CN107082788B - The synthetic method that one kind is efficiently esterified with imines catalysis P (O)-OH class compound and alcohol - Google Patents
The synthetic method that one kind is efficiently esterified with imines catalysis P (O)-OH class compound and alcohol Download PDFInfo
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- CN107082788B CN107082788B CN201710127845.0A CN201710127845A CN107082788B CN 107082788 B CN107082788 B CN 107082788B CN 201710127845 A CN201710127845 A CN 201710127845A CN 107082788 B CN107082788 B CN 107082788B
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 title claims abstract description 21
- 150000002466 imines Chemical class 0.000 title claims description 6
- 238000006555 catalytic reaction Methods 0.000 title description 4
- 238000010189 synthetic method Methods 0.000 title description 2
- -1 ester compound Chemical class 0.000 claims abstract description 60
- 238000006243 chemical reaction Methods 0.000 claims abstract description 43
- 238000000034 method Methods 0.000 claims abstract description 20
- 150000002148 esters Chemical class 0.000 claims abstract description 12
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 7
- 239000003960 organic solvent Substances 0.000 claims abstract description 5
- 238000009833 condensation Methods 0.000 claims abstract description 3
- 230000005494 condensation Effects 0.000 claims abstract description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 58
- 238000002360 preparation method Methods 0.000 claims description 29
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 21
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 17
- 239000002253 acid Substances 0.000 claims description 15
- YNPNZTXNASCQKK-UHFFFAOYSA-N phenanthrene Chemical compound C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 claims description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- 230000032050 esterification Effects 0.000 claims description 6
- 238000005886 esterification reaction Methods 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical class CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 230000003197 catalytic effect Effects 0.000 claims description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- OTEKOJQFKOIXMU-UHFFFAOYSA-N 1,4-bis(trichloromethyl)benzene Chemical compound ClC(Cl)(Cl)C1=CC=C(C(Cl)(Cl)Cl)C=C1 OTEKOJQFKOIXMU-UHFFFAOYSA-N 0.000 claims description 2
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 claims description 2
- 125000006281 4-bromobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Br)C([H])([H])* 0.000 claims description 2
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 2
- PLUDEAUQZKPAIN-UHFFFAOYSA-N bis(4-methylphenyl) hydrogen phosphate Chemical compound C1=CC(C)=CC=C1OP(O)(=O)OC1=CC=C(C)C=C1 PLUDEAUQZKPAIN-UHFFFAOYSA-N 0.000 claims description 2
- DWJKNKVOOAQBNT-UHFFFAOYSA-N bis[4-(trifluoromethyl)phenyl] hydrogen phosphate Chemical compound C(F)(F)(F)C1=CC=C(OP(=O)(OC2=CC=C(C=C2)C(F)(F)F)O)C=C1 DWJKNKVOOAQBNT-UHFFFAOYSA-N 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 2
- ZMNNFJBGZJTVJP-UHFFFAOYSA-N 2-phenylethoxy dihydrogen phosphate Chemical compound C1(=CC=CC=C1)CCOOP(O)(O)=O ZMNNFJBGZJTVJP-UHFFFAOYSA-N 0.000 claims 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 claims 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N N,N′-Dicyclohexylcarbodiimide Substances C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 abstract description 106
- 239000000758 substrate Substances 0.000 abstract description 10
- 238000003786 synthesis reaction Methods 0.000 abstract description 9
- 230000015572 biosynthetic process Effects 0.000 abstract description 8
- 125000000524 functional group Chemical group 0.000 abstract description 7
- 239000003054 catalyst Substances 0.000 abstract description 5
- 230000007812 deficiency Effects 0.000 abstract description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 96
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- 238000004440 column chromatography Methods 0.000 description 22
- ASMQGLCHMVWBQR-UHFFFAOYSA-N Diphenyl phosphate Chemical compound C=1C=CC=CC=1OP(=O)(O)OC1=CC=CC=C1 ASMQGLCHMVWBQR-UHFFFAOYSA-N 0.000 description 18
- 235000019441 ethanol Nutrition 0.000 description 16
- 229910052760 oxygen Inorganic materials 0.000 description 12
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- NPSJHQMIVNJLNN-UHFFFAOYSA-N 2-ethylhexyl 4-nitrobenzoate Chemical compound CCCCC(CC)COC(=O)C1=CC=C([N+]([O-])=O)C=C1 NPSJHQMIVNJLNN-UHFFFAOYSA-N 0.000 description 4
- 239000004808 2-ethylhexylester Substances 0.000 description 4
- MSHFRERJPWKJFX-UHFFFAOYSA-N 4-Methoxybenzyl alcohol Chemical compound COC1=CC=C(CO)C=C1 MSHFRERJPWKJFX-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 4
- ACVYVLVWPXVTIT-UHFFFAOYSA-M phosphinate Chemical compound [O-][PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-M 0.000 description 4
- 229910052698 phosphorus Inorganic materials 0.000 description 4
- 239000011574 phosphorus Substances 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- ZSPTYLOMNJNZNG-UHFFFAOYSA-N 3-Buten-1-ol Chemical compound OCCC=C ZSPTYLOMNJNZNG-UHFFFAOYSA-N 0.000 description 2
- JKTYGPATCNUWKN-UHFFFAOYSA-N 4-nitrobenzyl alcohol Chemical compound OCC1=CC=C([N+]([O-])=O)C=C1 JKTYGPATCNUWKN-UHFFFAOYSA-N 0.000 description 2
- VFJFOPRXIHJQEL-UHFFFAOYSA-N CCCCC(CC)C(C)OP(O)(O)=O Chemical compound CCCCC(CC)C(C)OP(O)(O)=O VFJFOPRXIHJQEL-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 2
- DDFGTVSLZJLQEV-UHFFFAOYSA-N [C](C1CCCCC1)C1CCCCC1 Chemical compound [C](C1CCCCC1)C1CCCCC1 DDFGTVSLZJLQEV-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- MOFLDTNKLMFGSU-UHFFFAOYSA-N bromobenzene;methanol Chemical compound OC.BrC1=CC=CC=C1 MOFLDTNKLMFGSU-UHFFFAOYSA-N 0.000 description 2
- NEEDEQSZOUAJMU-UHFFFAOYSA-N but-2-yn-1-ol Chemical compound CC#CCO NEEDEQSZOUAJMU-UHFFFAOYSA-N 0.000 description 2
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 2
- XCIXKGXIYUWCLL-UHFFFAOYSA-N cyclopentanol Chemical compound OC1CCCC1 XCIXKGXIYUWCLL-UHFFFAOYSA-N 0.000 description 2
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- AFMVESZOYKHDBJ-UHFFFAOYSA-N fluoren-9-ol Chemical compound C1=CC=C2C(O)C3=CC=CC=C3C2=C1 AFMVESZOYKHDBJ-UHFFFAOYSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 2
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- XECKTNQAABHDFZ-UHFFFAOYSA-N 1-(2-methylpropyl)-2-phenylbenzene Chemical compound CC(C)CC1=CC=CC=C1C1=CC=CC=C1 XECKTNQAABHDFZ-UHFFFAOYSA-N 0.000 description 1
- YTMGTYBSNMGOBK-UHFFFAOYSA-N 1-cyclopentyl-2-phenylbenzene Chemical compound C1CCCC1C1=CC=CC=C1C1=CC=CC=C1 YTMGTYBSNMGOBK-UHFFFAOYSA-N 0.000 description 1
- HKTCLPBBJDIBGF-UHFFFAOYSA-N 1-phenyl-2-propan-2-ylbenzene Chemical compound CC(C)C1=CC=CC=C1C1=CC=CC=C1 HKTCLPBBJDIBGF-UHFFFAOYSA-N 0.000 description 1
- AVSVJSGDSPDFLH-UHFFFAOYSA-N 2,2,2-trifluoroethylbenzene Chemical compound FC(F)(F)CC1=CC=CC=C1 AVSVJSGDSPDFLH-UHFFFAOYSA-N 0.000 description 1
- LJKDOMVGKKPJBH-UHFFFAOYSA-N 2-ethylhexyl dihydrogen phosphate Chemical compound CCCCC(CC)COP(O)(O)=O LJKDOMVGKKPJBH-UHFFFAOYSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 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
- HEZIRTDRAOLYOD-UHFFFAOYSA-N CCO[P]C1=CC=CC=C1 Chemical compound CCO[P]C1=CC=CC=C1 HEZIRTDRAOLYOD-UHFFFAOYSA-N 0.000 description 1
- 241001191009 Gymnomyza Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 125000006267 biphenyl group Chemical group 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- RAABOESOVLLHRU-UHFFFAOYSA-N diazene Chemical compound N=N RAABOESOVLLHRU-UHFFFAOYSA-N 0.000 description 1
- 229910000071 diazene Inorganic materials 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
- PHNWGDTYCJFUGZ-UHFFFAOYSA-N hexyl dihydrogen phosphate Chemical compound CCCCCCOP(O)(O)=O PHNWGDTYCJFUGZ-UHFFFAOYSA-N 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- GBHRVZIGDIUCJB-UHFFFAOYSA-N hydrogenphosphite Chemical class OP([O-])[O-] GBHRVZIGDIUCJB-UHFFFAOYSA-N 0.000 description 1
- 230000008676 import Effects 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000013110 organic ligand Substances 0.000 description 1
- 150000002903 organophosphorus compounds Chemical class 0.000 description 1
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 1
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 150000003003 phosphines Chemical class 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- BZCGWAXQDLXLQM-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O.ClP(Cl)(Cl)=O BZCGWAXQDLXLQM-UHFFFAOYSA-N 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000012916 structural analysis Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
Classifications
-
- 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
- Y02P20/582—Recycling of unreacted starting or intermediate materials
Abstract
A kind of method the present invention provides efficient, high selectivity containing the different organophosphorus ester analog derivatives for replacing functional groups, usesN,N’‑Dicyclohexylcarbodiimide catalyst is as condensation reagent, using containing P (O)-OH class compound, as reaction substrate, alcohol joined organic solvent as esterifying reagent, reaction system.The advantages of this method: catalyst is cheap and easy to get；Substrate applicability is high；Reaction condition is mild, securely and reliably；For the selectivity of gained target product close to 100%, yield is up to 90% or more.That this method solve the reaction selectivities of conventional synthesis organophosphorus ester compound is poor, reaction step is cumbersome, low yield and needs the deficiencies of using to environment harmful reagent, has good prospects for commercial application.The present invention additionally provides corresponding containing the different organophosphorus ester analog derivatives for replacing functional group simultaneously.
Description
Technical field
The present invention relates to the applied catalysis of organic phosphonates compound to synthesize field, relates in particular to one kind with imines
Efficient catalytic reacts the preparation side for preparing organic phospho acid ester derivative with the selective esterification of alcohol containing P (O)-OH class compound
Method.
Background technique
Organophosphonate is a kind of important organic compound, in functional material, pesticide, auxiliary agent, additive, organic ligand
And the fields such as asymmetry catalysis have a wide range of applications, and part chiral phosphonate is led in life science and medicine etc.
Domain also shows unique bioactivity.It is well known that P elements and organic phosphorus compound accounted in life it is very important
Substrate, such as people intracorporal ADP, ATP, RNA and organic phospholipid bilayer.But it is difficult to find pure day in nature
Right organophosphorus ester compound, and P elements, mostly in the form of inorganic salts there are among nature, current is people institute
The organophosphorus ester compound known is by being chemically synthesized mostly.
The prior synthesizing method of Organophosphonate mainly uses the skies such as P-Cl class compound and tri-alkoxy phosphonate ester
Gas responsive type phosphorus esterification reagent is starting material, and harsh, reaction selectivity that there is conditions and functional group are poor for applicability etc. lacks
It falls into；And it is difficult to find the pure natural compound with phosphorus chiral centre in nature.With the hair of modern organic synthesis chemistry
Exhibition, high atom economy and chemo-selective become chemists' focus of attention.But conventional method is generally used to sky
The reagent (P (O)-H compound, carbon tetrachloride, sulfonic acid chloride etc.) of air-sensitive sense, but also there is experimental procedures cumbersome, catalyst
It is expensive and be difficult to recycle, severe reaction conditions, substrate applicability intersect, yield is lower and larger etc. to the pollution of environment
Defect.Therefore, efficient, highly-solid selectively, economy are studied and environmentally protective synthetic route prepares (chirality) organic phospho acid
The method of ester is of great significance.
So far, organophosphorus ester compound efficiently synthesizes that there is the safety (trichlorines of material quality, production
Changing the compounds such as phosphorus, phosphorus pentachloride and phosphoryl chloride phosphorus oxychloride has stronger corrosivity) and the stability and purity etc. of product it is several
The problem of aspect, synthetic technology difficulty is larger, and only beautiful, Deng state several companies are producing at present, and China is high-end organic
Phosphonate product present case is mainly fixed against import.
For the deficiency of existing Organophosphonate synthesis technology, industry just puts forth effort on development by stabilization, cheap and easy to get
Containing P (O)-OH class compound as the efficient of raw material, the method for the corresponding organic phosphonates compound of high selectivity.
Summary of the invention
The object of the present invention is to provide a kind of by cheap and easy to getN, N’Dicyclohexylcarbodiimide condensing agent is catalyzed P
(O) the efficient esterification of-OH class compound and alcohol synthesizes corresponding containing the different organic phosphines for replacing functional group with high selectivity
The method of acid esters compound, to overcome drawbacks described above in the prior art.
Above-mentioned esterification includes following step: take reacting dose containing P (O)-OH class compound, alcohol, condensing agent and organic
Solvent is in N2It is placed in reaction vessel and is mixed under protection, reacted 3 ~ 12 hours at 25 ~ 80 DEG C under stiring, obtain phase
The Organophosphonate analog derivatives containing different substitution functional groups answered.Specific reaction equation is as follows:
Wherein,
R is selected from benzyl, methyl, ethyl, normal-butyl, isobutyl group, cyclohexyl, cyclopenta, trifluoroethyl, 3-(trimethyl
Silicon substrate)-propine, 3- cyclobutenyl, 2- butynyl, 1- methyl -2-propynyl, isopropyl, tert-butyl, 9- fluorenyl, 4- bromobenzyl, 4-
Nitrobenzyl, 4- methoxy-benzyl；
R1It is phenyl, 4- aminomethyl phenyl, 4- trifluoromethyl, 2- ethyl hexyl, the miscellaneous -10- phosphorus of 9,10- dihydro-9-oxy
Miscellaneous phenanthrene -10- oxygroup；
R2It is phenyl, ethyoxyl, 4- aminomethyl phenyl, 4- trifluoromethyl, 2- ethyl-hexyloxy.
In the above-mentioned method by P (O)-OH compound and the efficient lactate synthesis organic phosphonates compound of alcohol, contain P (O)-
OH class compound is selected from diphenylphosphoric acid, bis- (4- methylphenyl) phosphoric acid, bis- (4- trifluoromethyl-phenyl) phosphoric acid, phenyl second
Oxygroup phosphoric acid, 2- ethylhexyl phosphoric acid single 2-ethyl hexyl ester, the miscellaneous -10- phospho hetero phenanthrene -10- phosphoric acid of 9,10- dihydro-9-oxy.
In the above-mentioned method by P (O)-OH compound and the efficient lactate synthesis organic phosphonates compound of alcohol, the alcohol
Class compound is selected from benzyl alcohol, methanol, ethyl alcohol, n-butanol, isobutanol, cyclohexanol, cyclopentanol, trifluoroethanol, 3-(trimethyl
Silicon substrate)-propilolic alcohol, 3- butene-1-ol, 2- butyne-1-ol, 3- butyne-2-alcohol, isopropanol, the tert-butyl alcohol, 9- fluorenol, 4- bromobenzene
Methanol, 4- nitrobenzyl alcohol, 4- methoxy benzyl alcohol.
In the above-mentioned method by P (O)-OH compound and the efficient lactate synthesis organic phosphonates compound of alcohol, You Jirong
Agent refer to methylene chloride, dichloroethanes, tetrahydrofuran, acetonitrile, toluene,N, N’Dimethylformamide, ethyl acetate.
In the above-mentioned method by P (O)-OH compound and the efficient lactate synthesis organic phosphonates compound of alcohol, the contracting
Mixture isN, N’Dicyclohexylcarbodiimide.
It is described to contain P (O)-OH class in the above-mentioned method by P (O)-OH compound and alcohol synthesis of organo-phosphines acid ester class compound
The molar ratio of compound and alcohol is 1:[1.0 ~ 2.0], the molar ratio containing P (O)-OH class compound and condensation reagent be 1:[1.0 ~
2.0]。
It is provided by the present invention by contain P (O)-OH class compound and the efficient lactate synthesis organic phosphonates of alcohol compound
The method for closing object, reaction process are mildly easy to control.While obtaining higher yields and 100% selectivity, this method is simply easy
Row, and used catalyst is cheap and easy to get, and preparation is simple, has good prospects for commercial application.
[specific embodiment]
Below with reference to the embodiment of the present invention, the present invention will be further described:
One, test and analysis
The structural analysis of reaction product uses HP-5MS maos of configuration of Agilent company production in the following embodiments of the present invention
The gas phase of capillary chromatographic column (30m × 0.45mm × 0.8 μm)-mass spectrograph combined instrument GC/MS (6890N/5973N) and
500 magnetic nuclear resonance analyzer of Bruker Avance-III of Bruker company production.Point of target product selectivity and yield
Analysis then using produced by Agilent company configuration hydrogen flame detector, AB-FFAP capillary chromatographic column (30m × 0.25mm ×
0.25 μm) gas chromatograph Agilent GC 7820A.
Two, embodiment
Embodiment 1
By the diphenylphosphoric acid of 109 mg (0.5 mmol), the methanol and 103 mg of 40.5 uL (1.0 mmol)
(0.5 mmol) N, N’Dicyclohexylcarbodiimide (DCC) is added in Schlenk pipe in a nitrogen environment, in nitrogen protection
Be added under environment 1.0 mL organic solvents (methylene chloride, dichloroethanes, tetrahydrofuran, acetonitrile, toluene,N, NDimethyl methyl
Amide, ethyl acetate), it is stirred to react at room temperature 12 hours.Tested and analyzed by GC, acetonitrile as reaction dissolvent when
It waits, the yield of the coupling reaction can reach 98% yield.
Embodiment 2
By the diphenylphosphoric acid of 109 mg (0.5 mmol), the methanol and different mol ratio of 40.5 uL (1.0 mmol)
'sN, N’Dicyclohexylcarbodiimide (DCC): (0 mol%, 5 mol%, 10 mol%, 20 mol%, 50 mol%, 100
Mol%, 200 mol%), it is added in Schlenk pipe, is added under nitrogen protection environment in 1.0 mL acetonitriles in a nitrogen environment,
It is stirred to react at room temperature 12 hours.It is tested and analyzed by GC, only in CDI:N, N’The dosage of dicyclohexylcarbodiimide
When for one times of reaction equivalent, the yield of the coupling reaction can reach 98% yield.
Embodiment 3
By the diphenylphosphoric acid of 109 mg (0.5 mmol), different mol ratio methanol (0.5 mmol, 0.6 mmol,
0.75 mmol, 1.0 mmol) and 103 mg (0.5 mmol)N, N’Dicyclohexylcarbodiimide (DCC), in nitrogen ring
It is added in Schlenk pipe under border, is added in 1.0 mL acetonitriles, is stirred to react at room temperature 12 hours under nitrogen protection environment.
It is tested and analyzed by GC, only when methanol usage is 1.0 mmol, that is, twice of reaction equivalent, the yield of the coupling reaction
98% yield can be reached.
Embodiment 4
By the diphenylphosphoric acid of 109 mg (0.5 mmol), the methanol and 103 mg of 40.5 uL (1.0 mmol)
(0.5 mmol) N, N’Dicyclohexylcarbodiimide (DCC) is added in Schlenk pipe, in a nitrogen environment in nitrogen protection
It is added in acetonitrile (0.5 mL, 1.0 mL, 2.0 mL, 5.0 mL), is stirred to react at room temperature 12 hours under environment.Pass through
GC is tested and analyzed, and only when acetonitrile content is 1.0 mL, the yield of the coupling reaction can reach 98% yield.With solvent
Amount increases, and the yield of the reaction is in be gradually reduced trend.
Embodiment 5
OEthyl-phenyl-phenyl phosphinic acid ester preparation: by the diphenylphosphoric acid of 109 mg (0.5 mmol), 58.3
The ethyl alcohol and 103 mg (0.5 mmol) of uL (1.0 mmol)N, N’Dicyclohexylcarbodiimide (DCC), in nitrogen environment
It in lower addition Schlenk pipe, is added in 1.0 mL acetonitriles, is stirred to react at room temperature 12 hours under nitrogen protection environment.To
After reaction, by the available 95% separation yield of column chromatography chromatogram separating-purifyingOEthyl-phenyl-phenyl phosphinic acid
Ester.
Embodiment 6
OButyl-hohenyl-phenyl phosphinic acid ester preparation: by the diphenylphosphoric acid of 109 mg (0.5 mmol), 91.5
The n-butanol and 103 mg (0.5 mmol) of uL (1.0 mmol)N, N’Dicyclohexylcarbodiimide (DCC), in nitrogen ring
It is added in Schlenk pipe under border, is added in 1.0 mL acetonitriles, is stirred to react at room temperature 12 hours under nitrogen protection environment.
To after reaction, separate yield by column chromatography chromatogram separating-purifying available 96%OEthyl-phenyl-phenyl time phosphine
Acid esters.
Embodiment 7
OThe preparation of isobutvl-phenyl-phenyl phosphinic acid ester: by the diphenylphosphoric acid of 109 mg (0.5 mmol),
The isobutanol and 103 mg (0.5 mmol) of 92.4 uL (1.0 mmol)N, N’Dicyclohexylcarbodiimide (DCC),
It is added in Schlenk pipe under nitrogen environment, is added under nitrogen protection environment in 1.0 mL acetonitriles, is stirred to react 12 at room temperature
Hour.To after reaction, separate yield by column chromatography chromatogram separating-purifying available 92%OIsobutvl-phenyl-benzene
Base phosphinate.
Embodiment 8
OBenzyl-phenyl-phenyl phosphinic acid ester preparation: by the diphenylphosphoric acid of 109 mg (0.5 mmol), 103.8
The benzyl alcohol and 103 mg (0.5 mmol) of uL (1.0 mmol)N, N’Dicyclohexylcarbodiimide (DCC), in nitrogen ring
It is added in Schlenk pipe under border, is added in 1.0 mL acetonitriles, is stirred to react at room temperature 12 hours under nitrogen protection environment.
To after reaction, separate yield by column chromatography chromatogram separating-purifying available 87%OBenzyl-phenyl-phenyl time phosphine
Acid esters.
Embodiment 9
OCyclohexyl-phenyl-phenyl phosphinic acid ester preparation: by the diphenylphosphoric acid of 109 mg (0.5 mmol), 104
The cyclohexanol and 103 mg (0.5 mmol) of uL (1.0 mmol)N, N’Dicyclohexylcarbodiimide (DCC), in nitrogen ring
It is added in Schlenk pipe under border, is added in 1.0 mL acetonitriles, is stirred to react at room temperature 12 hours under nitrogen protection environment.
To after reaction, separate yield by column chromatography chromatogram separating-purifying available 91%OCyclohexyl-phenyl-phenyl
Phosphonate ester.
Embodiment 10
OThe preparation of cyclopentyl-phenyl-phenyl phosphinic acid ester: by the diphenylphosphoric acid of 109 mg (0.5 mmol),
The cyclopentanol and 103 mg (0.5 mmol) of 90.7 uL (1.0 mmol)N, N’Dicyclohexylcarbodiimide (DCC),
It is added in Schlenk pipe under nitrogen environment, is added under nitrogen protection environment in 1.0 mL acetonitriles, is stirred to react 12 at room temperature
Hour.To after reaction, separate yield by column chromatography chromatogram separating-purifying available 88%OCyclopentyl-phenyl-benzene
Base phosphinate.
Embodiment 11
OThe preparation of trifluoroethyl-phenyl-phenyl phosphinate: by the diphenylphosphoric acid of 109 mg (0.5 mmol),
The trifluoroethanol and 103 mg (0.5 mmol) of 72.4 uL (1.0 mmol)N, N’Dicyclohexylcarbodiimide (DCC),
It is added in Schlenk pipe in a nitrogen environment, is added under nitrogen protection environment in 1.0 mL acetonitriles, is stirred to react at room temperature
12 hours.To after reaction, separate yield by column chromatography chromatogram separating-purifying available 95%OTrifluoroethyl-benzene
Base-phenyl phosphinic acid ester.
Embodiment 12
O- 3-(trimethyl silicon substrate) preparation of-propinyl-phenyl-phenyl phosphinate: by 109 mg (0.5 mmol)
Diphenylphosphoric acid, 148.3 uL (1.0 mmol) 3-(trimethyl silicon substrate)-propilolic alcohol and 103 mg (0.5 mmol)N, N’Dicyclohexylcarbodiimide (DCC) is added in Schlenk pipe in a nitrogen environment, is added 1.0 under nitrogen protection environment
In mL acetonitrile, it is stirred to react at room temperature 12 hours.It is available by column chromatography chromatogram separating-purifying to after reaction
86% separation yieldO- 3-(trimethyl silicon substrate)-propinyl-phenyl-phenyl phosphinate.
Embodiment 13
OThe preparation of -3- cyclobutenyl-phenyl-phenyl phosphinate: by the diphenylphosphoric acid of 109 mg (0.5 mmol),
The 3- butene-1-ol and 103 mg (0.5 mmol) of 148.3 uL (1.0 mmol)N, N’Dicyclohexylcarbodiimide
(DCC), it is added in Schlenk pipe in a nitrogen environment, is added under nitrogen protection environment in 1.0 mL acetonitriles, stirs at room temperature
Mix reaction 12 hours.To after reaction, separate yield by column chromatography chromatogram separating-purifying available 91%O- 3- butylene
Base-phenyl-phenyl phosphinate.
Embodiment 14
OThe preparation of -2- butynyl-phenyl-phenyl phosphinate: by the diphenylphosphoric acid of 109 mg (0.5 mmol),
The 2- butyne-1-ol and 103 mg (0.5 mmol) of 74.8 uL (1.0 mmol)N, N’Dicyclohexylcarbodiimide
(DCC), it is added in Schlenk pipe in a nitrogen environment, is added under nitrogen protection environment in 1.0 mL acetonitriles, stirs at room temperature
Mix reaction 12 hours.To after reaction, separate yield by column chromatography chromatogram separating-purifying available 94%O- 2- butine
Base-phenyl-phenyl phosphinate.
Embodiment 15
OThe preparation of -1- methyl -2-propynyl-phenyl-phenyl phosphinate: by the hexichol of 109 mg (0.5 mmol)
Base phosphoric acid, the 3- butyne-2-alcohol of 78.4 uL (1.0 mmol) and 103 mg (0.5 mmol)N, N’Dicyclohexyl carbon two
Imines (DCC) is added in Schlenk pipe in a nitrogen environment, is added in 1.0 mL acetonitriles under nitrogen protection environment, in room temperature
Under be stirred to react 12 hours.To after reaction, separate yield by column chromatography chromatogram separating-purifying available 83%O-1-
Methyl -2-propynyl-phenyl-phenyl phosphinate.
Embodiment 16
OThe preparation of isopropyl-phenyl-phenyl phosphinic acid ester: by the diphenylphosphoric acid of 109 mg (0.5 mmol),
The isopropanol and 103 mg (0.5 mmol) of 76.5 uL (1.0 mmol)N, N’Dicyclohexylcarbodiimide (DCC),
It is added in Schlenk pipe under nitrogen environment, is added under nitrogen protection environment in 1.0 mL acetonitriles, is stirred to react 12 at room temperature
Hour.To after reaction, separate yield by column chromatography chromatogram separating-purifying available 92%OIsopropyl-phenyl-benzene
Base phosphinate.
Embodiment 17
OThe preparation of tbutyl-phenyl-phenyl phosphinic acid ester: by the diphenylphosphoric acid of 109 mg (0.5 mmol),
The tert-butyl alcohol and 103 mg (0.5 mmol) of 76.5 uL (1.0 mmol)N, N’Dicyclohexylcarbodiimide (DCC),
It is added in Schlenk pipe under nitrogen environment, is added under nitrogen protection environment in 1.0 mL acetonitriles, is stirred to react 12 at room temperature
Hour.To after reaction, separate yield by column chromatography chromatogram separating-purifying available 63%OTbutyl-phenyl-benzene
Base phosphinate.
Embodiment 18
OThe preparation of the bromo- Benzyl-phenyl of -4--phenyl phosphinic acid ester: by the diphenylphosphoric acid of 109 mg (0.5 mmol),
The 4- bromobenzene methanol and 103 mg (0.5 mmol) of 187 mg (1.0 mmol)N, N’Dicyclohexylcarbodiimide (DCC),
It is added in Schlenk pipe in a nitrogen environment, is added under nitrogen protection environment in 1.0 mL acetonitriles, is stirred to react at room temperature
12 hours.To after reaction, separate yield by column chromatography chromatogram separating-purifying available 82%OBromo- benzyl-the benzene of -4-
Base-phenyl phosphinic acid ester.
Embodiment 19
O- 4- Nitro-benzyl-phenyl-phenyl phosphinate preparation: by the diphenylphosphine of 109 mg (0.5 mmol)
Acid, the 4- nitrobenzyl alcohol of 153 mg (1.0 mmol) and 103 mg (0.5 mmol)N, N’Dicyclohexylcarbodiimide
(DCC), it is added in Schlenk pipe in a nitrogen environment, is added under nitrogen protection environment in 1.0 mL acetonitriles, stirs at room temperature
Mix reaction 12 hours.To after reaction, separate yield by column chromatography chromatogram separating-purifying available 79%O- 4- nitre
Base-Benzyl-phenyl-phenyl phosphinic acid ester.
Embodiment 20
O- 4- methyoxy-benzyl-phenyl-phenyl phosphinate preparation: by the diphenyl of 109 mg (0.5 mmol)
Phosphoric acid, the 4- methoxy benzyl alcohol of 124.1 ul (1.0 mmol) and 103 mg (0.5 mmol)N, N’Dicyclohexyl carbon
Diimine (DCC) is added in Schlenk pipe in a nitrogen environment, is added in 1.0 mL acetonitriles under nitrogen protection environment, in room
It is stirred to react under temperature 12 hours.To after reaction, separate yield by column chromatography chromatogram separating-purifying available 86%O-
4- methyoxy-benzyl-phenyl-phenyl phosphinate.
Embodiment 21
OThe preparation of -9- fluorenyl-Benzyl-phenyl-phenyl phosphinic acid ester: by the diphenylphosphine of 109 mg (0.5 mmol)
Acid, the 9- fluorenol of 182.2 mg (1.0 mmol) and 103 mg (0.5 mmol)N, N’Dicyclohexylcarbodiimide
(DCC), it is added in Schlenk pipe in a nitrogen environment, is added under nitrogen protection environment in 1.0 mL acetonitriles, stirs at room temperature
Mix reaction 12 hours.To after reaction, separate yield by column chromatography chromatogram separating-purifying available 87%O- 9- fluorenes
Base-Benzyl-phenyl-phenyl phosphinic acid ester.
Embodiment 22
OThe preparation of methyl-(double 4- aminomethyl phenyls)-phosphinate: by two (the 4- methyl of 123 mg (0.5 mmol)
Phenyl) phosphoric acid, the methanol of 40.5 uL (1.0 mmol) and 103 mg (0.5 mmol)N, N’Dicyclohexylcarbodiimide
(DCC), it is added in Schlenk pipe in a nitrogen environment, is added under nitrogen protection environment in 1.0 mL acetonitriles, stirs at room temperature
Mix reaction 12 hours.To after reaction, separate yield by column chromatography chromatogram separating-purifying available 95%OMethyl-
(double 4- aminomethyl phenyls)-phosphinate.
Embodiment 23
OThe preparation of methyl-(double 4- trifluoromethyls)-phosphinate: by the two (4- of 177 mg (0.5 mmol)
Trifluoromethyl) phosphoric acid, the methanol of 40.5 uL (1.0 mmol) and 103 mg (0.5 mmol)N, N’Dicyclohexyl
Carbodiimide (DCC) is added in Schlenk pipe in a nitrogen environment, is added in 1.0 mL acetonitriles under nitrogen protection environment, in
It is stirred to react at room temperature 12 hours.To after reaction, separate yield by column chromatography chromatogram separating-purifying available 93%OMethyl-(double 4- trifluoromethyls)-phosphinate.
Embodiment 24
OMethylphenyl-ethyoxyl-phosphinate preparation: by the phenyl ethoxy phosphorus of 93 mg (0.5 mmol)
Acid, the methanol of 40.5 uL (1.0 mmol) and 103 mg (0.5 mmol)N, N’Dicyclohexylcarbodiimide (DCC),
It is added in Schlenk pipe under nitrogen environment, is added under nitrogen protection environment in 1.0 mL acetonitriles, is stirred to react 12 at room temperature
Hour.To after reaction, separate yield by column chromatography chromatogram separating-purifying available 81%OMethylphenyl-ethoxy
Base-phosphinate.
Embodiment 25
OThe preparation of methyl -2- ethylhexyl phosphoric acid single 2-ethyl hexyl ester: by the 2- second of 105 mg (0.5 mmol)
Base hexyl phosphoric acid single 2-ethyl hexyl ester, the methanol of 40.5 uL (1.0 mmol) and 103 mg (0.5 mmol)N, N’- two
Carbodicyclo hexylimide (DCC) is added in Schlenk pipe in a nitrogen environment, 1.0 mL second is added under nitrogen protection environment
In nitrile, it is stirred to react at room temperature 12 hours.To after reaction, available 62% point by column chromatography chromatogram separating-purifying
From yieldOMethyl -2- ethylhexyl phosphoric acid single 2-ethyl hexyl ester.
Embodiment 26
OThe preparation of the miscellaneous -10- phospho hetero phenanthrene -10- phosphate of methyl -9,10- dihydro-9-oxy: by 116 mg (0.5 mmol)
Miscellaneous -10- phospho hetero phenanthrene -10- the phosphoric acid of 9,10- dihydro-9-oxy, 40.5 uL (1.0 mmol) methanol and 103 mg (0.5
mmol) N, N’Dicyclohexylcarbodiimide (DCC) is added in Schlenk pipe, in a nitrogen environment in nitrogen protection environment
In 1.0 mL acetonitriles of lower addition, it is stirred to react at room temperature 12 hours.To after reaction, by column chromatography chromatogram separating-purifying
Available 94% separation yieldOMiscellaneous -10- phospho hetero phenanthrene -10- the phosphate of methyl -9,10- dihydro-9-oxy.
As can be seen from the above-described embodiment, of the present invention to contain P (O)-OH class compound using imines efficient catalytic
Preparing the corresponding method containing the different Organophosphonate analog derivatives for replacing functional group with alcohol compound esterification has
Reaction condition is mild, catalyst is cheap and easy to get and prepares the advantages that simple.In addition, this method also have substrate applicability it is wide,
The advantages that high yield and highly selective (100%), provides a kind of efficiently synthesize containing the different Organophosphonates for replacing functional group
The method of analog derivative.
The embodiments described above only express several embodiments of the present invention, and the description thereof is more specific and detailed, but simultaneously
Limitations on the scope of the patent of the present invention therefore cannot be interpreted as.It should be pointed out that for those of ordinary skill in the art
For, without departing from the inventive concept of the premise, various modifications and improvements can be made, these belong to guarantor of the invention
Protect range.Therefore, the scope of protection of the patent of the invention shall be subject to the appended claims.
Claims (5)
1. a kind of preparation side for preparing organic phospho acid ester derivative by imines efficient catalytic P (O)-OH class compound and alcohol esterification
Method is as follows:
It is characterized in that, including following step:
Take reacting dose contains P (O)-OH class compound, alcohol, condensing agent and organic solvent in N2Be placed under protection in reaction vessel into
Row mixing, reacts 3 ~ 12 hours at 25 ~ 80 DEG C under stiring, obtains accordingly containing the different organic phospho acids for replacing functional group
Ester derivative；
Wherein,
R is selected from benzyl, methyl, ethyl, normal-butyl, isobutyl group, cyclohexyl, cyclopenta, trifluoroethyl, 3-(trimethyl silicane
Base)-propine, 3- cyclobutenyl, 2- butynyl, 1- methyl -2-propynyl, isopropyl, tert-butyl, 9- fluorenyl, 4- bromobenzyl, 4- nitre
Base benzyl, 4- methoxy-benzyl；
R1It is phenyl, 4- aminomethyl phenyl, 4- trifluoromethyl, 2- ethyl hexyl, the miscellaneous -10- phospho hetero phenanthrene-of 9,10- dihydro-9-oxy
10- oxygroup；
R2It is phenyl, ethyoxyl, 4- aminomethyl phenyl, 4- trifluoromethyl, 2- ethyl-hexyloxy.
2. preparation method according to claim 1, which is characterized in that described P (the O)-OH class compound that contains is selected from hexichol
Base phosphoric acid, bis- (4- methylphenyl) phosphoric acid, bis- (4- trifluoromethyl-phenyl) phosphoric acid, phenyl ethoxy phosphoric acid, 2- ethylhexyl
Miscellaneous -10- phospho hetero phenanthrene -10- the phosphoric acid of mono phosphoric acid ester 2- ethylhexyl, 9,10- dihydro-9-oxy.
3. preparation method according to claim 1, which is characterized in that the organic solvent be methylene chloride, dichloroethanes,
Tetrahydrofuran, acetonitrile, toluene,N, NDimethylformamide, ethyl acetate.
4. preparation method according to claim 1, which is characterized in that mole containing P (O)-OH class compound and alcohol
Than for 1:[1.0 ~ 2.0].
5. preparation method according to claim 1, which is characterized in that described to contain P (O)-OH class compound and condensation reagent
Molar ratio be 1:[1.0 ~ 2.0].
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| CN103980306A (en) * | 2014-04-28 | 2014-08-13 | 湖南大学 | Preparation method for hypophosphorous acid / phosphorous acid/ phosphate compounds by adopting P(O)-OH-contained compounds |
| CN105669743A (en) * | 2016-01-07 | 2016-06-15 | 湖南理工学院 | Method for preparing phosphinic acid ester/phosphorous acid ester/phosphoric acid ester from P(O)-OH compound and aryl boronic acid |
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| CN103980306A (en) * | 2014-04-28 | 2014-08-13 | 湖南大学 | Preparation method for hypophosphorous acid / phosphorous acid/ phosphate compounds by adopting P(O)-OH-contained compounds |
| CN105669743A (en) * | 2016-01-07 | 2016-06-15 | 湖南理工学院 | Method for preparing phosphinic acid ester/phosphorous acid ester/phosphoric acid ester from P(O)-OH compound and aryl boronic acid |
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