CN106432329B - A kind of beta-cyano phosphono analog derivative and the preparation method and application thereof - Google Patents

A kind of beta-cyano phosphono analog derivative and the preparation method and application thereof Download PDF

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CN106432329B
CN106432329B CN201610813913.4A CN201610813913A CN106432329B CN 106432329 B CN106432329 B CN 106432329B CN 201610813913 A CN201610813913 A CN 201610813913A CN 106432329 B CN106432329 B CN 106432329B
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phosphine oxide
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邹建平
张沛之
张令
李建安
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Suzhou University
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Abstract

The invention discloses a kind of β cyano phosphono analog derivatives and the preparation method and application thereof.The present invention is starting material using alkene, and raw material is easy to get, and type is extensive；The product types obtained using the method for the present invention are various, widely used, not only can be used directly, but also can be used for synthesis of organo-phosphines fire retardant, drug and extractant；In addition, method and step disclosed by the invention is simple, reaction condition is mild, target product high income, the small, operation of pollution and last handling process are simple, it is suitable for industrialized production.

Description

A kind of beta-cyano phosphono analog derivative and the preparation method and application thereof
Technical field
The invention belongs to the preparing technical fields of organic compound, and in particular to a kind of system of beta-cyano phosphono analog derivative Preparation Method.
Background technology
Organic phosphine fire retardant is functional, has fire-retardant, plasticising dual function, and can replace halogenation flame retardant, With good development prospect.The mechanism of action of this based flame retardant is organic phosphine compound by the oxyacid for thermally decomposing to generate phosphorus, This acid can make substrate surface generate the coke layer of graphite-like, the coke layer is fire retardant, it is heat-insulated, oxygen barrier, burning can be made to suffocate（Ginseng It examines：Tribute is long-living, the synthesis of monarch's Zhu Li phosphorus flame retardants and application Technological Economy of Chemical Engineering 2002,2:9;2, Jingjing perhaps, The progress colloids and polymer of the phosphorus series non-halogen fire retardants such as Hao Huijun, 2005,23 (2):39;3, Demir H., Balkose D., Ulku S.Influence of surface modification of fillers and polymer on flammability and tensile behaviour of polypropylene-composites. Polymer Degradation and stability, 2006, 91(5):1079;4, Demir H., Arkis E., Balkose D. et al. Synergistic effect of natural zeoliteson flame retardant additives.Polymer Degredation and Stability, 2005, 89(3):478.）.
Gu Lulu et al. discloses a kind of N- (5- hydrogenation of hydroxypentylaldehyd -5- bases) -3- dimethoxy phosphono propionamides（A）It is fire-retardant Agent, and test its flame retardant effect in the leather.The result shows that the fire retardant has good flame retardant effect, and to leather Performance itself influences little, fire retardant（A）Synthetic route it is as follows：
This method needs to use highly basic sodium methoxide and acrylamide, and acrylamide has potential neurotoxicity, heredity poison Property and carcinogenicity；In addition, the substance is easy polymerization when reaching 85 degree or more.
Alexandre discloses phosphorylated-amine formylated indole derivative（B）Synthetic method, compound B can be used as The efabirenz of HIV-1 infectious diseases（With reference to：Alexandre F. R., Amador A., Bot S., Caillet C., Convard T., Jakubik J., Musiu C., Poddesu B., Vargiu L., Liuzzi M., Roland A., Seifer M., Standring D., Storer R., Dousson C. B. Synthesis and Biological Evaluation of Aryl-phospho-indole as Novel HIV-1 Non- nucleoside Reverse Transcriptase Inhibitors. J. Med. Chem. 2011, 54, 392.）. The synthetic route of disclosed compound B is as follows：
This method is obtained using indole -2-ethyl formate as raw material by processes such as N- sulfonylations, bromo, phosphorylated, de- sulfuryls To compound B.This method route is long, severe reaction conditions, including need to use butyl lithium, grignard reagent and at -100 DEG C it is anti- It answers.
In addition, the compound of phosphorous acyl-amides structural unit can form stable cooperation with group of the lanthanides/actinide ion Object, for producing group of the lanthanides/actinide metals and removing micro group of the lanthanides/actinide metal ion in water；But published compound Synthetic method using N,N-DMAA as raw material, which is irritating to the skin effect, steam or mist to eyes, viscous Film and the upper respiratory tract have stimulation.Method disclosed in this patent can be to avoid N, the use of N- dimethacrylamide.
The prior art also discloses the synthetic method and bioactivity of aminophosphonic acid derivatives, wherein D1~D4 pairs of compound The tools such as streptococcus cinereus, Strepiomyces lavendulae, streptomyces fradiae, wine red streptomyces, penicillium purpurogenum, Achromobacter xylosoxidans There is preferable inhibitory activity；Meanwhile D1~D4 also has good inhibiting effect to hiv protease and serine protease（With reference to： Obojska A., Lejczak B. Utilisation of structurally diverse organophosphonates by Streptomycetes. Appl Microbiol Biotechnol, 2003, 62:557；Klimek-Ochab M., Obojska A., Picco A. M., Lejczak B. Isolation and characterization of two new microbial strains capable of degradation of the naturally occurring organophosphonate–ciliatine. Biodegradation, 2007, 18:223）.
But there are many deficiencies for the synthetic method of existing disclosed compound, as raw material is difficult to obtain, reaction condition is severe It carves, the deficiencies of reaction step is more, toxicity is big, therefore develops that reaction condition is mild, applied widely, reaction step is succinct, original It is extremely important that material synthetic method simple and easy to get prepares beta-cyano phosphono analog derivative.
Invention content
It is prepared the object of the present invention is to provide a kind ofβThe method of cyano phosphono analog derivative and related derivative product, tool Have the advantages that raw material sources are simple, reaction condition is mild, reaction process is short, post-processing is simple, yield is high；And the present invention discloses Method can overcome the big problem of prior art toxicity to avoid the use of sodium methoxide and acrylamide.
To achieve the above object of the invention, the technical solution adopted by the present invention is：It is a kind of to prepare beta-cyano phosphono analog derivative Method, include the following steps：Alkene, phosphorus reagent, trimethyl cyanoalkysilane, copper catalyst and manganese acetate are dissolved in solvent, It is reacted at room temperature ~ 100 DEG C, obtains beta-cyano phosphono analog derivative；
The alkene is as shown in following chemical structure of general formula：
Wherein R is selected from：One kind in hydrogen, alkyl, N- alkyl phthalic imides base, aryl alkyl, ethyl acetate base； Or R is one kind in following group：
、、
Wherein R1It is selected from：One kind in alkyl, alkoxy, aryl, halogen, nitro, ester group；X is selected from：O, one in S, N Kind；R2It is selected from：One kind in alkyl, alkoxy, halogen；
The phosphorus reagent is as shown in having structure general formula：
Wherein R3It is selected from：One kind of alkoxy, alkyl, aryl；
The beta-cyano phosphono analog derivative is as shown in following chemical structure of general formula：
The solvent is selected from：Methanol, ethyl alcohol, acetonitrile, acetone, ethyl acetate, water, 1,2- dichloroethanes, toluene, N, N- bis- One kind in methylformamide, N-Methyl pyrrolidone, glacial acetic acid.
In above-mentioned technical proposal, aryl alkyl indicates to be connected with alkyl on phenyl ring, and alkyl is connected directly with double bond；The alkene It is selected from:Ethylene, nitroethylene, N-Boc vinyl amines, styrene, 4- methyl styrenes, 4- methoxy styrenes, 4- fluorophenethyls Alkene, 4- chlorostyrenes, 4- bromstyrols, 4- cyano styrenes, 4- nitrostyrolenes, 4- vinylbenzoates, 3- methyl Styrene, 3- chlorostyrenes, 3- bromstyrols, 2-methyl styrene, 2- fluorobenzene ethenes, 2- chlorostyrenes, 2- bromstyrols, 2- Naphthalene ethylene, Beta-methyl styrene, benzo cyclopentene, benzo cyclohexene, 2- vinyl furans, 2- vinyl thiophenes, 2- vinyl Pyrroles, 2- vinylpyridines, 3- vinylpyridines, 4-vinylpridine, N- cyclobutenyls phthalimide, N- decene base are adjacent One kind in phthalimide, indoles, 3- phenylpropens, 3- phenylbutenes, positive octene, positive decene, vinyl acetate；It is described Phosphorus reagent is selected from:Dimethyl phosphite, diethyl phosphite, dimethyl phosphine oxide, diphenyl phosphine oxide, two（4- methoxybenzenes Base）Phosphine oxide, two（4- cyano-phenyls）One kind in phosphine oxide.
In above-mentioned technical proposal, thin-layer chromatography chromatography is utilized（TLC）Tracking reaction is until be fully completed.
In above-mentioned technical proposal, in molar ratio, alkene: phosphorus reagent: cyano trimethyl silane: copper catalyst: manganese acetate 1 ∶（1~3）∶（1~3）∶（0.1~0.3）∶（1~3）.
In above-mentioned technical proposal, column chromatography for separation purification processes are carried out to product after reaction.
The reaction process of above-mentioned technical proposal is represented by：
Due to the application of the above technical scheme, the present invention has following advantages compared with prior art:
1, the present invention is starting material using alkene derivatives, in phosphorus reagent, trimethyl cyanoalkysilane, copper catalyst and acetic acid In the presence of manganese, beta-cyano phosphono analog derivative is prepared for the first time, is not necessarily to noble metal catalyst and acrylic amide raw material；Tool Have the advantages that raw material is easy to get, toxicity is low, of low cost, product species are more.
2, the method disclosed by the invention for preparing beta-cyano phosphono analog derivative is applied widely, is applicable not only to aryl alkene Hydrocarbon and heteroaryl alkene, are also applied for alkyl alkene, greatly enrich the chemical constitution of product, have expanded phosphono analog derivative Application range.
3, cyanylation agent small toxicity used in the method disclosed by the invention for preparing beta-cyano phosphono analog derivative, convenient for behaviour Make, environmental-friendly, the recyclable recycling of solvent for use；It overcomes raw material in the prior art and there are problems that larger toxicity.
4, the method and step disclosed by the invention for preparing beta-cyano phosphono analog derivative is simple, reaction condition is mild, reaction Time is short；Single step reaction is only needed, at room temperature ~ 100 DEG C, product, and the receipts of target product can be prepared at preferably 50 DEG C Rate height, operation and last handling process are simple, are suitable for industrialized production.
Specific implementation mode
With reference to embodiment, the invention will be further described：
Embodiment one：The synthesis of 2- phenyl -3- diphenyl phosphine oxide base propionitrile
Using styrene, diphenyl phosphine oxide as raw material, reaction step is as follows：
Styrene is added in reaction bulb（0.042 gram, 0.4 mmol）, diphenyl phosphine oxide（0.081 gram, 0.4 mmol）, Trimethyl cyanoalkysilane（0.040 gram, 0.4 mmol）, CuCl (0.04g, 0.04 mmol), and manganese acetate (0.322 gram, 1.2 ) and toluene mmol（3 mL）, under argon gas protection, 100 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 73%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 7.92 – 7.81 (m, 2H), 7.77 – 7.69 (m, 2H), 7.58 – 7.48 (m, 4H), 7.46 – 7.37 (m, 4H), 7.33 – 7.23 (m, 3H), 4.39 (td, J = 9.4, 5.8 Hz, 1H), 3.12 – 2.94 (m, 1H), 2.95 – 2.56 (m, 1H)。
Embodiment two：2-（4- tolyls）The synthesis of -3- diphenyl phosphine oxide base propionitrile
Using 4- methyl styrenes, diphenyl phosphine oxide as raw material, reaction step is as follows：
4- methyl styrenes are added in reaction bulb（0.047 gram, 0.4 mmol）, diphenyl phosphine oxide（0.081 gram, 0.4 mmol）, trimethyl cyanoalkysilane（0.040 gram, 0.4 mmol）, CuCl (0.04g, 0.04 mmol), manganese acetate (0.322 gram, 1.2 mmol) and toluene（3 mL）, under argon gas protection, 90 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 72%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 7.79 (dd, J = 10.7, 7.8 Hz, 2H), 7.62 – 7.48 (m, 5H), 7.45 (t, J = 7.3 Hz, 1H), 7.35 (t, J = 6.6 Hz, 2H), 7.18 (d, J = 7.8 Hz, 2H), 7.02 (d, J = 7.6 Hz, 2H), 4.41 (d, J = 6.6 Hz, 1H), 3.01 (dt, J = 15.0, 7.6 Hz, 1H), 2.76 (t, J = 14.9 Hz, 1H), 2.26 (s, 3H)。
Embodiment three：2-（4- methoxyphenyls）The synthesis of -3- diphenyl phosphine oxide base propionitrile
Using 4- methoxy styrenes, diphenyl phosphine oxide as raw material, reaction step is as follows：
4- methoxy styrenes are added in reaction bulb（0.054 gram, 0.4 mmol）, diphenyl phosphine oxide（0.162 gram, 0.8 mmol）, trimethyl cyanoalkysilane（0.040 gram, 0.4 mmol）, CuCl (0.04g, 0.04 mmol), manganese acetate (0.322 gram, 1.2 mmol) and N,N-dimethylformamide（3 mL）, under argon gas protection, 80 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 70%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 7.78 (s, 2H), 7.63 – 7.49 (m, 5H), 7.43 (s, 1H), 7.35 (s, 2H), 7.21 (s, 2H), 6.72 (s, 2H), 4.42 (s, 1H), 3.73 (s, 3H), 3.03 (s, 1H), 2.80 (s, 1H)。
Example IV：2-（4- fluorophenyls）The synthesis of -3- diphenyl phosphine oxide base propionitrile
Using 4- fluorobenzene ethenes, diphenyl phosphine oxide as raw material, reaction step is as follows：
4- fluorobenzene ethenes are added in reaction bulb（0.049 gram, 0.4 mmol）, diphenyl phosphine oxide（0.162 gram, 0.8 mmol）, trimethyl cyanoalkysilane（0.079 gram, 0.8 mmol）, CuCl (0.08g, 0.08 mmol), manganese acetate (0.322 gram, 1.2 mmol) and N,N-dimethylformamide（3 mL）, under argon gas protection, 70 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 87%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 7.82 (dd, J = 11.3, 7.7 Hz, 2H), 7.68 – 7.46 (m, 6H), 7.45 – 7.26 (m, 4H), 6.93 (t, J = 8.5 Hz, 2H), 4.76 – 4.28 (m, 1H), 3.29 – 2.97 (m, 1H), 2.89 – 2.46 (m, 1H)。
Embodiment five：2-（4- chlorphenyls）The synthesis of -3- diphenyl phosphine oxide base propionitrile
Using 4- chlorostyrenes, diphenyl phosphine oxide as raw material, reaction step is as follows：
4- chlorostyrenes are added in reaction bulb（0.055 gram, 0.4 mmol）, diphenyl phosphine oxide（0.162 gram, 0.8 mmol）, trimethyl cyanoalkysilane（0.079 gram, 0.8 mmol）, CuCl (0.08g, 0.08 mmol), manganese acetate (0.322 gram, 1.2 mmol) and N,N-dimethylformamide（3 mL）, under argon gas protection, 60 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 89%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ7.80 (s, 2H), 7.53 (d, J = 23.9 Hz, 6H), 7.39 (s, 2H), 7.32 – 7.12 (m, 4H), 4.49 (s, 1H), 2.98 (d, J = 99.4 Hz, 2H)。
Embodiment six：2-（4- bromophenyls）The synthesis of -3- diphenyl phosphine oxide base propionitrile
Using 4- bromstyrols, diphenyl phosphine oxide as raw material, reaction step is as follows：
4- bromstyrols are added in reaction bulb（0.073 gram, 0.4 mmol）, diphenyl phosphine oxide（0.243 gram, 1.2 mmol）, trimethyl cyanoalkysilane（0.079 gram, 0.8 mmol）, CuCl (0.08g, 0.08 mmol), manganese acetate (0.322 gram, 1.2 mmol) and N,N-dimethylformamide（3 mL）, under argon gas protection, 50 DEG C of reactions；TLC tracking reaction until tie completely Beam；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 83%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 7.84 (s, 2H), 7.70 – 7.50 (m, 6H), 7.39 (dd, J = 20.2, 13.3 Hz, 4H), 7.25 (d, J = 7.0 Hz, 2H), 4.52 (s, 1H), 2.99 (d, J = 95.5 Hz, 2H)。
Embodiment seven：2-（3- chlorphenyls）The synthesis of -3- diphenyl phosphine oxide base propionitrile
Using 3- chlorostyrenes, diphenyl phosphine oxide as raw material, reaction step is as follows：
3- chlorostyrenes are added in reaction bulb（0.055 gram, 0.4 mmol）, diphenyl phosphine oxide（0.243 gram, 1.2 mmol）, trimethyl cyanoalkysilane（0.079 gram, 0.8 mmol）, CuCl (0.08g, 0.08 mmol), manganese acetate (0.107 gram, 0.4 mmol) and methanol（3 mL）, under argon gas protection, 40 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 81%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 7.82 (s, 2H), 7.58 (dt, J = 44.4, 16.5 Hz, 6H), 7.42 (d, J = 6.7 Hz, 2H), 7.36 – 7.15 (m, 4H), 4.51 (s, 1H), 3.08 (s, 1H), 2.84 (s, 1H)。
Embodiment eight：2-（3- aminomethyl phenyls）The synthesis of -3- diphenyl phosphine oxide base propionitrile
Using 3- methyl styrenes, diphenyl phosphine oxide as raw material, reaction step is as follows：
3- methyl styrenes are added in reaction bulb（0.047 gram, 0.4 mmol）, diphenyl phosphine oxide（0.243 gram, 1.2 mmol）, trimethyl cyanoalkysilane（0.079 gram, 0.8 mmol）, CuCl (0.08g, 0.08 mmol), manganese acetate (0.107 gram, 0.4 mmol) and methanol（3 mL）, under argon gas protection, 30 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 79%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 7.84 – 7.72 (m, 2H), 7.63 – 7.47 (m, 5H), 7.44 (t, J = 6.9 Hz, 1H), 7.35 (td, J = 7.4, 2.8 Hz, 2H), 7.17 – 7.06 (m, 3H), 4.41 (dt, J = 9.7, 7.3 Hz, 1H), 3.14 – 2.92 (m, 1H), 2.76 (ddd, J = 15.2, 10.5, 6.5 Hz, 1H), 2.24 (s, 3H)。
Embodiment nine：2-（3- methoxyphenyls）The synthesis of -3- diphenyl phosphine oxide base propionitrile
Using 3- methoxy styrenes, diphenyl phosphine oxide as raw material, reaction step is as follows：
3- methoxy styrenes are added in reaction bulb（0.054 gram, 0.4 mmol）, diphenyl phosphine oxide（0.243 gram, 1.2 mmol）, trimethyl cyanoalkysilane（0.079 gram, 0.8 mmol）, CuCl (0.12g, 0.12 mmol), manganese acetate (0.107 gram, 0.4 mmol) and methanol（3 mL）, under argon gas protection, room temperature reaction；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 78%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 7.86 – 7.71 (m, 2H), 7.64 – 7.41 (m, 6H), 7.36 (td, J = 7.5, 2.9 Hz, 2H), 7.15 (t, J = 8.0 Hz, 1H), 6.90 (d, J = 7.7 Hz, 1H), 6.81 (d, J = 1.9 Hz, 1H), 6.72 (dd, J = 8.3, 2.3 Hz, 1H), 4.41 (dt, J = 9.8, 7.3 Hz, 1H), 3.73 (s, 3H), 3.01 (ddd, J = 15.3, 9.0, 8.1 Hz, 1H), 2.77 (ddd, J = 15.2, 10.6, 6.4 Hz, 1H)。
Embodiment ten：2-（2- fluorophenyls）The synthesis of -3- diphenyl phosphine oxide base propionitrile
Using 2- fluorobenzene ethenes, diphenyl phosphine oxide as raw material, reaction step is as follows：
2- fluorobenzene ethenes are added in reaction bulb（0.049 gram, 0.4 mmol）, diphenyl phosphine oxide（0.243 gram, 1.2 mmol）, trimethyl cyanoalkysilane（0.079 gram, 0.8 mmol）, CuCl (0.12g, 0.12 mmol), manganese acetate (0.215 gram, 0.8 mmol) and methanol（3 mL）, under argon gas protection, 50 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 89%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ7.87 – 7.69 (m, 2H), 7.66 – 7.46 (m, 5H), 7.46 – 7.29 (m, 4H), 7.19 (ddd, J = 15.2, 5.3, 1.6 Hz, 1H), 7.02 (t, J = 7.2 Hz, 1H), 6.94 – 6.83 (m, 1H), 4.58 (dd, J = 16.6, 7.3 Hz, 1H), 2.96 (dddd, J = 16.6, 15.1, 10.0, 7.3 Hz, 2H)。
Embodiment 11：2-（2- chlorphenyls）The synthesis of -3- diphenyl phosphine oxide base propionitrile
Using 2- chlorostyrenes, diphenyl phosphine oxide as raw material, reaction step is as follows：
2- chlorostyrenes are added in reaction bulb（0.055 gram, 0.4 mmol）, diphenyl phosphine oxide（0.162 gram, 0.8 mmol）, trimethyl cyanoalkysilane（0.120 gram, 1.2 mmol）, CuCl (0.12g, 0.12 mmol), manganese acetate (0.215 gram, 0.8 mmol) and ethyl alcohol（3 mL）, under argon gas protection, 50 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 86%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 7.82 – 7.75 (m, 2H), 7.70 – 7.62 (m, 2H), 7.59 – 7.44 (m, 5H), 7.42 – 7.34 (m, 2H), 7.28 – 7.23 (m, 1H), 7.22 – 7.14 (m, 2H), 4.74 (ddd, J = 9.7, 8.0, 6.5 Hz, 1H), 2.93 (ddd, J = 10.5, 7.2, 3.3 Hz, 2H)。
Embodiment 12：2-（2- bromophenyls）The synthesis of -3- diphenyl phosphine oxide base propionitrile
Using 2- bromstyrols, diphenyl phosphine oxide as raw material, reaction step is as follows：
2- bromstyrols are added in reaction bulb（0.073 gram, 0.4 mmol）, diphenyl phosphine oxide（0.162 gram, 0.8 mmol）, trimethyl cyanoalkysilane（0.120 gram, 1.2 mmol）, CuCl (0.12g, 0.12 mmol), manganese acetate (0.215 gram, 0.8 mmol) and ethyl alcohol（3 mL）, under argon gas protection, 50 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 76%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 7.75 (ddd, J = 43.2, 11.5, 7.5 Hz, 4H), 7.62 – 7.37 (m, 8H), 7.25 (d, J = 6.0 Hz,1H), 7.11 (t, J = 7.6 Hz, 1H), 4.76 (dd, J = 16.4, 7.0 Hz, 1H), 2.84 (dd, J = 64.2, 54.8 Hz, 2H)。
Embodiment 13：2-（2- aminomethyl phenyls）The synthesis of -3- diphenyl phosphine oxide base propionitrile
Using 2-methyl styrene, diphenyl phosphine oxide as raw material, reaction step is as follows：
2-methyl styrene is added in reaction bulb（0.047 gram, 0.4 mmol）, diphenyl phosphine oxide（0.162 gram, 0.8 mmol）, trimethyl cyanoalkysilane（0.120 gram, 1.2 mmol）, CuBr (0.056g, 0.04 mmol), manganese acetate (0.215 Gram, 0.8 mmol) and ethyl alcohol（3 mL）, under argon gas protection, 50 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 82%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 7.87 – 7.49 (m, 6H), 7.43 (dd, J = 25.6, 18.5 Hz, 4H), 7.26 (s, 1H), 7.17 – 6.98 (m, 3H), 4.67 – 4.28 (m, 1H), 3.17 – 2.58 (m, 2H), 2.52 – 2.16 (m, 3H)。
Embodiment 14：2-（2,6- dichlorophenyls）The synthesis of -3- diphenyl phosphine oxide base propionitrile
With 2,6- dichlorostyrenes, diphenyl phosphine oxide as raw material, reaction step is as follows：
2,6- dichlorostyrenes are added in reaction bulb（0.069 gram, 0.4 mmol）, diphenyl phosphine oxide（0.162 gram, 0.8 mmol）, trimethyl cyanoalkysilane（0.120 gram, 1.2 mmol）, CuBr (0.056g, 0.04 mmol), manganese acetate (0.322 Gram, 1.2 mmol) and acetonitrile（3 mL）, under argon gas protection, 50 DEG C of reactions；TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 84%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 7.93 – 7.80 (m, 2H), 7.74 – 7.53 (m, 5H), 7.47 (dd, J = 12.8, 6.4 Hz, 1H), 7.39 (td, J = 7.4, 2.9 Hz, 2H), 7.28 – 7.21 (m, 2H), 7.17 – 7.07 (m, 1H), 5.43 (dt, J = 10.0, 7.1 Hz, 1H), 3.29 (ddd, J = 15.3, 11.1, 6.8 Hz, 1H), 3.18 – 3.01 (m, 1H)。
Embodiment 15：2-（2- naphthalenes）The synthesis of -3- diphenyl phosphine oxide base propionitrile
Using 2- naphthalenes ethylene, diphenyl phosphine oxide as raw material, reaction step is as follows：
2- naphthalene ethylene is added in reaction bulb（0.062 gram, 0.4 mmol）, diphenyl phosphine oxide（0.162 gram, 0.8 mmol）, trimethyl cyanoalkysilane（0.120 gram, 1.2 mmol）, CuBr (0.056g, 0.04 mmol), manganese acetate (0.322 Gram, 1.2 mmol) and acetonitrile（3 mL）, under argon gas protection, 50 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 88%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 7.87 – 7.65 (m, 6H), 7.61 – 7.43 (m, 7H), 7.39 (d, J = 8.3 Hz, 1H), 7.28 – 7.13 (m, 3H), 4.64 (d, J = 8.0 Hz, 1H), 3.27 – 2.97 (m, 1H), 3.00 – 2.72 (m, 1H)。
Embodiment 16：2-（4- cyano-phenyls）The synthesis of -3- diphenyl phosphine oxide base propionitrile
Using 4- cyano styrenes, diphenyl phosphine oxide as raw material, reaction step is as follows：
4- cyano styrenes are added in reaction bulb（0.052 gram, 0.4 mmol）, diphenyl phosphine oxide（0.162 gram, 0.8 mmol）, trimethyl cyanoalkysilane（0.079 gram, 0.8 mmol）, CuBr (0.112g, 0.08 mmol), manganese acetate (0.322 Gram, 1.2 mmol) and acetonitrile（3 mL）, under argon gas protection, 50 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 82%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 7.80 – 7.71 (m, 2H), 7.63 – 7.42 (m, 10H), 7.40 – 7.32 (m, 2H), 4.66 – 4.45 (m, 1H), 3.14 – 2.96 (m, 1H), 2.89 – 2.71 (m, 1H)。
Embodiment 17：2-（4- carbomethoxvphenvls）The synthesis of -3- diphenyl phosphine oxide base propionitrile
Using 4- vinylbenzoates, diphenyl phosphine oxide as raw material, reaction step is as follows：
4- vinylbenzoates are added in reaction bulb（0.065 gram, 0.4 mmol）, diphenyl phosphine oxide（0.162 Gram, 0.8 mmol）, trimethyl cyanoalkysilane（0.079 gram, 0.8 mmol）, CuBr (0.168g, 0.12 mmol), manganese acetate (0.322 gram, 1.2 mmol) and acetonitrile（3 mL）, under argon gas protection, 50 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 84%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 7.93 (d, J = 8.1 Hz, 2H), 7.83 (dd, J = 11.4, 7.6 Hz, 2H), 7.59 (dd, J = 18.9, 9.8 Hz, 5H), 7.44 (ddd, J = 14.1, 11.2, 6.3 Hz, 5H), 4.56 (dd, J = 16.6, 7.2 Hz, 1H), 3.94 (s, 3H), 3.19 – 3.00 (m, 1H), 2.88 – 2.74 (m, 1H)。
Embodiment 18：The synthesis of 2- phenyl -3- diphenyl phosphine oxide base butyronitrile
WithβAs raw material, reaction step is as follows for methyl styrene, diphenyl phosphine oxide：
It is added in reaction bulbβMethyl styrene（0.047 gram, 0.4 mmol）, diphenyl phosphine oxide（0.162 gram, 0.8 mmol）, trimethyl cyanoalkysilane（0.079 gram, 0.8 mmol）, CuI (0.076g, 0.04 mmol), manganese acetate (0.322 gram, 1.2 mmol) and acetone（3 mL）, under argon gas protection, 50 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 80%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 7.92 – 7.63 (m, 4H), 7.50 (qdd, J = 8.2, 6.6, 3.9 Hz, 6H), 7.36 – 7.27 (m, 4H), 7.23 (dd, J = 6.0, 3.4 Hz, 1H), 4.51 (dd, J = 9.0, 4.0 Hz, 1H), 2.88 – 2.60 (m, 1H), 1.41 – 1.24 (m, 3H)。
Embodiment 19：The synthesis of 2- diphenyl phosphine oxide base -2,3- indane -1- formonitrile HCNs
Using indenes, diphenyl phosphine oxide as raw material, reaction step is as follows：
Indenes is added in reaction bulb（0.046 gram, 0.4 mmol）, diphenyl phosphine oxide（0.162 gram, 0.8 mmol）, front three Base cyanoalkysilane（0.079 gram, 0.8 mmol）, CuI (0.152g, 0.08 mmol), manganese acetate (0.322 gram, 1.2 mmol) And acetone（3 mL）, under argon gas protection, 50 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 81%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 8.02 – 7.82 (m, 4H), 7.66 – 7.46 (m, 6H), 7.35 (dd, J = 8.1, 4.7 Hz, 1H), 7.26 (dd, J = 6.1, 2.7 Hz, 2H), 7.18 (s, 1H), 4.64 (dd, J = 13.8, 9.5 Hz, 1H), 3.73 – 3.58 (m, 1H), 3.45 (td, J = 15.6, 9.8 Hz, 1H), 3.11 (ddd, J = 16.1, 9.3, 4.0 Hz, 1H)。
Embodiment 20：NThe synthesis of (3- cyano -4- diphenyl phosphine oxide base butyl- 1- yls) phthalimide
WithNAs raw material, reaction step is as follows for cyclobutenyl phthalimide, diphenyl phosphine oxide：
It is added in reaction bulbNCyclobutenyl phthalimide（0.081 gram, 0.4 mmol）, diphenyl phosphine oxide （0.162 gram, 0.8 mmol）, trimethyl cyanoalkysilane（0.079 gram, 0.8 mmol）, CuI (0.228g, 0.12 mmol), vinegar Sour manganese (0.322 gram, 1.2 mmol) and acetone（3 mL）, under argon gas protection, 50 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 78%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 7.84 (dd, J = 5.4, 3.0 Hz, 2H), 7.81 – 7.70 (m, 7H), 7.56 – 7.44 (m, 5H), 3.84 (t, J = 6.3 Hz, 2H), 3.13 (s, 1H), 2.85 – 2.73 (m, 1H), 2.71 – 2.58 (m, 1H), 2.30 (ddd, J = 13.7, 11.3, 7.0 Hz, 1H), 2.13 (ddd, J = 14.3, 8.8, 4.4 Hz, 1H)。
Embodiment 21：NThe synthesis of (9- cyano -10- diphenyl phosphine oxide base decyl- 1- yls) phthalimide
WithNAs raw material, reaction step is as follows for decene base phthalimide, diphenyl phosphine oxide：
N- decene base phthalimides are added in reaction bulb（0.114 gram, 0.4 mmol）, diphenyl phosphine oxide （0.081 gram, 0.4 mmol）, trimethyl cyanoalkysilane（0.079 gram, 0.8 mmol）, cuprous cyanide（0.007 gram, 0.08 mmol）, manganese acetate (0.322 gram, 1.2 mmol) and ethyl acetate（3 mL）, under argon gas protection, 60 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 65%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 7.91 – 7.74 (m, 6H), 7.67 – 7.46 (m, 8H), 3.45 (t, J = 6.8 Hz, 2H), 3.19 – 3.08 (m, 1H), 2.77 (ddd, J = 15.1, 8.3, 6.7 Hz, 1H), 2.58 – 2.49 (m, 1H), 1.93 – 1.83 (m, 3H), 1.49 – 1.39 (m, 3H), 1.30 (d, J = 4.4 Hz, 8H)。
Embodiment 22：The synthesis of 2- benzyl -3- diphenyl phosphine oxide base propionitrile
Using 3- phenylpropens, diphenyl phosphine oxide as raw material, reaction step is as follows：
3- phenylpropens are added in reaction bulb（0.047 gram, 0.4 mmol）, diphenyl phosphine oxide（0.081 gram, 0.4 mmol）, trimethyl cyanoalkysilane（0.079 gram, 0.8 mmol）, cuprous cyanide（0.004 gram, 0.04 mmol）, manganese acetate (0.322 gram, 1.2 mmol) and ethyl acetate（3 mL）, under argon gas protection, 60 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 71%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 7.78 (dd, J = 10.2, 8.1 Hz, 2H), 7.71 (dd, J = 10.0, 8.0 Hz, 2H), 7.61 – 7.43 (m, 7H), 7.34 – 7.27 (m, 2H), 7.23 (t, J = 6.2 Hz, 2H), 3.35 – 3.24 (m, 1H), 3.20 – 3.09 (m, 1H), 3.03 – 2.93 (m, 1H), 2.74 – 2.46 (m, 2H)。
Embodiment 23：The synthesis of 2- ((diphenyl phosphine oxide base) methyl) -4- phenylbutyronitriles
Using 3- phenylbutenes, diphenyl phosphine oxide as raw material, reaction step is as follows：
3- phenylbutenes are added in reaction bulb（0.053 gram, 0.4 mmol）, diphenyl phosphine oxide（0.162 gram, 0.8 mmol）, trimethyl cyanoalkysilane（0.079 gram, 0.8 mmol）, cuprous cyanide（0.011 gram, 0.12 mmol）, manganese acetate (0.322 gram, 1.2 mmol) and ethyl acetate（3 mL）, under argon gas protection, 60 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 73%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 7.72 (dd, J = 10.8, 7.6 Hz, 4H), 7.58 – 7.41 (m, 6H), 7.23 (d, J = 7.5 Hz, 2H), 7.19 – 7.05 (m, 3H), 2.70 – 2.48 (m, 2H), 2.41 (s, 1H), 2.37 – 2.23 (m, 2H), 1.72 (s, 2H)。
Embodiment 24：The synthesis of 2- ((diphenyl phosphine oxide base) methyl) n-capric nitrile
Using 1- decene, diphenyl phosphine oxide as raw material, reaction step is as follows：
1- decene is added in reaction bulb（0.056 gram, 0.4 mmol）, diphenyl phosphine oxide（0.162 gram, 0.8 mmol）, Trimethyl cyanoalkysilane（0.079 gram, 0.8 mmol）, copper cyanider（0.046 gram, 0.04 mmol）, manganese acetate (0.322 gram, 1.2 ) and water mmol（3 mL）, under argon gas protection, 60 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 71%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 7.89 – 7.70 (m, 4H), 7.61 – 7.45 (m, 6H), 3.04 (t, J = 26.8 Hz, 1H), 2.91 – 2.57 (m, 1H), 2.49 (dt, J = 15.0, 7.3 Hz, 1H), 1.84 – 1.70 (m, 1H), 1.63 (ddd, J = 18.1, 11.8, 4.6 Hz, 1H), 1.55 – 1.42 (m, 1H), 1.42 (s, 1H), 1.33 – 1.13 (m, 10H), 0.87 (t, J = 6.9 Hz, 3H)。
Embodiment 25：The synthesis of 2- ((diphenyl phosphine oxide base) methyl) caprylic nitrile
Using 1- octenes, diphenyl phosphine oxide as raw material, reaction step is as follows：
1- octenes are added in reaction bulb（0.045 gram, 0.4 mmol）, diphenyl phosphine oxide（0.162 gram, 0.8 mmol）, Trimethyl cyanoalkysilane（0.079 gram, 0.8 mmol）, copper cyanider（0.092 gram, 0.08 mmol）, manganese acetate (0.322 gram, 1.2 ) and 1,2- dichloroethanes mmol（3 mL）, under argon gas protection, 60 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 70%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 7.85 – 7.69 (m, 4H), 7.61 – 7.43 (m, 6H), 3.08 (ddd, J = 11.0, 9.3, 4.7 Hz,1H), 2.71 (ddd, J = 15.2, 8.5, 6.6 Hz, 1H), 2.48 (ddd, J = 15.2, 12.8, 7.0 Hz, 1H), 1.82 – 1.56 (m, 2H), 1.47 (ddd, J = 15.3, 12.9, 9.0 Hz, 1H), 1.41 – 1.30 (m, 1H), 1.24 (dd, J = 9.3, 7.6 Hz, 6H), 0.85 (t, J = 6.9 Hz, 3H)。
Embodiment 26：Acetic acid (the synthesis of 1- cyano -2- ((diphenyl phosphine oxide base) ethyl) ester
Using vinyl acetate, diphenyl phosphine oxide as raw material, reaction step is as follows：
Vinyl acetate is added in reaction bulb（0.035 gram, 0.4 mmol）, diphenyl phosphine oxide（0.081 gram, 0.4 mmol）, trimethyl cyanoalkysilane（0.079 gram, 0.8 mmol）, copper cyanider（0.138 gram, 0.12 mmol）, manganese acetate (0.322 Gram, 1.2 mmol) and 1,2- dichloroethanes（3 mL）, under argon gas protection, 60 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 62%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 7.79 (td, J = 12.9, 7.7 Hz, 4H), 7.58 (dt, J = 6.8, 5.5 Hz, 6H), 5.80 (td, J = 9.2, 4.2 Hz, 1H), 3.12 (ddd, J = 16.8, 9.3, 7.8 Hz, 1H), 2.99 – 2.84 (m, 1H), 1.75 (s, 3H)。
Embodiment 27：2-（4- nitrobenzophenones）The synthesis of -3- diphenyl phosphine oxide base propionitrile
Using 4- nitrostyrolenes, diphenyl phosphine oxide as raw material, reaction step is as follows：
4- nitrostyrolenes are added in reaction bulb（0.060 gram, 0.4 mmol）, diphenyl phosphine oxide（0.081 gram, 0.4 mmol）, trimethyl cyanoalkysilane（0.079 gram, 0.8 mmol）, CuCl2(0.056g, 0.04 mmol), manganese acetate (0.322 Gram, 1.2 mmol) and N-Methyl pyrrolidone（3 mL）, under argon gas protection, 60 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 64%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ8.20 –8.11 (m, 2H), 7.83 – 7.62 (m, 4H), 7.56 – 7.40 (m, 8H), 3.86 – 3.80 (m, 1H), 3.38 – 3.34 (m, 1H), 3.13 – 3.27 (m, 1H)。
Embodiment 28：2-（Furans -2- bases）The synthesis of -3- diphenyl phosphine oxide base propionitrile
Using 2- vinyl furans, diphenyl phosphine oxide as raw material, reaction step is as follows：
2- vinyl furans are added in reaction bulb（0.038 gram, 0.4 mmol）, diphenyl phosphine oxide（0.162 gram, 0.8 mmol）, trimethyl cyanoalkysilane（0.079 gram, 0.8 mmol）, CuCl2(0.112g, 0.08 mmol), manganese acetate (0.322 Gram, 1.2 mmol) and N-Methyl pyrrolidone（3 mL）, under argon gas protection, 60 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 82%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ7.78 – 7.72 (m, 4H), 7.53 – 7.47 (m, 7H), 6.36-6.30 (m, 1H), 6.13-6.09 (m, 1H), 4.04 – 3.96 (m, 1H), 3.38 – 3.34 (m, 1H), 3.15 – 3.06 (m, 1H)。
Embodiment 29：2-（Thiophene -2- bases）The synthesis of -3- diphenyl phosphine oxide base propionitrile
Using 2- vinyl thiophenes, diphenyl phosphine oxide as raw material, reaction step is as follows：
2- vinyl thiophenes are added in reaction bulb（0.044 gram, 0.4 mmol）, diphenyl phosphine oxide（0.162 gram, 0.8 mmol）, trimethyl cyanoalkysilane（0.079 gram, 0.8 mmol）, CuCl2(0.168g, 0.12 mmol), manganese acetate (0.322 Gram, 1.2 mmol) and n,N-Dimethylformamide（3 mL）, under argon gas protection, 60 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 79%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ7.78 – 7.72 (m, 4H), 7.53 – 7.47 (m, 6H), 7.39-7.37 (m, 1H), 7.01-6.81 (m, 2H), 3.86 – 3.75 (m, 1H), 3.30 – 3.20 (m, 1H), 3.05 – 2.96 (m, 1H)。
Embodiment 30：2-（Pyrroles's -2- bases）The synthesis of -3- diphenyl phosphine oxide base propionitrile
Using 2- vinyl pyrroles, diphenyl phosphine oxide as raw material, reaction step is as follows：
2- vinyl pyrroles are added in reaction bulb（0.037 gram, 0.4 mmol）, diphenyl phosphine oxide（0.162 gram, 0.8 mmol）, trimethyl cyanoalkysilane（0.079 gram, 0.8 mmol）, CuI2(0.128g, 0.04 mmol), manganese acetate (0.322 Gram, 1.2 mmol) and n,N-Dimethylformamide（3 mL）, under argon gas protection, 60 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 81%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ11.84 (s, 1H), 7.78 – 7.72 (m, 4H), 7.53 – 7.47 (m, 6H), 6.67-6.62 (m, 1H), 6.14-6.09 (m, 1H), 5.90-5.86 (m, 1H), 3.86 – 3.75 (m, 1H), 3.31 – 3.27 (m, 1H), 3.07 – 3.00 (m, 1H)。
Embodiment 31：2-（6- chloropyridine -2- bases）The synthesis of -3- diphenyl phosphine oxide base propionitrile
Using 2- vinyl -6- chloropyridines, diphenyl phosphine oxide as raw material, reaction step is as follows：
2- vinyl -6- chloropyridines are added in reaction bulb（0.056 gram, 0.4 mmol）, diphenyl phosphine oxide（0.162 gram, 0.8 mmol）, trimethyl cyanoalkysilane（0.079 gram, 0.8 mmol）, CuI2(0.256g, 0.08 mmol), manganese acetate (0.322 gram, 1.2 mmol) and n,N-Dimethylformamide（3 mL）, under argon gas protection, 60 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 78%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 7.88-7.86 (m, 1H), 7.78 – 7.72 (m, 4H), 7.53 – 7.36 (m, 8H), 3.86 – 3.75 (m, 1H), 3.30 – 3.20 (m, 1H), 3.05 – 2.96 (m, 1H)。
Embodiment 32：2-（5- methoxypyridine -2- bases）The synthesis of -3- diphenyl phosphine oxide base propionitrile
Using 2- vinyl -5- methoxypyridines, diphenyl phosphine oxide as raw material, reaction step is as follows：
2- vinyl -5- methoxypyridines are added in reaction bulb（0.054 gram, 0.4 mmol）, diphenyl phosphine oxide （0.162 gram, 0.8 mmol）, trimethyl cyanoalkysilane（0.079 gram, 0.8 mmol）, CuBr2(0.088g, 0.04 mmol), Manganese acetate (0.322 gram, 1.2 mmol) and glacial acetic acid（3 mL）, under argon gas protection, 40 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 81%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ8.22 (s, 1H), 7.78 – 7.72 (m, 4H), 7.53 – 7.47 (m, 6H), 7.31-7.17 (m, 2H), 3.83 (s, 3H), 3.82 – 3.78 (m, 1H), 3.40 – 3.30 (m, 1H), 3.05 – 2.96 (m, 1H)。
Embodiment 33：2-（4- picoline -2- bases）The synthesis of -3- diphenyl phosphine oxide base propionitrile
Using 2- vinyl -4- picolines, diphenyl phosphine oxide as raw material, reaction step is as follows：
2- vinyl -4- picolines are added in reaction bulb（0.048 gram, 0.4 mmol）, diphenyl phosphine oxide（0.162 Gram, 0.8 mmol）, trimethyl cyanoalkysilane（0.079 gram, 0.8 mmol）, CuBr2(0.176g, 0.08 mmol), manganese acetate (0.322 gram, 1.2 mmol) and glacial acetic acid（3 mL）, under argon gas protection, 40 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 82%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ8.44 (d, J = 57 Hz, 1H), 7.78 – 7.72 (m, 4H), 7.53 – 7.47 (m, 6H), 7.41 (s, 1H), 7.32-7.27 (d, J = 57 Hz, 1H), 3.86 – 3.75 (m, 1H), 3.38 – 3.30 (m, 1H), 3.05 – 2.96 (m, 1H), 2.13 (s, 3H)。
Embodiment 34：2-（Pyridin-3-yl）The synthesis of -3- diphenyl phosphine oxide base propionitrile
Using 3- vinylpyridines, diphenyl phosphine oxide as raw material, reaction step is as follows：
3- vinylpyridines are added in reaction bulb（0.042 gram, 0.4 mmol）, diphenyl phosphine oxide（0.162 gram, 0.8 mmol）, trimethyl cyanoalkysilane（0.079 gram, 0.8 mmol）, CuBr2(0.264g, 0.12 mmol), manganese acetate (0.322 Gram, 1.2 mmol) and acetonitrile（3 mL）, under argon gas protection, 40 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 74%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ8.41 (s, 1H), 8.35 (d, J = 5.7 Hz, 1H), 7.78 – 7.72 (m, 5H), 7.53 – 7.47 (m, 6H), 7.27-7.21 (m, 1H), 3.86 – 3.75 (m, 1H), 3.38 – 3.30 (m, 1H), 3.05 – 2.96 (m, 1H)。
Embodiment 35：2-（Pyridin-4-yl）The synthesis of -3- diphenyl phosphine oxide base propionitrile
Using 4-vinylpridine, diphenyl phosphine oxide as raw material, reaction step is as follows：
4-vinylpridine is added in reaction bulb（0.042 gram, 0.4 mmol）, diphenyl phosphine oxide（0.162 gram, 0.8 mmol）, trimethyl cyanoalkysilane（0.079 gram, 0.8 mmol）, cuprous cyanide（0.007 gram, 0.08 mmol）, manganese acetate (0.322 gram, 1.2 mmol) and acetonitrile（3 mL）, under argon gas protection, 40 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 77%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ8.55 (d, J = 5.7 Hz, 2H), 7.78 – 7.72 (m, 5H), 7.53 – 7.47 (m, 6H), 7.22 (d, J = 57 Hz, 2H), 3.86 – 3.75 (m, 1H), 3.39 – 3.33 (m, 1H), 3.15 – 2.97 (m, 1H)。
Embodiment 36：The synthesis of 2- phenyl -3- dimethyl phosphonate base propionitrile
Using styrene, dimethyl phosphite as raw material, reaction equation and experimental procedure are as follows：
Styrene is added in reaction bulb（0.042 gram, 0.4 mmol）, dimethyl phosphite（0.088 gram, 0.8 mmol）, trimethyl cyanoalkysilane（0.079 gram, 0.8 mmol）, cuprous cyanide（0.007 gram, 0.08 mmol）, manganese acetate (0.322 gram, 1.2 mmol) and acetonitrile（3 mL）, under argon gas protection, 40 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 78%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ7.33-7.17 (m, 5H), 3.86 – 3.75 (m, 1H), 3.25 (d, J = 7.8 Hz, 6H), 2.59-2.51 (m, 1H), 2,34-2,28 (m, 1H)。
Embodiment 37：The synthesis of 2- phenyl -3- diethyl phosphonate base propionitrile
Using styrene, diethyl phosphite as raw material, reaction equation and experimental procedure are as follows：
Styrene is added in reaction bulb（0.042 gram, 0.4 mmol）, diethyl phosphite（0.110 gram, 0.8 mmol）, trimethyl cyanoalkysilane（0.079 gram, 0.8 mmol）, CuCl (0.08g, 0.08 mmol), manganese acetate (0.322 gram, 1.2 mmol) and N,N-dimethylformamide（3 mL）, under argon gas protection, 40 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 76%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ7.33-7.17 (m, 5H), 4.24-4.14 (m, 4H), 3.86 – 3.75 (m, 1H), 2.59-2.51 (m, 1H), 2.34-2.28 (m, 1H), 1.36 (t, J = 7.5 Hz, 6H)。
Embodiment 38：2- phenyl -3- two（4- methoxyphenyls）The synthesis of phosphinyl propionitrile
With styrene, two（4- methoxyphenyls）For phosphine oxide as raw material, reaction step is as follows：
Styrene is added in reaction bulb（0.042 gram, 0.4 mmol）, two（4- methoxyphenyls）Phosphine oxide（0.210 Gram, 0.8 mmol）, trimethyl cyanoalkysilane（0.079 gram, 0.8 mmol）, CuCl (0.08g, 0.08 mmol), manganese acetate (0.322 gram, 1.2 mmol) and n,N-Dimethylformamide（3 mL）, under argon gas protection, 40 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 86%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 7.79-7.75 (m, 4H), 7.33-7.06 (m, 9H), 3.81 (s, 6H), 3.86 – 3.75 (m, 1H), 3.39-3.31 (m, 1H), 3.14-3.08 (m, 1H)。
Embodiment 39：2- phenyl -3- two（4- cyano-phenyls）The synthesis of phosphinyl propionitrile
With styrene, two（4- cyano-phenyls）For phosphine oxide as raw material, reaction step is as follows：
Styrene is added in reaction bulb（0.042 gram, 0.4 mmol）, two（4- cyano-phenyls）Phosphine oxide（0.202 gram, 0.8 mmol）, trimethyl cyanoalkysilane（0.079 gram, 0.8 mmol）, CuCl (0.08g, 0.08 mmol), manganese acetate (0.322 gram, 1.2 mmol) and acetone（3 mL）, under argon gas protection, room temperature reaction；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product（Yield 89%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ7.99-7.91 (m, 4H), 7.83-7.76 (m, 4H), 7.32-7.18 (m, 5H), 3.86 – 3.75 (m, 1H), 3.39-3.31 (m, 1H), 3.14-3.08 (m, 1H)。
Example IV ten：N- (5- hydrogenation of hydroxypentylaldehyd -5- bases) -3- dimethoxy phosphono propionamides（A）Synthesis
Using ethylene, dimethyl phosphite as raw material, reaction step is as follows：
Ethylene is passed through in reaction bulb（0.026 gram, 0.8 mmol）, dimethyl phosphite is added（0.088 gram, 0.8 mmol）, trimethyl cyanoalkysilane（0.079 gram, 0.8 mmol）, CuCl (0.08g, 0.08 mmol), manganese acetate (0.322 gram, 1.2 mmol) and acetonitrile（3 mL）, under argon gas protection, room temperature reaction；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product 40-1（Yield 76%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ3.65 (d, J = 7.8 Hz, 6H), 2.68-2.62 (m, 2H), 2.18-2.10 (m, 2H)。
(4) the addition 40-1 (0.163 gram, 1 mmol) in reaction bulb, N, N- diethyl hydroxylamines (0.267 gram, 3 mmol), Copper acetate (0.004 gram, 0.02 mmol) and water (1 mL), 35 DEG C of reactions are to terminating.Decompression is lower to remove solvent, and crude product is through column Chromatography (dichloromethane:Methanol=95:5) target product 40-2, is obtained（Yield 80%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 7.03 (s, 2H), 3.65 (d, J = 7.8 Hz, 6H), 2.44-2.40 (m, 2H), 2.08-2.01 (m, 2H)。
(5) 40-2 (0.181 gram, 1 mmol) is added in reaction bulb, pH to 6.5- is adjusted with 10% sodium carbonate liquor 7.0,80 DEG C are heated to, glutaraldehyde (0.100 gram, 1 mmol) is added dropwise into system, is dripped off in half an hour, reacts 3 hours, obtains light Yellow liquid is target product N- (5- hydrogenation of hydroxypentylaldehyd -5- bases) -3- dimethoxy phosphono propionamides（A）（Yield 80%）.Product Analysis data it is as follows：9.72 (t,J = 3.6 Hz, 1H), 9.18 (s, 1H), 5.60 (t, J = 3.0 Hz, 1H), 5.31 (s, 1H), 3.65 (d, J = 7.8 Hz, 6H), 2.44-2.40 (m, 4H), 2.08-2.01 (m, 2H), 1.68-1.61 (m, 4H)。
Example IV 11：Methyl（2- carbamoyl -1H- indol-3-yls）（Phenyl）Phosphinate（B）Synthesis
Using indoles, methoxyphenyl phosphine oxide as raw material, reaction step is as follows：
Indoles is added in reaction bulb（0.047 gram, 0.4 mmol）, methoxyphenyl phosphine oxide（0.125 gram, 0.8 mmol）, trimethyl cyanoalkysilane（0.079 gram, 0.8 mmol）, CuCl (0.08g, 0.08 mmol), manganese acetate (0.322 gram, 1.2 mmol) and acetone（3 mL）, under argon gas protection, 50 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product 41-1（Yield 79%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ11.53 (s, 1H), 7.94 (d, J = 11.7 Hz, 1H), 7.72-7.64 (m, 3H), 7.44-7.48 (m, 3H), 7.0-6.9 (m, 2H), 3.78 (d, J = 11.7 Hz, 3H)。
(4) the addition 41-1 (0.296 gram, 1 mmol) in reaction bulb, N, N- diethyl hydroxylamines (0.267 gram, 3 mmol), Copper acetate (0.004 gram, 0.02 mmol) and water (1 mL), 35 DEG C of reactions are to terminating.Decompression is lower to remove solvent, and crude product is through column Chromatography (dichloromethane:Methanol=95:5) target product B, is obtained（Yield 81%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 11.55 (s, 1H), 8.18 (s, 2H), 7.94 (d, J = 11.7 Hz, 1H), 7.72-7.64 (m, 3H), 7.44-7.48 (m, 3H), 7.0-6.9 (m, 2H), 3.78 (d, J = 11.7 Hz, 3H)。
Example IV 12：2,3- diamino -3- oxygen propyl group phosphonic acids（D4）Synthesis
With beta-cyano phosphonate ester（40-1）For raw material, reaction step is as follows：
The addition 40-1 (0.163 gram, 1 mmol) in reaction bulb, n-Hydroxyphthalimide (0.049 gram, 0.3 mmol), benzotrifluoride (5 mL) and concentrated nitric acid（0.27 gram, 3 mmol）, it is heated to 70 DEG C and reacts 14 hours.Reaction terminates Afterwards, it is concentrated under reduced pressure, crude by column chromatography separating-purifying obtains target product 42-1（Yield 68%）.The analysis data of product are as follows ：1H NMR (400 MHz, CDCl3): δ 4.81-4.79 (m, 1H), 3.65 (d, J = 7.8 Hz, 6H), 2.85- 2.60 (m, 2H)。
The addition 42-1 (0.208 gram, 1 mmol) in reaction bulb, N, N- diethyl hydroxylamines (0.267 gram, 3 mmol), Copper acetate (0.004 gram, 0.02 mmol) and water (1 mL) are heated to 35 DEG C of 3 h of reaction.Solvent is removed under reduced pressure, crude product is through column Chromatography (dichloromethane:Methanol=95:5) target product 42-2, is obtained（Yield 83%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 7.21 (s, 2H), 4.81-4.79 (m, 1H), 3.65 (d, J = 7.8 Hz, 6H), 2.85-2.60 (m, 2H)。
42-2 (0.226 gram, 1 mmol) and concentrated hydrochloric acid (20 mL) are added in reaction bulb, is heated to reflux to reaction and ties Shu Hou is added in 50 milliliters of water, is extracted with dichloromethane, concentrates, dry, and crude product recrystallizes to obtain target product with ethanol/water 42-3（Yield 79%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 7.21 (s, 2H), 4.81-4.79 (m, 3H), 2.85-2.60 (m, 2H)。
(4) the addition 42-3 (0.198 gram, 1 mmol) in reaction bulb, and n,N-diisopropylethylamine (0.452 gram, 3.5 Mmol) and dichloromethane (5 mL), reactant is cooled with an ice bath to 0 DEG C, N2It protects, stir in lower 10 minutes trichlorosilane is added dropwise 2 mL of dichloromethane solution of alkane (0.335 gram, 2.5 mmol)；Continue stirring 18 hours after completion of dropwise addition, is then added dropwise 5 mL of saturated sodium bicarbonate solution continues stirring 0.5 hour；Reactant is extracted with ethyl acetate, dry, is concentrated to give target product D4（Yield 87%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 8.76 (s, 2H), 7.21 (s, 2H), 4.81-4.79 (m, 3H), 2.85-2.60 (m, 2H)。
Example IV 13：2- amino -3- carboxy phosphonic acids（D1）Synthesis
Using nitroethylene, dimethyl phosphite as raw material, reaction step is as follows：
Nitroethylene is added in reaction bulb（0.292 gram, 0.4 mmol）, dimethyl phosphite（0.088 gram, 0.8 mmol）, 0.079 gram of trimethyl cyanoalkysilane, 0.8 mmol）, CuCl (0.08g, 0.08 mmol), manganese acetate (0.322 gram, 1.2 mmol) and N,N-dimethylformamide（3 mL）, under argon gas protection, 40 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product 43-1（Yield 76%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ3.81-3.79 (m, 1H), 3.65 (d, J = 7.8 Hz, 6H), 3.35-3.10 (m, 2H)。
(4) 43-1 (0.208 gram, 1 mmol) and concentrated hydrochloric acid (20 mL) are added in reaction bulb, is heated to reflux to reaction and ties Shu Hou is added 50 milliliters of water, is extracted with dichloromethane, concentrates, dry, and crude product recrystallizes to obtain target product 43- with ethanol/water 2（Yield 82%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 12.01 (s, 1H), 4.81- 4.79 (m, 2H), 4.11-4.10 (m, 1H), 2.85-2.60 (m, 2H)。
(5) the addition 43-2 (0.199 gram, 1 mmol) in reaction bulb, and n,N-diisopropylethylamine (0.452 gram, 3.5 Mmol) and dichloromethane (5 mL), reactant is cooled with an ice bath to 0 DEG C, N2It protects, stir in lower 10 minutes trichlorosilane is added dropwise 2 mL of dichloromethane solution of alkane (0.335 gram, 2.5 mmol)；Continue stirring 18 hours after completion of dropwise addition, saturation is added dropwise 5 mL of sodium bicarbonate solution continues stirring 0.5 hour；Reactant is extracted with ethyl acetate, dry, is concentrated to give target product D1 （Yield 85%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 12.01 (s, 1H), 8.52 (s, 2H), 4.81-4.79 (m, 2H), 2.85-2.60 (m, 3H)。
Example IV 14：1,3- diamino -3- oxygen propyl group phosphonic acids（D2）Synthesis
With 3- nitro -3- dimethyl phosphonate base propionitrile（43-1）As raw material, reaction step is as follows：
The addition 43-1 (0.180 gram, 1 mmol) in reaction bulb, N, N- diethyl hydroxylamines (0.267 gram, 3 mmol), Copper acetate (0.004 gram, 0.02 mmol) and water (1 mL) are heated to 35 DEG C of 3 h of reaction.Solvent is removed under reduced pressure, crude product is through column Chromatography (dichloromethane:Methanol=95:5) target product 44-1, is obtained（Yield 78%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 7.03 (s, 2H), 4.13-4.09 (m, 1H), 3.65 (d, J = 7.8 Hz, 6H), 3.05-2.80 (m, 2H)。
44-1 (0.226 gram, 1 mmol) and concentrated hydrochloric acid (20 mL) is added in reaction bulb, is heated to reflux to having reacted Quan Hou is added 50 milliliters of water, is extracted with dichloromethane, concentrates, dry, and crude product recrystallizes to obtain target product 44- with ethanol/water 2（Yield 84%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 7.03 (s, 2H), 4.81- 4.79 (m, 2H), 4.13-4.09 (m, 1H), 2.85-2.60 (m, 2H)。
The addition 44-2 (0.198 gram, 1 mmol) in reaction bulb, and n,N-diisopropylethylamine (0.452 gram, 3.5 Mmol) and dichloromethane (5 mL), reactant is cooled with an ice bath to 0 DEG C, N2It protects, stir in lower 10 minutes trichlorosilane is added dropwise 2 mL of dichloromethane solution of alkane (0.335 gram, 2.5 mmol)；Continue stirring 18 hours after completion of dropwise addition, saturation is added dropwise 5 mL of sodium bicarbonate solution continues stirring 0.5 hour；Reactant is extracted with ethyl acetate, dry, is concentrated to give target product D2 （Yield 82%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ8.52 (s, 2H), 7.03 (s, 2H), 4.81-4.79 (m, 2H), 2.90 (m, 1H), 2.85-2.60 (m, 3H)。
Example IV 15：（2- amino -2- carboxyls）Ethylphosphonic acid（D3）Synthetic method one
With beta-cyano-β-nitro-ethyl dimethyl phosphonate（42-1）As raw material, reaction step is as follows：
42-1 (0.208 gram, 1 mmol) and concentrated hydrochloric acid (20 mL) is added in reaction bulb, is heated to reflux to having reacted Quan Hou is added 50 milliliters of water, is extracted with dichloromethane, concentrates, dry, and crude product recrystallizes to obtain target product 45- with ethanol/water 1（Yield 83%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 12.01 (s, 1H), 4.81- 4.79 (m, 2H), 4.11-4.10 (m, 1H), 3.15-2.87 (m, 2H)。
The addition 45-1 (0.199 gram, 1 mmol) in reaction bulb, and n,N-diisopropylethylamine (0.452 gram, 3.5 Mmol) and dichloromethane (5 mL), reactant is cooled with an ice bath to 0 DEG C, N2It protects, stir in lower 10 minutes trichlorosilane is added dropwise 2 mL of dichloromethane solution of alkane (0.335 gram, 2.5 mmol)；Continue stirring 18 hours after completion of dropwise addition, saturation is added dropwise 5 mL of sodium bicarbonate solution continues stirring 0.5 hour；Reactant is extracted with ethyl acetate, dry, is concentrated to give target product D3 （Yield 80%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 12.01 (s, 1H), 8.52 (s, 2H), 4.81-4.79 (m, 2H), 2.85-2.60 (m, 3H)。
Example IV 16：（2- amino -2- carboxyls）Ethylphosphonic acid（D3）Synthetic method two
With N-Boc vinyl amines（46-1）, dimethylphosphite as raw material, reaction step is as follows：
N-Boc vinyl amines are added in reaction bulb（0.572 gram, 0.4 mmol）, dimethyl phosphite is added （0.088 gram, 0.8 mmol）, trimethyl cyanoalkysilane（0.079 gram, 0.8 mmol）, CuI (0.076g, 0.04 mmol), vinegar Sour manganese (0.322 gram, 1.2 mmol) and n,N-Dimethylformamide（3 mL）, under argon gas protection, 30 DEG C of reactions；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product 46-2（Yield 76%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ8.18 (s, 1H), 4.63-4.58 (m, 1H), 3.65 (d, J = 7.8 Hz, 6H), 2.48-2.23 (m, 2H), 1.42 (s, 9H)。
(4) 46-2 (0.278 gram, 1 mmol) and concentrated hydrochloric acid (20 mL) are added in reaction bulb, is heated to reflux to reaction and ties Shu Hou is added 50 milliliters of water, is extracted with dichloromethane, concentrates, dry, and crude product recrystallizes to obtain target product D3 with ethanol/water （Yield 81%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 12.01 (s, 1H), 8.52 (s, 2H), 4.81-4.79 (m, 2H), 2.85-2.60 (m, 3H)。
Example IV 17：3- dimethyl phosphine acyl group-N, N- dimethylpropionamides（C）Synthesis
Using ethylene, dimethyl phosphine oxide as raw material, reaction step is as follows：
Ethylene is passed through in reaction bulb（0.026 gram, 0.8 mmol）, dimethyl phosphine oxide is added（0.062 gram, 0.8 mmol）, trimethyl cyanoalkysilane（0.079 gram, 0.8 mmol）, CuCl (0.08g, 0.08 mmol), manganese acetate (0.322 gram, 1.2 mmol) and acetonitrile（3 mL）, under argon gas protection, room temperature reaction；
TLC tracking reactions are until be fully completed；
Crude by column chromatography separation (the ethyl acetate obtained after reaction:Petroleum ether=1:1) target, is obtained Product 47-1（Yield 71%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 2.70-2.61 (m, 2H), 2.20-2.06 (m, 2H), 1.26 (d, J= 13.1 Hz, 6H）.
(4) 47-1 (0.131 gram, 1 mmol) and concentrated hydrochloric acid (10 mL) are added in reaction bulb, is heated to reflux to reaction and ties Beam；Methanol (5 mL) is added, back flow reaction, with 5% sodium hydroxide solution neutralization reaction liquid to neutrality, adds 40% after 2 hours Dimethylamine agueous solution (10 mL), back flow reaction is after 3 hours, is concentrated under reduced pressure, dry, and crude by column chromatography detaches (acetic acid second Ester:Petroleum ether=1:1) target product C, is obtained（Yield 77%）.The analysis data of product are as follows：1H NMR (400 MHz, CDCl3): δ 2.91 (s, 6H), 2.74-2.60 (m, 2H), 2.23-2.02 (m, 2H), 1.24 (d, J = 13.1 Hz, 6H）.

Claims (7)

1. a kind of method preparing beta-cyano phosphono analog derivative, which is characterized in that include the following steps：By alkene, phosphorus reagent, Trimethyl cyanoalkysilane, copper catalyst and manganese acetate are dissolved in solvent, are reacted at room temperature ~ 100 DEG C, and beta-cyano phosphono class is obtained Derivative；
The alkene is as shown in following chemical structure of general formula：
Wherein R is selected from：One kind in hydrogen, alkyl, N- alkyl phthalic imides base, aryl alkyl, ethyl acetate base；Or R is one kind in following group：
、、
Wherein R1It is selected from：One kind in alkyl, alkoxy, aryl, halogen, nitro, ester group；X is selected from：O, one kind in S, N；R2 It is selected from：One kind in alkyl, alkoxy, halogen；
The phosphorus reagent is as shown in having structure general formula：
Wherein R3It is selected from：One kind of alkoxy, alkyl, aryl；
The chemical formula of the copper catalyst is CuXn, wherein X is one kind in Cl, Br, I, CN；N is 1 or 2；
The solvent is selected from：Methanol, ethyl alcohol, acetonitrile, acetone, ethyl acetate, water, 1,2- dichloroethanes, toluene, N, N- dimethyl One kind in formamide, N-Methyl pyrrolidone, glacial acetic acid；
The beta-cyano phosphono analog derivative is as shown in following chemical structure of general formula：
。
2. the preparation method of beta-cyano phosphono analog derivative according to claim 1, it is characterised in that：In molar ratio, alkene: Phosphorus reagent: cyano trimethyl silane: copper catalyst: manganese acetate 1:（1~3）∶（1~3）∶（0.1~0.3）∶（1~3）.
3. the preparation method of beta-cyano phosphono analog derivative according to claim 1, it is characterised in that：After reaction to production Object carries out column chromatography for separation purification processes.
4. the preparation method of beta-cyano phosphono analog derivative according to claim 1, it is characterised in that：The alkene is selected from second Alkene, nitroethylene, N-Boc vinyl amines, styrene, 4- methyl styrenes, 4- methoxy styrenes, 4- fluorobenzene ethenes, 4- chlorine Styrene, 4- bromstyrols, 4- cyano styrenes, 4- nitrostyrolenes, 4- vinylbenzoates, 3- methyl styrenes, 3- chlorostyrenes, 3- bromstyrols, 2-methyl styrene, 2- fluorobenzene ethenes, 2- chlorostyrenes, 2- bromstyrols, 2- naphthalene ethylene, Beta-methyl styrene, 2- vinyl furans, 2- vinyl thiophenes, 2- vinyl pyrroles, 2- vinylpyridines, 3- vinylpyridines Pyridine, 4-vinylpridine, N- cyclobutenyls phthalimide, N- decene bases phthalimide, 3- phenylpropens, 3- benzene One kind in base butylene, positive octene, positive decene, vinyl acetate.
5. the preparation method of beta-cyano phosphono analog derivative according to claim 1, it is characterised in that：The phosphorus reagent is selected from Dimethyl phosphite, diethyl phosphite, dimethyl phosphine oxide, diphenyl phosphine oxide, two（4- methoxyphenyls）Phosphine oxide, two（4- Cyano-phenyl）One kind in phosphine oxide.
6. the preparation method of beta-cyano phosphono analog derivative according to claim 1, it is characterised in that：Utilize thin-layer chromatography color Spectrum tracking reaction is until be fully completed.
7. the preparation method of beta-cyano phosphono analog derivative according to claim 1, it is characterised in that：Reaction is in ar gas environment Middle progress.
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