CN110669070B - O-(二烷基次膦酰基)酮肟的合成方法 - Google Patents
O-(二烷基次膦酰基)酮肟的合成方法 Download PDFInfo
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- CN110669070B CN110669070B CN201911010242.8A CN201911010242A CN110669070B CN 110669070 B CN110669070 B CN 110669070B CN 201911010242 A CN201911010242 A CN 201911010242A CN 110669070 B CN110669070 B CN 110669070B
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- 238000001308 synthesis method Methods 0.000 title description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims abstract description 56
- 238000000034 method Methods 0.000 claims abstract description 4
- 238000005691 oxidative coupling reaction Methods 0.000 claims abstract description 4
- 239000007800 oxidant agent Substances 0.000 claims abstract description 3
- 230000001590 oxidative effect Effects 0.000 claims abstract description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 81
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 28
- 239000011630 iodine Substances 0.000 claims description 28
- 229910052740 iodine Inorganic materials 0.000 claims description 28
- YFPJFKYCVYXDJK-UHFFFAOYSA-N Diphenylphosphine oxide Chemical group C=1C=CC=CC=1[P+](=O)C1=CC=CC=C1 YFPJFKYCVYXDJK-UHFFFAOYSA-N 0.000 claims description 18
- 239000000126 substance Substances 0.000 claims description 12
- -1 5-fluoro-1-indenone oxime Chemical compound 0.000 claims description 9
- 230000002194 synthesizing effect Effects 0.000 claims description 3
- JHNRZXQVBKRYKN-VQHVLOKHSA-N (ne)-n-(1-phenylethylidene)hydroxylamine Chemical compound O\N=C(/C)C1=CC=CC=C1 JHNRZXQVBKRYKN-VQHVLOKHSA-N 0.000 claims description 2
- YPFOSEYKSLTSSF-UXBLZVDNSA-N (ne)-n-[1-(4-fluorophenyl)ethylidene]hydroxylamine Chemical compound O\N=C(/C)C1=CC=C(F)C=C1 YPFOSEYKSLTSSF-UXBLZVDNSA-N 0.000 claims description 2
- RCUXWEHXMOUJCX-FNORWQNLSA-N (ne)-n-[1-(furan-2-yl)ethylidene]hydroxylamine Chemical compound O\N=C(/C)C1=CC=CO1 RCUXWEHXMOUJCX-FNORWQNLSA-N 0.000 claims description 2
- HZCRFUPEBRNAAI-WAYWQWQTSA-N (nz)-n-(3-methylbutan-2-ylidene)hydroxylamine Chemical compound CC(C)C(\C)=N/O HZCRFUPEBRNAAI-WAYWQWQTSA-N 0.000 claims description 2
- BAYUSCHCCGXLAY-UHFFFAOYSA-N 1-(3-methoxyphenyl)ethanone Chemical compound COC1=CC=CC(C(C)=O)=C1 BAYUSCHCCGXLAY-UHFFFAOYSA-N 0.000 claims description 2
- HHAISVSEJFEWBZ-UHFFFAOYSA-N 1-[4-(trifluoromethyl)phenyl]ethanone Chemical compound CC(=O)C1=CC=C(C(F)(F)F)C=C1 HHAISVSEJFEWBZ-UHFFFAOYSA-N 0.000 claims description 2
- QDWOIMWUGPSJMU-UHFFFAOYSA-N 1-chloro-4-(4-chlorophenyl)phosphonoylbenzene Chemical compound C1=CC(Cl)=CC=C1P(=O)C1=CC=C(Cl)C=C1 QDWOIMWUGPSJMU-UHFFFAOYSA-N 0.000 claims description 2
- JNNKFUNOEOWVSD-UHFFFAOYSA-N 1-fluoro-3-(3-fluorophenyl)phosphonoylbenzene Chemical compound FC1=CC=CC(P(=O)C=2C=C(F)C=CC=2)=C1 JNNKFUNOEOWVSD-UHFFFAOYSA-N 0.000 claims description 2
- CCBDFSFCAHWFJF-UHFFFAOYSA-N 1-methoxy-3-(3-methoxyphenyl)phosphonoylbenzene Chemical compound COC1=CC=CC(P(=O)C=2C=C(OC)C=CC=2)=C1 CCBDFSFCAHWFJF-UHFFFAOYSA-N 0.000 claims description 2
- AWEYNESSDVPHQZ-UHFFFAOYSA-N C1CCCC1P(=O)C1CCCC1 Chemical compound C1CCCC1P(=O)C1CCCC1 AWEYNESSDVPHQZ-UHFFFAOYSA-N 0.000 claims description 2
- MWYXORYWUKRJEX-UHFFFAOYSA-N bis(2-methoxyphenyl)-oxophosphanium Chemical compound COC1=CC=CC=C1[P+](=O)C1=CC=CC=C1OC MWYXORYWUKRJEX-UHFFFAOYSA-N 0.000 claims 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 claims 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 claims description 2
- 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 claims description 2
- KXCHBSNEAXRGCM-UHFFFAOYSA-N n-(1-thiophen-3-ylethylidene)hydroxylamine Chemical compound ON=C(C)C=1C=CSC=1 KXCHBSNEAXRGCM-UHFFFAOYSA-N 0.000 claims description 2
- OFWZPQGMRGQECG-UHFFFAOYSA-N n-(2-fluoro-1-phenylethylidene)hydroxylamine Chemical compound ON=C(CF)C1=CC=CC=C1 OFWZPQGMRGQECG-UHFFFAOYSA-N 0.000 claims description 2
- YGNXYFLJZILPEK-UHFFFAOYSA-N n-cyclopentylidenehydroxylamine Chemical compound ON=C1CCCC1 YGNXYFLJZILPEK-UHFFFAOYSA-N 0.000 claims description 2
- FSPSELPMWGWDRY-UHFFFAOYSA-N m-Methylacetophenone Chemical compound CC(=O)C1=CC=CC(C)=C1 FSPSELPMWGWDRY-UHFFFAOYSA-N 0.000 claims 1
- JTOHKUYNGYXLJO-UHFFFAOYSA-N n-inden-1-ylidenehydroxylamine Chemical group C1=CC=C2C(=NO)C=CC2=C1 JTOHKUYNGYXLJO-UHFFFAOYSA-N 0.000 claims 1
- AUONHKJOIZSQGR-UHFFFAOYSA-N oxophosphane Chemical compound P=O AUONHKJOIZSQGR-UHFFFAOYSA-N 0.000 claims 1
- 239000002904 solvent Substances 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 32
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 239000000047 product Substances 0.000 abstract description 2
- 238000006237 Beckmann rearrangement reaction Methods 0.000 abstract 1
- 239000006227 byproduct Substances 0.000 abstract 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 abstract 1
- 239000003863 metallic catalyst Substances 0.000 abstract 1
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 156
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 62
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 52
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 26
- 239000012043 crude product Substances 0.000 description 26
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- 239000003208 petroleum Substances 0.000 description 26
- 238000010898 silica gel chromatography Methods 0.000 description 26
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 26
- 235000019345 sodium thiosulphate Nutrition 0.000 description 26
- 238000003756 stirring Methods 0.000 description 26
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- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 24
- 239000011734 sodium Substances 0.000 description 24
- ATEGUFMEFAGONB-KTKRTIGZSA-N (nz)-n-(2,3-dihydroinden-1-ylidene)hydroxylamine Chemical compound C1=CC=C2C(=N/O)\CCC2=C1 ATEGUFMEFAGONB-KTKRTIGZSA-N 0.000 description 8
- 150000002923 oximes Chemical group 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 5
- VWBYXJRDIQCSLW-UHFFFAOYSA-N O=[P](c1ccccc1)c1ccccc1 Chemical group O=[P](c1ccccc1)c1ccccc1 VWBYXJRDIQCSLW-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 2
- QPQGTZMAQRXCJW-UHFFFAOYSA-N [chloro(phenyl)phosphoryl]benzene Chemical compound C=1C=CC=CC=1P(=O)(Cl)C1=CC=CC=C1 QPQGTZMAQRXCJW-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000006053 organic reaction Methods 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 238000003383 Atherton-Todd reaction Methods 0.000 description 1
- AORZSDLQSDEAJF-UHFFFAOYSA-N CC(=NOP(=O)(C1=CC=CC=C1)C2=CC=CC=C2)CC3=CC(=CC=C3)OC Chemical compound CC(=NOP(=O)(C1=CC=CC=C1)C2=CC=CC=C2)CC3=CC(=CC=C3)OC AORZSDLQSDEAJF-UHFFFAOYSA-N 0.000 description 1
- 238000005684 Liebig rearrangement reaction Methods 0.000 description 1
- KYQXDMCIEQMAKZ-UHFFFAOYSA-N P(=O)(OC)(OC)OC.P(=O)(OC1=CC=CC=C1)(OC1=CC=CC=C1)O Chemical compound P(=O)(OC)(OC)OC.P(=O)(OC1=CC=CC=C1)(OC1=CC=CC=C1)O KYQXDMCIEQMAKZ-UHFFFAOYSA-N 0.000 description 1
- SCHRRICRQNJJKN-UHFFFAOYSA-N P.[O] Chemical compound P.[O] SCHRRICRQNJJKN-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- PXAJQJMDEXJWFB-UHFFFAOYSA-N acetone oxime Chemical compound CC(C)=NO PXAJQJMDEXJWFB-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 229940125681 anticonvulsant agent Drugs 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 229940121357 antivirals Drugs 0.000 description 1
- QGEXDLKDFKFMNP-UHFFFAOYSA-N bis(2-methoxyphenyl)phosphinic acid Chemical compound COC1=CC=CC=C1P(O)(=O)C1=CC=CC=C1OC QGEXDLKDFKFMNP-UHFFFAOYSA-N 0.000 description 1
- FMSREEOWTKNAQP-UHFFFAOYSA-N bis(3,5-dimethylphenyl)phosphinic acid Chemical compound CC1=CC(C)=CC(P(O)(=O)C=2C=C(C)C=C(C)C=2)=C1 FMSREEOWTKNAQP-UHFFFAOYSA-N 0.000 description 1
- QUCQPKNPPISEMG-UHFFFAOYSA-N bis(3-fluorophenyl)phosphinic acid Chemical compound C=1C=CC(F)=CC=1P(=O)(O)C1=CC=CC(F)=C1 QUCQPKNPPISEMG-UHFFFAOYSA-N 0.000 description 1
- RIPTXIMLLIHZCE-UHFFFAOYSA-N bis(3-methoxyphenyl)phosphinic acid Chemical compound COC1=CC=CC(P(O)(=O)C=2C=C(OC)C=CC=2)=C1 RIPTXIMLLIHZCE-UHFFFAOYSA-N 0.000 description 1
- PQTLSVRQJMZPSJ-UHFFFAOYSA-N bis(4-chlorophenyl)phosphinic acid Chemical compound C=1C=C(Cl)C=CC=1P(=O)(O)C1=CC=C(Cl)C=C1 PQTLSVRQJMZPSJ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- FKYMKKHQAGMHRY-UHFFFAOYSA-N bis(4-fluorophenyl)phosphinic acid Chemical compound C=1C=C(F)C=CC=1P(=O)(O)C1=CC=C(F)C=C1 FKYMKKHQAGMHRY-UHFFFAOYSA-N 0.000 description 1
- BFPBWJGVRNQWEK-UHFFFAOYSA-N bis(4-methoxyphenyl)phosphinic acid Chemical compound C1=CC(OC)=CC=C1P(O)(=O)C1=CC=C(OC)C=C1 BFPBWJGVRNQWEK-UHFFFAOYSA-N 0.000 description 1
- KLLICJFQHGANFI-UHFFFAOYSA-N bis(4-methylphenyl)phosphinic acid Chemical compound C1=CC(C)=CC=C1P(O)(=O)C1=CC=C(C)C=C1 KLLICJFQHGANFI-UHFFFAOYSA-N 0.000 description 1
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- PYFRLDVYGBCYLI-UHFFFAOYSA-N decyl dihydrogen phosphite Chemical compound CCCCCCCCCCOP(O)O PYFRLDVYGBCYLI-UHFFFAOYSA-N 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- LXCYSACZTOKNNS-UHFFFAOYSA-N diethoxy(oxo)phosphanium Chemical compound CCO[P+](=O)OCC LXCYSACZTOKNNS-UHFFFAOYSA-N 0.000 description 1
- 239000012039 electrophile Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
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- 125000005842 heteroatom Chemical group 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
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- OTVSUGXVPKEVLH-UHFFFAOYSA-N n-(4-methoxy-2,3-dihydroinden-1-ylidene)hydroxylamine Chemical compound COC1=CC=CC2=C1CCC2=NO OTVSUGXVPKEVLH-UHFFFAOYSA-N 0.000 description 1
- UQTIJEKCRQCDEK-UHFFFAOYSA-N n-(5-chloro-2,3-dihydroinden-1-ylidene)hydroxylamine Chemical compound ClC1=CC=C2C(=NO)CCC2=C1 UQTIJEKCRQCDEK-UHFFFAOYSA-N 0.000 description 1
- ZLWFPSSCVOCJAI-UHFFFAOYSA-N n-(5-fluoro-2,3-dihydroinden-1-ylidene)hydroxylamine Chemical compound FC1=CC=C2C(=NO)CCC2=C1 ZLWFPSSCVOCJAI-UHFFFAOYSA-N 0.000 description 1
- ROZVRQXOAGSIOW-UHFFFAOYSA-N n-(5-methoxy-2,3-dihydroinden-1-ylidene)hydroxylamine Chemical compound COC1=CC=C2C(=NO)CCC2=C1 ROZVRQXOAGSIOW-UHFFFAOYSA-N 0.000 description 1
- AAKSFBFMXXWCSH-UHFFFAOYSA-N n-(6-bromo-2,3-dihydroinden-1-ylidene)hydroxylamine Chemical compound C1=C(Br)C=C2C(=NO)CCC2=C1 AAKSFBFMXXWCSH-UHFFFAOYSA-N 0.000 description 1
- HNDWBTRBKZBCDC-UHFFFAOYSA-N n-[1-(3-methylphenyl)propan-2-ylidene]hydroxylamine Chemical compound ON=C(C)CC1=CC=CC(C)=C1 HNDWBTRBKZBCDC-UHFFFAOYSA-N 0.000 description 1
- VPCDQGACGWYTMC-UHFFFAOYSA-N nitrosyl chloride Chemical compound ClN=O VPCDQGACGWYTMC-UHFFFAOYSA-N 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 150000002894 organic compounds Chemical class 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
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- 230000002048 spasmolytic effect Effects 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
- C07F9/30—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
- C07F9/3294—Compounds containing the structure R2P(=X)-X-acyl, R2P(=X)-X-heteroatom, R2P(=X)-X-CN (X = O, S, Se)
-
- 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)
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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)
- Crystallography & Structural Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
O‑(二烷基次膦酰基)酮肟在药物和有机合成有着重要用途。本申请开发出一种新的酮肟与二烷基膦氧化物的氧化偶联方法。过氧化氢用作绿色氧化剂，分子碘用作非金属催化剂，该反应具有较高的原子经济性，且副产物仅是水。另外，该反应避免了贝克曼重排反应的发生，并且以高收率获得了26种O‑(二烷基次膦酰基)酮肟目标产物。
Description
技术领域
该专利涉及有机合成、药物合成、有机化工的研究领域，具体的方法就是从酮肟和二烷烃膦氧化合物进行氧化偶联一步合成O-(二烷基次膦酰基)酮肟类化合物的合成方法。
背景技术
近年来，越来越多的肟官能团被用于生物活性化合物和药物，如杀真菌剂，解痉剂，抗惊厥药和抗病毒药(Kleeman A, Engel J, Kutscher B, Reichert D (1999)Pharmaceutical substances, 3rd edn. Thieme, Stuttgart)。另外，肟的衍生物在有机反应中起重要作用，并且其中一些可以作为高活性前体参与有机反应。根据它们不同的活性表现形式，它们可以用作1,3-偶极子、亲电试剂、亲核试剂和羰基化合物的保护基等(Sandler SR, Karo W (1989) Organic functional group preparation. Academic Press, San Diego)。在农药领域，某些带有荧光肟的衍生物可用于检测农药和其他有机磷酸盐(Walton, I., Davis, M., Munro, L., Catalano, V. J., Cragg, P. J.,Huggins, M. T., & Wallace, K. J. (2012). Organic Letters, 14(11), 2686–2689)。因此，将反应性杂原子掺入肟链已成为科学家越来越关注的研究热点，特别是磷原子的引入具有相当大的应用潜力。在各种含磷有机化合物中，膦酸酯是聚合物科学和具有生物活性的化合物的关键组成部分(Wester, R. T., Chambers, R. J., Green, M. D., &Murphy, W. R. (1994). Bioorganic & Medicinal Chemistry Letters, 4(16), 2005–2010)。
由肟和有机磷试剂构建N-O-P键也引起了化学家的极大关注。1978年初期，Hudson直接用肟和氯二烷基膦氧化物取代，生成O-(二烷基次膦酰基)酮肟(Hudson, R. F., &Woodcock, R. C. (1978). Justus Liebigs Annalen Der Chemie, 1978(1), 176–187)。1981年，Harger分别使用了二苯羟胺和丙酮，丙酮肟和氯二苯膦氧化物。用相同的产物取代O-(二烷基次膦酰基)酮肟(Harger, M. J. P. (1981). Journal of the Chemical Society, Perkin Transactions 1, 3284)；1987年，索科洛夫用氯亚硝基化合物和二苯膦氧化物制得相应的二烷基膦氧化物酯(Sokolov, V. B., Ivanov, A. N., Epishina, T.A., & Martynov, I. V. (1987). Bulletin of the Academy of Sciences of the USSR Division of Chemical Science, 36(11), 2401–2402)。1990年，索科洛夫又通过与亚硝基氯化合物和活性更强的二苯基磷酸三甲基磷酸酯通过艾伦反应获得了相应的邻苯二甲酸二烷基phosph酯(Sokolov, V. B., Ivanov, A. N., Epishina, T. A., Goreva, T.V., & Martynov, I. V. (1990). Bulletin of the Academy of Sciences of the USSR Division of Chemical Science, 39(2), 413–414)；2007年，Wu用肟和亚磷酸二乙酯通过Atherton-Todd反应合成了肟磷酸酯(Wu, S. M.; Zhang, X. H. (2007). Journal of Chemical Research, 2007(3), 146–147)。2015年，Hashemi使用肟和亚磷酸三烷基酯在偶氮二异丙基二羧酸酯的作用下生产亚磷酸癸酯(Hashemi, S. A., & Khalili, G.(2015). Monatshefte Für Chemie - Chemical Monthly, 146(6), 965–968)。
尽管有许多关于O-(二烷基次膦酰基)酮肟的合成的报道，但是这些方法大多数都使用卤素取代的物质，例如氯二苯基氧化膦，氯亚硝基化合物等。对环境不友好，并增加了原材料成本。许多其他反应使用有毒的氯化烷烃，例如二氯乙烷，四氯化碳等(Zhu, J.-L.,Wu, S.-T., & Shie, J.-Y. (2014). The Journal of Organic Chemistry, 79(8),3623–3633)。在反应的另一部分中，使用了具有较高活性的有机前体，该反应必须在-78 oC下进行，这无疑大大增加了反应的难度(Russell, G. A., Ros, F., Hershberger, J., &Tashtoush, H. (1982). The Journal of Organic Chemistry, 47(8), 1480–1483)。
尽我们所知，未见与本申请相同的文献报道。
发明内容
本发明提供一种O-(二烷基次膦酰基)酮肟的合成方法。
本发明公开的O-(二烷基次膦酰基)酮肟的合成方法均一步完成，即在氧化剂存在下，碘单质催化酮肟和二烷基膦氧化合物发生氧化偶联反应一步合成O-(二烷基次膦酰基)酮肟。
结合下面的实施例,更详细地阐述本发明，但并不认为它们是对本发明范围的限制。
具体实施方式
实施例一
往烘干带磁力搅拌子的磨口试管里加入1-茚酮肟(0.5毫摩尔)、二苯基氧膦 (0.6毫摩尔)、碘单质(0.025毫摩尔)、30%的过氧化氢水溶液(0.6毫摩尔)、乙腈(2毫升)，最后用橡皮塞密封磨口试管。把该试管置于40℃下搅拌反应4小时。然后用硫代硫酸钠水溶液淬灭反应，用25毫升的乙酸乙酯萃取三次，合并有机相，用无水硫酸镁干燥。滤液经浓缩所得的粗产物用硅胶柱层析、以石油醚：乙酸乙酯=2:1洗脱得到白色固体O-(二苯基次膦酰基)-1-茚酮肟，产率88%。
1 (400 MHz, CDCl3) δ 7.83 (ddd, J = 12.2, 8.3, 1.4 Hz, 1H), 7.59 (d, J= 7.7 Hz, 1H), 7.51 – 7.44 (m, 1H), 7.40 (td, J = 7.3, 3.6 Hz, 1H), 7.34 –7.27 (m, 1H), 7.24 (d, J = 7.6 Hz, 1H), 7.13 (t, J = 7.4 Hz, 1H), 3.32 – 2.84(m, 1H).13C NMR (101 MHz, cdcl3) δ 149.48, 134.36, 132.22, 132.20, 132.10,132.00, 131.74, 131.40, 130.05, 128.48, 128.35, 127.03, 125.53, 123.15,77.33, 77.01, 76.69, 29.68, 28.35, 27.73.HRMS(ESI) calcd for C21H18NO2P [M+H]+348.1153, found: 348.1144; HRMS(ESI) calcd for C21H18NO2P [M+Na]+ 370.0972,found: 370.0948.Mp: 170-173 ºC.
实施例二
往烘干带磁力搅拌子的磨口试管里加入5-氟-1-茚酮肟(0.5毫摩尔)、二苯基氧膦(0.6毫摩尔)、碘单质(0.025毫摩尔)、30%的过氧化氢水溶液(0.6毫摩尔)、乙腈(2毫升)，最后用橡皮塞密封磨口试管。把该试管置于40℃下搅拌反应4小时。然后用硫代硫酸钠水溶液淬灭反应，用25毫升的乙酸乙酯萃取三次，合并有机相，用无水硫酸镁干燥。滤液经浓缩所得的粗产物用硅胶柱层析、以石油醚：乙酸乙酯=2:1洗脱得到白色固体O-(二苯基次膦酰基)-5氟-1-茚酮肟，产率90%。
1 (400 MHz, CDCl3) δ 7.89 (ddd, J = 12.3, 8.3, 1.4 Hz, 4H), 7.63 (dd,J = 8.6, 5.3 Hz, 1H), 7.58 – 7.52 (m, 2H), 7.51 – 7.40 (m, 4H), 6.99 (dd, J =8.7, 2.2 Hz, 1H), 6.92 (td, J = 8.8, 2.4 Hz, 1H), 3.21 – 3.13 (m, 2H), 3.11 –2.98 (m, 2H).13C NMR (101 MHz, CDCl3) δ 170.54, 170.42, 166.57, 164.06,152.06, 151.97, 132.31, 132.28, 132.14, 132.04, 131.40, 130.50, 130.04,128.55, 128.41, 124.93, 124.83, 115.27, 115.04, 112.45, 112.23, 28.42, 28.40,28.17.HRMS(ESI) calcd for C21H17FNO2P [M+H]+ 366.1059, found: 366.1066; HRMS(ESI) calcd for C21H17FNO2P [M+Na]+388.0878, found: 388.0851.Mp: 171-174 ºC.
实施例三
往烘干带磁力搅拌子的磨口试管里加入5-氯-1-茚酮肟(0.5毫摩尔)、二苯基氧膦(0.6毫摩尔)、碘单质(0.025毫摩尔)、30%的过氧化氢水溶液(0.6毫摩尔)、乙腈(2毫升)，最后用橡皮塞密封磨口试管。把该试管置于40℃下搅拌反应4小时。然后用硫代硫酸钠水溶液淬灭反应，用25毫升的乙酸乙酯萃取三次，合并有机相，用无水硫酸镁干燥。滤液经浓缩所得的粗产物用硅胶柱层析、以石油醚：乙酸乙酯=2:1洗脱得到白色固体O-(二苯基次膦酰基)-5氯-1-茚酮肟，产率87%。
1 (400 MHz, CDCl3) δ 7.90 – 7.76 (m, 4H), 7.56 – 7.44 (m, 3H), 7.40(tdd, J = 8.2, 3.5, 1.2 Hz, 4H), 7.24 (d, J = 1.1 Hz, 1H), 7.12 (dd, J = 8.3,1.9 Hz, 1H), 3.15 – 3.05 (m, 2H), 3.04 – 2.93 (m, 2H).13C NMR (101 MHz, cdcl3)δ 151.07, 137.87, 132.44, 132.42, 131.95, 131.85, 128.56, 128.43, 127.71,125.73, 123.98, 57.86, 28.14, 27.83, 18.06. HRMS (ESI) calcd for C21H17ClNO2P[M+H]+ 382.0763, found: 382.0770; HRMS (ESI) calcd for C21H17ClNO2P [M+Na]+404.0583, found: 404.0570.Mp: 158-161 ºC.
实施例四
往烘干带磁力搅拌子的磨口试管里加入6-溴-1-茚酮肟(0.5毫摩尔)、二苯基氧膦(0.6毫摩尔)、碘单质(0.025毫摩尔)、30%的过氧化氢水溶液(0.6毫摩尔)、乙腈(2毫升)，最后用橡皮塞密封磨口试管。把该试管置于40℃下搅拌反应4小时。然后用硫代硫酸钠水溶液淬灭反应，用25毫升的乙酸乙酯萃取三次，合并有机相，用无水硫酸镁干燥。滤液经浓缩所得的粗产物用硅胶柱层析、以石油醚：乙酸乙酯=2:1洗脱得到白色固体O-(二苯基次膦酰基)-6-溴-1-茚酮肟，产率84%。
1 (400 MHz, CDCl3) δ 7.96 – 7.83 (m, 4H), 7.61 (dd, J = 7.7, 0.6 Hz,1H), 7.58 – 7.52 (m, 3H), 7.47 (tdd, J = 8.2, 3.5, 1.2 Hz, 4H), 7.10 (t, J =7.8 Hz, 1H), 3.23 – 3.11 (m, 2H), 3.06 (dd, J = 10.7, 5.0 Hz, 2H).13C NMR (101MHz, cdcl3) δ 171.44, 171.32, 149.33, 136.24, 134.44, 132.34, 132.31, 132.07,131.97, 131.15, 129.79, 128.91, 128.53, 128.40, 121.97, 120.69, 77.32, 77.01,76.69, 29.91, 27.18.HRMS (ESI) calcd for C21H17BrNO2P [M+Na]+ 448.0078, found:448.0066.Mp: 180-183ºC.
实施例五
往烘干带磁力搅拌子的磨口试管里加入5-甲氧基-1-茚酮肟(0.5毫摩尔)、二苯基氧膦 (0.6毫摩尔)、碘单质(0.025毫摩尔)、30%的过氧化氢水溶液(0.6毫摩尔)、乙腈(2毫升)，最后用橡皮塞密封磨口试管。把该试管置于40℃下搅拌反应4小时。然后用硫代硫酸钠水溶液淬灭反应，用25毫升的乙酸乙酯萃取三次，合并有机相，用无水硫酸镁干燥。滤液经浓缩所得的粗产物用硅胶柱层析、以石油醚：乙酸乙酯=2:1洗脱得到白色固体O-(二苯基次膦酰基)-5-甲氧基-1-茚酮肟，产率89%。
1 (400 MHz, CDCl3) δ 7.90 (ddd, J = 12.2, 8.2, 1.3 Hz, 4H), 7.62 –7.50 (m, 3H), 7.49 – 7.40 (m, 4H), 6.85 – 6.64 (m, 2H), 3.80 (s, 3H), 3.14(dd, J = 11.7, 5.0 Hz, 2H), 3.03 (dd, J = 11.5, 5.3 Hz, 2H).13C NMR (101 MHz,cdcl3) δ 172.19, 158.92, 142.12, 132.39, 132.36, 131.92, 131.82, 128.56,128.43, 126.19, 120.83, 105.11, 57.78, 57.70, 55.52, 28.40, 27.52, 18.04,17.98.HRMS (ESI) calcd for C22H20NO3P [M+H]+ 378.1259, found: 378.1260; HRMS(ESI) calcd for C22H20NO3P [M+Na]+ 400.1078, found: 400.1068.Mp: 167-170 ºC.
实施例六
往烘干带磁力搅拌子的磨口试管里加入4-甲氧基-1-茚酮肟(0.5毫摩尔)、二苯基氧膦 (0.6毫摩尔)、碘单质(0.025毫摩尔)、30%的过氧化氢水溶液(0.6毫摩尔)、乙腈(2毫升)，最后用橡皮塞密封磨口试管。把该试管置于40℃下搅拌反应4小时。然后用硫代硫酸钠水溶液淬灭反应，用25毫升的乙酸乙酯萃取三次，合并有机相，用无水硫酸镁干燥。滤液经浓缩所得的粗产物用硅胶柱层析、以石油醚：乙酸乙酯=2:1洗脱得到白色固体O-(二苯基次膦酰基)-4-甲氧基-1-茚酮肟，产率83%。
1 (400 MHz, CDCl3) δ 7.87 – 7.76 (m, 4H), 7.54 – 7.43 (m, 3H), 7.43 –7.34 (m, 4H), 6.79 – 6.59 (m, 2H), 3.73 (s, 3H), 3.06 (dd, J = 11.9, 5.1 Hz,2H), 2.96 (dd, J = 11.6, 5.4 Hz, 2H).13C NMR (101 MHz, CDCl3) δ 162.98,151.87, 134.89, 132.20, 132.15, 132.05, 130.32, 128.50, 128.37, 124.37,114.60, 109.43, 55.47, 29.71, 29.34, 28.46, 28.24.HRMS (ESI) calcd forC22H20NO3P [M+H]+ 378.1259, found: 378.1260; HRMS (ESI) calcd for C22H20NO3P [M+Na]+ 400.1078, found: 400.1053.Mp: 124-127 ºC.
实施例七
往烘干带磁力搅拌子的磨口试管里加入苯乙酮肟(0.5毫摩尔)、二苯基氧膦 (0.6毫摩尔)、碘单质(0.025毫摩尔)、30%的过氧化氢水溶液(0.6毫摩尔)、乙腈(2毫升)，最后用橡皮塞密封磨口试管。把该试管置于40℃下搅拌反应4小时。然后用硫代硫酸钠水溶液淬灭反应，用25毫升的乙酸乙酯萃取三次，合并有机相，用无水硫酸镁干燥。滤液经浓缩所得的粗产物用硅胶柱层析、以石油醚：乙酸乙酯=2:1洗脱得到白色固体O-(二苯基次膦酰基)苯乙酮肟，产率91%。
1 (400 MHz, CDCl3) δ 7.96 – 7.86 (m, 4H), 7.61 – 7.52 (m, 4H), 7.51 –7.45 (m, 4H), 7.37 (d, J = 7.3 Hz, 1H), 7.32 (t, J = 7.5 Hz, 2H), 2.46 (s,3H).13C NMR (101 MHz, cdcl3) δ 163.78, 163.67, 134.54, 132.31, 132.28, 132.08,131.98, 131.22, 130.37, 129.87, 128.74, 128.53, 128.39, 126.85, 14.05.HRMS(ESI) calcd for C20H18NO2P [M+Na]+ 358.0972, found: 358.0954.Mp: 112-115 ºC.
实施例八
往烘干带磁力搅拌子的磨口试管里加入3-甲基苯乙酮肟(0.5毫摩尔)、二苯基氧膦 (0.6毫摩尔)、碘单质(0.025毫摩尔)、30%的过氧化氢水溶液(0.6毫摩尔)、乙腈(2毫升)，最后用橡皮塞密封磨口试管。把该试管置于40℃下搅拌反应4小时。然后用硫代硫酸钠水溶液淬灭反应，用25毫升的乙酸乙酯萃取三次，合并有机相，用无水硫酸镁干燥。滤液经浓缩所得的粗产物用硅胶柱层析、以石油醚：乙酸乙酯=2:1洗脱得到白色固体O-(二苯基次膦酰基)-3-甲基苯乙酮肟，产率93%。
1 (400 MHz, CDCl3) δ 7.90 (ddd, J = 12.3, 8.2, 1.3 Hz, 4H), 7.59 –7.51 (m, 2H), 7.51 – 7.40 (m, 4H), 7.24 (dd, J = 13.6, 5.6 Hz, 1H), 7.17 –6.99 (m, 2H), 6.92 (ddd, J = 8.2, 2.6, 0.9 Hz, 1H), 3.73 (s, 3H), 2.43 (s,3H).13C NMR (101 MHz, cdcl3) δ 172.29, 172.17, 149.61, 139.09, 139.06, 134.03,133.46, 133.35, 132.02, 129.55, 129.01, 128.87, 128.16, 127.14, 125.61,123.11, 28.35, 27.81.Mp: 160-163 ºC.
实施例九
往烘干带磁力搅拌子的磨口试管里加入3-甲氧基苯乙酮肟(0.5毫摩尔)、二苯基氧膦 (0.6毫摩尔)、碘单质(0.025毫摩尔)、30%的过氧化氢水溶液(0.6毫摩尔)、乙腈(2毫升)，最后用橡皮塞密封磨口试管。把该试管置于40℃下搅拌反应4小时。然后用硫代硫酸钠水溶液淬灭反应，用25毫升的乙酸乙酯萃取三次，合并有机相，用无水硫酸镁干燥。滤液经浓缩所得的粗产物用硅胶柱层析、以石油醚：乙酸乙酯=2:1洗脱得到白色固体O-(二苯基次膦酰基)-3-甲氧基苯乙酮肟，产率85%。
1 (400 MHz, CDCl3) δ 7.89 – 7.75 (m, 4H), 7.54 – 7.44 (m, 2H), 7.43 –7.36 (m, 4H), 7.17 (dd, J = 12.9, 4.9 Hz, 1H), 7.11 – 7.05 (m, 1H), 7.05 –7.01 (m, 1H), 6.84 (ddd, J = 8.2, 2.6, 0.9 Hz, 1H), 3.69 (s, 3H), 2.38 (s,3H).13C NMR (101 MHz, cdcl3) δ 163.59, 163.48, 159.40, 135.91, 132.30, 132.27,132.09, 131.99, 131.23, 129.87, 129.39, 128.50, 128.37, 119.38, 116.22,112.03, 55.25, 29.68, 14.14.HRMS (ESI) calcd for HRMS (ESI) C21H20NO3P [M+Na]+388.1078, found: 388.1066.Mp: 156-159 ºC.
实施例十
往烘干带磁力搅拌子的磨口试管里加入4-氟苯乙酮肟(0.5毫摩尔)、二苯基氧膦(0.6毫摩尔)、碘单质(0.025毫摩尔)、30%的过氧化氢水溶液(0.6毫摩尔)、乙腈(2毫升)，最后用橡皮塞密封磨口试管。把该试管置于40℃下搅拌反应4小时。然后用硫代硫酸钠水溶液淬灭反应，用25毫升的乙酸乙酯萃取三次，合并有机相，用无水硫酸镁干燥。滤液经浓缩所得的粗产物用硅胶柱层析、以石油醚：乙酸乙酯=2:1洗脱得到黄色固体O-(二苯基次膦酰基)-4-氟苯乙酮肟，产率90%。
1 (400 MHz, CDCl3) δ 7.99 – 7.84 (m, 4H), 7.64 – 7.52 (m, 4H), 7.51 –7.41 (m, 4H), 6.99 (t, J = 8.7 Hz, 2H), 2.43 (s, 3H).1H NMR (400 MHz, CDCl3) δ7.92, 7.92, 7.91, 7.90, 7.90, 7.89, 7.89, 7.88, 7.88, 7.87, 7.87, 7.86, 7.58,7.58, 7.57, 7.57, 7.56, 7.55, 7.55, 7.55, 7.54, 7.54, 7.53, 7.50, 7.49, 7.49,7.48, 7.48, 7.47, 7.46, 7.46, 7.46, 7.45, 7.02, 6.99, 6.97, 2.43.HRMS (ESI)calcd for C20H17FNO2P [M+H]+ 354.1059, found: 354.1069; HRMS (ESI) calcd forC20H17FNO2P [M+Na]+ 376.0878, found: 376.0876.Mp: 120-123 ºC.
实施例十一
往烘干带磁力搅拌子的磨口试管里加入2-氟苯乙酮肟(0.5毫摩尔)、二苯基氧膦(0.6毫摩尔)、碘单质(0.025毫摩尔)、30%的过氧化氢水溶液(0.6毫摩尔)、乙腈(2毫升)，最后用橡皮塞密封磨口试管。把该试管置于40℃下搅拌反应4小时。然后用硫代硫酸钠水溶液淬灭反应，用25毫升的乙酸乙酯萃取三次，合并有机相，用无水硫酸镁干燥。滤液经浓缩所得的粗产物用硅胶柱层析、以石油醚：乙酸乙酯=2:1洗脱得到黄色固体O-(二苯基次膦酰基)-2-氟苯乙酮肟，产率80%。
1 (400 MHz, CDCl3) δ 7.92, 7.92, 7.92, 7.91, 7.90, 7.90, 7.89, 7.89,7.89, 7.88, 7.87, 7.87, 7.57, 7.56, 7.55, 7.54, 7.53, 7.53, 7.50, 7.49, 7.48,7.48, 7.47, 7.47, 7.46, 7.46, 7.45, 7.45, 7.38, 7.38, 7.36, 7.36, 7.35, 7.34,7.34, 7.33, 7.32, 7.32, 7.31, 7.31, 7.07, 7.07, 7.05, 7.05, 7.04, 7.04, 7.03,7.02, 2.47, 2.46.13C NMR (101 MHz, cdcl3) δ 132.35, 132.33, 132.07, 131.97,131.79, 131.71, 131.12, 130.11, 130.08, 129.76, 128.54, 128.41, 124.17,124.13, 116.19, 115.97, 29.68, 16.72, 16.67.HRMS (ESI) calcd for C20H17FNO2P [M+H]+ 354.1059, found: 354.1076; HRMS (ESI) calcd for C20H17FNO2P [M+Na]+376.0878, found: 376.0872.Mp: 104-107 ºC.
实施例十二
往烘干带磁力搅拌子的磨口试管里加入4-三氟甲基苯乙酮肟(0.5毫摩尔)、二苯基氧膦 (0.6毫摩尔)、碘单质(0.025毫摩尔)、30%的过氧化氢水溶液(0.6毫摩尔)、乙腈(2毫升)，最后用橡皮塞密封磨口试管。把该试管置于40℃下搅拌反应4小时。然后用硫代硫酸钠水溶液淬灭反应，用25毫升的乙酸乙酯萃取三次，合并有机相，用无水硫酸镁干燥。滤液经浓缩所得的粗产物用硅胶柱层析、以石油醚：乙酸乙酯=2:1洗脱得到白色固体O-(二苯基次膦酰基)-4-三氟甲基苯乙酮肟，产率81%。
1 (400 MHz, CDCl3) δ 7.98 – 7.84 (m, 4H), 7.69 (d, J = 8.2 Hz, 2H),7.56 (dd, J = 11.2, 5.0 Hz, 4H), 7.49 (td, J = 7.4, 3.6 Hz, 4H), 2.48 (s,3H).13C NMR (101 MHz, CDCl3) δ 162.72, 162.60, 138.00, 132.52, 132.49, 132.27,132.09, 131.99, 131.94, 131.62, 130.98, 129.62, 128.64, 128.51, 127.25,125.46, 125.43, 125.39, 125.35, 125.14, 122.43, 119.72, 29.70, 13.99.HRMS(ESI) calcd for C21H17F3NO2P [M+H]+ 404.1027, found: 404.1047; HRMS (ESI) calcdfor C21H17F3NO2P [M+Na]+ 426.0846, found: 426.0848.Mp: 115-118 ºC.
实施例十三
往烘干带磁力搅拌子的磨口试管里加入3-甲基-2-丁酮肟(0.5毫摩尔)、二苯基氧膦 (0.6毫摩尔)、碘单质(0.025毫摩尔)、30%的过氧化氢水溶液(0.6毫摩尔)、乙腈(2毫升)，最后用橡皮塞密封磨口试管。把该试管置于40℃下搅拌反应4小时。然后用硫代硫酸钠水溶液淬灭反应，用25毫升的乙酸乙酯萃取三次，合并有机相，用无水硫酸镁干燥。滤液经浓缩所得的粗产物用硅胶柱层析、以石油醚：乙酸乙酯=2:1洗脱得到黄色粘稠液体O-(二苯基次膦酰基)-3-甲基-2-丁酮肟，产率86%。
1 (400 MHz, CDCl3) δ 7.90 – 7.79 (m, 4H), 7.51 (dq, J = 8.9, 1.4 Hz,2H), 7.48 – 7.40 (m, 4H), 1.99 (s, 3H), 1.04 (d, J = 6.9 Hz, 6H).13C NMR (101MHz, cdcl3) δ 171.40, 171.29, 132.13, 132.09, 132.06, 131.98, 131.94, 131.88,131.84, 131.54, 130.18, 128.47, 128.39, 128.34, 128.26, 34.23, 27.59, 19.47,18.88, 15.43, 12.23.HRMS (ESI) calcd for C17H20NO2P [M+H]+ 302.1309, found:302.1299; HRMS (ESI) calcd for C17H20NO2P [M+Na]+ 324.1129, found: 324.1116.
实施例十四
往烘干带磁力搅拌子的磨口试管里加入环戊酮肟(0.5毫摩尔)、二苯基氧膦 (0.6毫摩尔)、碘单质(0.025毫摩尔)、30%的过氧化氢水溶液(0.6毫摩尔)、乙腈(2毫升)，最后用橡皮塞密封磨口试管。把该试管置于40℃下搅拌反应4小时。然后用硫代硫酸钠水溶液淬灭反应，用25毫升的乙酸乙酯萃取三次，合并有机相，用无水硫酸镁干燥。滤液经浓缩所得的粗产物用硅胶柱层析、以石油醚：乙酸乙酯=2:1洗脱得到黑色固体O-(二苯基次膦酰基)环戊酮肟，产率63%。
1 (400 MHz, CDCl3) δ 7.85 (ddd, J = 12.2, 8.3, 1.4 Hz, 4H), 7.56 –7.49 (m, 2H), 7.49 – 7.41 (m, 4H), 2.67 (t, J = 7.4 Hz, 2H), 2.44 (t, J = 6.6Hz, 2H), 1.86 – 1.68 (m, 4H).13C NMR (101 MHz, cdcl3) δ 176.85, 176.74,132.15, 132.13, 131.98, 131.89, 131.53, 130.17, 128.48, 128.35, 31.36, 29.45,25.33, 24.35.HRMS (ESI) calcd for C17H18NO2P [M+H]+ 300.1153, found: 300.1143;HRMS (ESI) calcd for C17H18NO2P [M+Na]+ 322.0972, found: 322.0947.Mp: 138-141 ºC.
实施例十五
往烘干带磁力搅拌子的磨口试管里加入3-乙酰基噻吩肟(0.5毫摩尔)、二苯基氧膦 (0.6毫摩尔)、碘单质(0.025毫摩尔)、30%的过氧化氢水溶液(0.6毫摩尔)、乙腈(2毫升)，最后用橡皮塞密封磨口试管。把该试管置于40℃下搅拌反应4小时。然后用硫代硫酸钠水溶液淬灭反应，用25毫升的乙酸乙酯萃取三次，合并有机相，用无水硫酸镁干燥。滤液经浓缩所得的粗产物用硅胶柱层析、以石油醚：乙酸乙酯=2:1洗脱得到白色固体O-(二苯基次膦酰基)-3-乙酰基噻吩肟，产率83%。
1 (400 MHz, CDCl3) δ 7.94 – 7.82 (m, 4H), 7.54 (tq, J = 4.3, 1.4 Hz,3H), 7.47 (tdd, J = 8.3, 3.5, 1.3 Hz, 4H), 7.32 (dd, J = 5.1, 1.3 Hz, 1H),7.22 (dd, J = 5.1, 2.9 Hz, 1H), 2.43 (s, 3H).13C NMR (101 MHz, cdcl3) δ159.50, 159.38, 136.56, 132.29, 132.27, 132.07, 131.97, 131.20, 129.85,128.50, 128.37, 126.27, 126.12, 125.63, 29.68, 14.20.HRMS (ESI) calcd forC18H16NO2PS [M+H]+ 342.0717, found: 342.0715; HRMS (ESI) calcd for C18H16NO2PS [M+Na]+ 364.0537, found: 364.0529.Mp: 127-130 ºC.
实施例十六
往烘干带磁力搅拌子的磨口试管里加入2-乙酰基呋喃肟(0.5毫摩尔)、二苯基氧膦 (0.6毫摩尔)、碘单质(0.025毫摩尔)、30%的过氧化氢水溶液(0.6毫摩尔)、乙腈(2毫升)，最后用橡皮塞密封磨口试管。把该试管置于40℃下搅拌反应4小时。然后用硫代硫酸钠水溶液淬灭反应，用25毫升的乙酸乙酯萃取三次，合并有机相，用无水硫酸镁干燥。滤液经浓缩所得的粗产物用硅胶柱层析、以石油醚：乙酸乙酯=2:1洗脱得到白色固体O-(二苯基次膦酰基)-2-乙酰基呋喃肟，产率84%。
1 (400 MHz, CDCl3) δ 7.96 – 7.83 (m, 4H), 7.61 – 7.53 (m, 2H), 7.53 –7.39 (m, 5H), 7.34 (d, J = 3.5 Hz, 1H), 6.51 (dd, J = 3.6, 1.8 Hz, 1H), 2.29(s, 3H).13C NMR (101 MHz, cdcl3) δ 151.95, 144.84, 143.79, 132.40, 132.37,132.08, 131.97, 131.00, 129.65, 128.62, 128.48, 119.73, 112.50, 17.49.HRMS(ESI) calcd for C18H16NO3P [M+Na]+ 348.0765, found: 348.0743.Mp: 118-121 ºC.
实施例十七
往烘干带磁力搅拌子的磨口试管里加入1-茚酮肟(0.5毫摩尔)、双(3-氟苯基)氧膦(0.6毫摩尔)、碘单质(0.025毫摩尔)、30%的过氧化氢水溶液(0.6毫摩尔)、乙腈(2毫升)，最后用橡皮塞密封磨口试管。把该试管置于40℃下搅拌反应4小时。然后用硫代硫酸钠水溶液淬灭反应，用25毫升的乙酸乙酯萃取三次，合并有机相，用无水硫酸镁干燥。滤液经浓缩所得的粗产物用硅胶柱层析、以石油醚：乙酸乙酯=2:1洗脱得到白色固体O-(双(3-氟苯基)次膦酰基)-1-茚酮肟，产率82%。
1 (400 MHz, CDCl3) δ 7.68 (ddd, J = 8.7, 7.6, 3.8 Hz, 3H), 7.63 – 7.55(m, 2H), 7.53 – 7.43 (m, 2H), 7.40 (td, J = 7.6, 1.1 Hz, 1H), 7.34 (d, J =7.6 Hz, 1H), 7.28 (d, J = 2.6 Hz, 1H), 7.26 – 7.20 (m, 2H), 3.20 – 3.14 (m,2H), 3.11 (dd, J = 7.3, 3.6 Hz, 2H).13C NMR (101 MHz, cdcl3) δ 172.44, 172.32,149.66, 133.99, 132.04, 130.69, 130.61, 130.53, 130.46, 127.86, 127.83,127.77, 127.74, 127.14, 125.61, 123.15, 119.82, 119.79, 119.61, 119.58,119.01, 118.90, 118.79, 118.68, 28.35, 27.84.
HRMS (ESI) calcd for C21H16F2NO2P [M+H]+ 384.0965, found: 384.0971;HRMS (ESI) calcd for C21H16F2NO2P [M+Na]+ 406.0784, found: 406.0766.Mp: 177-180ºC.
实施例十八
往烘干带磁力搅拌子的磨口试管里加入1-茚酮肟(0.5毫摩尔)、双(4-氟苯基)氧膦(0.6毫摩尔)、碘单质(0.025毫摩尔)、30%的过氧化氢水溶液(0.6毫摩尔)、乙腈(2毫升)，最后用橡皮塞密封磨口试管。把该试管置于40℃下搅拌反应4小时。然后用硫代硫酸钠水溶液淬灭反应，用25毫升的乙酸乙酯萃取三次，合并有机相，用无水硫酸镁干燥。滤液经浓缩所得的粗产物用硅胶柱层析、以石油醚：乙酸乙酯=2:1洗脱得到白色固体O-(双(4-氟苯基)次膦酰基)-1-茚酮肟，产率85%。
1 (400 MHz, CDCl3) δ 7.81 (dd, J = 11.9, 8.6 Hz, 4H), 7.64 (d, J = 7.8Hz, 1H), 7.46 (dd, J = 8.6, 2.9 Hz, 4H), 7.43 – 7.37 (m, 1H), 7.33 (d, J =7.6 Hz, 1H), 7.22 (t, J = 7.1 Hz, 1H), 3.17 – 3.11 (m, 2H), 3.09 (dd, J =9.5, 3.6 Hz, 2H).13C NMR (101 MHz, cdcl3) δ 149.57, 134.68, 134.59, 134.56,134.47, 131.95, 127.11, 125.60, 123.08, 116.10, 115.96, 115.89, 115.75,28.34, 27.78.HRMS (ESI) calcd for C21H16F2NO2P [M+H]+ 384.0965, found:384.0971; HRMS (ESI) calcd for C21H16F2NO2P [M+Na]+ 406.0784, found:406.0772.Mp: 170-173 ºC.
实施例十九
往烘干带磁力搅拌子的磨口试管里加入1-茚酮肟(0.5毫摩尔)、双(4-氯苯基)氧膦(0.6毫摩尔)、碘单质(0.025毫摩尔)、30%的过氧化氢水溶液(0.6毫摩尔)、乙腈(2毫升)，最后用橡皮塞密封磨口试管。把该试管置于40℃下搅拌反应4小时。然后用硫代硫酸钠水溶液淬灭反应，用25毫升的乙酸乙酯萃取三次，合并有机相，用无水硫酸镁干燥。滤液经浓缩所得的粗产物用硅胶柱层析、以石油醚：乙酸乙酯=2:1洗脱得到白色固体O-(双(4-氯苯基)次膦酰基)-1-茚酮肟，产率83%。
1 (400 MHz, CDCl3) δ 7.86 – 7.76 (m, 4H), 7.64 (d, J = 7.8 Hz, 1H),7.46 (dd, J = 8.6, 2.9 Hz, 4H), 7.40 (td, J = 7.6, 1.1 Hz, 1H), 7.33 (d, J =7.6 Hz, 1H), 7.23 (t, J = 7.5 Hz, 1H), 3.16 – 3.11 (m, 2H), 3.09 (dd, J =9.5, 3.6 Hz, 2H).HRMS (ESI) calcd for C21H16Cl2NO4P [M+H]+ 416.0374, found:416.0375; HRMS (ESI) calcd for C21H16Cl2NO4P [M+Na]+ 438.0193, found:438.0178.Mp: 161-164 ºC.
实施例二十
往烘干带磁力搅拌子的磨口试管里加入1-茚酮肟(0.5毫摩尔)、双(4-甲氧基苯基)氧膦(0.6毫摩尔)、碘单质(0.025毫摩尔)、30%的过氧化氢水溶液(0.6毫摩尔)、乙腈(2毫升)，最后用橡皮塞密封磨口试管。把该试管置于40℃下搅拌反应4小时。然后用硫代硫酸钠水溶液淬灭反应，用25毫升的乙酸乙酯萃取三次，合并有机相，用无水硫酸镁干燥。滤液经浓缩所得的粗产物用硅胶柱层析、以石油醚：乙酸乙酯=2:1洗脱得到白色固体O-(双(4-甲氧基苯基)次膦酰基)-1-茚酮肟，产率87%。
1 (400 MHz, CDCl3) δ 7.77 (dd, J = 12.1, 8.1 Hz, 4H), 7.67 (d, J = 7.8Hz, 1H), 7.37 (t, J = 7.4 Hz, 1H), 7.31 (d, J = 7.6 Hz, 1H), 7.26 (dd, J =7.8, 3.3 Hz, 4H), 7.20 (t, J = 7.4 Hz, 1H), 3.16 – 3.10 (m, 2H), 3.09 – 3.04(m, 2H), 2.39 (s, 6H).13C NMR (101 MHz, CDCl3) δ 171.44, 171.32, 162.64,162.61, 149.45, 134.58, 134.00, 133.89, 131.66, 127.03, 125.55, 123.17,123.14, 121.74, 114.04, 113.90, 55.32, 29.71, 28.38, 27.71.HRMS (ESI) calcdfor C23H22NO4P [M+H]+ 408.1364, found: 408.1368; HRMS (ESI) calcd for C23H22NO4P[M+Na]+ 430.1184, found: 430.1173.Mp: 146-149 ºC.
实施例二十一
往烘干带磁力搅拌子的磨口试管里加入1-茚酮肟(0.5毫摩尔)、双(3-甲氧基苯基)氧膦(0.6毫摩尔)、碘单质(0.025毫摩尔)、30%的过氧化氢水溶液(0.6毫摩尔)、乙腈(2毫升)，最后用橡皮塞密封磨口试管。把该试管置于40℃下搅拌反应4小时。然后用硫代硫酸钠水溶液淬灭反应，用25毫升的乙酸乙酯萃取三次，合并有机相，用无水硫酸镁干燥。滤液经浓缩所得的粗产物用硅胶柱层析、以石油醚：乙酸乙酯=2:1洗脱得到白色固体O-(双(3-甲氧基苯基)次膦酰基)-1-茚酮肟，产率81%。
1 (400 MHz, CDCl3) δ 7.68 (d, J = 7.8 Hz, 1H), 7.49 (dd, J = 2.6, 1.1Hz, 1H), 7.47 – 7.41 (m, 2H), 7.42 – 7.33 (m, 4H), 7.31 (d, J = 7.6 Hz, 1H),7.20 (t, J = 7.8 Hz, 1H), 7.11 – 7.01 (m, 2H), 3.82 (s, 6H), 3.17 – 3.10 (m,2H), 3.10 – 3.01 (m, 2H).13C NMR (101 MHz, cdcl3) δ 171.85, 171.73, 159.46,159.29, 149.50, 134.31, 132.53, 131.77, 131.18, 129.74, 129.58, 127.04,125.54, 124.26, 124.16, 123.16, 118.52, 118.49, 116.84, 116.73, 55.43, 29.68,28.35, 27.76.HRMS (ESI) calcd for C23H22NO4P [M+H]+ 408.1364, found: 408.1378;HRMS (ESI) calcd for C23H22NO4P [M+Na]+ 430.1184, found: 430.1171.Mp: 107-110 ºC.
实施例二十二
往烘干带磁力搅拌子的磨口试管里加入1-茚酮肟(0.5毫摩尔)、双(2-甲氧基苯基)氧膦(0.6毫摩尔)、碘单质(0.025毫摩尔)、30%的过氧化氢水溶液(0.6毫摩尔)、乙腈(2毫升)，最后用橡皮塞密封磨口试管。把该试管置于40℃下搅拌反应4小时。然后用硫代硫酸钠水溶液淬灭反应，用25毫升的乙酸乙酯萃取三次，合并有机相，用无水硫酸镁干燥。滤液经浓缩所得的粗产物用硅胶柱层析、以石油醚：乙酸乙酯=2:1洗脱得到白色固体O-(双(2-甲氧基苯基)次膦酰基)-1-茚酮肟，产率76%。
1 (400 MHz, CDCl3) δ 8.02 (ddd, J = 13.7, 7.6, 1.7 Hz, 2H), 7.67 (d, J= 7.7 Hz, 1H), 7.54 – 7.44 (m, 2H), 7.40 – 7.28 (m, 2H), 7.19 (t, J = 7.4 Hz,1H), 7.06 (td, J = 7.8, 3.0 Hz, 2H), 6.85 (dd, J = 8.1, 6.4 Hz, 2H), 3.61 (s,6H), 3.25 – 3.13 (m, 2H), 3.11 – 3.01 (m, 2H).13C NMR (101 MHz, cdcl3) δ161.18, 161.14, 149.26, 134.75, 134.69, 133.63, 133.61, 131.37, 126.92,125.42, 123.19, 120.61, 120.31, 120.18, 119.22, 111.27, 111.19, 55.64, 28.37,27.57.HRMS (ESI) calcd for C23H22NO4P [M+H]+ 408.1364, found: 408.1372; HRMS(ESI) calcd for C23H22NO4P [M+Na]+ 430.1184, found: 430.1171.Mp: 156-159 ºC。
实施例二十三
往烘干带磁力搅拌子的磨口试管里加入1-茚酮肟(0.5毫摩尔)、双(4-甲基苯基)氧膦(0.6毫摩尔)、碘单质(0.025毫摩尔)、30%的过氧化氢水溶液(0.6毫摩尔)、乙腈(2毫升)，最后用橡皮塞密封磨口试管。把该试管置于40℃下搅拌反应4小时。然后用硫代硫酸钠水溶液淬灭反应，用25毫升的乙酸乙酯萃取三次，合并有机相，用无水硫酸镁干燥。滤液经浓缩所得的粗产物用硅胶柱层析、以石油醚：乙酸乙酯=2:1洗脱得到白色固体O-(双(4-甲基苯基)次膦酰基)-1-茚酮肟，产率81%。
1 (400 MHz, CDCl3) δ 7.77 (dd, J = 12.1, 8.1 Hz, 4H), 7.67 (d, J = 7.8Hz, 1H), 7.37 (t, J = 7.4 Hz, 1H), 7.31 (d, J = 7.6 Hz, 1H), 7.26 (dd, J =7.8, 3.3 Hz, 4H), 7.20 (t, J = 7.4 Hz, 1H), 3.16 – 3.10 (m, 2H), 3.09 – 3.04(m, 2H), 2.39 (s, 6H).13C NMR (101 MHz, cdcl3) δ 171.36, 149.41, 142.63,142.60, 132.08, 131.98, 131.62, 129.19, 129.06, 128.39, 127.01, 126.97,125.49, 123.16, 28.35, 27.68, 21.67, 21.66。
实施例二十四
往烘干带磁力搅拌子的磨口试管里加入1-茚酮肟(0.5毫摩尔)、双(3,5-二甲基苯基)氧膦(0.6毫摩尔)、碘单质(0.025毫摩尔)、30%的过氧化氢水溶液(0.6毫摩尔)、乙腈(2毫升)，最后用橡皮塞密封磨口试管。把该试管置于40℃下搅拌反应4小时。然后用硫代硫酸钠水溶液淬灭反应，用25毫升的乙酸乙酯萃取三次，合并有机相，用无水硫酸镁干燥。滤液经浓缩所得的粗产物用硅胶柱层析、以石油醚：乙酸乙酯=2:1洗脱得到白色固体O-(双(3,5-二甲基苯基)次膦酰基)-1-茚酮肟，产率72%。
1 (400 MHz, CDCl3) δ 7.68 (d, J = 7.7 Hz, 1H), 7.51 (d, J = 12.5 Hz,4H), 7.39 – 7.33 (m, 1H), 7.31 (d, J = 7.5 Hz, 1H), 7.20 (t, J = 7.5 Hz, 1H),7.15 (s, 2H), 3.19 – 3.11 (m, 2H), 3.11 – 3.00 (m, 2H), 2.34 (s, 12H).13C NMR(101 MHz, cdcl3) δ 171.65, 171.52, 149.44, 138.09, 137.95, 134.52, 133.96,133.93, 131.61, 131.19, 129.85, 129.62, 129.52, 126.96, 125.49, 123.22,29.68, 28.36, 27.77, 21.32, 21.31.HRMS (ESI) calcd for C25H26NO2P [M+H]+404.1779, found: 404.1790; HRMS (ESI) calcd for C25H26NO2P [M+Na]+ 426.1598,found: 426.1588.Mp: 141-144 ºC。
实施例二十五
往烘干带磁力搅拌子的磨口试管里加入1-茚酮肟(0.5毫摩尔)、二噻吩基氧膦(0.6毫摩尔)、碘单质(0.025毫摩尔)、30%的过氧化氢水溶液(0.6毫摩尔)、乙腈(2毫升)，最后用橡皮塞密封磨口试管。把该试管置于40℃下搅拌反应4小时。然后用硫代硫酸钠水溶液淬灭反应，用25毫升的乙酸乙酯萃取三次，合并有机相，用无水硫酸镁干燥。滤液经浓缩所得的粗产物用硅胶柱层析、以石油醚：乙酸乙酯=2:1洗脱得到白色固体O-(二噻吩基次膦酰基)-1-茚酮肟，产率75%。
1 (400 MHz, CDCl3) δ 7.86 – 7.75 (m, 3H), 7.73 (td, J = 4.9, 1.1 Hz,2H), 7.41 (td, J = 7.6, 1.1 Hz, 1H), 7.34 (d, J = 7.6 Hz, 1H), 7.29 – 7.24(m, 1H), 7.22 – 7.14 (m, 2H), 3.16 – 3.11 (m, 2H), 3.08 (dd, J = 9.2, 3.9 Hz,2H).13C NMR (101 MHz, cdcl3) δ 149.74, 137.27, 137.15, 134.15, 134.09, 131.95,128.01, 127.85, 127.15, 125.64, 123.11, 28.39, 27.78.HRMS (ESI) calcd forC17H14NO2PS2 [M+H]+ 360.0281, found: 360.0275; HRMS (ESI) calcd for C17H14NO2PS2[M+Na]+ 382.0101, found: 382.0081.Mp: 156-159 ºC。
实施例二十六
往烘干带磁力搅拌子的磨口试管里加入1-茚酮肟(0.5毫摩尔)、二环戊基氧膦(0.6毫摩尔)、碘单质(0.025毫摩尔)、30%的过氧化氢水溶液(0.6毫摩尔)、乙腈(2毫升)，最后用橡皮塞密封磨口试管。把该试管置于40℃下搅拌反应4小时。然后用硫代硫酸钠水溶液淬灭反应，用25毫升的乙酸乙酯萃取三次，合并有机相，用无水硫酸镁干燥。滤液经浓缩所得的粗产物用硅胶柱层析、以石油醚：乙酸乙酯=2:1洗脱得到白色固体O-(二环戊基次膦酰基)-1-茚酮肟，产率79%。
1 (400 MHz, CDCl3) δ 7.72 (d, J = 7.7 Hz, 1H), 7.44 – 7.37 (m, 1H),7.34 (d, J = 7.5 Hz, 1H), 7.31 – 7.15 (m, 1H), 3.13 – 3.05 (m, 2H), 3.04 –2.92 (m, 2H), 2.48 – 2.33 (m, 2H), 2.04 – 1.86 (m, 8H), 1.83 – 1.68 (m, 4H),1.67 – 1.53 (m, 4H).13C NMR (101 MHz, cdcl3) δ 170.18, 170.07, 149.32, 134.82,131.46, 127.05, 125.66, 122.43, 36.83, 35.95, 28.36, 27.18, 26.88, 26.70,26.68, 26.62, 26.51, 26.31, 26.21.HRMS (ESI) calcd for C19H26NO2P [M+H]+332.1779, found: 332.1779; HRMS (ESI) calcd for C19H26NO2P [M+Na]+ 354.1598,found: 354.1573.Mp: 124-127 ºC。
Claims (1)
1.一种O-(二烷基次膦酰基)酮肟的合成方法，其特征在于：在氧化剂双氧水存在下，乙腈作溶剂，碘单质催化酮肟和二烷基膦氧化物进行氧化偶联一步合成O-(二烷基次膦酰基)酮肟；所述的酮肟选自1-茚酮肟、5-氟-1-茚酮肟、5-氯-1-茚酮肟、6-溴-1-茚酮肟、5-甲氧基-1-茚酮肟、4-甲氧基-1-茚酮肟、苯乙酮肟、3-甲基苯乙酮肟、3-甲氧基苯乙酮肟、4-氟苯乙酮肟、2-氟苯乙酮肟、4-三氟甲基苯乙酮肟、3-甲基-2-丁酮肟、环戊酮肟、3-乙酰基噻吩肟和2-乙酰基呋喃肟；所述的二烷基膦氧化物选自二苯基氧膦、双(3-氟苯基)氧膦、双(4-氟苯基)氧膦、双(4-氯苯基)氧膦、双(4-甲氧基苯基)氧膦、双(3-甲氧基苯基)氧膦、双(2-甲氧基苯基)氧膦、双(4-甲基苯基)氧膦、双(3,5-二甲基苯基)氧膦、二噻吩基氧膦和二环戊基氧膦。
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