CN105503945B - A kind of method for preparing the Dicarbonyl derivatives of 2 phosphonate group 1,3 - Google Patents
A kind of method for preparing the Dicarbonyl derivatives of 2 phosphonate group 1,3 Download PDFInfo
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- CN105503945B CN105503945B CN201510927543.2A CN201510927543A CN105503945B CN 105503945 B CN105503945 B CN 105503945B CN 201510927543 A CN201510927543 A CN 201510927543A CN 105503945 B CN105503945 B CN 105503945B
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- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical group OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 title claims abstract description 13
- 238000000034 method Methods 0.000 title claims abstract description 11
- 125000004989 dicarbonyl group Chemical group 0.000 title claims abstract description 6
- 238000006243 chemical reaction Methods 0.000 claims abstract description 157
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 93
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 61
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 33
- 238000004440 column chromatography Methods 0.000 claims description 32
- 238000000926 separation method Methods 0.000 claims description 31
- 238000004809 thin layer chromatography Methods 0.000 claims description 30
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 27
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 27
- CYTQBVOFDCPGCX-UHFFFAOYSA-N trimethyl phosphite Chemical group COP(OC)OC CYTQBVOFDCPGCX-UHFFFAOYSA-N 0.000 claims description 19
- 238000002360 preparation method Methods 0.000 claims description 14
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 claims description 13
- NZZIMKJIVMHWJC-UHFFFAOYSA-N dibenzoylmethane Chemical compound C=1C=CC=CC=1C(=O)CC(=O)C1=CC=CC=C1 NZZIMKJIVMHWJC-UHFFFAOYSA-N 0.000 claims description 12
- 239000000126 substance Substances 0.000 claims description 11
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 10
- 239000010949 copper Substances 0.000 claims description 10
- 229910052802 copper Inorganic materials 0.000 claims description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
- 239000003054 catalyst Substances 0.000 claims description 9
- 150000001451 organic peroxides Chemical class 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 6
- HVLLSGMXQDNUAL-UHFFFAOYSA-N triphenyl phosphite Chemical compound C=1C=CC=CC=1OP(OC=1C=CC=CC=1)OC1=CC=CC=C1 HVLLSGMXQDNUAL-UHFFFAOYSA-N 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- NKXMBTKMOVMBPH-UHFFFAOYSA-N 1-phenylpentane-1,3-dione Chemical class CCC(=O)CC(=O)C1=CC=CC=C1 NKXMBTKMOVMBPH-UHFFFAOYSA-N 0.000 claims description 4
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 claims description 4
- 238000000746 purification Methods 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims description 4
- QASWQXKZQZCVST-UHFFFAOYSA-N propan-2-yl dihydrogen phosphite Chemical compound CC(C)OP(O)O QASWQXKZQZCVST-UHFFFAOYSA-N 0.000 claims description 3
- 235000019260 propionic acid Nutrition 0.000 claims description 3
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical class ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 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
- KYARBIJYVGJZLB-UHFFFAOYSA-N 7-amino-4-hydroxy-2-naphthalenesulfonic acid Chemical compound OC1=CC(S(O)(=O)=O)=CC2=CC(N)=CC=C21 KYARBIJYVGJZLB-UHFFFAOYSA-N 0.000 claims description 2
- 239000003480 eluent Substances 0.000 claims description 2
- XTTGYFREQJCEML-UHFFFAOYSA-N tributyl phosphite Chemical compound CCCCOP(OCCCC)OCCCC XTTGYFREQJCEML-UHFFFAOYSA-N 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 2
- FHSUFDYFOHSYHI-UHFFFAOYSA-N 3-oxopentanoic acid Chemical compound CCC(=O)CC(O)=O FHSUFDYFOHSYHI-UHFFFAOYSA-N 0.000 claims 1
- 239000002994 raw material Substances 0.000 abstract description 32
- 238000004519 manufacturing process Methods 0.000 abstract description 5
- 230000035484 reaction time Effects 0.000 abstract description 2
- 239000007858 starting material Substances 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 description 28
- 238000005160 1H NMR spectroscopy Methods 0.000 description 27
- 230000015572 biosynthetic process Effects 0.000 description 27
- 239000003208 petroleum Substances 0.000 description 27
- -1 pyrazole ether phosphate derivatives Chemical class 0.000 description 20
- YFPJFKYCVYXDJK-UHFFFAOYSA-N Diphenylphosphine oxide Chemical compound C=1C=CC=CC=1[P+](=O)C1=CC=CC=C1 YFPJFKYCVYXDJK-UHFFFAOYSA-N 0.000 description 15
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 9
- 239000004342 Benzoyl peroxide Substances 0.000 description 8
- 150000008301 phosphite esters Chemical class 0.000 description 8
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 7
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 7
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 6
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- YIVJZNGAASQVEM-UHFFFAOYSA-N Lauroyl peroxide Chemical compound CCCCCCCCCCCC(=O)OOC(=O)CCCCCCCCCCC YIVJZNGAASQVEM-UHFFFAOYSA-N 0.000 description 6
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 6
- 235000019400 benzoyl peroxide Nutrition 0.000 description 6
- 235000011150 stannous chloride Nutrition 0.000 description 6
- 239000001119 stannous chloride Substances 0.000 description 6
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 4
- UDRCONFHWYGWFI-UHFFFAOYSA-N ethyl 3-oxopentanoate Chemical compound CCOC(=O)CC(=O)CC UDRCONFHWYGWFI-UHFFFAOYSA-N 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 3
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000002367 phosphate rock Substances 0.000 description 3
- BSAIUMLZVGUGKX-BQYQJAHWSA-N (E)-non-2-enal Chemical compound CCCCCC\C=C\C=O BSAIUMLZVGUGKX-BQYQJAHWSA-N 0.000 description 2
- HXUIDZOMTRMIOE-UHFFFAOYSA-N 3-oxo-3-phenylpropionic acid Chemical class OC(=O)CC(=O)C1=CC=CC=C1 HXUIDZOMTRMIOE-UHFFFAOYSA-N 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 2
- 102000030621 adenylate cyclase Human genes 0.000 description 2
- 108060000200 adenylate cyclase Proteins 0.000 description 2
- ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 description 2
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 2
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 2
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- UWDMKTDPDJCJOP-UHFFFAOYSA-N 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-ium-4-carboxylate Chemical compound CC1(C)CC(O)(C(O)=O)CC(C)(C)N1 UWDMKTDPDJCJOP-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 102000003923 Protein Kinase C Human genes 0.000 description 1
- 108090000315 Protein Kinase C Proteins 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 241000209140 Triticum Species 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- YWGHUJQYGPDNKT-UHFFFAOYSA-N hexanoyl chloride Chemical compound CCCCCC(Cl)=O YWGHUJQYGPDNKT-UHFFFAOYSA-N 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 108010042388 protease C Proteins 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 150000003217 pyrazoles Chemical class 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4056—Esters of arylalkanephosphonic acids
- C07F9/4059—Compounds containing the structure (RY)2P(=X)-(CH2)n-C(=O)-(CH2)m-Ar, (X, Y = O, S, Se; n>=1, m>=0)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4006—Esters of acyclic acids which can have further substituents on alkyl
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4018—Esters of cycloaliphatic acids
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)
- Crystallography & Structural Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The use of 1,3 Dicarbonyl derivatives and trialkyl phosphite is starting material, raw material is easy to get, species is many invention discloses the method that one kind prepares the Dicarbonyl derivatives of 2 phosphonate group 1,3；The product types that profit is obtained by the present invention are various, not only can directly using but also can be used for other and further react；In addition, in method disclosed by the invention, reaction is carried out in atmosphere, and mild condition, the reaction time is short, the high income of target product, pollute small, operation and last handling process are simple, suitable for industrialized production.
Description
Technical field
The invention belongs to the preparing technical field of organic compound, and in particular to a kind of 2- phosphonate groups -1,3- dicarbapentaborane
The preparation method of derivative.
Background technology
2- phosphonate group -1,3- Dicarbonyl derivatives are widely used in witting and Horner-Wardsworth-
In Emmons (HWE) reactions, prepared with aldehydes or ketones reaction various importantα,β- beta-unsaturated carbonyl compounds.Such as 4- hydroxyls -2
(E)-nonenyl aldehyde (4-hydroxy-2 (E)-nonenal (HNE)) and 4- oxos -2 (E)-nonenyl aldehyde (4-oxo-2 (E)-
Nonenal (ONE)), they are the products during biological body lipid peroxidating, with important bioactivity, its structure
It is as follows：
Wherein HNE can effectively suppress the activity of many biology enzymes, such as protease C (protein kinase C),
Adenyl cyclase (adenylate cyclase), glyceraldehyde-3-phosphate dehydrogenase (glyceraldehyde-3-
Phosphate dehydrogenase) etc.；Gene expression pattern etc. can be changed with inducing cell apoptosis simultaneously；In addition, it with
Alzheimer disease（Alzheimer’s disease）, Parkinson's（Parkinson’s disease）Have closely with cancer
Relation.ONE has stronger neurotoxicity, while it is reactive stronger with protein.
2- phosphonate group -1,3- Dicarbonyl derivatives are the key intermediate of synthesizing pyrazole ether phosphate derivatives, the latter
With important bioactivity, such as Miller et al. discloses 4- phosphonate group pyrazoles ether derivants, and these compounds are to miscellaneous
The development of the crops such as wheat is handed over to play an important roll；2- phosphonate group -1,3- Dicarbonyl derivatives can also be used to synthesize alkenyl
Pyrazolone derivative, such compound has important bacteriostatic activity, such as Janecki et al. discloses a kind of alkenyl pyrazoles
Quinoline ketone derivatives, such compound can be used as potential cytotoxic agent.
The synthetic route of existing 2- phosphonate groups -1,3- Dicarbonyl derivatives is as follows：
There is raw material and be difficult to obtain in synthetic route above, such as 2- diethoxies phosphinylidyne ethyl is unconventional production
Product, it is difficult to obtain；Reaction condition is strict, and caproyl chloride is used in reaction, and the substance toxicity is big, runs into air and smolders, therefore reaction
In to have strict personnel protection measure, it is impossible to suction can not contact the material；Simultaneous reactions environment, solvent and reactant will
Keep drying；Pollution is larger to wait not enough；Therefore find that a kind of raw material sources are simple, meet Green Chemistry requirement, reaction condition temperature
Good preparation method is necessary effectively to synthesize 2- phosphonate group -1,3- Dicarbonyl derivatives with, universality.
The content of the invention
It is an object of the invention to provide the method that one kind prepares 2- phosphonate group -1,3- Dicarbonyl derivatives, it has original
Material source is simple, in high yield, the advantage that reaction condition is gentle, universality is good, safe.
To achieve the above object of the invention, the technical solution adopted by the present invention is：One kind prepares the carbonyls of 2- phosphonate groups -1,3- two
The method of radical derivative, comprises the following steps：By 1,3- Dicarbonyl derivatives, trialkyl phosphite, organic peroxide and
Copper catalyst is added in solvent, in 70~120 DEG C of reactions, obtains 2- phosphonate group -1,3- Dicarbonyl derivatives；
The 1,3- Dicarbonyl derivatives are as shown in following chemical structure of general formula：
Wherein R1It is selected from：One kind in alkyl, aryl or alkoxy；R2It is selected from：One kind in alkyl, aryl or alkoxy；
The trialkyl phosphite derivative is as shown in following chemical formula：
P(OR3)3；R3For alkyl or aryl；
The organic peroxide is as shown in following chemical structure of general formula：
Wherein R4It is selected from：One kind in hydrogen, the tert-butyl group and benzoyl；R5It is selected from：In hydrogen, the tert-butyl group and benzoyl
It is a kind of；
The chemical formula of the copper catalyst is CuXn, wherein X is selected from：One kind in Cl, Br, I or trifluoromethanesulfonic acid base；
N is 1 or 2；
The solvent is selected from：One in ethanol, acetonitrile, acetic acid, propionic acid, 1,2- dichloroethanes, toluene, dimethylformamide
Kind；
2- phosphonate groups -1,3- the Dicarbonyl derivatives are as shown in following chemical structure of general formula：
。
In above-mentioned technical proposal, 1, the 3- Dicarbonyl derivatives are selected from 1,3- diphenyl -1,3- propanedione, 1-（4- first
Base phenyl）- 3- diphenylpropane-1,3-dione (DPPO)s, 1,3- bis- (4- aminomethyl phenyls) -1,3- propanedione, 1,3- bis- (4- methoxyphenyls)
- 1,3- propanedione, 1-（4- chlorphenyls）- 3- diphenylpropane-1,3-dione (DPPO)s, 1-（4- bromophenyls）-3-（4- methoxyphenyls）-1,3-
Propanedione, 1,3- bis- (4- bromophenyls) -1,3- propanedione, 1-（4- bromophenyls）- 3- diphenylpropane-1,3-dione (DPPO)s, 1-（4- methoxies
Base phenyl）- 3- diphenylpropane-1,3-dione (DPPO)s, 1-（3- bromophenyls）- 3- diphenylpropane-1,3-dione (DPPO)s, 2,2,6,6- tetramethyls -3,5-
Heptadione, 1- phenyl -1,3- pentanediones, 5,5- dimedones -1,3,3- phenyl -3- oxopropanoates, 3-（4- bromines
Phenyl）- 3- oxopropanoates, 3-（4- methoxyphenyls）- 3- oxopropanoates, 3-（2- methoxyphenyls）- 3- oxos
Ethyl propionate, 3-（2- bromophenyls）- 3- oxopropanoates, 3-（4- aminomethyl phenyls）- 3- oxopropanoates, 3-（4- chlorobenzenes
Base）One kind in -3- oxopropanoates, Propionylacetic acid ethyl ester, diethyl malonate；The trialkyl phosphite is selected from three
In methylisothiouronium methylphosphite ester, triethyl phosphorite, tri isopropyl phosphorite, tributyl phosphite ester, triphenyl phosphite
One kind.
In above-mentioned technical proposal, thin-layer chromatography is utilized（TLC）Tracking reaction is until be fully completed.
In above-mentioned technical proposal, in molar ratio, 1,3- Dicarbonyl derivatives: trialkyl phosphite: organic peroxide:
Copper catalyst is 1:（1~8）∶（1~8）: (0.05~0.2）；Preferably 1: 7: 7: 0.1.
In above-mentioned technical proposal, the reaction is carried out in atmosphere.Operation is simple and safe.
It is preferred that technical scheme in, reaction terminate after to product carry out column chromatography for separation purification processes；Column chromatography for separation is carried
Using petrol ether/ethyl acetate as eluant, eluent during pure processing.
Preparation method disclosed by the invention is simple, and universality is good, therefore the invention also discloses according to above-mentioned preparation method
2- phosphonate group -1,3- the Dicarbonyl derivatives of preparation.
The course of reaction of above-mentioned technical proposal is represented by：
Due to the utilization of above-mentioned technical proposal, the present invention has following advantages compared with prior art:
1. the present invention is first starting material using 1,3- Dicarbonyl derivatives and trialkyl phosphite, only in organic oxidation
In the presence of agent and copper catalyst, in air, 2- phosphonate group -1,3- Dicarbonyl derivatives are efficiently prepared；Raw material is easy to get, species
Many, the product prepared can be used directly, and other further reactions can also be used for as intermediate.
2. the present invention is simple using raw material, without a variety of reagents of prior art requirement, cost is low, and avoids
Wastage of material；Existing acyl chlorides be particular avoid as reactant, environmental pollution is reduced；Only need a small amount of catalyst high
Effect obtains product, not only simplify the purification process of product, reduces the generation of discarded object, and has for commercial Application positive
Realistic meaning.
3. preparation method reaction condition disclosed by the invention is simple, without the complicated atmosphere of prior art, in air
Reaction can efficiently obtain product, post-process very simple, column chromatography, it is to avoid existing course of reaction exist it is dangerous because
Element, is conducive to chemical synthesis safety in production, ensures the security of the lives and property.
4. in method disclosed by the invention, reaction is carried out in atmosphere, reaction condition is gentle, and the pollution small, reaction time is short,
A variety of 1,3- Dicarbonyl derivatives are particularly suitable for use in, the high income of target product, operation and last handling process are simple, are suitable to
Industrialized production.
Embodiment
With reference to embodiment, the invention will be further described：
Embodiment one：The synthesis of 2- dimethyl phosphonate base -1,3- diphenyl -1,3- propanedione
With 1,3- diphenyl -1,3- propanedione, trimethyl phosphite as raw material, its reactions steps is as follows：
1,3- diphenyl -1,3- propanedione is added in reaction bulb（0.224 g, 1.0 mmol）, trimethyl phosphorous acid
Ester（0.124 g, 1.0 mmol）, stannous chloride（0.010 g, 0.1 mmol）, TBHP（0.09 g, 1
mmol）, and ethanol（5 milliliters）, 70 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the petroleum ether that reaction is obtained after terminating:Ethyl acetate=4:1) target production, is obtained
Thing（Yield 54%）.The analyze data of product is as follows：1H NMR (400 MHz, DMSO-d 6 ): δ 8.09 (d, J = 7.4
Hz, 4H), 7.71 (t, J = 7.4 Hz, 2H), 7.58 (t, J = 7.7 Hz, 4H), 7.17 (d, 1H),
3.71 (d, 6H)。
Embodiment two：2- dimethyl phosphonate bases -1-（4- aminomethyl phenyls）The synthesis of -3- diphenylpropane-1,3-dione (DPPO)s
With 1-（4- aminomethyl phenyls）- 3- phenyl -1,3- propanedione, trimethyl phosphite are used as raw material, its reactions steps
It is as follows：
1- is added in reaction bulb（4- aminomethyl phenyls）- 3- diphenylpropane-1,3-dione (DPPO)s（0.238 g, 1.0 mmol）, three
Methylisothiouronium methylphosphite ester（0.248 g, 2.0 mmol）, stannous chloride（0.010 g, 0.1 mmol）, TBHP（0.18
G, 2 mmol）And acetonitrile（5 milliliters）, 70 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the petroleum ether that reaction is obtained after terminating:Ethyl acetate=4:1) target, is obtained
Product（Yield 64%）.The analyze data of product is as follows：1H NMR (400 MHz, DMSO-d 6 ): δ 8.03 (dd, J =
25.2, 7.9 Hz, 4H), 7.70 (s, 1H), 7.57 (d, J = 7.7 Hz, 2H), 7.38 (d, J = 8.0
Hz, 2H), 3.84 – 3.64 (m, 6H), 2.49 – 2.33 (m, 3H)。
Embodiment three：2- dimethyl phosphonate bases -1,3- two（4- aminomethyl phenyls）The synthesis of -1,3- propanedione
With 1,3- bis-（4- aminomethyl phenyls）- 1,3- propanedione, trimethyl phosphite are as raw material, and its reactions steps is such as
Under：
1,3- bis- is added in reaction bulb（4- aminomethyl phenyls）- 1,3- propanedione（0.252 g, 1.0 mmol）, front three
Base phosphite ester（0.372 g, 3.0 mmol）, copper chloride（0.013 g, 0.1 mmol）, TBHP（0.27 g, 3
mmol）And acetic acid（5 milliliters）, 70 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the petroleum ether that reaction is obtained after terminating:Ethyl acetate=4:1) target, is obtained
Product（Yield 90%）.The analyze data of product is as follows：1H NMR (400 MHz, DMSO-d 6 ): δ 8.05 (d, J = 7.9
Hz, 4H), 7.08 (d, J = 7.9 Hz, 4H), 6.98 (d, J = 7.8 Hz, 1H), 3.87 (s, 6H),
3.71 (d, J = 11.2 Hz, 6H)。
Example IV：2- dimethyl phosphonate bases -1,3- two（4- methoxyphenyls）The synthesis of -1,3- propanedione
With 1,3- bis-（4- methoxyphenyls）- 1,3- propanedione, trimethyl phosphite are as raw material, and its reactions steps is such as
Under：
1,3- bis- is added in reaction bulb（4- methoxyphenyls）- 1,3- propanedione（0.284 g, 1.0 mmol）, three
Methylisothiouronium methylphosphite ester（0.496 g, 4.0 mmol）, copper chloride（0.013 g, 0.1 mmol）, TBHP（0.36
G, 4 mmol）And propionic acid（5 milliliters）, 80 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the petroleum ether that reaction is obtained after terminating:Ethyl acetate=4:1) target, is obtained
Product（Yield 86%）.The analyze data of product is as follows：1H NMR (400 MHz, DMSO-d 6 ): δ 7.97 (d, J = 8.0
Hz, 4H), 7.36 (d, J = 7.9 Hz, 4H), 7.05 (d, J = 22.8 Hz, 1H), 3.71 (d, J =
11.3 Hz, 6H), 2.39 (s, 6H)。
Embodiment five：2- dimethyl phosphonate bases -1-（4- chlorphenyls）The synthesis of -3- diphenylpropane-1,3-dione (DPPO)s
With 1-（4- chlorphenyls）- 3- phenyl -1,3- propanedione, trimethyl phosphite are as raw material, and its reactions steps is such as
Under：
1- is added in reaction bulb（4- chlorphenyls）- 3- diphenylpropane-1,3-dione (DPPO)s（0.259 g, 1.0 mmol）, front three
Base phosphite ester（0.620 g, 5.0 mmol）, copper bromide（0.022 g, 0.1 mmol）, TBHP（0.45 g, 5
mmol）With 1,2- dichloroethanes（5 milliliters）, 70 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the petroleum ether that reaction is obtained after terminating:Ethyl acetate=4:1) target, is obtained
Product（Yield 82%）.The analyze data of product is as follows：1H NMR (400 MHz, DMSO-d 6 ): δ 8.15 – 7.97 (m,
4H), 7.76 – 7.64 (m, 3H), 7.58 (t, J = 7.7 Hz, 2H), 7.16 (d, J = 23.3 Hz,1H),
3.72 (d, J = 4.7 Hz, 3H), 3.69 (d, J = 4.8 Hz, 3H)。
Embodiment six：2- dimethyl phosphonate bases -1-（4- bromophenyls）-3-（4- methoxyphenyls）- 1,3- propanedione
Synthesis
With 1-（4- bromophenyls）-3-（4- methoxyphenyls）- 1,3- propanedione, trimethyl phosphite as raw material, its
Reactions steps are as follows：
1- is added in reaction bulb（4- bromophenyls）-3-（4- methoxyphenyls）- 1,3- propanedione（0.333 g, 1.0
mmol）, trimethyl phosphite（0.744 g, 6.0 mmol）, copper bromide（0.022 g, 0.1 mmol）, tert-butyl hydroperoxide
Hydrogen（0.54 g, 6 mmol）And toluene（5 milliliters）, 90 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the petroleum ether that reaction is obtained after terminating:Ethyl acetate=4:1) target, is obtained
Product（Yield 80%）.The analyze data of product is as follows：1H NMR (400 MHz, DMSO-d 6 ): δ 8.05 (d, J = 8.9
Hz, 4H), 7.99 (d, J = 8.7 Hz, 2H), 7.80 (d, J = 8.6 Hz, 3H), 7.08 (dd, J =
16.0, 11.3 Hz, 3H), 3.88 (s, 3H), 3.73 (d, J = 5.0 Hz, 3H), 3.70 (d, J = 5.0
Hz, 3H)。
Embodiment seven：2- dimethyl phosphonate bases -1,3- two（4- bromophenyls）The synthesis of -1,3- propanedione
With 1,3- bis-（4- bromophenyls）- 1,3- propanedione, trimethyl phosphite are as raw material, and its reactions steps is as follows：
1,3- bis- is added in reaction bulb（4- bromophenyls）- 1,3- propanedione（0.382 g, 1.0 mmol）, trimethyl
Phosphite ester（0.868 g, 7.0 mmol）, cuprous bromide（0.014 g, 0.1 mmol）, TBHP（0.63 g, 7
mmol）And toluene（5 milliliters）, 100 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the petroleum ether that reaction is obtained after terminating:Ethyl acetate=4:1) target, is obtained
Product（Yield 81%）.The analyze data of product is as follows：1H NMR (400 MHz, DMSO-d 6 ): δ 7.99 (d, J = 8.6
Hz, 4H), 7.81 (d, J = 8.6 Hz, 4H), 7.14 (d, J = 23.5 Hz, 1H), 3.71 (d, J =
11.3 Hz, 6H)。
Embodiment eight：2- dimethyl phosphonate bases -1-（4- bromophenyls）The synthesis of -3- diphenylpropane-1,3-dione (DPPO)s
With 1-（4- bromophenyls）- 3- phenyl -1,3- propanedione, trimethyl phosphite are as raw material, and its reactions steps is such as
Under：
1- is added in reaction bulb（4- bromophenyls）- 3- diphenylpropane-1,3-dione (DPPO)s（0.301 g, 1.0 mmol）, front three
Base phosphite ester（0.992 g, 8.0 mmol）, cuprous bromide（0.014 g, 0.1 mmol）, TBHP（0.81
G, 8 mmol）And toluene（5 milliliters）, 110 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the petroleum ether that reaction is obtained after terminating:Ethyl acetate=4:1) target, is obtained
Product（Yield 83%）.The analyze data of product is as follows：1H NMR (400 MHz, DMSO-d 6 ): δ8.02 – 7.98 (m,
4H), 7.78 (d, J = 8.6 Hz, 2H), 7.68 (t, J = 7.4 Hz, 1H), 7.54 (t, J = 7.7 Hz,
2H), 7.11 (d, J = 23.3 Hz, 1H), 3.69 (d, J = 5.0 Hz, 3H), 3.66 (d, J = 5.0
Hz, 3H)。
Embodiment nine：2- dimethyl phosphonate bases -1-（4- methoxyphenyls）The synthesis of -3- diphenylpropane-1,3-dione (DPPO)s
With 1-（4- methoxyphenyls）- 3- phenyl -1,3- propanedione, trimethyl phosphite are as raw material, and it reacts step
It is rapid as follows：
1- is added in reaction bulb（4- methoxyphenyls）- 3- diphenylpropane-1,3-dione (DPPO)s（0.254 g, 1.0 mmol）、
Trimethyl phosphite（0.868 g, 7.0 mmol）, cuprous iodide（0.010 g, 0.05 mmol）, tert-butyl-benzoyl mistake
Oxide（1.362 g, 7 mmol）And dimethylformamide（5 milliliters）, 120 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the petroleum ether that reaction is obtained after terminating:Ethyl acetate=4:1) target, is obtained
Product（Yield 77%）.The analyze data of product is as follows：1H NMR (400 MHz, DMSO-d 6 ): δ8.07 – 8.02 (m,
4H), 7.66 (t, J = 7.4 Hz, 1H), 7.53 (t, J = 7.7 Hz, 2H), 7.07 – 7.02 (m, J =
8.8 Hz, 3H), 3.85 (s, 3H), 3.69 (d, J = 11.3 Hz, 6H).
Embodiment ten：2- dimethyl phosphonate bases -1-（3- bromophenyls）The synthesis of -3- diphenylpropane-1,3-dione (DPPO)s
With 1-（3- bromophenyls）- 3- phenyl -1,3- propanedione, trimethyl phosphite are as raw material, and its reactions steps is such as
Under：
1- is added in reaction bulb（3- bromophenyls）- 3- diphenylpropane-1,3-dione (DPPO)s（0.301 g, 1.0 mmol）, front three
Base phosphite ester（0.868 g, 7.0 mmol）, cuprous iodide（0.019 g, 0.1 mmol）, tert-butyl-benzoyl peroxidating
Thing（1.362 g, 7 mmol）And dimethylformamide（5 milliliters）, 110 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the petroleum ether that reaction is obtained after terminating:Ethyl acetate=4:1) target, is obtained
Product（Yield 82%）.The analyze data of product is as follows：1H NMR (400 MHz, DMSO-d 6 ): δ8.23 (t, J = 1.7
Hz, 1H), 8.03 (d, J = 8.0 Hz, 3H), 7.92 – 7.81 (m, 1H), 7.68 (t, J = 7.4 Hz,
1H), 7.57 – 7.50 (m, 3H), 7.15 (d, J = 23.4 Hz, 1H), 3.69 (d, J = 3.4 Hz,
3H), 3.66 (d, J = 3.4 Hz, 3H)。
Embodiment 11：The synthesis of 4- dimethyl phosphonates base-DPM dpm,dipivalomethane
With 2,2,6,6- tetramethyl -3,5- heptadione, trimethyl phosphite as raw material, its reactions steps is as follows：
DPM dpm,dipivalomethane is added in reaction bulb（0.184 g, 1 mmol）, trimethyl phosphorous
Acid esters（0.868 g, 7.0 mmol）, cupric iodide（0.064 g, 0.2 mmol）, tert-butyl-benzoyl peroxide（1.362
G, 7 mmol）And dimethylformamide（5 milliliters）, 100 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the petroleum ether that reaction is obtained after terminating:Ethyl acetate=4:1) target, is obtained
Product（Yield 85%）.The analyze data of product is as follows：1H NMR (400 MHz, CDCl3): δ 6.19 – 6.17 (m,
1H), 3.69 (d, J = 3.4 Hz, 3H), 3.66 (d, J = 3.4 Hz, 3H), 1.18 – 1.15 (m, 9H),
1.15 – 1.12 (m, 9H)。
Embodiment 12：The synthesis of 2- dimethyl phosphonate base -1- phenyl -1,3- pentanediones
With 1- phenyl -1,3- pentanedione, trimethyl phosphite as raw material, its reactions steps is as follows：
1- phenyl -1,3- pentanediones are added in reaction bulb（0.176 g, 1.0 mmol）, trimethyl phosphite
（0.868 g, 7.0 mmol）, cupric iodide（0.032 g, 0.1 mmol）, tert-butyl-benzoyl peroxide（1.362 g, 7
mmol）And dimethylformamide（5 milliliters）, 90 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the petroleum ether that reaction is obtained after terminating:Ethyl acetate=4:1) target, is obtained
Product（Yield 68%）.The analyze data of product is as follows：1H NMR (400 MHz, DMSO-d 6 ): δ8.07 – 7.95 (m,
2H), 7.69 (t, J = 7.4 Hz, 1H), 7.56 (t, J = 7.7 Hz, 2H), 6.17 (d, J = 23.3
Hz, 1H), 3.71 (dd, J = 11.3, 1.7 Hz, 6H), 2.75 (qd, J = 7.2, 2.8 Hz, 2H),
0.92 (t, J = 7.2 Hz, 3H)。
Embodiment 13：The synthesis of 2- dimethyl phosphonate base -5,5- dimedones -1,3
With 5,5- dimedones -1,3, trimethyl phosphite as raw material, its reactions steps is as follows：
5,5- dimedones -1,3 are added in reaction bulb（0.140 g, 1 mmol）, trimethyl phosphite
（0.868 g, 7.0 mmol）, trifluoromethanesulfonic acid it is cuprous（0.021 g, 0.1 mmol）, di-tert-butyl peroxide（1.022 g,
7 mmol）And dimethylformamide（5 milliliters）, 80 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the petroleum ether that reaction is obtained after terminating:Ethyl acetate=4:1) target, is obtained
Product（Yield 69%）.The analyze data of product is as follows：1H NMR (400 MHz, CDCl3):δ 5.89 (s, 1H), 3.69
(d, J = 3.4 Hz, 3H), 3.66 (d, J = 3.4 Hz, 3H), 2.45 (s, 2H), 2.25 (s, 2H),
1.10 (s, 6H)。
Embodiment 14：The synthesis of 2- diethyl phosphonate base -1,3- diphenyl -1,3- propanedione
With 1,3- diphenyl -1,3- propanedione, triethyl phosphorite as raw material, its reactions steps is as follows：
1,3- diphenyl -1,3- propanedione is added in reaction bulb（0.224 g, 1.0 mmol）, triethyl group phosphorous acid
Ester（1.162 g, 7.0 mmol）, trifluoromethanesulfonic acid it is cuprous（0.021 g, 0.1 mmol）, di-tert-butyl peroxide（1.022
G, 7 mmol）And toluene（5 milliliters）, 110 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the petroleum ether that reaction is obtained after terminating:Ethyl acetate=4:1) target, is obtained
Product（Yield 72%）.The analyze data of product is as follows：1H NMR (400 MHz, DMSO-d 6 ): δ8.07 (d, J = 7.3
Hz, 4H), 7.67 (t, J = 7.4 Hz, 2H), 7.54 (t, J = 7.7 Hz, 4H), 7.08 (d, J =
23.2 Hz, 1H), 4.23 – 3.92 (m, 4H), 1.08 (t, J = 7.0 Hz, 6H)。
Embodiment 15：The synthesis of 2- diisopropyl phosphonate group -1,3- diphenyl -1,3- propanedione
With 1,3- diphenyl -1,3- propanedione, tri isopropyl phosphorite as raw material, its reactions steps is as follows：
1,3- diphenyl -1,3- propanedione is added in reaction bulb（0.224 g, 1.0 mmol）, triisopropyl base it is sub-
Phosphate（1.456 g, 7.0 mmol）, copper trifluoromethanesulfcomposite（0.036 g, 0.1 mmol）, di-tert-butyl peroxide
（1.022 g, 7 mmol）And toluene（5 milliliters）, 110 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the petroleum ether that reaction is obtained after terminating:Ethyl acetate=4:1) target, is obtained
Product（Yield 63%）.The analyze data of product is as follows：1H NMR (400 MHz, DMSO) δ 8.09 (d, J = 7.4
Hz, 4H), 7.69 (t, J = 7.4 Hz, 2H), 7.56 (t, J = 7.7 Hz, 4H), 7.02 (d, J =
23.3 Hz, 1H), 3.85 – 3.05 (m, 2H), 1.14 (dd, J = 5.9, 4.8 Hz, 12H)。
Embodiment 16：The synthesis of 2- di-n-butyl phosphonate group -1,3- diphenyl -1,3- propanedione
With 1,3- diphenyl -1,3- propanedione, three normal-butyl phosphite esters as raw material, its reactions steps is as follows：
1,3- diphenyl -1,3- propanedione is added in reaction bulb（0.224 g, 1.0 mmol）, three normal-butyl phosphorous
Acid esters（1.862 g, 7.0 mmol）, cuprous bromide（0.014 g, 0.1 mmol）, benzoyl peroxide（1.694 g, 7.0
mmol）And toluene（5 milliliters）, 110 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the petroleum ether that reaction is obtained after terminating:Ethyl acetate=4:1) target, is obtained
Product（Yield 65%）.The analyze data of product is as follows：1H NMR (400 MHz, DMSO) δ 8.09 (d, J = 7.4
Hz, 4H), 7.69 (t, J = 7.4 Hz, 2H), 7.56 (t, J = 7.7 Hz, 4H), 7.02 (d, J =
23.3 Hz, 1H), 3.44 – 3.37 (m, 2H), 3.35 – 3.27 (m, 2H), 1.66 (m, 4H), 1.37
(m, 4H), 0.99 (m, 6H)。
Embodiment 17：The synthesis of 2- diethyl phosphonate base -3- phenyl -3- oxopropanoates
Using 3- phenyl -3- oxopropanoates, triethyl phosphorite as raw material, its reactions steps is as follows：
3- phenyl -3- oxopropanoates are added in reaction bulb（0.192 g, 1.0 mmol）, triethyl group phosphorous acid
Ester（1.162 g, 7.0 mmol）, copper trifluoromethanesulfcomposite（0.036 g, 0.1 mmol）, benzoyl peroxide（1.694 g, 7.0
mmol）And toluene（5 milliliters）, 110 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the petroleum ether that reaction is obtained after terminating:Ethyl acetate=4:1) target, is obtained
Product（Yield 73%）.The analyze data of product is as follows：1H NMR (400 MHz, DMSO-d 6 ):δ 8.03 (d, J = 7.4
Hz, 2H), 7.69 (t, J = 7.4 Hz, 1H), 7.55 (t, J = 7.7 Hz, 2H), 5.84 (d, J =
23.1 Hz, 1H), 4.40 – 3.85 (m, 6H), 1.34 – 0.99 (m, 9H)。
Embodiment 18：2- diethyl phosphonate bases -3-（4-bromophenyl）The synthesis of -3- oxopropanoates
With 3-（4- bromophenyls）- 3- oxopropanoates, triethyl phosphorite are as raw material, and its reactions steps is as follows：
3- is added in reaction bulb（4- bromophenyls）- 3- oxopropanoates（0.269 g, 1.0 mmol）, triethyl group
Phosphite ester（1.162 g, 7.0 mmol）, copper chloride（0.013 g, 0.1 mmol）, benzoyl peroxide（1.694 g, 7.0
mmol）And dimethylformamide（5 milliliters）, 110 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the petroleum ether that reaction is obtained after terminating:Ethyl acetate=4:1) target, is obtained
Product（Yield 73%）.The analyze data of product is as follows：1H NMR (400 MHz, DMSO-d 6 ):δ7.99 (d, J = 8.7
Hz, 2H), 7.81 (d, J = 8.7 Hz, 2H), 5.88 (d, J = 23.3 Hz, 1H), 4.29 – 3.88 (m,
6H), 1.22 – 1.16 (m, 9H)。
Embodiment 19：2- diethyl phosphonate bases -3-（4-methoxyphenyl）The synthesis of -3- oxopropanoates
With 3-（4- methoxyphenyls）- 3- oxopropanoates, triethyl phosphorite are as raw material, and its reactions steps is such as
Under：
3- is added in reaction bulb（4- methoxyphenyls）- 3- oxopropanoates（0.222 g, 1.0 mmol）, three
Ethide phosphite ester（1.162 g, 7.0 mmol）, copper chloride（0.013 g, 0.1 mmol）, benzoyl peroxide（1.694 g,
7.0 mmol）And dimethylformamide（5 milliliters）, 110 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the petroleum ether that reaction is obtained after terminating:Ethyl acetate=4:1) target, is obtained
Product（Yield 70%）.The analyze data of product is as follows：1H NMR (400 MHz, DMSO-d 6 ):δ 7.57 (dd, J =
384.1, 8.9 Hz, 2H), 7.09 (d, J = 8.9 Hz, 2H), 5.77 (d, J = 22.8 Hz, 1H), 4.15
– 3.89 (m, 6H), 3.89 (s, 3H), 1.34 – 0.90 (m, 9H)。
Embodiment 20：2- diethyl phosphonate bases -3-（2-methoxyphenyl）The synthesis of -3- oxopropanoates
With 3-（2- methoxyphenyls）- 3- oxopropanoates, triethyl phosphorite are as raw material, and its reactions steps is such as
Under：
3- is added in reaction bulb（2- methoxyphenyls）- 3- oxopropanoates（0.222 g, 1.0 mmol）, three
Ethide phosphite ester（1.162 g, 7.0 mmol）, stannous chloride（0.010 g, 0.1 mmol）, benzoyl peroxide（1.694
G, 7.0 mmol）And acetic acid（5 milliliters）, 110 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the petroleum ether that reaction is obtained after terminating:Ethyl acetate=4:1) target, is obtained
Product（Yield 72%）.The analyze data of product is as follows：1H NMR (400 MHz, DMSO-d 6 ): δ 7.89 – 7.56 (m,
2H), 7.22 (d, J = 8.2 Hz, 1H), 7.17 – 7.05 (m, 1H), 5.36 (d, J = 22.4 Hz,
1H), 4.28 – 4.01 (m, 6H), 3.90 (s, 3H), 1.28 – 1.16 (m, 9H)。
Embodiment 21：2- diethyl phosphonate bases -3-（2-bromophenyl）The synthesis of -3- oxopropanoates
With 3-（2- bromophenyls）- 3- oxopropanoates, triethyl phosphorite are as raw material, and its reactions steps is as follows：
3- is added in reaction bulb（2- bromophenyls）- 3- oxopropanoates（0.269 g, 1.0 mmol）, triethyl group
Phosphite ester（1.162 g, 7.0 mmol）, stannous chloride（0.010 g, 0.1 mmol）, benzoyl peroxide（1.694 g,
7.0 mmol）And dimethylformamide（5 milliliters）, 110 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the petroleum ether that reaction is obtained after terminating:Ethyl acetate=4:1) target, is obtained
Product（Yield 79%）.The analyze data of product is as follows：1H NMR (400 MHz, DMSO-d 6 ): δ 13.85 (s, 1H),
7.70 (d, J = 7.9 Hz, 1H), 7.55 – 7.44 (m, 1H), 7.42 – 7.38 (m, 2H), 4.51 –
4.07 (m, 4H), 3.88 (q, J = 7.1 Hz, 2H), 1.33 (t, J = 7.0 Hz, 6H), 0.89 (t, J
= 7.1 Hz, 4=3H)。
Embodiment 22：2- diethyl phosphonate bases -3-（4-aminomethyl phenyl）The synthesis of -3- oxopropanoates
With 3-（4- aminomethyl phenyls）- 3- oxopropanoates, triethyl phosphorite are as raw material, and its reactions steps is such as
Under：
3- is added in reaction bulb（4- aminomethyl phenyls）- 3- oxopropanoates（0.206 g, 1.0 mmol）, three second
Base phosphite ester（1.162 g, 7.0 mmol）, stannous chloride（0.010 g, 0.1 mmol）, lauroyl peroxide（2.80 g,
7.0 mmol）And dimethylformamide（5 milliliters）, 110 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the petroleum ether that reaction is obtained after terminating:Ethyl acetate=4:1) target, is obtained
Product（Yield 73%）.The analyze data of product is as follows：1H NMR (400 MHz, DMSO-d 6 ): δ 7.92 (d, J = 8.3
Hz, 2H), 7.35 (d, J = 8.1 Hz, 2H), 5.76 (d, J = 22.9 Hz, 1H), 4.51 – 3.84 (m,
6H), 2.38 (s, 3H), 1.19 – 1.12 (m, 9H)。
Embodiment 23：2- diethyl phosphonate bases -3-（4-chlorphenyl）The synthesis of -3- oxopropanoates
With 3-（4- chlorphenyls）- 3- oxopropanoates, triethyl phosphorite are as raw material, and its reactions steps is as follows：
3- is added in reaction bulb（4- chlorphenyls）- 3- oxopropanoates（0.226 g, 1.0 mmol）, triethyl group
Phosphite ester（1.162 g, 7.0 mmol）, stannous chloride（0.010 g, 0.1 mmol）, lauroyl peroxide（2.80 g, 7.0
mmol）And acetic acid（5 milliliters）, 110 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the petroleum ether that reaction is obtained after terminating:Ethyl acetate=4:1) target, is obtained
Product（Yield 71%）.The analyze data of product is as follows：1H NMR (400 MHz, DMSO-d 6 ): δ 8.05 (d, J = 8.7
Hz, 2H), 7.64 (d, J = 8.7 Hz, 2H), 5.86 (d, J = 23.3 Hz, 1H), 4.70 – 3.88 (m,
6H), 1.19 – 1.13 (m, 9H)。
Embodiment 24：The synthesis of 2- diethyl phosphonate base Propionylacetic acid ethyl esters
Using Propionylacetic acid ethyl ester, triethyl phosphorite as raw material, its reactions steps is as follows：
Propionylacetic acid ethyl ester is added in reaction bulb（0.144 g, 1 mmol）, triethyl phosphorite（1.162 g,
7.0 mmol）, cuprous bromide（0.014 g, 0.1 mmol）, lauroyl peroxide（2.80 g, 7.0 mmol）And acetic acid（5 millis
Rise）, 110 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the petroleum ether that reaction is obtained after terminating:Ethyl acetate=4:1) target, is obtained
Product（Yield 93%）.The analyze data of product is as follows：1H NMR (400 MHz, CDCl3): δ 5.55 (t, J = 0.9,
1H), 4.23 – 3.92 (m, 6H), 2.34 (qd, J = 7.4 Hz, 0.9 Hz, 2H), 1.25 (t, J = 7.1
Hz, 3H), 1.12 (t, J = 7.4 Hz, 3H), 1.08 (t, J = 7.0 Hz, 6H)。
Embodiment 25：The synthesis of 2- diethyl phosphonate propylmalonic acid diethylesters
Using diethyl malonate, triethyl phosphorite as raw material, its reactions steps is as follows：
Diethyl malonate is added in reaction bulb（0.160 g, 1 mmol）, triethyl phosphorite（1.162 g,
7.0 mmol）, cuprous bromide（0.014 g, 0.1 mmol）, lauroyl peroxide（2.80 g, 7.0 mmol）And acetic acid（5 millis
Rise）, 110 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the petroleum ether that reaction is obtained after terminating:Ethyl acetate=4:1) target, is obtained
Product（Yield 93%）.The analyze data of product is as follows：1H NMR (400 MHz, CDCl3): δ 5.16 (s, 1H), 4.23
– 3.92 (m, 8H), 1.12 (t, J = 7.4 Hz, 6H), 1.08 (t, J = 7.0 Hz, 6H)。
Embodiment 26：The synthesis of 2- diphenylphosphine perester radical -1,3- diphenyl -1,3- propanedione
With 1,3- diphenyl -1,3- propanedione, triphenyl phosphite as raw material, its reactions steps is as follows：
1,3- diphenyl -1,3- propanedione is added in reaction bulb（0.224 g, 1.0 mmol）, triphenyl phosphorous acid
Ester（2.282 g, 7.0 mmol）, cuprous bromide（0.014 g, 0.1 mmol）, lauroyl peroxide（2.80 g, 7.0 mmol）
And acetic acid（5 milliliters）, 110 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the petroleum ether that reaction is obtained after terminating:Ethyl acetate=4:1) target, is obtained
Product（Yield 68%）.The analyze data of product is as follows：1H NMR (400 MHz, DMSO-d 6) δ 8.00–7.50 (m,
10H), 7.45–7.10 (m, 10H), 7.02 (d, J = 23.3 Hz, 1H)。
Embodiment 27：The synthesis of 2- diethyl phosphonate base hexanoyl ethyl acetate
Using hexanoyl ethyl acetate, triethyl phosphorite as raw material, its reactions steps is as follows：
Hexanoyl ethyl acetate is added in reaction bulb（0.186 g, 1 mmol）, triethyl phosphorite（1.162 g,
7.0 mmol）, cuprous bromide（0.014 g, 0.1 mmol）, lauroyl peroxide（2.80 g, 7.0 mmol）And acetic acid（5 millis
Rise）, 110 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the petroleum ether that reaction is obtained after terminating:Ethyl acetate=4:1) target, is obtained
Product（Yield 88%）.The analyze data of product is as follows：1H NMR (400 MHz, CDCl3): δ5.86 (d, J = 23.3
Hz, 1H), 4.23 – 3.92 (m, 6H), 2.34 (t, J = 6.0 Hz, 2H), 1.60 –1.20 (m, 6H),
1.12 (t, J = 7.4 Hz, 3H), 1.08 (t, J = 7.0 Hz, 6H), 0.90 (t, J = 6.0 Hz, 3H)。
Claims (9)
1. the method that one kind prepares 2- phosphonate group -1,3- Dicarbonyl derivatives, it is characterised in that comprise the following steps：By 1,
3- Dicarbonyl derivatives, trialkyl phosphite, organic peroxide and copper catalyst are added in solvent, anti-in 70~120 DEG C
Should, obtain 2- phosphonate group -1,3- Dicarbonyl derivatives；
The 1,3- Dicarbonyl derivatives are as shown in following chemical structure of general formula：
Wherein R1It is selected from：One kind in alkyl, aryl or alkoxy；R2It is selected from：One kind in alkyl, aryl or alkoxy；
The chemical formula of the trialkyl phosphite derivative is：P(OR3)3；R3For alkyl or aryl；
The organic peroxide is as shown in following chemical structure of general formula：
Wherein R4It is selected from：One kind in hydrogen, the tert-butyl group and benzoyl；R5It is selected from：One kind in hydrogen, the tert-butyl group and benzoyl；
The chemical formula of the copper catalyst is CuXn, wherein X is selected from：One kind in Cl, Br, I or trifluoromethanesulfonic acid base；N is 1
Or 2；
The solvent is selected from：One kind in ethanol, acetonitrile, acetic acid, propionic acid, 1,2- dichloroethanes, toluene, dimethylformamide；
2- phosphonate groups -1,3- the Dicarbonyl derivatives are as shown in following chemical structure of general formula：
。
2. the preparation method of 2- phosphonate groups -1,3- Dicarbonyl derivatives according to claim 1, it is characterised in that：It is described
1,3- Dicarbonyl derivatives are selected from 1,3- diphenyl -1,3- propanedione, 1-（4- aminomethyl phenyls）- 3- diphenylpropane-1,3-dione (DPPO)s, 1,
3- bis- (4- aminomethyl phenyls) -1,3- propanedione, 1,3- bis- (4- methoxyphenyls) -1,3- propanedione, 1-（4- chlorphenyls）-3-
Diphenylpropane-1,3-dione (DPPO), 1-（4- bromophenyls）-3-（4- methoxyphenyls）- 1,3- propanedione, 1,3- bis- (4- bromophenyls) -1,
3- propanedione, 1-（4- bromophenyls）- 3- diphenylpropane-1,3-dione (DPPO)s, 1-（4- methoxyphenyls）- 3- diphenylpropane-1,3-dione (DPPO)s, 1-
（3- bromophenyls）- 3- diphenylpropane-1,3-dione (DPPO)s, DPM dpm,dipivalomethane, 1- phenyl -1,3- pentanediones, 5,5-
Dimedone -1,3,3- phenyl -3- oxopropanoates, 3-（4- bromophenyls）- 3- oxopropanoates, 3-（4- first
Phenyl）- 3- oxopropanoates, 3-（2- methoxyphenyls）- 3- oxopropanoates, 3-（2- bromophenyls）- 3- oxos
Ethyl propionate, 3-（4- aminomethyl phenyls）- 3- oxopropanoates, 3-（4- chlorphenyls）- 3- oxopropanoates, propionyl acetic acid second
One kind in ester, diethyl malonate.
3. the preparation method of 2- phosphonate groups -1,3- Dicarbonyl derivatives according to claim 1, it is characterised in that：It is described
Trialkyl phosphite is selected from trimethyl phosphite, triethyl phosphorite, tri isopropyl phosphorite, tributyl phosphorous acid
One kind in ester, triphenyl phosphite.
4. the preparation method of 2- phosphonate groups -1,3- Dicarbonyl derivatives according to claim 1, it is characterised in that：Massage
You compare, 1,3- Dicarbonyl derivatives: trialkyl phosphite: organic peroxide: copper catalyst is 1:（1~8）∶（1~8）∶
(0.05~0.2）.
5. the preparation method of 2- phosphonate groups -1,3- Dicarbonyl derivatives according to claim 4, it is characterised in that：Massage
You compare, 1,3- Dicarbonyl derivatives: trialkyl phosphite: organic peroxide: copper catalyst is 1: 7: 7: 0.1.
6. the preparation method of 2- phosphonate groups -1,3- Dicarbonyl derivatives according to claim 1, it is characterised in that：Utilize
Thin-layer chromatography tracking reaction is until be fully completed.
7. the preparation method of 2- phosphonate groups -1,3- Dicarbonyl derivatives according to claim 1, it is characterised in that：It is described
Reaction is carried out in atmosphere.
8. the preparation method of 2- phosphonate groups -1,3- Dicarbonyl derivatives according to claim 1, it is characterised in that：Reaction
Column chromatography for separation purification processes are carried out to product after end.
9. the preparation method of 2- phosphonate groups -1,3- Dicarbonyl derivatives according to claim 8, it is characterised in that：It is described
Using petrol ether/ethyl acetate as eluant, eluent during column chromatography for separation purification processes.
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| SU1203095A1 (en) * | 1984-05-22 | 1986-01-07 | Казанский Ордена Ленина И Ордена Трудового Красного Знамени Государственный Университет Им.В.И.Ульянова-Ленина | Method of producing 2-phosphonsubstituted 1,3-diketones |
| CN104277072A (en) * | 2014-09-30 | 2015-01-14 | 江苏强盛功能化学股份有限公司 | Method for preparing (E)-2-aryl vinyl phosphonate derivatives |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| SU1203095A1 (en) * | 1984-05-22 | 1986-01-07 | Казанский Ордена Ленина И Ордена Трудового Красного Знамени Государственный Университет Им.В.И.Ульянова-Ленина | Method of producing 2-phosphonsubstituted 1,3-diketones |
| CN104277072A (en) * | 2014-09-30 | 2015-01-14 | 江苏强盛功能化学股份有限公司 | Method for preparing (E)-2-aryl vinyl phosphonate derivatives |
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| Convenient and Efficient Syntheses of 4-Hydroxy-2(E)-nonenal and 4-Oxo-2(E)-nonenal;Reshma F. Kurangia et al.;《Lipids》;20060930;第41卷(第9期);第877-880页 * |
| Isomerization of alkyl phosphites. V. The synthesis of phosphonoacetic and phosphonomalonic esters;Kosolapoff et al.;《Journal of the American Chemistry》;19460630;第1103-1105页 * |
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