Base, or (C1-C4Alkylidene)-C5-C12Any one of heteroaryl；
Preferably, R1For substituted or non-substituted C1-C6Linear or branched alkyl group, C2-C6Linear chain or branched chain alkenyl, C2-C6's
Linear chain or branched chain alkynyl, C5-C12Aryl, C5-C12Heteroaryl, (C1-C4Alkylidene)-C5-C12Aryl, or (C1-C4Alkylidene)-
C5-C12Any one of heteroaryl.
3. synthetic method according to claim 1, which is characterized in that the phosphorous acid trialkyl ester structure is as follows:
Wherein, R2For substituted or non-substituted C1-C20Linear or branched alkyl group, C2-C20Linear chain or branched chain alkenyl, C2-C20's
Linear chain or branched chain alkynyl, C3-C7Naphthenic base, C5-C12Aryl, C5-C12Heteroaryl, (C1-C4Alkylidene)-C5-C12Aryl, or
(C1-C4Alkylidene)-C5-C12Any one of heteroaryl；
Wherein, different R2It can individually optional be same or different；
Preferably, R2For substituted or non-substituted C1-C6Linear or branched alkyl group, C2-C6Linear chain or branched chain alkenyl, C2-C6's
Linear chain or branched chain alkynyl, C5-C12Aryl, C5-C12Heteroaryl, (C1-C4Alkylidene)-C5-C12Aryl, or (C1-C4Alkylidene)-
C5-C12Any one of heteroaryl.
4. synthetic method according to claim 1, which is characterized in that the catalyst Wei quaternary phosphine salt compounded of iodine or metal iodide ions liquid
At least one of body.
5. synthetic method according to claim 4, which is characterized in that the quaternary phosphine salt compounded of iodine includes: tributyl methyl phosphonium iodide
At least one of phosphine or methyl triphenyl phosphonium iodide；
Preferably, the quaternary phosphine salt compounded of iodine includes tributyl methyl phosphonium iodide phosphine；
And/or the metal iodide ions liquid includes: imidazoles or alkyl imidazole metal iodide ions liquid, pyridine or alkyl pyridine salt compounded of iodine
At least one of ionic liquid, piperidines or Alkylpiperidine metal iodide ions liquid or morpholine or alkyl morpholine metal iodide ions liquid；
Preferably, the metal iodide ions liquid includes: at least one of imidazoles/alkyl imidazole metal iodide ions liquid；
It is furthermore preferred that the metal iodide ions liquid includes 1- butyl -3- methylimidazole salt compounded of iodine or 1- ethyl-3-methylimidazole iodine
At least one of salt.
6. synthetic method according to claim 1, which is characterized in that phosphorous acid trialkyl ester and 2- methyl -2- hydroxyl -3-
The molar ratio of butenoic acid hydrocarbyl carbonate is 0.8~3:1；
Preferably, phosphorous acid trialkyl ester and 2- methyl -2- hydroxyl -3-butenoic acid hydrocarbyl carbonate molar ratio are 1~1.4:1.
7. synthetic method according to claim 1, which is characterized in that catalyst and 2- methyl -2- hydroxyl -3-butenoic acid hydrocarbon
The molar ratio of base ester is 0.0001~1:1；
Preferably, catalyst and 2- methyl -2- hydroxyl -3-butenoic acid hydrocarbyl carbonate molar ratio are 0.001~0.1:1.
8. synthetic method according to claim 1, which is characterized in that reaction temperature is 70~150 DEG C；
Preferably, reaction temperature is 100~130 DEG C；
And/or the reaction time is 1~60h；
Preferably, the reaction time is 8~30h.
9. synthetic method according to claim 1, which is characterized in that reaction under the conditions of solvent-free or atent solvent into
Row；
Preferably, reaction carries out under solvent-free conditions.
10. the synthetic method of a Carotenoids, which is characterized in that in the method, appoint first, in accordance in claim 1-9
Method described in one obtains bis- oxyl phosphono -2- methyl-2-butenoic acid hydrocarbyl carbonate of 4-, then with bis- oxyl phosphono of 4-
Base -2- methyl-2-butenoic acid hydrocarbyl carbonate is that raw material obtains carotenoid；
Preferably, the carotenoid is β-apo- -8 '-carrotene acetoacetic ester or β-apo- -4 '-carotenic acid second
Ester.
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| CN113527359A (en) * | 2021-07-20 | 2021-10-22 | 万华化学集团股份有限公司 | Method for preparing apoester intermediate C5 phosphate by one-pot method |
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| CN113527359A (en) * | 2021-07-20 | 2021-10-22 | 万华化学集团股份有限公司 | Method for preparing apoester intermediate C5 phosphate by one-pot method |
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