CN114031639A - Preparation method of biphosphonate with P-O-C-P structure - Google Patents
Preparation method of biphosphonate with P-O-C-P structure Download PDFInfo
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- CN114031639A CN114031639A CN202111387738.4A CN202111387738A CN114031639A CN 114031639 A CN114031639 A CN 114031639A CN 202111387738 A CN202111387738 A CN 202111387738A CN 114031639 A CN114031639 A CN 114031639A
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- reaction
- anhydride
- phosphorus
- oxide
- carbonyl
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- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- 238000006243 chemical reaction Methods 0.000 claims abstract description 196
- -1 diphosphorus compound Chemical class 0.000 claims abstract description 41
- 239000002994 raw material Substances 0.000 claims abstract description 32
- 238000004440 column chromatography Methods 0.000 claims abstract description 30
- 150000001875 compounds Chemical class 0.000 claims abstract description 25
- 238000000034 method Methods 0.000 claims abstract description 25
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 24
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 22
- 229910052698 phosphorus Inorganic materials 0.000 claims abstract description 22
- 239000011574 phosphorus Substances 0.000 claims abstract description 22
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000003513 alkali Substances 0.000 claims abstract description 8
- 239000003960 organic solvent Substances 0.000 claims abstract description 5
- 239000012299 nitrogen atmosphere Substances 0.000 claims abstract description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 90
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 70
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 66
- 229960000549 4-dimethylaminophenol Drugs 0.000 claims description 33
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 claims description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- PEHFQQWAINXOQG-UHFFFAOYSA-N (2-methoxyacetyl) 2-methoxyacetate Chemical compound COCC(=O)OC(=O)COC PEHFQQWAINXOQG-UHFFFAOYSA-N 0.000 claims description 4
- MWUSAETYTBNPDG-UHFFFAOYSA-N (4-chlorobenzoyl) 4-chlorobenzoate Chemical compound C1=CC(Cl)=CC=C1C(=O)OC(=O)C1=CC=C(Cl)C=C1 MWUSAETYTBNPDG-UHFFFAOYSA-N 0.000 claims description 4
- BBLXFRIGTQYGOT-UHFFFAOYSA-N (4-fluorobenzoyl) 4-fluorobenzoate Chemical compound C1=CC(F)=CC=C1C(=O)OC(=O)C1=CC=C(F)C=C1 BBLXFRIGTQYGOT-UHFFFAOYSA-N 0.000 claims description 4
- YGMHIBLUWGDWKP-UHFFFAOYSA-N (4-methoxybenzoyl) 4-methoxybenzoate Chemical compound C1=CC(OC)=CC=C1C(=O)OC(=O)C1=CC=C(OC)C=C1 YGMHIBLUWGDWKP-UHFFFAOYSA-N 0.000 claims description 4
- BJMLLSSSTGHJJE-UHFFFAOYSA-N (4-methylbenzoyl) 4-methylbenzoate Chemical compound C1=CC(C)=CC=C1C(=O)OC(=O)C1=CC=C(C)C=C1 BJMLLSSSTGHJJE-UHFFFAOYSA-N 0.000 claims description 4
- XETRHNFRKCNWAJ-UHFFFAOYSA-N 2,2,3,3,3-pentafluoropropanoyl 2,2,3,3,3-pentafluoropropanoate Chemical compound FC(F)(F)C(F)(F)C(=O)OC(=O)C(F)(F)C(F)(F)F XETRHNFRKCNWAJ-UHFFFAOYSA-N 0.000 claims description 4
- NOGFHTGYPKWWRX-UHFFFAOYSA-N 2,2,6,6-tetramethyloxan-4-one Chemical compound CC1(C)CC(=O)CC(C)(C)O1 NOGFHTGYPKWWRX-UHFFFAOYSA-N 0.000 claims description 4
- FREZLSIGWNCSOQ-UHFFFAOYSA-N 3-methylbutanoyl 3-methylbutanoate Chemical compound CC(C)CC(=O)OC(=O)CC(C)C FREZLSIGWNCSOQ-UHFFFAOYSA-N 0.000 claims description 4
- 239000004342 Benzoyl peroxide Substances 0.000 claims description 4
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 claims description 4
- YIVJZNGAASQVEM-UHFFFAOYSA-N Lauroyl peroxide Chemical compound CCCCCCCCCCCC(=O)OOC(=O)CCCCCCCCCCC YIVJZNGAASQVEM-UHFFFAOYSA-N 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- STSCVKRWJPWALQ-UHFFFAOYSA-N TRIFLUOROACETIC ACID ETHYL ESTER Chemical compound CCOC(=O)C(F)(F)F STSCVKRWJPWALQ-UHFFFAOYSA-N 0.000 claims description 4
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims description 4
- 239000012346 acetyl chloride Substances 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 claims description 4
- 235000019400 benzoyl peroxide Nutrition 0.000 claims description 4
- YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical compound CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 0.000 claims description 4
- LSACYLWPPQLVSM-UHFFFAOYSA-N isobutyric acid anhydride Chemical compound CC(C)C(=O)OC(=O)C(C)C LSACYLWPPQLVSM-UHFFFAOYSA-N 0.000 claims description 4
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- FILKGCRCWDMBKA-UHFFFAOYSA-N 2,6-dichloropyridine Chemical compound ClC1=CC=CC(Cl)=N1 FILKGCRCWDMBKA-UHFFFAOYSA-N 0.000 claims description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
- WSNMPAVSZJSIMT-UHFFFAOYSA-N COc1c(C)c2COC(=O)c2c(O)c1CC(O)C1(C)CCC(=O)O1 Chemical compound COc1c(C)c2COC(=O)c2c(O)c1CC(O)C1(C)CCC(=O)O1 WSNMPAVSZJSIMT-UHFFFAOYSA-N 0.000 claims description 2
- 239000002585 base Substances 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- PKHMTIRCAFTBDS-UHFFFAOYSA-N hexanoyl hexanoate Chemical compound CCCCCC(=O)OC(=O)CCCCC PKHMTIRCAFTBDS-UHFFFAOYSA-N 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
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 2
- 235000011009 potassium phosphates Nutrition 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 235000017550 sodium carbonate Nutrition 0.000 claims description 2
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 claims 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims 2
- KGNCPCNAWUTBGB-UHFFFAOYSA-N [P].C1(=CC=CC=C1)OC1=CC=CC=C1 Chemical compound [P].C1(=CC=CC=C1)OC1=CC=CC=C1 KGNCPCNAWUTBGB-UHFFFAOYSA-N 0.000 claims 1
- 238000006555 catalytic reaction Methods 0.000 claims 1
- 239000012973 diazabicyclooctane Substances 0.000 claims 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims 1
- 235000017557 sodium bicarbonate Nutrition 0.000 claims 1
- 239000000758 substrate Substances 0.000 abstract description 6
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 238000005580 one pot reaction Methods 0.000 abstract description 3
- 230000015572 biosynthetic process Effects 0.000 abstract description 2
- FOBPTJZYDGNHLR-UHFFFAOYSA-N diphosphorus Chemical class P#P FOBPTJZYDGNHLR-UHFFFAOYSA-N 0.000 abstract description 2
- 239000003054 catalyst Substances 0.000 abstract 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 57
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 54
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 38
- 239000000047 product Substances 0.000 description 28
- 238000005160 1H NMR spectroscopy Methods 0.000 description 27
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 27
- 229910001873 dinitrogen Inorganic materials 0.000 description 27
- 239000003921 oil Substances 0.000 description 27
- 238000000926 separation method Methods 0.000 description 27
- 239000000243 solution Substances 0.000 description 27
- VWBYXJRDIQCSLW-UHFFFAOYSA-N O=[P](c1ccccc1)c1ccccc1 Chemical compound O=[P](c1ccccc1)c1ccccc1 VWBYXJRDIQCSLW-UHFFFAOYSA-N 0.000 description 24
- 239000003480 eluent Substances 0.000 description 19
- 239000011259 mixed solution Substances 0.000 description 19
- 239000003208 petroleum Substances 0.000 description 19
- YFPJFKYCVYXDJK-UHFFFAOYSA-N Diphenylphosphine oxide Chemical compound C=1C=CC=CC=1[P+](=O)C1=CC=CC=C1 YFPJFKYCVYXDJK-UHFFFAOYSA-N 0.000 description 13
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 6
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 4
- 102000000536 PPAR gamma Human genes 0.000 description 3
- 108010016731 PPAR gamma Proteins 0.000 description 3
- 150000001263 acyl chlorides Chemical class 0.000 description 3
- 150000008064 anhydrides Chemical class 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 150000002978 peroxides Chemical class 0.000 description 3
- ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 description 2
- QBRQTQSIWMMJGR-UHFFFAOYSA-N 1-(trifluoromethyl)-4-[4-(trifluoromethyl)phenyl]phosphonoylbenzene Chemical compound C1=CC(C(F)(F)F)=CC=C1P(=O)C1=CC=C(C(F)(F)F)C=C1 QBRQTQSIWMMJGR-UHFFFAOYSA-N 0.000 description 2
- YCDSWKRPWOGGLZ-UHFFFAOYSA-N C1=CC(Br)=CC=C1P(=O)C1=CC=C(Br)C=C1 Chemical compound C1=CC(Br)=CC=C1P(=O)C1=CC=C(Br)C=C1 YCDSWKRPWOGGLZ-UHFFFAOYSA-N 0.000 description 2
- ICYMNRZVLLTNSE-UHFFFAOYSA-N Cc1ccc(cc1)[P](=O)c1ccc(C)cc1 Chemical compound Cc1ccc(cc1)[P](=O)c1ccc(C)cc1 ICYMNRZVLLTNSE-UHFFFAOYSA-N 0.000 description 2
- AHLBQELLCIQSHC-UHFFFAOYSA-N Cc1cccc(c1)[P](=O)c1cccc(C)c1 Chemical compound Cc1cccc(c1)[P](=O)c1cccc(C)c1 AHLBQELLCIQSHC-UHFFFAOYSA-N 0.000 description 2
- 229940123464 Thiazolidinedione Drugs 0.000 description 2
- LMXRTXPFJNGAAX-UHFFFAOYSA-N bis(3,5-dimethylphenyl)-oxophosphanium Chemical compound CC1=CC(C)=CC([P+](=O)C=2C=C(C)C=C(C)C=2)=C1 LMXRTXPFJNGAAX-UHFFFAOYSA-N 0.000 description 2
- MIYITCTXDGORJJ-UHFFFAOYSA-N bis(4-fluorophenyl)-oxophosphanium Chemical compound C1=CC(F)=CC=C1[P+](=O)C1=CC=C(F)C=C1 MIYITCTXDGORJJ-UHFFFAOYSA-N 0.000 description 2
- RREGWFNURZJKNB-UHFFFAOYSA-N bis(4-methoxyphenyl)-oxophosphanium Chemical compound C1=CC(OC)=CC=C1[P+](=O)C1=CC=C(OC)C=C1 RREGWFNURZJKNB-UHFFFAOYSA-N 0.000 description 2
- UJBHOFPPZWFQKO-UHFFFAOYSA-N dinaphthalen-2-yl(oxo)phosphanium Chemical compound C1=CC=CC2=CC([P+](C=3C=C4C=CC=CC4=CC=3)=O)=CC=C21 UJBHOFPPZWFQKO-UHFFFAOYSA-N 0.000 description 2
- 239000003063 flame retardant Substances 0.000 description 2
- VQHUQHAPWMNBLP-UHFFFAOYSA-N phosphoric acid [(4-chlorophenyl)-dimethoxyphosphorylmethyl] dimethyl ester Chemical compound COP(=O)(OC)OC(P(=O)(OC)OC)C1=CC=C(Cl)C=C1 VQHUQHAPWMNBLP-UHFFFAOYSA-N 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- GGIQQYHOHRKDNO-UHFFFAOYSA-N 1-methyl-3-(3-methylphenyl)phosphonoylbenzene Chemical compound CC1=CC=CC(P(=O)C=2C=C(C)C=CC=2)=C1 GGIQQYHOHRKDNO-UHFFFAOYSA-N 0.000 description 1
- AKHPZCUBCXFMPZ-UHFFFAOYSA-N 1-tert-butyl-4-(4-tert-butylphenyl)phosphonoylbenzene Chemical compound C1=CC(C(C)(C)C)=CC=C1P(=O)C1=CC=C(C(C)(C)C)C=C1 AKHPZCUBCXFMPZ-UHFFFAOYSA-N 0.000 description 1
- RNFJDJUURJAICM-UHFFFAOYSA-N 2,2,4,4,6,6-hexaphenoxy-1,3,5-triaza-2$l^{5},4$l^{5},6$l^{5}-triphosphacyclohexa-1,3,5-triene Chemical compound N=1P(OC=2C=CC=CC=2)(OC=2C=CC=CC=2)=NP(OC=2C=CC=CC=2)(OC=2C=CC=CC=2)=NP=1(OC=1C=CC=CC=1)OC1=CC=CC=C1 RNFJDJUURJAICM-UHFFFAOYSA-N 0.000 description 1
- MGYJFVVDKRKQDE-UHFFFAOYSA-N CC(C)(C)c1ccc(cc1)[P](=O)c1ccc(cc1)C(C)(C)C Chemical compound CC(C)(C)c1ccc(cc1)[P](=O)c1ccc(cc1)C(C)(C)C MGYJFVVDKRKQDE-UHFFFAOYSA-N 0.000 description 1
- CRTMHFYHYMQVSB-UHFFFAOYSA-N CC=1C=C(C=C(C1)C)[P](C1=CC(=CC(=C1)C)C)=O Chemical compound CC=1C=C(C=C(C1)C)[P](C1=CC(=CC(=C1)C)C)=O CRTMHFYHYMQVSB-UHFFFAOYSA-N 0.000 description 1
- DTQFYZAIOBOXCO-UHFFFAOYSA-N COc1ccc(cc1)[P](=O)c1ccc(OC)cc1 Chemical compound COc1ccc(cc1)[P](=O)c1ccc(OC)cc1 DTQFYZAIOBOXCO-UHFFFAOYSA-N 0.000 description 1
- BQSJPEBMBLBURW-UHFFFAOYSA-N FC(C1=CC=C(C=C1)[P](C1=CC=C(C=C1)C(F)(F)F)=O)(F)F Chemical compound FC(C1=CC=C(C=C1)[P](C1=CC=C(C=C1)C(F)(F)F)=O)(F)F BQSJPEBMBLBURW-UHFFFAOYSA-N 0.000 description 1
- VCKQRKMYCBNCSF-UHFFFAOYSA-N Fc1ccc(cc1)[P](=O)c1ccc(F)cc1 Chemical compound Fc1ccc(cc1)[P](=O)c1ccc(F)cc1 VCKQRKMYCBNCSF-UHFFFAOYSA-N 0.000 description 1
- 101000603876 Homo sapiens Bile acid receptor Proteins 0.000 description 1
- JUJOGOQCZTWFLP-UHFFFAOYSA-N O=[P](C(C=C1)=CC=C1Br)C(C=C1)=CC=C1Br Chemical compound O=[P](C(C=C1)=CC=C1Br)C(C=C1)=CC=C1Br JUJOGOQCZTWFLP-UHFFFAOYSA-N 0.000 description 1
- IXRGRZXBSUOFOX-UHFFFAOYSA-N O=[P](c1ccc2ccccc2c1)c1ccc2ccccc2c1 Chemical compound O=[P](c1ccc2ccccc2c1)c1ccc2ccccc2c1 IXRGRZXBSUOFOX-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 102000023984 PPAR alpha Human genes 0.000 description 1
- 108010028924 PPAR alpha Proteins 0.000 description 1
- 108010044210 PPAR-beta Proteins 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- ZHIPXAFNKGZMSC-UHFFFAOYSA-N bis(4-methylphenyl)-oxophosphanium Chemical compound C1=CC(C)=CC=C1[P+](=O)C1=CC=C(C)C=C1 ZHIPXAFNKGZMSC-UHFFFAOYSA-N 0.000 description 1
- WLQIAVPVRXPZJA-UHFFFAOYSA-N bis(4-tert-butylphenyl)-oxophosphanium Chemical compound C1=CC(C(C)(C)C)=CC=C1[P+](=O)C1=CC=C(C(C)(C)C)C=C1 WLQIAVPVRXPZJA-UHFFFAOYSA-N 0.000 description 1
- 125000005340 bisphosphate group Chemical group 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 238000007036 catalytic synthesis reaction Methods 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000005548 dental material Substances 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229950007960 mifobate Drugs 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000003541 multi-stage reaction Methods 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229910001392 phosphorus oxide Inorganic materials 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/50—Organo-phosphines
- C07F9/53—Organo-phosphine oxides; Organo-phosphine thioxides
- C07F9/5325—Aromatic phosphine oxides or thioxides (P-C aromatic linkage)
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
Abstract
The invention discloses a preparation method of a diphosphide with a P-O-C-P structure. The method takes a carbonyl-containing compound and a phosphorus reagent as initial raw materials, takes alkali as a catalyst in a nitrogen atmosphere, and takes the alkali as a catalyst in an organic solvent at a reaction temperature of 60-120 DEG CoAnd C, reacting for 6-16 hours, and then carrying out column chromatography to obtain the diphosphorus compound. The preparation method has the advantages of simple reaction system, high reaction efficiency, cheap and easily-obtained raw materials, convenient reaction operation and wide substrate applicability, and can synthesize various diphosphorus compounds containing P-O-C-P structures by one step in a one-pot method. Moreover, most of the diphosphides prepared by the method belong to the first synthesis.
Description
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a method for efficiently preparing a biphosphonate, and further relates to a method for preparing a biphosphonate with a P-O-C-P structure.
Background
The diphosphide with a P-O-C-P structure in the molecule is an important organic phosphine molecule. It has wide application in many fields of human production and life. For example, in the field of organic synthesis, it can be used as a key synthetic intermediate for preparing functional organic molecules (CN 104418887A); in the field of biochemistry, the bisphosphate Mifobate (SR-202) is a commercial and highly effective PPAR γ (peroxisome proliferator-activated receptor γ) antagonist that selectively inhibits Thiazolidinedione (TZD) -induced PPAR γ transcriptional activity without affecting the transcriptional activity of PPAR α, PPAR β or FXR (Rieusset, j.; et. molecular endocrinology.2002,16,2628; Wu, h.s.; et. acta pharmacolsin.2007,28,417); particularly in the field of materials science, the diphosphides can be used as excellent dental materials (EP3225228A1) and can also be widely used in the field of polymer flame retardance as a high-efficiency organic phosphorus flame retardant (Wang, X.; oral. progressive organic coatings,2011,71, 72; CN 110229190A).
At present, the diphosphide with a P-O-C-P structure is mainly synthesized by reacting a phosphorus reagent with acyl phosphine, alpha-hydroxy phosphorus and other reagents, and both the acyl phosphine reagent and the alpha-hydroxy phosphine reagent need to be prepared in advance through one-step or multi-step reaction, so that the synthesis steps for preparing the diphosphide product are increased undoubtedly, and the preparation cost is high and the economy is low; in addition, most acylphosphine compounds, especially acyldiarylphosphine compounds, are chemically unstable and easily decomposed at room temperature, thus increasing the difficulty of preparing biphosphates using the acylphosphine compounds as substrates.
Therefore, the method for synthesizing the diphosphide with the P-O-C-P structure has the advantages of simple development and operation, safety, high efficiency and good economy, and has good application prospect in the field of actual production or scientific research.
Disclosure of Invention
In order to solve the technical problems, the invention provides a biphosphonate containing a P-O-C-P structure and a catalytic synthesis method for preparing the biphosphonate containing the P-O-C-P structure. The preparation method has the advantages of simple reaction system, cheap and easily-obtained raw materials, safety, high efficiency, convenient operation and wide applicability of reaction substrates, and can be used for synthesizing various diphosphorus compounds containing P-O-C-P structures in one step by a one-pot method, wherein various carbonyl-containing compounds (anhydride, acyl chloride, ester and peroxide) can be applied to the method, and various phosphorus reagents can also be reacted.
The technical scheme for realizing the invention is as follows:
a method for preparing diphosphide with a P-O-C-P structure, which comprises the following steps of using a carbonyl-containing compound and a phosphorus reagent as starting materials, and reacting the carbonyl-containing compound and the phosphorus reagent in a nitrogen atmosphere under the action of a catalytic amount of alkali according to a molar ratio: phosphorus reagent: the ratio of alkali is 1: 2-5: 0.1-0.5, an organic solvent is added to ensure that the concentration of the phosphorus reagent is 0.05-0.3mol/L, the reaction is carried out for 6-16 hours at the reaction temperature of 60-120 ℃, and then the diphosphorus compound with the structural general formula (I) is prepared by column chromatography,
wherein R in the formula I1、R2Is aryl;
the carbonyl-containing compound is selected from any one of the following structural formulas II to V:
when the carbonyl-containing compound is selected from the structure II, R is selected from any one of C1-C8 linear alkyl, methoxymethyl, trifluoromethyl, pentafluoroethyl, isopropyl, isobutyl, phenyl, p-methylphenyl, p-methoxyphenyl, p-fluorophenyl and p-chlorophenyl;
when the carbonyl-containing compound is selected from the structural formula III, R is selected from alkyl or aryl;
when the compound containing carbonyl is selected from a structure formula IV, R is selected from trifluoromethyl, and R is selected from3Selected from methyl or ethyl;
when the carbonyl-containing compound is selected from a structural formula V, R is selected from phenyl or n-undecyl.
Preferably, the carbonyl group-containing compound is any one selected from acetic anhydride, propionic anhydride, butyric anhydride, hexanoic anhydride, methoxyacetic anhydride, trifluoroacetic anhydride, pentafluoropropionic anhydride, isovaleric anhydride, isobutyric anhydride, benzoic anhydride, 4-methylbenzoic anhydride, 4-methoxybenzoic anhydride, 4-fluorobenzoic anhydride, 4-chlorobenzoic anhydride, acetyl chloride, benzoyl chloride, ethyl trifluoroacetate, lauroyl peroxide, and benzoyl peroxide.
Preferably, the diarylphosphine oxide is any one selected from the group consisting of diphenylphosphine oxide, bis (4-methylphenyl) phosphine oxide, bis (4-methoxyphenyl) phosphine oxide, bis (4-tert-butylphenyl) phosphine oxide, bis (4-fluorophenyl) phosphine oxide, bis (4-bromophenyl) phosphine oxide, bis (4-trifluoromethylphenyl) phosphine oxide, bis (3-methylphenyl) phosphine oxide, bis (3, 5-dimethylphenyl) phosphine oxide, and bis (2-naphthyl) phosphine oxide;
preferably, the base is selected from any one of pyridine, 2, 6-dichloropyridine, DMAP (4-dimethylaminopyridine), DBU (1, 8-diazabicyclo [5.4.0] undec-7-ene), sodium carbonate, sodium bicarbonate, potassium phosphate, preferably DMAP.
Preferably, the organic solvent is selected from any one of toluene, acetonitrile, Tetrahydrofuran (THF), and 1, 4-dioxane, and more preferably toluene.
Preferably, the carbonyl-containing compound: phosphorus reagent: the molar ratio of alkali to be fed is 1:2 to 5:0.1 to 0.5, and more preferably 1:3: 0.2.
Preferably, the concentration of the phosphorus reagent is 0.05-0.3mol/L, and preferably 0.1 mol/L.
Compared with the prior art, the invention has the beneficial effects that:
1. the reaction reagent used in the invention is safe, stable and easy to store, has low price, is green and environment-friendly, and avoids using acyl phosphate and phosphorus oxychloride which have poor stability, difficult storage and high toxicity as raw materials; the carbonyl-containing compound (anhydride, acyl chloride, ester and peroxide) and the phosphorus reagent (diaryl phosphorus oxide) used in the invention are generally and easily available, low in toxicity and good in stability, and particularly the alkaline accelerator (DMAP) used in the invention is not only stable and low in toxicity, but also very low in cost (DMAP: 99%, 1kg and 150 yuan), so that the invention is environment-friendly, high in economical efficiency, high in production safety and suitable for large-scale production.
2. In the invention, the diphosphorization reaction of the phosphorus reagent and the carbonyl-containing compound (anhydride, acyl chloride, ester and peroxide) can be promoted only by the catalytic amount (20 mol%) of DMAP, so that the reaction has high efficiency and economy; at present, in the reported preparation reactions of diphosphides, it is necessary to add an excessive amount of promoter to complete the reaction (1 Sun, Y.W.; equivalent. tetrahedron,2012,68, 9924; 2R a dai, Z.; equivalent. Mendeleev Commun, 2019,29, 153; 3 Hosseini, A.; equivalent. phosphorus, Sulfur, and silicon,2011,186,225) compared with the reaction substrate, so that the use of catalytic amounts of alkaline promoter to efficiently achieve the diphosphination reaction is previously hard to be imagined by those skilled in the art and is an innovation of the present invention.
3. The substrates (carbonyl compound, phosphorus reagent and alkaline reagent) used in the method are all commercial reagents and can be purchased, and compared with the traditional synthetic method, the method does not need to add extra synthetic steps to prepare the substrates in advance, so that the method shortens the synthetic steps, avoids the generation of a large amount of toxic byproducts, saves the reaction cost, and has higher step economy and atom economy.
4. Most of the diphosphides with P-O-C-P structures prepared by the invention are reported for the first time, and the diphosphides with P-O-C-P structures in molecules are important organic phosphine molecules, so that the diphosphides are widely applied to multiple fields of human production and life, and particularly can be widely applied to the field of polymer flame retardance as efficient organic phosphorus flame retardants.
Detailed Description
The invention will be further described with reference to specific examples, but the scope of the invention is not limited thereto. The first embodiment is as follows:
acetic anhydride and diphenyl phosphorus oxide are used as raw materials, and the reaction formula and the experimental steps are as follows:
diphenylphosphorus oxide (121.2mg,0.6mmol) and DMAP (4.9mg,0.04mmol) were charged into a 10mL reaction tube, the air in the reaction tube was replaced with nitrogen gas using a double row tube three times, 2mL of toluene and acetic anhydride (20.4mg,0.2mmol) were sequentially added thereto, and the reaction was placed in an oil bath at 90 ℃ for reaction for 11 hours. After the reaction was completed, the reaction solution was concentrated, and the volume ratio was 2: 1, using a mixed solution of petroleum ether and ethyl acetate as an eluent, and carrying out column chromatography separation to obtain a product 1- (diphenylphosphoryl) diphenyl phosphonic acid ethyl ester, wherein the yield is 85%.
1H NMR(500MHz,CDCl3):δ7.97-7.93(m,2H),7.79-7.76(m,2H),7.70-7.66(m,2H),7.56-7.50(m,3H),7.46-7.39(m,7H),7.28-7.24(m,4H),5.46-5.42(m,1H),1.52(dd,J＝6.9Hz,14.5Hz,3H).
The following examples, which are two to twenty-seven, demonstrate the general applicability of the preparation method of the present invention.
Example two:
propionic anhydride and diphenyl phosphorus oxide are taken as raw materials, and the reaction formula and the experimental steps are as follows:
diphenylphosphine oxide (121.2mg,0.6mmol) and DMAP (4.9mg,0.04mmol) were charged into a 10mL reaction tube, the air in the reaction tube was replaced with nitrogen gas using a double row tube three times, then 2mL of toluene and propionic anhydride (26.0mg,0.2mmol) were sequentially added thereto, and the reaction was placed in an oil bath at 90 ℃ for reaction for 11 hours. After the reaction was completed, the reaction solution was concentrated, and the volume ratio was 2: 1, using a mixed solution of petroleum ether and ethyl acetate as an eluent, and carrying out column chromatography separation to obtain a product 1- (diphenylphosphoryl) propyl diphenylphosphonate with the yield of 76%.
1H NMR(500MHz,CDCl3):δ7.96-7.92(m,2H),7.79-7.75(m,2H),7.72-7.68(m,2H),7.51-7.48(m,2H),7.46-7.7.36(m,8H),7.30-7.7.26(m,2H),7.22-7.18(m,2H),5.43-5.38(m,1H),2.05-1.93(m,2H),0.85(t,J＝7.5Hz,3H).
Example three:
the method takes butyric anhydride and diphenyl phosphorus oxide as raw materials, and comprises the following reaction formula and experimental steps:
diphenylphosphine oxide (121.2mg,0.6mmol) and DMAP (4.9mg,0.04mmol) were introduced into a 10mL reaction tube, the air in the reaction tube was replaced with nitrogen gas three times using a double row tube, 2mL of toluene and butyric anhydride (31.6mg,0.2mmol) were sequentially added thereto, and the reaction was allowed to stand in an oil bath at 90 ℃ for 11 hours. After the reaction was completed, the reaction solution was concentrated, and the volume ratio was 2: 1, using a mixed solution of petroleum ether and ethyl acetate as an eluent, and carrying out column chromatography separation to obtain a product 1- (diphenylphosphoryl) diphenyl butyl phosphonate, wherein the yield is 72%.
1H NMR(500MHz,CDCl3):δ7.95-7.91(m,2H),7.78-7.74(m,2H),7.71-7.67(m,2H),7.51-7.48(m,2H),7.46-7.7.35(m,8H),7.30-7.7.26(m,2H),7.22-7.18(m,2H),5.49-5.44(m,1H),1.92-1.85(m,2H),1.36-1.21(m,2H),0.66(t,J＝7.4Hz,3H).
Example four:
methoxy acetic anhydride and diphenyl phosphorus oxide are taken as raw materials, and the reaction formula and the experimental steps are as follows:
diphenylphosphorus oxide (121.2mg,0.6mmol) and DMAP (4.9mg,0.04mmol) were charged into a 10mL reaction tube, the air in the reaction tube was replaced with nitrogen gas using a double row tube three times, then 2mL of toluene and methoxyacetic anhydride (32.4mg,0.2mmol) were added thereto in this order, and the reaction was placed in an oil bath at 90 ℃ for reaction for 11 hours. After the reaction was completed, the reaction solution was concentrated, and the volume ratio was 2: 1, using a mixed solution of petroleum ether and ethyl acetate as an eluent, and carrying out column chromatography separation to obtain a product (diphenyl phosphoryl) (methoxy) methyl diphenyl phosphonate with the yield of 78%.
1H NMR(500MHz,CDCl3):δ7.95-7.91(m,2H),7.84-7.80(m,2H),7.74-7.69(m,2H),7.54-7.36(m,10H),7.28-7.18(m,4H),5.68-5.63(m,1H),3.82-3.78(m,1H),3.73-3.68(m,1H),2.85(s,3H).
Example five:
trifluoroacetic anhydride and diphenyl phosphorus oxide are taken as raw materials, and the reaction formula and the experimental steps are as follows:
diphenylphosphine oxide (121.2mg,0.6mmol) and DMAP (4.9mg,0.04mmol) were introduced into a 10mL reaction tube, the air in the reaction tube was replaced with nitrogen gas using a double row tube three times, 2mL of toluene and trifluoroacetic anhydride (42.0mg,0.2mmol) were sequentially added thereto, and the reaction was allowed to stand in an oil bath at 120 ℃ for 11 hours. After the reaction was completed, the reaction solution was concentrated, and the volume ratio was 2: 1, and performing column chromatography separation by using a mixed solution of petroleum ether and ethyl acetate as an eluent to obtain a product 1- (diphenyl phosphoryl) -2,2, 2-trifluoroethyl diphenyl phosphonate, wherein the yield is 52%.
1H NMR(500MHz,CDCl3):δ7.92-7.83(m,4H),7.74-7.70(m,2H),7.55-7.50(m,2H),7.46-7.32(m,8H),7.30-7.26(m,2H),7.22-7.19(m,2H),6.01-5.93(m,1H).
Example six:
the method takes pentafluoropropionic anhydride and diphenyl phosphorus oxide as raw materials, and comprises the following reaction formula and experimental steps:
diphenylphosphorus oxide (121.2mg,0.6mmol) and DMAP (4.9mg,0.04mmol) were taken and charged into a 10mL reaction tube, the air in the reaction tube was replaced with nitrogen gas using a double row tube three times, then 2mL of toluene and pentafluoropropionic anhydride (62.0mg,0.2mmol) were sequentially added thereto, and the reaction was placed in an oil bath at 120 ℃ for reaction for 11 hours. After the reaction was completed, the reaction solution was concentrated, and the volume ratio was 2: 1, and performing column chromatography separation by using a mixed solution of petroleum ether and ethyl acetate as an eluent to obtain a product 1- (diphenylphosphoryl) -2,2,3,3, 3-pentafluoropropyldiphenylphosphonate, wherein the yield is 46%.
1H NMR(500MHz,CDCl3):δ7.91-7.81(m,4H),7.73-7.69(m,2H),7.50-7.47(m,2H),7.41-7.33(m,8H),7.30-7.27(m,2H),7.22-7.19(m,2H),6.18-6.10(m,1H).
Example seven:
3-methylbutyric anhydride and diphenyl phosphorus oxide are taken as raw materials, and the reaction formula and the experimental steps are as follows:
diphenylphosphine oxide (121.2mg,0.6mmol) and DMAP (4.9mg,0.04mmol) were introduced into a 10mL reaction tube, the air in the reaction tube was replaced with nitrogen gas three times using a double row tube, 2mL of toluene and 3-methylbutyric anhydride (37.2mg,0.2mmol) were sequentially added thereto, and the reaction was allowed to stand in an oil bath at 120 ℃ for 11 hours. After the reaction was completed, the reaction solution was concentrated, and the volume ratio was 2: 1, using a mixed solution of petroleum ether and ethyl acetate as an eluent, and carrying out column chromatography separation to obtain a product 1- (diphenylphosphoryl) -3-methylbutyl diphenylphosphonate with the yield of 71%.
1H NMR(500MHz,CDCl3):δ7.95-7.91(m,2H),7.80-7.76(m,2H),7.72-7.67(m,2H),7.50-7.46(m,2H),7.42-7.28(m,10H),7.21-7.17(m,2H),5.56-5.52(m,1H),1.93-1.85(m,1H),1.67-1.60(m,1H),1.53-1.46(m,1H),0.73(d,J＝6.5Hz,3H),0.63(d,J＝6.6Hz,3H).
Example eight:
the method takes isobutyric anhydride and diphenyl phosphorus oxide as raw materials, and comprises the following reaction formula and experimental steps:
diphenylphosphorus oxide (121.2mg,0.6mmol) and DMAP (4.9mg,0.04mmol) were charged into a 10mL reaction tube, the air in the reaction tube was replaced with nitrogen gas using a double row tube three times, then 2mL of toluene and isobutyric anhydride (31.6mg,0.2mmol) were sequentially added thereto, and the reaction was allowed to stand in an oil bath at 120 ℃ for 11 hours. After the reaction was completed, the reaction solution was concentrated, and the volume ratio was 2: 1, using a mixed solution of petroleum ether and ethyl acetate as an eluent, and carrying out column chromatography separation to obtain a product 1- (diphenylphosphoryl) -2-methylpropyl diphenylphosphonate, wherein the yield is 42%.
1H NMR(500MHz,CDCl3):δ7.92-7.87(m,2H),7.83-7.73(m,4H),7.50-7.39(m,6H),7.35-7.23(m,6H),5.54(dd,J1＝2.7Hz,J2＝11.6Hz,1H),2.35-2.26(m,1H),1.00(d,J＝6.9Hz,3H),0.85(d,J＝7.0Hz,3H).
Example nine:
benzoic anhydride and diphenyl phosphorus oxide are used as raw materials, and the reaction formula and the experimental steps are as follows:
diphenylphosphine oxide (121.2mg,0.6mmol) and DMAP (4.9mg,0.04mmol) were introduced into a 10mL reaction tube, the air in the reaction tube was replaced with nitrogen gas using a double row tube three times, 2mL of toluene and benzoic anhydride (45.2mg,0.2mmol) were sequentially added thereto, and the reaction was put in an oil bath at 90 ℃ for reaction for 11 hours. After the reaction was completed, the reaction solution was concentrated, and the volume ratio was 2: 1, using a mixed solution of petroleum ether and ethyl acetate as an eluent, and carrying out column chromatography separation to obtain a product (diphenyl phosphoryl) (phenyl) methyl diphenyl phosphonate with the yield of 75%.
1H NMR(500MHz,CDCl3):δ8.03-7.99(m,2H),7.62-7.53(m,3H),7.49-7.24(m,13H),7.17-7.08(m,5H),7.02(t,J＝7.7Hz,2H),6.30(dd,J1＝2.5Hz,J2＝10.4Hz,1H).
Example ten:
the method takes 4-methyl benzoic anhydride and diphenyl phosphorus oxide as raw materials, and comprises the following reaction formula and experimental steps:
diphenylphosphine oxide (121.2mg,0.6mmol) and DMAP (4.9mg,0.04mmol) were introduced into a 10mL reaction tube, the air in the reaction tube was replaced with nitrogen gas using a double row tube three times, 2mL of toluene and 4-methylbenzoic anhydride (50.8mg,0.2mmol) were sequentially added thereto, and the reaction was allowed to stand in an oil bath at 90 ℃ for 11 hours. After the reaction was completed, the reaction solution was concentrated, and the volume ratio was 2: 1, using a mixed solution of petroleum ether and ethyl acetate as an eluent, and carrying out column chromatography separation to obtain a product (diphenyl phosphoryl) (p-tolyl) methyl diphenylphosphonate with the yield of 80%.
1H NMR(500MHz,CDCl3):δ8.02-7.98(m,2H),7.64-7.60(m,2H),7.54-7.51(m,1H),7.47-7.38(m,6H),7.35-7.29(m,5H),7.27-7.22(m,2H),7.16-7.12(m,2H),7.06(d,J＝7.1Hz,2H),6.82(d,J＝7.9Hz,2H),6.27(dd,J1＝2.3Hz,J2＝10.2Hz,1H),2.18(s,3H).
Example eleven:
the method takes 4-methoxy benzoic anhydride and diphenyl phosphorus oxide as raw materials, and comprises the following reaction formula and experimental steps:
diphenylphosphine oxide (121.2mg,0.6mmol) and DMAP (4.9mg,0.04mmol) were charged into a 10mL reaction tube, the air in the reaction tube was replaced with nitrogen gas using a double row tube three times, 2mL of toluene and 4-methoxybenzoic anhydride (57.2mg,0.2mmol) were sequentially added thereto, and the reaction was placed in an oil bath at 90 ℃ for reaction for 11 hours. After the reaction was completed, the reaction solution was concentrated, and the volume ratio was 2: 1, using a mixed solution of petroleum ether and ethyl acetate as an eluent, and carrying out column chromatography separation to obtain a product (diphenyl phosphoryl) (4-methoxyphenyl) methyl diphenyl phosphonate, wherein the yield is 77%.
1H NMR(500MHz,CDCl3):δ8.03-7.99(m,2H),7.62-7.52(m,3H),7.49-7.37(m,6H),7.34-7.29(m,5H),7.27-7.22(m,2H),7.17-7.12(m,4H),6.56(d,J＝8.7Hz,2H),6.26(dd,J1＝1.9Hz,J2＝10.1Hz,1H),3.69(s,3H).
Example twelve:
4-fluorobenzoic anhydride and diphenyl phosphorus oxide are taken as raw materials, and the reaction formula and the experimental steps are as follows:
diphenylphosphine oxide (121.2mg,0.6mmol) and DMAP (4.9mg,0.04mmol) were introduced into a 10mL reaction tube, the air in the reaction tube was replaced with nitrogen gas using a double row tube three times, 2mL of toluene and 4-fluorobenzoic anhydride (52.4mg,0.2mmol) were sequentially added thereto, and the reaction was allowed to stand in an oil bath at 90 ℃ for 11 hours. After the reaction was completed, the reaction solution was concentrated, and the volume ratio was 2: 1, using a mixed solution of petroleum ether and ethyl acetate as an eluent, and carrying out column chromatography separation to obtain a product (diphenylphosphoryl) (4-fluorophenyl) methyl diphenylphosphonate, wherein the yield is 76%.
1H NMR(500MHz,CDCl3):δ8.03-7.99(m,2H),7.62-7.54(m,3H),7.50-7.38(m,6H),7.35-7.30(m,5H),7.28-7.24(m,2H),7.18-7.15(m,4H),6.70(t,J＝8.7Hz,2H),6.30(dd,J1＝2.2Hz,J2＝10.1Hz,1H).
Example thirteen:
4-chlorobenzoic anhydride and diphenyl phosphorus oxide are taken as raw materials, and the reaction formula and the experimental steps are as follows:
diphenylphosphine oxide (121.2mg,0.6mmol) and DMAP (4.9mg,0.04mmol) were charged into a 10mL reaction tube, the air in the reaction tube was replaced with nitrogen gas using a double row tube three times, 2mL of toluene and 4-chlorobenzoic acid anhydride (58.8mg,0.2mmol) were sequentially added thereto, and the reaction was placed in an oil bath at 90 ℃ for reaction for 11 hours. After the reaction was completed, the reaction solution was concentrated, and the volume ratio was 2: 1, using a mixed solution of petroleum ether and ethyl acetate as an eluent, and carrying out column chromatography separation to obtain a product (4-chlorphenyl) (diphenyl phosphoryl) methyl diphenyl phosphonate with the yield of 76%.
1H NMR(500MHz,CDCl3):δ8.03-7.99(m,2H),7.62-7.54(m,3H),7.50-7.38(m,6H),7.35-7.30(m,5H),7.28-7.24(m,2H),7.18-7.15(m,4H),6.70(t,J＝8.7Hz,2H),6.30(dd,J1＝2.2Hz,J2＝10.1Hz,1H).
Example fourteen:
acetic anhydride and bis (4-fluorophenyl) phosphorus oxide are used as raw materials, and the reaction formula and the experimental steps are as follows:
bis (4-fluorophenyl) phosphine oxide (142.8mg,0.6mmol) and DMAP (4.9mg,0.04mmol) were introduced into a 10mL reaction tube, the air in the reaction tube was replaced with nitrogen gas three times using a double row tube, 2mL of toluene and acetic anhydride (20.4mg,0.2mmol) were sequentially added thereto, and the reaction was allowed to stand in an oil bath at 90 ℃ for 11 hours. After the reaction was completed, the reaction solution was concentrated, and the volume ratio was 2: 1, and performing column chromatography separation to obtain a product 1- (bis (4-fluorophenyl) phosphoryl) ethyl bis (4-fluorophenyl) phosphonate with the yield of 87%.
1H NMR(500MHz,CDCl3):δ7.93-7.88(m,2H),7.81-7.69(m,4H),7.35-7.30(m,2H),7.19-7.12(m,6H),7.01-6.97(m,2H),5.52-5.46(m,1H),1.49(dd,J1＝7.0Hz,J2＝14.6Hz,3H).
Example fifteen:
acetic anhydride and bis (4-bromophenyl) phosphorus oxide are used as raw materials, and the reaction formula and the experimental steps are as follows:
bis (4-bromophenyl) phosphine oxide (214.7mg,0.6mmol) and DMAP (4.9mg,0.04mmol) were charged into a 10mL reaction tube, the air in the reaction tube was replaced with nitrogen gas three times using a double row tube, 2mL of toluene and acetic anhydride (20.4mg,0.2mmol) were sequentially added thereto, and the reaction was placed in an oil bath at 90 ℃ for reaction for 11 hours. After the reaction was completed, the reaction solution was concentrated, and the volume ratio was 2: 1, and performing column chromatography separation to obtain a product 1- (bis (4-fluorophenyl) phosphoryl) ethyl bis (4-bromophenyl) phosphonate with the yield of 95%.
1H NMR(500MHz,CDCl3):δ7.73-7.69(m,2H),7.63-7.52(m,10H),7.45-7.43(m,2H),7.16-7.12(m,2H),5.52-5.46(m,1H),1.50(dd,J1＝7.0Hz,J2＝14.7Hz,3H).
Example sixteen:
acetic anhydride and bis (4-trifluoromethylphenyl) phosphorus oxide are taken as raw materials, and the reaction formula and the experimental steps are as follows:
bis (4-trifluoromethylphenyl) phosphine oxide (202.8mg,0.6mmol) and DMAP (4.9mg,0.04mmol) were introduced into a 10mL reaction tube, the air in the reaction tube was replaced with nitrogen gas three times using a double row tube, 2mL of toluene and acetic anhydride (20.4mg,0.2mmol) were sequentially added thereto, and the reaction was allowed to stand in an oil bath at 90 ℃ for 11 hours. After the reaction was completed, the reaction solution was concentrated, and the volume ratio was 2: 1, and performing column chromatography separation to obtain a product 1- (bis (4-fluorophenyl) phosphoryl) ethyl bis (4-trifluoromethylphenyl) phosphonate with the yield of 98 percent.
1H NMR(500MHz,CDCl3):δ8.09-7.89(m,6H),7.77-7.74(m,4H),7.68-7.66(m,2H),7.55-7.47(m,4H),5.81-5.75(m,1H),1.59(dd,J1＝7.0Hz,J2＝14.7Hz,3H).
Example seventeen:
acetic anhydride and bis (4-methoxyphenyl) phosphorus oxide are taken as raw materials, and the reaction formula and the experimental steps are as follows:
bis (4-methoxyphenyl) phosphine oxide (157.3mg,0.6mmol) and DMAP (4.9mg,0.04mmol) were charged into a 10mL reaction tube, the air in the reaction tube was replaced with nitrogen gas three times using a double row tube, 2mL of toluene and acetic anhydride (20.4mg,0.2mmol) were sequentially added thereto, and the reaction was placed in an oil bath at 90 ℃ for reaction for 11 hours. After the reaction was completed, the reaction solution was concentrated, and the volume ratio was 2: 1, and performing column chromatography separation to obtain a product 1- (bis (4-fluorophenyl) phosphoryl) ethyl bis (4-methoxyphenyl) phosphonate with the yield of 74 percent.
1H NMR(500MHz,CDCl3):δ7.84(dd,J1＝8.8Hz,J2＝10.6Hz,2H),7.68-7.56(m,4H),7.20(dd,J1＝8.8Hz,J2＝12.1Hz,2H),6.97-6.89(m,6H),6.74(dd,J1＝2.7Hz,J2＝8.8Hz,2H),5.33-5.29(m,1H),3.84(d,J＝3.5Hz,6H),3.81(d,J＝7.2Hz,6H),1.50(dd,J1＝7.0Hz,J2＝14.5Hz,3H).
Example eighteen:
acetic anhydride and bis (4-methylphenyl) phosphorus oxide are taken as raw materials, and the reaction formula and the experimental steps are as follows:
bis (4-methylphenyl) phosphorus oxide (138.1mg,0.6mmol) and DMAP (4.9mg,0.04mmol) were charged into a 10mL reaction tube, the air in the reaction tube was replaced with nitrogen gas three times using a double row tube, 2mL of toluene and acetic anhydride (20.4mg,0.2mmol) were sequentially added thereto, and the reaction was placed in an oil bath at 90 ℃ for reaction for 11 hours. After the reaction was completed, the reaction solution was concentrated, and the volume ratio was 2: 1, and performing column chromatography separation to obtain a product 1- (bis (4-fluorophenyl) phosphoryl) ethyl bis (4-methylphenyl) phosphonate with the yield of 66 percent.
1H NMR(500MHz,CDCl3):δ7.82(dd,J1＝8.1Hz,J2＝10.9Hz,2H),7.64(dd,J1＝8.1Hz,J2＝11.2Hz,2H),7.54(dd,J1＝8.1Hz,J2＝12.2Hz,2H),7.28-7.12(m,8H),7.04-7.02(m,2H),5.38-5.31(m,1H),2.39(s,6H),2.36(s,3H),2.34(s,3H),1.50(dd,J1＝7.0Hz,J2＝14.5Hz,3H).
Example nineteenth:
acetic anhydride and di (4-tert-butylphenyl) phosphorus oxide are used as raw materials, and the reaction formula and the experimental steps are as follows:
bis (4-t-butylphenyl) phosphine oxide (188.5mg,0.6mmol) and DMAP (4.9mg,0.04mmol) were introduced into a 10mL reaction tube, the air in the reaction tube was replaced with nitrogen gas three times using a double row tube, 2mL of toluene and acetic anhydride (20.4mg,0.2mmol) were sequentially added thereto, and the reaction was allowed to stand in an oil bath at 90 ℃ for reaction for 11 hours. After the reaction was completed, the reaction solution was concentrated, and the volume ratio was 2: 1, using a mixed solution of petroleum ether and ethyl acetate as an eluent, and carrying out column chromatography separation to obtain a product 1- (bis (4-fluorophenyl) phosphoryl) ethyl bis (4-tert-butylphenyl) phosphonate with the yield of 76%.
1H NMR(500MHz,CDCl3):δ7.92(dd,J1＝8.4Hz,J2＝10.7Hz,2H),7.73(dd,J1＝8.4Hz,J2＝11.0Hz,2H),7.58(dd,J1＝8.4Hz,J2＝12.0Hz,2H),7.53-7.48(m,4H),7.41-7.39(m,2H),7.28-7.25(m,2H),7.17-7.13(m,2H),5.35-5.28(m,1H),1.51(dd,J1＝7.0Hz,J2＝14.6Hz,3H),1.34(d,J＝2.1Hz,18H),1.31(s,9H),1.28(s,9H).
Example twenty:
acetic anhydride and di (2-naphthyl) phosphorus oxide are taken as raw materials, and the reaction formula and the experimental steps are as follows:
bis (2-naphthyl) phosphine oxide (181.3mg,0.6mmol) and DMAP (4.9mg,0.04mmol) were introduced into a 10mL reaction tube, the air in the reaction tube was replaced with nitrogen gas three times using a double row tube, 2mL of toluene and acetic anhydride (20.4mg,0.2mmol) were sequentially added thereto, and the reaction was allowed to stand in an oil bath at 90 ℃ for 11 hours. After the reaction was completed, the reaction solution was concentrated, and the volume ratio was 2: 1, and performing column chromatography separation to obtain a product 1- (di (naphthalene-2-yl) phosphoryl) ethyl di (naphthalene-2-yl) phosphonate with the yield of 67 percent.
1H NMR(500MHz,CDCl3):δ8.69(d,J＝13.2Hz,1H),8.43(d,J＝13.3Hz,1H),8.34(d,J＝14.4Hz,1H),7.98-7.75(m,12H),7.68-7.47(m,9H),7.39-7.34(m,2H),7.28-7.25(m,1H),7.10-7.06(m,1H),5.81-5.78(m,1H),1.68(dd,J1＝7.0Hz,J2＝14.5Hz,3H).
Example twenty one:
acetic anhydride and bis (3-methylphenyl) phosphorus oxide are taken as raw materials, and the reaction formula and the experimental steps are as follows:
bis (3-methylphenyl) phosphorus oxide (138.1mg,0.6mmol) and DMAP (4.9mg,0.04mmol) were charged into a 10mL reaction tube, the air in the reaction tube was replaced with nitrogen gas three times using a double row tube, 2mL of toluene and acetic anhydride (20.4mg,0.2mmol) were sequentially added thereto, and the reaction was placed in an oil bath at 90 ℃ for reaction for 11 hours. After the reaction was completed, the reaction solution was concentrated, and the volume ratio was 2: 1, and a mixed solution of petroleum ether and ethyl acetate is used as an eluent, and the product 1- (di-m-tolyl phosphoryl) di-m-tolyl phosphonic acid ethyl ester is obtained by column chromatography separation, wherein the yield is 79%.
1H NMR(500MHz,CDCl3):δ7.80(d,J＝11.6Hz,1H),7.75-7.71(m,1H),7.62(d,J＝11.7Hz,1H),7.55-7.53(m,2H),7.48-7.44(m,1H),7.34-7.27(m,6H),7.23-7.10(m,3H),7.03-6.99(m,1H),5.44-5.38(m,1H),2.34(s,6H),2.33(s,3H),2.23(s,3H),1.52(dd,J1＝7.0Hz,J2＝14.5Hz,3H).
Example twenty two:
acetic anhydride and bis (3, 5-dimethylphenyl) phosphorus oxide are used as raw materials, and the reaction formula and the experimental steps are as follows:
bis (3, 5-dimethylphenyl) phosphine oxide (154.9mg,0.6mmol) and DMAP (4.9mg,0.04mmol) were charged into a 10mL reaction tube, the air in the reaction tube was replaced with nitrogen gas three times using a double row tube, 2mL of toluene and acetic anhydride (20.4mg,0.2mmol) were sequentially added thereto, and the reaction was placed in an oil bath at 90 ℃ for reaction for 11 hours. After the reaction was completed, the reaction solution was concentrated, and the volume ratio was 2: 1, and performing column chromatography separation to obtain a product 1- (bis (3, 5-dimethylphenyl) phosphoryl) ethyl bis (3, 5-dimethylphenyl) phosphonate with the yield of 31 percent.
1H NMR(500MHz,CDCl3):δ7.58(d,J＝11.4Hz,2H),7.40(d,J＝11.5Hz,2H),7.33(d,J＝12.7Hz,2H),7.11(s,3H),7.02(s,1H),6.92(d,J＝12.9Hz,2H),5.46-5.40(m,1H),2.30(s,6H),2.27(s,12H),2.17(s,6H),1.50(dd,J1＝7.0Hz,J2＝14.4Hz,3H).
Example twenty three:
benzoyl chloride and diphenyl phosphorus oxide are used as raw materials, and the reaction formula and the experimental steps are as follows:
diphenylphosphine oxide (121.2mg,0.6mmol) and DMAP (4.9mg,0.04mmol) were introduced into a 10mL reaction tube, the air in the reaction tube was replaced with nitrogen gas three times using a double row tube, 2mL of toluene and benzoyl chloride (28.0mg,0.2mmol) were sequentially added thereto, and the reaction was allowed to stand in an oil bath at 90 ℃ for 11 hours. After the reaction was completed, the reaction solution was concentrated, and the volume ratio was 2: 1, using a mixed solution of petroleum ether and ethyl acetate as an eluent, and carrying out column chromatography separation to obtain a product (diphenyl phosphoryl) (phenyl) methyl diphenyl phosphonate, wherein the yield is 71%.
1H NMR(500MHz,CDCl3):δ8.03-7.99(m,2H),7.62-7.53(m,3H),7.49-7.24(m,13H),7.17-7.08(m,5H),7.02(t,J＝7.7Hz,2H),6.30(dd,J1＝2.5Hz,J2＝10.4Hz,1H).
Example twenty-four:
acetyl chloride and diphenyl phosphorus oxide are taken as raw materials, and the reaction formula and the experimental steps are as follows:
diphenylphosphorus oxide (121.2mg,0.6mmol) and DMAP (4.9mg,0.04mmol) were charged into a 10mL reaction tube, the air in the reaction tube was replaced with nitrogen gas using a double row tube three times, then 2mL of toluene and acetyl chloride (15.7mg,0.2mmol) were sequentially added thereto, and the reaction was placed in an oil bath at 90 ℃ for reaction for 11 hours. After the reaction was completed, the reaction solution was concentrated, and the volume ratio was 2: 1, and performing column chromatography separation to obtain a product 1- (diphenylphosphoryl) diphenyl phosphonic acid ethyl ester, wherein the yield is 33%.
1H NMR(500MHz,CDCl3):δ7.97-7.93(m,2H),7.79-7.76(m,2H),7.70-7.66(m,2H),7.56-7.50(m,3H),7.46-7.39(m,7H),7.28-7.24(m,4H),5.46-5.42(m,1H),1.52(dd,J＝6.9Hz,14.5Hz,3H).
Example twenty-five:
the method takes ethyl trifluoroacetate and diphenyl phosphorus oxide as raw materials, and comprises the following reaction formula and experimental steps:
diphenylphosphine oxide (121.2mg,0.6mmol) and DMAP (4.9mg,0.04mmol) were introduced into a 10mL reaction tube, the air in the reaction tube was replaced with nitrogen gas using a double row tube three times, 2mL of toluene and ethyl trifluoroacetate (28.4mg,0.2mmol) were sequentially added thereto, and the reaction was allowed to stand in an oil bath at 90 ℃ for 11 hours. After the reaction was completed, the reaction solution was concentrated, and the volume ratio was 2: 1, and performing column chromatography separation by using a mixed solution of petroleum ether and ethyl acetate as an eluent to obtain a product 1- (diphenyl phosphoryl) -2,2, 2-trifluoroethyl diphenyl phosphonate, wherein the yield is 29%.
1H NMR(500MHz,CDCl3):δ7.92-7.83(m,4H),7.74-7.70(m,2H),7.55-7.50(m,2H),7.46-7.32(m,8H),7.30-7.26(m,2H),7.22-7.19(m,2H),6.01-5.93(m,1H).
Example twenty-six:
the method takes lauroyl peroxide and diphenyl phosphorus oxide as raw materials, and comprises the following reaction formula and experimental steps:
diphenylphosphorus oxide (121.2mg,0.6mmol), lauroyl peroxide (79.7mg,0.2mmol) and DMAP (4.9mg,0.04mmol) were charged into a 10mL reaction tube, the air in the reaction tube was replaced with nitrogen gas using a double row tube, three times of replacement was performed, 2mL of toluene was then added thereto, and the reaction was allowed to stand in an oil bath at 90 ℃ for reaction for 11 hours. After the reaction was completed, the reaction solution was concentrated, and the volume ratio was 2: 1, using a mixed solution of petroleum ether and ethyl acetate as an eluent, and carrying out column chromatography separation to obtain a product 1- (diphenylphosphoryl) dodecyl diphenyl phosphonate with the yield of 63%.
1H NMR(500MHz,CDCl3):δ7.95-7.92(m,2H),7.80-7.69(m,4H),7.50-7.47(m,2H),7.43-7.34(m,8H),7.30-7.26(m,2H),7.20-7.19(m,2H),5.52-5.47(m,1H),1.92-1.85(m,2H),1.29-1.10(m,14H),1.03-1.01(m,2H),0.97-0.95(m,2H),0.90-0.87(td,J1＝1.3Hz,J2＝6.9Hz,3H).
Example twenty-seven:
benzoyl peroxide and diphenyl phosphorus oxide are used as raw materials, and the reaction formula and the experimental steps are as follows:
diphenylphosphine oxide (121.2mg,0.6mmol), benzoyl peroxide (48.4mg,0.2mmol), and DMAP (4.9mg,0.04mmol) were charged into a 10mL reaction tube, the air in the reaction tube was replaced with nitrogen gas using a double row tube three times, 2mL of toluene was then added thereto, and the reaction was placed in an oil bath at 90 ℃ for reaction for 11 hours. After the reaction was completed, the reaction solution was concentrated, and the volume ratio was 2: 1, using a mixed solution of petroleum ether and ethyl acetate as an eluent, and carrying out column chromatography separation to obtain a product 1- (diphenylphosphoryl) dodecyl diphenyl phosphonate with the yield of 45%.
1H NMR(500MHz,CDCl3):δ8.03-7.99(m,2H),7.62-7.53(m,3H),7.49-7.24(m,13H),7.17-7.08(m,5H),7.02(t,J＝7.7Hz,2H),6.30(dd,J1＝2.5Hz,J2＝10.4Hz,1H).
Although the preferred embodiments of the present invention have been described in detail, the present invention is not limited to the details of the embodiments, and various equivalent modifications can be made within the technical spirit of the present invention, and the scope of the present invention is also within the scope of the present invention. Meanwhile, the patent is funded by national science foundation (22001225) and Shandong province science foundation (ZR2020MB021), and is one of the research results of the funded projects.
Claims (7)
1. A preparation method of a biphosphonate with a P-O-C-P structure is characterized in that a compound containing carbonyl and a phosphorus reagent are used as initial raw materials, the compound containing carbonyl, the phosphorus reagent and the alkali are added according to a molar ratio of 1: 2-5: 0.1-0.5 in a nitrogen atmosphere under the catalysis of alkali, an organic solvent is added to enable the concentration of the phosphorus reagent to be 0.05-0.3mol/L, the reaction is carried out for 6-16 hours at a reaction temperature of 60-120 ℃, and then the biphosphonate with the P-O-C-P structure and a general structural formula I is prepared through column chromatography,
wherein R in the formula I1、R2Is aryl;
the carbonyl-containing compound is selected from any one of the following structural formulas II to V:
when the carbonyl-containing compound is selected from the structure II, R is selected from any one of C1-C8 linear alkyl, methoxymethyl, trifluoromethyl, pentafluoroethyl, isopropyl, isobutyl, phenyl, p-methylphenyl, p-methoxyphenyl, p-fluorophenyl and p-chlorophenyl;
when the carbonyl-containing compound is selected from the structural formula III, R is selected from alkyl or aryl;
when the compound containing carbonyl is selected from a structure formula IV, R is selected from trifluoromethyl, and R is selected from3Selected from methyl or ethyl;
when the carbonyl-containing compound is selected from a structural formula V, R is selected from aryl or n-undecyl.
2. The method according to claim 1, wherein the organic solvent is selected from the group consisting of toluene, acetonitrile, Tetrahydrofuran (THF), and 1, 4-dioxane.
3. The method according to claim 1, wherein the carbonyl group-containing compound is any one selected from acetic anhydride, propionic anhydride, butyric anhydride, hexanoic anhydride, methoxyacetic anhydride, trifluoroacetic anhydride, pentafluoropropionic anhydride, isovaleric anhydride, isobutyric anhydride, benzoic anhydride, 4-methylbenzoic anhydride, 4-methoxybenzoic anhydride, 4-fluorobenzoic anhydride, 4-chlorobenzoic anhydride, acetyl chloride, benzoyl chloride, ethyl trifluoroacetate, lauroyl peroxide, and benzoyl peroxide.
4. The method according to claim 1, wherein the phosphorus reagent is selected from the group consisting of phosphorus diphenyl oxide, phosphorus di (4-methylphenyl) oxide, phosphorus di (4-methoxyphenyl) oxide, phosphorus di (4-tert-butylphenyl) oxide, phosphorus di (4-fluorophenyl) oxide, phosphorus di (4-bromophenyl) oxide, phosphorus di (4-trifluoromethylphenyl) oxide, phosphorus di (3-methylphenyl) oxide, phosphorus di (3, 5-dimethylphenyl) oxide, and phosphorus di (2-naphthyl) oxide.
5. The method according to claim 1, wherein the base is selected from the group consisting of pyridine, 2, 6-dichloropyridine, DMAP (4-dimethylaminopyridine), DBU (1, 8-diazabicyclo [5.4.0] undec-7-ene), DABCO (triethylenediamine), sodium carbonate, sodium bicarbonate and potassium phosphate.
6. The production method according to claim 1, characterized in that the carbonyl group-containing compound: phosphorus reagent: the molar ratio of alkali fed is 1:3: 0.2.
7. The method according to claim 1, wherein the concentration of the phosphorus reagent is 0.1 mol/L.
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| KAIQIANG XU等: "Controllable Phosphorylation of Thioesters: Selective Synthesis of Aryl and Benzyl Phosphoryl Compounds", J. ORG. CHEM., vol. 85, pages 14653 - 14663 * |
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