CN111662322A - Efficient green preparation method of sulfo-organic phosphonic acid derivative - Google Patents
Efficient green preparation method of sulfo-organic phosphonic acid derivative Download PDFInfo
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- CN111662322A CN111662322A CN202010701423.1A CN202010701423A CN111662322A CN 111662322 A CN111662322 A CN 111662322A CN 202010701423 A CN202010701423 A CN 202010701423A CN 111662322 A CN111662322 A CN 111662322A
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- 150000003007 phosphonic acid derivatives Chemical class 0.000 title claims abstract description 18
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- 238000006243 chemical reaction Methods 0.000 claims abstract description 54
- 150000001875 compounds Chemical class 0.000 claims abstract description 21
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 17
- 238000000034 method Methods 0.000 claims abstract description 16
- 239000000654 additive Substances 0.000 claims abstract description 6
- 230000000996 additive effect Effects 0.000 claims abstract description 6
- 239000003054 catalyst Substances 0.000 claims abstract description 6
- 229910052755 nonmetal Inorganic materials 0.000 claims abstract description 6
- 238000005580 one pot reaction Methods 0.000 claims abstract description 6
- 229910052723 transition metal Inorganic materials 0.000 claims abstract description 6
- 150000003624 transition metals Chemical class 0.000 claims abstract description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 5
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 90
- -1 Phenyl Chemical group 0.000 claims description 17
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 9
- 125000000524 functional group Chemical group 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 125000003107 substituted aryl group Chemical group 0.000 claims description 5
- 125000004104 aryloxy group Chemical group 0.000 claims description 4
- 125000001072 heteroaryl group Chemical group 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 4
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- MDDUHVRJJAFRAU-YZNNVMRBSA-N tert-butyl-[(1r,3s,5z)-3-[tert-butyl(dimethyl)silyl]oxy-5-(2-diphenylphosphorylethylidene)-4-methylidenecyclohexyl]oxy-dimethylsilane Chemical class C1[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)C(=C)\C1=C/CP(=O)(C=1C=CC=CC=1)C1=CC=CC=C1 MDDUHVRJJAFRAU-YZNNVMRBSA-N 0.000 claims description 3
- 125000003944 tolyl group Chemical group 0.000 claims description 3
- 239000006227 byproduct Substances 0.000 abstract description 4
- 239000011261 inert gas Substances 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 3
- 230000004913 activation Effects 0.000 abstract 1
- 150000001298 alcohols Chemical class 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 168
- 239000012043 crude product Substances 0.000 description 56
- LXCYSACZTOKNNS-UHFFFAOYSA-N diethoxy(oxo)phosphanium Chemical compound CCO[P+](=O)OCC LXCYSACZTOKNNS-UHFFFAOYSA-N 0.000 description 42
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 28
- 238000005160 1H NMR spectroscopy Methods 0.000 description 28
- 238000004679 31P NMR spectroscopy Methods 0.000 description 28
- 238000004440 column chromatography Methods 0.000 description 28
- 238000003756 stirring Methods 0.000 description 28
- 238000010490 three component reaction Methods 0.000 description 27
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 26
- 239000012230 colorless oil Substances 0.000 description 19
- 239000003921 oil Substances 0.000 description 9
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 9
- KMTDMTZBNYGUNX-UHFFFAOYSA-N 4-methylbenzyl alcohol Chemical compound CC1=CC=C(CO)C=C1 KMTDMTZBNYGUNX-UHFFFAOYSA-N 0.000 description 8
- QILSFLSDHQAZET-UHFFFAOYSA-N diphenylmethanol Chemical compound C=1C=CC=CC=1C(O)C1=CC=CC=C1 QILSFLSDHQAZET-UHFFFAOYSA-N 0.000 description 7
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Natural products P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 6
- XPNGNIFUDRPBFJ-UHFFFAOYSA-N alpha-methylbenzylalcohol Natural products CC1=CC=CC=C1CO XPNGNIFUDRPBFJ-UHFFFAOYSA-N 0.000 description 5
- OOCCDEMITAIZTP-QPJJXVBHSA-N (E)-cinnamyl alcohol Chemical compound OC\C=C\C1=CC=CC=C1 OOCCDEMITAIZTP-QPJJXVBHSA-N 0.000 description 4
- BBMCTIGTTCKYKF-UHFFFAOYSA-N 1-heptanol Chemical compound CCCCCCCO BBMCTIGTTCKYKF-UHFFFAOYSA-N 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
- OSPSWZSRKYCQPF-UHFFFAOYSA-N dibutoxy(oxo)phosphanium Chemical compound CCCCO[P+](=O)OCCCC OSPSWZSRKYCQPF-UHFFFAOYSA-N 0.000 description 4
- NFORZJQPTUSMRL-UHFFFAOYSA-N dipropan-2-yl hydrogen phosphite Chemical compound CC(C)OP(O)OC(C)C NFORZJQPTUSMRL-UHFFFAOYSA-N 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 239000002585 base Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 3
- PBLNHHSDYFYZNC-UHFFFAOYSA-N (1-naphthyl)methanol Chemical compound C1=CC=C2C(CO)=CC=CC2=C1 PBLNHHSDYFYZNC-UHFFFAOYSA-N 0.000 description 2
- MXHXXJOHFRHBFB-UHFFFAOYSA-N (2-methylphenyl)-phenylmethanol Chemical compound CC1=CC=CC=C1C(O)C1=CC=CC=C1 MXHXXJOHFRHBFB-UHFFFAOYSA-N 0.000 description 2
- GEZMEIHVFSWOCA-UHFFFAOYSA-N (4-fluorophenyl)methanol Chemical compound OCC1=CC=C(F)C=C1 GEZMEIHVFSWOCA-UHFFFAOYSA-N 0.000 description 2
- IHASOVONMUHDND-UHFFFAOYSA-N (4-methylphenyl)-phenylmethanol Chemical compound C1=CC(C)=CC=C1C(O)C1=CC=CC=C1 IHASOVONMUHDND-UHFFFAOYSA-N 0.000 description 2
- WAPNOHKVXSQRPX-UHFFFAOYSA-N 1-phenylethanol Chemical compound CC(O)C1=CC=CC=C1 WAPNOHKVXSQRPX-UHFFFAOYSA-N 0.000 description 2
- HZFRKZWBVUJYDA-UHFFFAOYSA-N 2-(4-chlorophenyl)ethanol Chemical compound OCCC1=CC=C(Cl)C=C1 HZFRKZWBVUJYDA-UHFFFAOYSA-N 0.000 description 2
- MWUVGXCUHWKQJE-UHFFFAOYSA-N 4-fluorophenethyl alcohol Chemical compound OCCC1=CC=C(F)C=C1 MWUVGXCUHWKQJE-UHFFFAOYSA-N 0.000 description 2
- YFPJFKYCVYXDJK-UHFFFAOYSA-N Diphenylphosphine oxide Chemical compound C=1C=CC=CC=1[P+](=O)C1=CC=CC=C1 YFPJFKYCVYXDJK-UHFFFAOYSA-N 0.000 description 2
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 2
- VEILTOCGHIDGHC-UHFFFAOYSA-N OC[S+]1C=CC=C1 Chemical compound OC[S+]1C=CC=C1 VEILTOCGHIDGHC-UHFFFAOYSA-N 0.000 description 2
- VLLNJDMHDJRNFK-UHFFFAOYSA-N adamantan-1-ol Chemical compound C1C(C2)CC3CC2CC1(O)C3 VLLNJDMHDJRNFK-UHFFFAOYSA-N 0.000 description 2
- OOCCDEMITAIZTP-UHFFFAOYSA-N allylic benzylic alcohol Natural products OCC=CC1=CC=CC=C1 OOCCDEMITAIZTP-UHFFFAOYSA-N 0.000 description 2
- 235000019445 benzyl alcohol Nutrition 0.000 description 2
- NEEDEQSZOUAJMU-UHFFFAOYSA-N but-2-yn-1-ol Chemical compound CC#CCO NEEDEQSZOUAJMU-UHFFFAOYSA-N 0.000 description 2
- XCIXKGXIYUWCLL-UHFFFAOYSA-N cyclopentanol Chemical compound OC1CCCC1 XCIXKGXIYUWCLL-UHFFFAOYSA-N 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- PUINPNFEXGNBEY-UHFFFAOYSA-N ethyl phenyl hydrogen phosphite Chemical compound CCOP(O)OC1=CC=CC=C1 PUINPNFEXGNBEY-UHFFFAOYSA-N 0.000 description 2
- 150000008282 halocarbons Chemical class 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- KNSQDHMBDAMMNO-UHFFFAOYSA-N methyl 3-hydroxy-1-benzothiophene-2-carboxylate Chemical compound C1=CC=C2C(O)=C(C(=O)OC)SC2=C1 KNSQDHMBDAMMNO-UHFFFAOYSA-N 0.000 description 2
- FVEINXLJOJPHLH-UHFFFAOYSA-N p-tert-Butylbenzyl alcohol Chemical compound CC(C)(C)C1=CC=C(CO)C=C1 FVEINXLJOJPHLH-UHFFFAOYSA-N 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 238000003383 Atherton-Todd reaction Methods 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- AFOKUMSSGQSPII-UHFFFAOYSA-N C(C)OP(O)(O)C1=CC=CC=C1 Chemical compound C(C)OP(O)(O)C1=CC=CC=C1 AFOKUMSSGQSPII-UHFFFAOYSA-N 0.000 description 1
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Divinylene sulfide Natural products C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- JKOQGQFVAUAYPM-UHFFFAOYSA-N amifostine Chemical compound NCCCNCCSP(O)(O)=O JKOQGQFVAUAYPM-UHFFFAOYSA-N 0.000 description 1
- 229960001097 amifostine Drugs 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 125000006267 biphenyl group Chemical group 0.000 description 1
- VZGDMQKNWNREIO-UHFFFAOYSA-N carbon tetrachloride Substances ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- FAXIJTUDSBIMHY-UHFFFAOYSA-N diethoxy-(2-ethylsulfanylethoxy)-sulfanylidene-$l^{5}-phosphane;1-diethoxyphosphorylsulfanyl-2-ethylsulfanylethane Chemical compound CCOP(=O)(OCC)SCCSCC.CCOP(=S)(OCC)OCCSCC FAXIJTUDSBIMHY-UHFFFAOYSA-N 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 229960002017 echothiophate Drugs 0.000 description 1
- BJOLKYGKSZKIGU-UHFFFAOYSA-N ecothiopate Chemical compound CCOP(=O)(OCC)SCC[N+](C)(C)C BJOLKYGKSZKIGU-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- VTXBWQYIQGCPNB-UHFFFAOYSA-N ethyl-trihydroxy-phenyl-lambda5-phosphane Chemical compound C(C)P(O)(O)(O)C1=CC=CC=C1 VTXBWQYIQGCPNB-UHFFFAOYSA-N 0.000 description 1
- 239000003063 flame retardant Substances 0.000 description 1
- 229920001002 functional polymer Polymers 0.000 description 1
- 150000002240 furans Chemical class 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- MPQXHAGKBWFSNV-UHFFFAOYSA-N oxidophosphanium Chemical class [PH3]=O MPQXHAGKBWFSNV-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 150000003385 sodium Chemical class 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 150000003577 thiophenes Chemical class 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000002699 waste material Substances 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
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/16—Esters of thiophosphoric acids or thiophosphorous acids
- C07F9/165—Esters of thiophosphoric acids
- C07F9/17—Esters of thiophosphoric acids with hydroxyalkyl compounds without further substituents on alkyl
-
- 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
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/32—Esters thereof
- C07F9/3205—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/3229—Esters of aromatic acids (P-C aromatic linkage)
-
- 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
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/32—Esters thereof
- C07F9/3258—Esters thereof the ester moiety containing a substituent or a structure which is considered as characteristic
- C07F9/3288—Esters with arylalkanols
-
- 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
- C07F9/4021—Esters of aromatic acids (P-C aromatic linkage)
-
- 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
- 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
- C07F9/4087—Esters with arylalkanols
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms
- C07F9/655345—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms the sulfur atom being part of a five-membered ring
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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)
Abstract
The invention discloses a high-efficiency green preparation method of a sulfo-organic phosphonic acid derivative, which is characterized in that a P (O) -H compound, sulfur powder and alcohol react to directly prepare the sulfo-organic phosphonic acid derivative at the temperature of 80-120 ℃ for 12-48 hours. The method can directly use stable, easily obtained, relatively green alcohols and sulfur powder as raw materials, the P (O) -H compound can be directly used without any activation treatment, and the three directly react under the condition of one pot to efficiently prepare the sulfo-organic phosphonic acid derivative without any transition metal or nonmetal catalyst and additive. The method has low requirement on reaction conditions, simple and easy operation, no need of inert gas protection, and small pollution due to the fact that the byproduct is water.
Description
Technical Field
The invention relates to the technical field of chemical synthesis, in particular to a high-efficiency green preparation method of a sulfo-organic phosphonic acid derivative.
Background
The organic phosphine compound plays an extremely important role in the origin and evolution of living matters, the organic phosphonic acid derivative structure also exists in a plurality of natural products, bioactive molecules, medicines and pesticides widely, for example, the star drug 'Ruidexiwei' currently used for treating the new coronary pneumonia contains the organic phosphonic acid derivative structure, the famous medicines and pesticides such as Ecothiopate, Amifostine, Demeton, Fensunfothion, Azomethions and the like, the organic phosphine small molecule and the organic phosphine ligand are widely applied to various fields such as catalysis, synthesis and the like, and the organic phosphine structure also plays a very important role in material science and is widely used for preparing various functional polymers, photoelectric materials, flame retardants, lubricants and the like. The structure of the organic phosphonic acid derivative can transform the organic phosphine functional group through substitution, coupling and other reactions, so that the organic phosphonic acid derivative such as organic phosphate is an important biochemical molecule and a synthetic intermediate.
For the synthesis of the thioaganophosphonic acid derivatives, conventional methods such as the Atherton-Todd reaction, i.e., reaction of the P (O) -H compound with thiophenol or a thiol in CCl4The compound is synthesized by using a large amount of base in a solvent, or reacting toxic and moisture-sensitive phosphonyl halide P (O) Cl with thiophenol or mercaptan under an alkaline condition, or reacting RSX with P (O) -M (M ═ Na and the like), or reacting thiophosphonic acid P (S) OH with halogenated hydrocarbon under the presence of base. However, in these methods, organic sulfides with high odor and toxicity, such as thiophenol and mercaptan, are used as raw materials, or halogenated hydrocarbons, unstable and easily hydrolyzable halides, such as RSX or p (o) Cl, and a large amount of alkali are required, so that the reaction conditions are high, the amount of by-product waste is large, the method is highly polluted, and the synthesis equipment is severely corroded. In addition, because the raw materials used are active, the methods also have the defects of poor functional group compatibility and the like, and the application range is limited.
Disclosure of Invention
Aiming at the defects in the prior art, the invention aims to provide an efficient and green preparation method of a thiophosphonic acid derivative, which has the advantages of low requirement on reaction conditions, wide application range, high reaction efficiency and low pollution.
In order to achieve the purpose, the invention provides the following technical scheme: a high-efficiency green preparation method of a sulfo-organic phosphonic acid derivative is characterized in that a P (O) -H compound, sulfur powder and alcohol react to directly prepare the sulfo-organic phosphonic acid derivative, the reaction temperature is 80-120 ℃, the reaction time is 12-48 hours, and the reaction formula is as follows:
wherein:
R1is hydrogen or alkyl or substituted alkyl;
R2and R3Phenyl substituted at 2-, 3-, or 4-with various functional groups or substituted heteroaryl or hydrocarbyl;
R4and R5Is alkoxy, aryloxy, phenyl with functional groups substituted at 2-, 3-, or 4-, or substituted aryl.
Preferably, the P (O) -H compound is a phosphorous acid diester, a disubstituted phosphine oxide, or R4(R5O, P (O) -H compound such as P (O), H and the like, wherein the dosage of the P (O) -H compound and the sulfur powder is 2.0-5.0 equivalent.
Preferably, the P (O) -H compound and the sulfur powder are used in an amount of 4.0 equivalents.
Preferably, the solvent is toluene, tetrahydrofuran, DMSO, DMF, 1, 4-dioxane or acetonitrile solvent.
Preferably, the reaction is carried out under nitrogen or under air, at a temperature of 100 ℃ and for a time of 24 to 36 hours.
Preferably, the reaction is carried out directly without any transition metal or nonmetal catalyst and additive under one-pot conditions.
The invention has the advantages that: compared with the prior art, the invention directly prepares the sulfo-organic phosphonic acid derivative by the reaction of three components of P (O) -H compound, sulfur powder and alcohol, does not need any transition metal or nonmetal catalyst and additive, can directly and efficiently realize the green preparation of the sulfo-organic phosphonic acid derivative by a one-pot method, has lower requirement on reaction conditions, simple and easy operation, does not need the protection of inert gas, has water as a byproduct, little green pollution, lower requirement on reaction conditions and wider application range, has obvious advantages compared with the known method, not only has higher academic value, but also has potential and wide application prospect.
The present invention will be further described with reference to the following specific examples.
Detailed Description
The invention discloses a high-efficiency green preparation method of a sulfo-organic phosphonic acid derivative, which is characterized in that a P (O) -H compound, sulfur powder and alcohol react to directly prepare the sulfo-organic phosphonic acid derivative, the reaction temperature is 80-120 ℃, the reaction time is 12-48 hours, and the reaction formula is as follows:
wherein:
R1is hydrogen or alkyl or substituted alkyl;
R2and R3Phenyl substituted at 2-, 3-, or 4-with various functional groups or substituted heteroaryl or hydrocarbyl;
R4and R5Is alkoxy, aryloxy, phenyl with functional groups substituted at 2-, 3-, or 4-, or substituted aryl.
Preferably, the method comprises the following steps: r1Hydrogen (H) or various simple to complicated substituted alkyl groups such as methyl and ethyl, alkyl groups substituted with alkyl groups, aryl groups, or alkoxy groups;
R2and R3Can be phenyl substituted by various functional groups at 2-, 3-or 4-or various substituted heteroaryl such as substituted aryl, substituted furan, substituted thiophene and the like, and can also be alkyl of alkenyl, allyl, alkynyl and the like;
R4and R5Various simple to complex alkoxy groups and aryloxy groups such as methoxy, ethoxy, isopropoxy, n-butoxy, benzyloxy, phenoxy and the like; or can be phenyl or various substituted aryls with various functional groups substituted on 2-, 3-, or 4-And (4) a base.
Preferably, the P (O) -H compound is a phosphorous acid diester, a disubstituted phosphine oxide, or R4(R5O, P (O) -H compound such as P (O), H and the like, wherein the dosage of the P (O) -H compound and the sulfur powder is 2.0-5.0 equivalent. The sulfur powder is sulfur powder (S)8)。
Preferably, the P (O) -H compound and the sulfur powder are used in an amount of 4.0 equivalents.
Preferably, the solvent is toluene, tetrahydrofuran, DMSO, DMF, 1, 4-dioxane or acetonitrile solvent.
Preferably, the reaction is carried out under nitrogen or under air, at a temperature of 100 ℃ and for a time of 24 to 36 hours. The method is preferably carried out in the air, does not need inert gas protection, and is simple and easy to operate.
Preferably, the reaction is carried out directly without any transition metal or nonmetal catalyst and additive under one-pot conditions. The alcohol compound and the sulfur powder which are stable, easy to obtain, low in price and relatively green can be used as direct raw materials.
The invention is composed of phosphorous acid diester or disubstituted phosphine oxide and other P (O) -H compounds and sulfur powder (S)8) The method can directly and efficiently realize the green preparation of the thiophosphonic acid derivative by a one-pot method without any transition metal or nonmetal catalyst and additive, has lower requirement on reaction conditions, simple and easy operation, no need of inert gas protection, water as a byproduct and little pollution.
The following embodiments will help to understand the present invention, but are not limited to the contents of the present invention.
Example 1
Diphenylmethanol, sulfur powder (S)8) Reaction of three components of diethyl phosphite
The tube reactor was charged with benzhydrol (0.0921g,0.5mmol),S8(0.0640g, 4.0equiv.), diethyl phosphite (0.2578mL, 4.0equiv.), acetonitrile (2.0mL), sealed under air, then reacted at 100 ℃ for 24h with stirring.after the reaction was monitored by TLC, the crude product was purified by column chromatography to obtain a crude product, which was washed three times with saturated sodium bicarbonate (50mL × 3), isolated in 97% yield, as a colorless oil.1H NMR(500MHz,CDCl3):7.44-7.22(m,4H),7.33-7.30(m,4H),7.26-7.22(m,2H),5.63(d,J＝12.0Hz,1H),4.05-3.97(m,2H),3.89-3.81(m,2H),1.60(t,J＝7,0Hz,6H).13C NMR(125.4MHz,CDCl3):141.5(d,J＝5.5Hz),128.6,128.2,127.5,63.5(d,J＝5.6Hz),54.2(d,J＝3.3Hz),15.8(d,J＝7.5Hz).31P NMR(202MHz,CDCl3):25.31。
Example 2
4, 4' -dichloro-diphenylmethanol, S8Three-component reaction of diethyl phosphite
4, 4' -dichloro-diphenylmethanol (0.1266g,0.5mmol), S were added sequentially to a tubular reactor8(0.0640g, 4.0equiv.), diethyl phosphite (0.2578mL, 4.0equiv.), acetonitrile (2.0mL), sealed under air, then reacted at 100 ℃ for 24h with stirring.after the reaction was monitored by tlc, the crude product was purified by column chromatography to obtain a crude product, which was washed three times with saturated sodium bicarbonate (50mL × 3) with an isolated yield of 95% as a colorless oil.1H NMR(500MHz,CDCl3):7.34-7.29(m,8H),5.61(d,J＝11.0Hz,1H),4.07-3.99(m,2H),3.94-3.87(m,2H),1.20(t,J＝7.0Hz,6H).13C NMR(125.4MHz,CDCl3):139.5(d,J＝5.6Hz),133.6,129.5,128.8,63.8(d,J＝6.1Hz),52.8(d,J＝3.1Hz),15.8(d,J＝7.4Hz),31P NMR(202MHz,CDCl3):24.44。
Example 3
4-methyl-diphenylmethanol, S8Three-component reaction of diethyl phosphite
4-methyl-diphenylmethanol (0.0991g,0.5mmol), S were added sequentially to a tubular reactor8(0.0640g, 4.0equiv.), diethyl phosphite (0.2578mL, 4.0equiv.), acetonitrile (2.0mL), sealed under air, then reacted at 100 ℃ for 24h with stirring.after the reaction was monitored by TLC, the crude product was purified by column chromatography to obtain a crude product, which was washed three times with saturated sodium bicarbonate (50mL × 3) with an isolated yield of 90% as a colorless oil.1H NMR(500MHz,CDCl3):7.43(d,J＝8.0Hz,2H),7.33-7.22(m,5H),7.12(d,J＝7.5Hz,2H),5.60(d,J＝11.5Hz,1H),4.05-3.97(m,2H),3.89-3.81(m,2H),2.32(s,3H),1.18-1.15(m,6H).13C NMR(125.4MHz,CDCl3):141.7(d,J＝5.0Hz),138.5(d,J＝6.1Hz),137.2,129.2,128.5,128.2,128.0,127.4,63.4(d,J＝5.4Hz),54.0(d,J＝3.3Hz),21.0,15.8(d.J＝7.6Hz).31P NMR(202MHz,CDCl3):25.49。
Example 4
2-methyl-diphenylmethanol, S8Three-component reaction of diethyl phosphite
2-methyl-diphenylmethanol (0.0991g,0.5mmol), S were added sequentially to a tubular reactor8(0.0640g, 4.0equiv.), diethyl phosphite (0.2578mL, 4.0equiv.), acetonitrile (2.0mL), sealed under air, then reacted at 100 ℃ for 24h with stirring.after the reaction was monitored by TLC, the crude product was purified by column chromatography to obtain a crude product, which was washed three times with saturated sodium bicarbonate (50mL × 3) with an isolated yield of 86% and was colorless oil.1H NMR(500MHz,CDCl3):7.56(d,J＝7.5Hz,1H),7.40(d,J＝7.5Hz,2H),7.30(t,J＝7.5Hz,2H),7.24-7.13(m,4H),5.87(d,J＝12.0Hz,1H),4.07-3.97(m,2H),3.93-3.78(m,2H),2.38(s,3H),1.20-1.12(m,6H).13C NMR(125.4MHz,CDCl3):140.8(d,J＝5.6Hz),139.3(d,J＝5.0Hz),135.7,130.6,128.7,128.5,128.4,127.5,127.3,126.2,63.5(d,J＝5.9Hz),50.9(d,J＝3.1Hz),19.6,15.8-15.7(m).31P NMR(202MHz,CDCl3):25.73。
Example 5
1-Phenylethanol, S8Three-component reaction of diethyl phosphite
1-phenethyl alcohol (0.0604mL,0.5mmol) and S are sequentially added into a tubular reactor8(0.0640g, 4.0equiv.), diethyl phosphite (0.2578mL, 4.0equiv.), acetonitrile (2.0mL), sealed under air, then reacted at 120 ℃ for 24h with stirring.after the reaction was monitored by tlc, the crude product was purified by column chromatography to obtain a crude product, which was washed three times with saturated sodium bicarbonate (50mL × 3) with an isolated yield of 89% as a pale yellow oil.1H NMR(500MHz,CDCl3):7.39-7.37(m,2H),7.34-7.31(m,2H),7.27-7.24(m,1H),4.51-4.45(m,1H),4.14-3.88(m,4H),1.75(d,J＝7.0Hz,3H),1.24(t,J＝6.5Hz,6H).13C NMR(125.4MHz,CDCl3):143.5(d,J＝5.3Hz),128.6,127.5,126.9,63.4(d,J＝5.8Hz),45.8(d,J＝3.5Hz),24.7(d,J＝7.4Hz),15.9(d,J＝7.4Hz).31P NMR(202MHz,CDCl3):25.96。
Example 6
4-fluoro-phenethyl alcohol, S8Three-component reaction of diethyl phosphite
4-fluoro-phenethyl alcohol (0.0632mL,0.5mmol), S were added sequentially to a tubular reactor8(0.0640g, 4.0equiv.), diethyl phosphite (0.2578mL, 4.0equiv.), acetonitrile (2.0mL), sealed under air, then reacted at 120 ℃ for 24h with stirring.after the reaction was monitored by tlc, the crude product was purified by column chromatography to obtain a crude product which was washed three times with saturated sodium bicarbonate (50mL × 3) with an isolated yield of 90% as a pale yellow oil.1H NMR(500MHz,CDCl3):7.37-7.34(m,2H),7.03-6.99(m,2H),4.52-4.46(m,1H),4.15-4.08(m,1H),4.03-3.91(m,3H),1.73(d,J＝7.5Hz,3H),1.28-1.22(m,6H).13C NMR(125.4MHz,CDCl3):162.0(d,J＝245.7Hz),139.4-139.3(m),128.7(d,J＝8.2Hz),115.4(d,J＝21.4Hz),63.5-63.4(m),45.1(d,J＝3.5Hz),24.7(d,J＝7.8Hz),15.9-15.8(m).31P NMR(202MHz,CDCl3):25.64。
Example 7
4-chloro-phenethyl alcohol, S8Three-component reaction of diethyl phosphite
4-chloro-phenethyl alcohol (0.0669mL,0.5mmol), S were added sequentially to a tubular reactor8(0.0640g, 4.0equiv.), diethyl phosphite (0.2578mL, 4.0equiv.), acetonitrile (2.0mL), sealed under air, then reacted at 120 ℃ for 24h with stirring, after the completion of the reaction was monitored by tlc, the crude product was separated and purified by column chromatography to obtain a crude product, which was washed three times with saturated sodium bicarbonate (50mL × 3), and the isolated yield was 82% as a pale yellow oil.1H NMR(500MHz,CDCl3):7.33-7.29(m,4H),4.50-4.44(m,1H),4.16-4.07(m,1H),4.03-3.92(m,3H),1.72(d,J＝7.5Hz,3H),1.28-1.23(m,6H).13C NMR(125.4MHz,CDCl3):142.2(d,J＝4.9Hz),133.3,128.7,128.4,63.5-63.4(m),45.0(d,J＝3.5Hz),24.5(d,J＝7.9Hz),15.9-15.8(m).31P NMR(202MHz,CDCl3):25.48。
Example 8
3, 5-dichloro-phenethyl alcohol, S8Three-component reaction of diethyl phosphite
3, 5-dichloro-phenethyl alcohol (0.0741mL,0.5mmol), S were added sequentially to a tubular reactor8(0.0640g, 4.0equiv.), diethyl phosphite (0.2578mL, 4.0equiv.), acetonitrile (2.0mL), sealed under air, then reacted at 120 ℃ for 24h with stirring.after the reaction was monitored by tlc, the crude product was purified by column chromatography to obtain a crude product, which was washed three times with saturated sodium bicarbonate (50mL × 3), isolated in 31% yield, colorless oil.1H NMR(500MHz,CDCl3):7.46(d,J＝8.5Hz,1H),7.38(d,J＝2.5Hz,1H),7.27-7.25(m,1H),4.91-4.86(m,1H),4.17-4.06(m,3H),3.99-3.91(m,1H),1.73(d,J＝7.0Hz,3H),1.32(t,J＝7.0Hz,3H),1.25(t,J＝7.0Hz,3H).13C NMR(125.4MHz,CDCl3):139.3(d,J＝5.5Hz),133.7,133.4,129.5(d,J＝7.1Hz),127.5,63.7-63.5(m),41.4(d,J＝3.5Hz),23.9(d,J＝6.3Hz),16.0-15.8(m).31P NMR(202MHz,CDCl3):25.03。
Example 9
Benzyl alcohol, S8Three-component reaction of diethyl phosphite
Benzyl alcohol (0.0517mL,0.5mmol), S were added sequentially to a tubular reactor8(0.0640g, 4.0equiv.), diethyl phosphite (0.2578mL, 4.0equiv.), acetonitrile (2.0mL), sealed under air, then reacted at 100 ℃ for 24h with stirring.after the reaction was monitored by tlc, the crude product was purified by column chromatography to obtain a crude product, which was washed three times with saturated sodium bicarbonate (50mL × 3) with an isolated yield of 89% as a colorless oil.1H NMR(500MHz,CDCl3):7.39-7.25(m,5H),4.19-3.98(m,4H),1.29(t,J＝7.5Hz,6H).13C NMR(125.4MHz,CDCl3):137.5(d,J＝5.3Hz),128.9,128.6,127.6,63.5(d,J＝5.8Hz),34.9(d,J＝3.9Hz),15.9(d,J＝7.3Hz).31P NMR(202MHz,CDCl3):26.71。
Example 10
4-methoxy-benzyl alcohol, S8Three-component reaction of diethyl phosphite
4-methoxy-benzyl alcohol (0.0517mL,0.5mmol), S were added sequentially to a tubular reactor8(0.0640g, 4.0equiv.), diethyl phosphite (0.2578mL, 4.0equiv.), acetonitrile (2.0mL), sealed under air, then reacted at 100 ℃ for 24h with stirring.after the reaction was monitored by TLC, the crude product was purified by column chromatography to obtain a crude product, which was washed three times with saturated sodium bicarbonate (50mL × 3) with an isolated yield of 86% and was colorless oil.1H NMR(500MHz,CDCl3):7.28(d,J＝8.5Hz,2H),6.85(d,J＝8.5Hz,2H),4.16-4.01(m,2H),4.06-3.99(m,4H),3.80(s,3H),1.30(t,J＝7.0Hz,6H).13C NMR(125.4MHz,CDCl3):159.1,130.1,129.4,114.0,63.4(d,J＝5.9Hz),55.3,34.6(d,J＝3.9Hz),16.0(d,J＝7.3Hz).31P NMR(202MHz,CDCl3):26.91。
Example 11
4-methyl-benzyl alcohol, S8Three-component reaction of diethyl phosphite
4-methyl-benzyl alcohol (0.0611g,0.5mmol), S was added sequentially to a tubular reactor8(0.0640g, 4.0equiv.), diethyl phosphite (0.2578mL, 4.0equiv.), acetonitrile (2.0mL), sealed under air, then reacted at 100 ℃ for 24h with stirring.after the reaction was monitored by tlc, the crude product was purified by column chromatography to obtain a crude product, which was washed three times with saturated sodium bicarbonate (50mL × 3), isolated in 84% yield, colorless oil.1H NMR(500MHz,CDCl3):7.24(d,J＝8.0Hz,2H),7.13(d,J＝8.0Hz,2H),4.17-4.09(m,2H),4.06-3.98(m,4H),2.33(s,3H),1.29(t,J＝7.0Hz,6H).13C NMR(125.4MHz,CDCl3):137.4,134.4(d,J＝5.6Hz),129.3,128.8,63.5(d,J＝5.8Hz),34.8(d,J＝3.8Hz),21.1,15.9(d,J＝7.4Hz).31P NMR(202MHz,CDCl3):26.88。
Example 12
2-methyl-benzyl alcohol, S8Three-component reaction of diethyl phosphite
2-methyl-benzyl alcohol (0.0611g,0.5mmol), S was added sequentially to a tubular reactor8(0.0640g, 4.0equiv.), diethyl phosphite (0.2578mL, 4.0equiv.), acetonitrile (2.0mL), the tube was sealed under air, and then reacted at 100 ℃ for 24 hours with stirring. After TLC monitoring reaction is completed, the crude product is separated and purified by column chromatography, and the crude product is saturatedSodium bicarbonate was washed three times (50mL × 3) and isolated in 96% yield as a pale yellow oil.1H NMR(500MHz,CDCl3):7.31(d,J＝7.0Hz,1H),7.21-7.14(m,3H),4.18-4.11(m,2H),4.09-4.11(m,4H),2.31(s,3H),1.31(t,J＝7.5Hz,6H).13C NMR(125.4MHz,CDCl3):136.7,135.1(d,J＝6.3Hz),130.5,129.9,128.0,126.2,63.5(d,J＝5.8Hz),33.1(d,J＝3.8Hz),19.1,15.9(d,J＝7.3Hz).31P NMR(202MHz,CDCl3):26.80。
Example 13
4-tert-butyl-benzyl alcohol, S8Three-component reaction of diethyl phosphite
4-tert-butyl-benzyl alcohol (0.0885mL,0.5mmol), S were added sequentially to a tubular reactor8(0.0640g, 4.0equiv.), diethyl phosphite (0.2578mL, 4.0equiv.), acetonitrile (2.0mL), sealed under air, then reacted at 100 ℃ for 24h with stirring.after the reaction was monitored by tlc, the crude product was purified by column chromatography to obtain a crude product, which was washed three times with saturated sodium bicarbonate (50mL × 3) with an isolated yield of 66% as a pale yellow oil.1H NMR(500MHz,CDCl3):7.34(d,J＝8.5Hz,2H),7.29(d,J＝8.5Hz,2H),4.15-4.09(m,2H),4.05-3.97(m,4H),1.30(s,9H),1.27(t,J＝7.0Hz,6H).13C NMR(125.4MHz,CDCl3):150.7,134.4(d,J＝5.5Hz),128.6,125.5,63.4(d,J＝5.6Hz),34.7-34.5(m),31.3,15.9(d,J＝7.4Hz).31P NMR(202MHz,CDCl3):26.84。
Example 14
4-fluoro-benzyl alcohol, S8Three-component reaction of diethyl phosphite
4-fluoro-benzyl alcohol (0.0546mL,0.5mmol), S were added sequentially to a tubular reactor8(0.0640g, 4.0equiv.), diethyl phosphite (0.2578mL, 4.0equiv.), acetonitrile (2.0mL), sealing the tube under air, and stirring at 100 deg.CAfter the reaction was carried out for 24 hours under stirring and the completion of the reaction was monitored by TLC, the crude product was purified by column chromatography to obtain a crude product which was washed three times with saturated sodium bicarbonate (50mL × 3), and the isolated yield was 78% as a colorless oil.1H NMR(500MHz,CDCl3):7.35-7.33(m,2H),7.03-6.99(m,2H),4.14-4.09(m,2H),4.05-3.98(m,4H),1.29(t,J＝7.0Hz,6H).13CNMR(125.4MHz,CDCl3):162.2(d,J＝245.9Hz),133.5-133.4(m),130.6(d,J＝8.2Hz),115.5(d,J＝21.4Hz),63.5(d,J＝5.9Hz),34.2(d,J＝4.0Hz),15.9(d,J＝7.3Hz).31P NMR(202MHz,CDCl3):26.44。
Example 15
1-Naphthalenemethanol, S8Three-component reaction of diethyl phosphite
1-Naphthalenemethanol (0.0791g,0.5mmol), S were added sequentially to a tubular reactor8(0.0640g, 4.0equiv.), diethyl phosphite (0.2578mL, 4.0equiv.), acetonitrile (2.0mL), sealed under air, then reacted at 100 ℃ for 24h with stirring.after the reaction was monitored by tlc, the crude product was purified by column chromatography to obtain a crude product which was washed three times with saturated sodium bicarbonate (50mL × 3) with an isolated yield of 92% as a pale yellow oil.1H NMR(500MHz,CDCl3):8.08(d,J＝8.5Hz,1H),7.87(d,J＝8.0Hz,1H),7.81(d,J＝8.5Hz,1H),7.60-7.57(m,1H),7.54-7.50(m,2H),7.41(t,J＝8.0Hz,1H),4.52(d,J＝12.5Hz,1H),4.16-4.09(m,2H),4.05-4.00(m,2H),1.28(t,J＝7.0Hz,6H).13C NMR(125.4MHz,CDCl3):133.9,132.9(d,J＝5.9Hz),131.1,128.9,128.8,127.7,126.5,125.9,125.3,123.6,63.6(d,J＝6.0Hz),32.9(d,J＝3.9Hz),15.9(d,J＝7.3Hz).31P NMR(202MHz,CDCl3):26.66。
Example 16
1-Thiophenemethanol, S8Three-component reaction of diethyl phosphite
1-thiophenemethanol (0.0474mL,0.5mmol), S were added sequentially to a tubular reactor8(0.0640g, 4.0equiv.), diethyl phosphite (0.2578mL, 4.0equiv.), acetonitrile (2.0mL), sealed under air, then reacted at 100 ℃ for 24h with stirring, after the completion of the reaction was monitored by tlc, the crude product was separated and purified by column chromatography to obtain a crude product, which was washed three times with saturated sodium bicarbonate (50mL × 3), isolated in 93% yield, as a pale yellow oil.1H NMR(500MHz,CDCl3):7.24-7.23(m,1H),7.04(d,J＝3.0Hz,1H),6.93-6.91(m,1H),4.27(d,J＝14.0Hz.2H),4.19-4.13(m,2H),4.09-4.03(m,2H),1.32(t,J＝7.0Hz,6H).13C NMR(125.4MHz,CDCl3):140.2(d,J＝5.8Hz),127.1,126.9,125.6,63.6(d,J＝5.8Hz),29.6(d,J＝4.0Hz),15.9(d,J＝7.3Hz).31P NMR(202MHz,CDCl3):25.99。
Example 17
Cinnamyl alcohol, S8Three-component reaction of diethyl phosphite
Cinnamyl alcohol (0.0671g,0.5mmol) and S were added sequentially to a tubular reactor8(0.0640g, 4.0equiv.), diethyl phosphite (0.2578mL, 4.0equiv.), acetonitrile (2.0mL), sealed under air, then reacted at 100 ℃ for 24h with stirring, after the completion of the reaction was monitored by tlc, the crude product was separated and purified by column chromatography to obtain a crude product, which was washed three times with saturated sodium bicarbonate (50mL × 3), isolated in 93% yield, as a pale yellow oil.1H NMR(500MHz,CDCl3):7.37(d,J＝7.5Hz,2H),7.32(t,J＝7.5Hz,2H),7.27-7.23(m,1H),6.60(d,J＝15.5Hz,1H),6.30-6.23(m,1H),4.25-4.12(m,4H),3.66(dd,J＝7.0,15.5Hz,1H),1.34(t,J＝7.0Hz,6H).13C NMR(125.4MHz,CDCl3):136.3,133.5,128.6,127.9,126.4,124.9,124.8,63.6(d,J＝5.8Hz),33.4(d,J＝3.9Hz),16.0(d,J＝7.0Hz).31P NMR(202MHz,CDCl3):27.16。
Example 18
Diphenylmethanol, S8Three-component reaction of diisopropyl phosphite
Diphenyl methanol (0.0921g,0.5mmol), S were added sequentially to the tube reactor8(0.0640g, 4.0equiv.), diisopropyl phosphite (0.3333mL, 4.0equiv.), acetonitrile (2.0mL), sealed tube under air, then reacted for 24h under stirring at 100 ℃ after the completion of the reaction, the crude product was purified by column chromatography to obtain a crude product, which was washed three times with saturated sodium bicarbonate (50mL × 3), isolated in 78% yield, as a colorless oil.1H NMR(500MHz,CDCl3):7.43(d,J＝7.5Hz,4H),7.31(t,J＝7.0Hz,4H),7.22(t,J＝7.0Hz,2H),5.69(d,J＝12.0Hz,1H),4.57-4.50(m,2H),1.22(d,J＝6.0Hz,6H),1.11(d,J＝6.0Hz,6H).13C NMR(125.4MHz,CDCl3):141.8(d,J＝5.5Hz),128.5,128.2,127.3,72.8(d,J＝6.4Hz),54.4(d,J＝3.1Hz),23.7(d,J＝4.0Hz),23.4(d,J＝5.9Hz).31P NMR(202MHz,CDCl3):22.99。
Example 19
Diphenyl group, S8Three-component reaction of di-n-butyl phosphite
Diphenyl methanol (0.0921g,0.5mmol), S were added sequentially to the tube reactor8(0.0640g, 4.0equiv.), di-n-butyl phosphite (0.3904mL, 4.0equiv.), acetonitrile (2.0mL), air-sealed, and then reacted at 100 ℃ for 24h with stirring.after the completion of the reaction was monitored by TLC, the crude product was purified by column chromatography to obtain a crude product which was washed three times with saturated sodium bicarbonate (50mL × 3), isolated in 75% yield, as a colorless oil.1H NMR(500MHz,CDCl3):7.43(d,J＝7.5Hz,4H),7.31(t,J＝7.5Hz,4H),7.26-7.22(m,2H),5.64(d,J＝11.5Hz,1H),3.97-3.90(m,2H),3.80-3.74(m,2H),1.52-1.45(m,4H),1.31-1.23(m,4H),0.86(t,J＝7.5Hz,6H).13C NMR(125.4MHz,CDCl3):141.6(d,J＝5.4Hz),128.5,128.2,127.4,67.2(d,J＝6.3Hz),54.2(d,J＝3.3Hz),32.0(d,J＝7.4Hz),18.6,13.5.31P NMR(202MHz,CDCl3):25.52。
Example 20
Diphenylmethanol, S8Three-component reaction of phenyl ethyl phosphite
Diphenyl methanol (0.0921g,0.5mmol), S were added sequentially to the tube reactor8(0.0640g, 4.0equiv.), ethyl phenylphosphite (0.3014mL, 4.0equiv.), acetonitrile (2.0mL), tube-sealed under air, then reacted for 24h under stirring at 100 ℃, after completion of the reaction monitored by tlc, the crude product was purified by column chromatography to obtain a crude product which was washed three times with saturated sodium bicarbonate (50mL × 3), isolated in 54% yield, colorless oil.1H NMR(500MHz,CDCl3):7.58-7.53(m,2H),7.39-7.33(m,1H),7.27-7.16(m,8H),7.13-7.05(m,4H),5.49(d,J＝10.5Hz,1H),4.12-4.06(m,1H),3.92-3.87(m,1H),1.16(t,J＝7.5Hz,3H).13C NMR(125.4MHz,CDCl3):140.3(d,J＝6.3Hz),139.9(d,J＝2.9Hz),132.1,131.1(d,J＝3.3Hz),130.9,130.0(d,J＝10.9Hz),127.5,127.3,127.3,127.2,127.1,126.2(d,J＝11.9Hz),61.2(d,J＝6.8Hz),52.9(d,J＝2.1Hz),15.1(d,J＝7.0Hz).31P NMR(202MHz,CDCl3):14.98。
Example 21
4-methylbenzyl alcohol, S8Three-component reaction of diisopropyl phosphite
4-methylbenzyl alcohol (0.0611g,0.5mmol), S were added sequentially to a tubular reactor8(0.0640g, 4.0equiv.), diisopropyl phosphite (0.3333mL, 4.0equiv.), acetonitrile (2.0mL), sealed tube under air, then reacted for 24h under stirring at 100 ℃, after the completion of the reaction was monitored by TLC, the crude product was purified by column chromatography to obtain a crude product, which was washed three times with saturated sodium bicarbonate (50mL × 3), isolated in 64% yield, as a colorless oil.1H NMR(500MHz,CDCl3):7.24(d,J＝7.5Hz,2H),7.12(d,J＝7.5Hz,2H),4.73-4.65(m,2H),4.03(d,J＝12.5Hz,2H),2.33(s,3H),1.34(d,J＝6.5Hz,6H),1.29(d,J＝6.5Hz,6H).13C NMR(125.4MHz,CDCl3):137.3,134.3(d,J＝6.8Hz),129.3,128.8,72.6(d,J＝6.3Hz),35.0(d,J＝3.8Hz),23.8(d,J＝4.3Hz),23.5(d,J＝5.5Hz),21.1.31P NMR(202MHz,CDCl3):24.26。
Example 22
4-methylbenzyl alcohol, S8Three-component reaction of di-n-butyl phosphite
4-methylbenzyl alcohol (0.0611g,0.5mmol), S were added sequentially to a tubular reactor8(0.0640g, 4.0equiv.), di-n-butyl phosphite (0.3904mL, 4.0equiv.), acetonitrile (2.0mL), sealed under air, and then reacted at 100 ℃ under stirring for 24 h.TLC to monitor the completion of the reaction, the crude product was purified by column chromatography to obtain a crude product, which was washed three times with saturated sodium bicarbonate (50mL × 3) with an isolated yield of 68% as a yellow oil.1H NMR(500MHz,CDCl3):7.24(d,J＝8.0Hz,2H),7.12(d,J＝8.0Hz,2H),4.08-3.92(m,6H),2.33(s,3H),1.64-1.58(m,4H),1.40-1.33(m,4H),0.91(t,J＝7.5Hz,6H).13C NMR(125.4MHz,CDCl3):137.3,134.4(d,J＝5.5Hz),129.3,128.8,67.2(d,J＝6.4Hz),34.7(d,J＝3.9Hz),32.1(d,J＝7.3Hz),21.1,18.7,13.5.31P NMR(202MHz,CDCl3):27.01。
Example 23
4-methyl-benzyl alcohol, S8Three-component reaction of phenyl ethyl phosphite
4-methyl-benzyl alcohol (0.0611g,0.5mmol), S was added sequentially to a tubular reactor8(0.0640g, 4.0equiv.), ethylphenylphosphite (0.3014mL, 4.0equiv.), acetonitrile (2.0mL), the tube was sealed under air, and then reacted at 100 ℃ for 24 hours with stirring. After TLC monitoring reaction is completed, the crude product is separated and purified by column chromatography, and the crude product is washed with saturated sodium bicarbonateThis time (50mL × 3) and isolated in 75% yield as a colorless oil.1H NMR(500MHz,CDCl3):7.78-7.74(m,2H),7.46(t,J＝7.5Hz,1H),7.40-7.36(m,2H),7.02(d,J＝7.5Hz,2H),6.96(d,J＝7.5Hz,2H),4.21-4.15(m,1H),4.12-4.04(m,1H),3.90-3.77(m,2H),2.21(s,3H),1.28(t,J＝7.0Hz,3H).13C NMR(125.4MHz,CDCl3):136.1,133.1(d,J＝5.5Hz),132.2,131.4(d,J＝3.3Hz),131.0,130.2(d,J＝10.9Hz),128.2,127.7,127.4(d,J＝15.0Hz).31P NMR(202MHz,CDCl3):43.71。
Example 24
Cyclopentanol, S8Three-component reaction of diethyl phosphite
Cyclopentanol (0.0454mL,0.5mmol), S were added sequentially to the tube reactor8(0.0640g, 4.0equiv.), diethyl phosphite (0.2578mL, 4.0equiv.), acetonitrile (2.0mL), sealed under air, and then reacted at 120 ℃ for 24h with stirring.after the completion of the reaction was monitored by tlc, the crude product was separated and purified by column chromatography to obtain a crude product, which was washed three times with saturated sodium bicarbonate (50mL × 3), and the yield was 47% as a colorless oil.1H NMR(500MHz,CDCl3):4.24-4.08(m,4H),2.90-2.81(m,1H),2.17-2.08(m,2H),1.77-1.59(m,4H),1.39-1.34(m,8H).13C NMR(125.4MHz,CDCl3):62.4(d,J＝5.9Hz),43.7(d,J＝3.8Hz),34.3(d,J＝6.7Hz),23.3,15.1(d,J＝7.3Hz).31P NMR(202MHz,CDCl3):27.52。
Example 25
1-adamantanol, S8Three-component reaction of diethyl phosphite
1-adamantanol (0.0761g,0.5mmol), S were added sequentially to a tubular reactor8(0.0640g, 4.0equiv.), diethyl phosphite (0.2578mL, 4.0equiv.), acetonitrile (2.0mL), the tube was sealed under air, and then reacted at 100 ℃ for 24 hours with stirring. TLAfter the reaction was monitored to be complete, the crude product was purified by column chromatography to give a crude product which was washed three times with saturated sodium bicarbonate (50mL × 3) in 54% isolated yield as a colorless oil.1H NMR(500MHz,CDCl3):4.22-4.07(m,4H),2.17-2.16(m,5H),2.08-2.03(m,3H),1.74-1.67(m,5H),1.40-1.21(m,8H).13C NMR(125.4MHz,CDCl3):63.3(d,J＝6.3Hz),52.5(d,J＝4.4Hz),44.9(d,J＝6.0Hz),35.9,30.4,16.0(d,J＝7.4Hz).31P NMR(202MHz,CDCl3):24.69。
Example 26
2-butyn-1-ol, S8Three-component reaction of diethyl phosphite
2-butyn-1-ol (0.0374mL,0.5mmol), S were added sequentially to a tubular reactor8(0.0640g, 4.0equiv.), diethyl phosphite (0.2578mL, 4.0equiv.), acetonitrile (2.0mL), sealed under air, then reacted at 100 ℃ for 24h with stirring.after the reaction was monitored by tlc, the crude product was purified by column chromatography to obtain a crude product, which was washed three times with saturated sodium bicarbonate (50mL × 3), isolated in 31% yield, colorless oil.1H NMR(500MHz,CDCl3):4.26-4.13(m,4H),3.54-3.50(m,2H),1.82-1.81(m,2H),1.38-1.35(m,6H).13C NMR(125.4MHz,CDCl3):80.2,74.2(d,J＝7.3Hz),63.7(d,J＝5.5Hz),19.6(d,J＝3.9Hz),16.0(d,J＝8.7Hz),3.6.31P NMR(202MHz,CDCl3):26.04。
Example 27
1-heptanol, S8Three-component reaction of diethyl phosphite
1-heptanol (0.0707mL,0.5mmol), S were added sequentially to a tubular reactor8(0.0640g, 4.0equiv.), diethyl phosphite (0.2578mL, 4.0equiv.), acetonitrile (2.0mL), the tube was sealed under air, and the reaction was carried out at 120 ℃ for 36 hours with stirring. After TLC monitoring reaction is complete, crude product is obtainedThe product was purified by column chromatography to give the crude product which was washed three times with saturated sodium bicarbonate (50mL × 3) in 42% yield and as a colorless oil.1H NMR(400MHz,CDCl3):4.29-4.06(m,4H),2.95-2.84(m,2H),1.78-1.69(m,2H),1.46-1.30(m,15H),0.93(t,J＝6.4Hz,3H).13C NMR(125.4MHz,CDCl3):67.5,63.4,31.7,28.7(d,J＝13.8Hz),28.5,25.4(d,J＝13.7Hz),22.5,16.1(d,J＝2.9Hz),14.0.31P NMR(202MHz,CDCl3):28.17。
Example 28
Benzyl alcohol, S8Three-component reaction of diphenyl phosphine oxide
Benzyl alcohol (0.0517mL,0.5mmol), S were added sequentially to a tubular reactor8(0.0640g, 4.0equiv.), diphenylphosphine oxide (0.4044g, 4.0equiv.),1, 2-dichloroethane (2.0mL), nitrogen gas was sealed, and the mixture was stirred at 120 ℃ for 36 h.TLC to monitor the completion of the reaction, and the crude product was purified by column chromatography to obtain a crude product, which was washed three times with saturated sodium bicarbonate (50mL × 3), with an isolated yield of 86% and a colorless oil.1H NMR(400MHz,CDCl3):7.89-7.84(m,4H),7.55-7.51(m,2H),7.48-7.43(m,4H),7.22-7.17(m,5H),4.03(d,J＝9.2Hz).13C NMR(125.4MHz,CDCl3):136.8,132.3(d,J＝3.1Hz),131.6,131.5,129.0,128.7,128.6,128.5,127.4,33.2(d,J＝2.0Hz).31P NMR(202MHz,CDCl3):42.94。
The above embodiments are described in detail for the purpose of further illustrating the present invention and should not be construed as limiting the scope of the present invention, and the skilled engineer can make insubstantial modifications and variations of the present invention based on the above disclosure.
Claims (6)
1. A high-efficiency green preparation method of a sulfo-organic phosphonic acid derivative is characterized by comprising the following steps: the P (O) -H compound, sulfur powder and alcohol react to prepare the sulfo-organic phosphonic acid derivative directly, the reaction temperature is 80-120 ℃, the reaction time is 12-48 hours, and the reaction formula is as follows:
wherein:
R1is hydrogen or alkyl or substituted alkyl;
R2and R3Phenyl substituted at 2-, 3-, or 4-with various functional groups or substituted heteroaryl or hydrocarbyl;
R4and R5Is alkoxy, aryloxy, phenyl with functional groups substituted at 2-, 3-, or 4-, or substituted aryl.
2. The efficient green process for the preparation of a thiophosphonic acid derivative as claimed in claim 1, wherein: the P (O) -H compound is a phosphorous acid diester, a disubstituted phosphine oxide, or R4(R5O, P (O) -H compound such as P (O), H and the like, wherein the dosage of the P (O) -H compound and the sulfur powder is 2.0-5.0 equivalent.
3. The efficient green process for the preparation of a thiophosphonic acid derivative as claimed in claim 2, wherein: the P (O) -H compound and sulfur powder are used in an amount of 4.0 equivalents.
4. The efficient green process for the preparation of a thiophosphonic acid derivative as claimed in claim 1, wherein: the solvent is toluene, tetrahydrofuran, DMSO, DMF, 1, 4-dioxane or acetonitrile solvent.
5. The efficient green process for the preparation of a thiophosphonic acid derivative as claimed in claim 1, wherein: the reaction is carried out under nitrogen or air, the reaction temperature is 100 ℃, and the reaction time is 24-36 hours.
6. The efficient green process for the preparation of a thiophosphonic acid derivative as claimed in claim 1, wherein: the reaction is directly carried out under one-pot condition without any transition metal or nonmetal catalyst and additive.
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| CN109232642A (en) * | 2018-09-07 | 2019-01-18 | 信阳师范学院 | A kind of synthetic method of benzyl thiophosphate |
| CN109970794A (en) * | 2019-03-19 | 2019-07-05 | 厦门大学 | S- substitution -3- indoles sulphur phosphoric acid ester derivant and preparation method and application |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN109232642A (en) * | 2018-09-07 | 2019-01-18 | 信阳师范学院 | A kind of synthetic method of benzyl thiophosphate |
| CN109970794A (en) * | 2019-03-19 | 2019-07-05 | 厦门大学 | S- substitution -3- indoles sulphur phosphoric acid ester derivant and preparation method and application |
Non-Patent Citations (1)
| Title |
|---|
| VIOLETA PHILIPPITSCH等: ""Rearrangement of lithiated S-alkyl O,O-dialkyl thiophosphates: Scope and stereochemistry of the thiophosphate–mercaptophosphonate rearrangement"", 《ORG. BIOMOL. CHEM》 * |
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