CN107501328B - A kind of β-thiocyanogen alkenyl phosphono analog derivative and preparation method thereof - Google Patents

A kind of β-thiocyanogen alkenyl phosphono analog derivative and preparation method thereof Download PDF

Info

Publication number
CN107501328B
CN107501328B CN201710808044.0A CN201710808044A CN107501328B CN 107501328 B CN107501328 B CN 107501328B CN 201710808044 A CN201710808044 A CN 201710808044A CN 107501328 B CN107501328 B CN 107501328B
Authority
CN
China
Prior art keywords
mmol
gram
alkyl
thiocyanogen
reaction
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN201710808044.0A
Other languages
Chinese (zh)
Other versions
CN107501328A (en
Inventor
邹建平
应立
张沛之
李建安
陶泽坤
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
JIANGSU CHINASUN SPECIALTY PRODUCTS CO Ltd
Original Assignee
JIANGSU CHINASUN SPECIALTY PRODUCTS CO Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by JIANGSU CHINASUN SPECIALTY PRODUCTS CO Ltd filed Critical JIANGSU CHINASUN SPECIALTY PRODUCTS CO Ltd
Priority to CN201910606597.7A priority Critical patent/CN110256496B/en
Priority to CN201710808044.0A priority patent/CN107501328B/en
Priority to CN201910606598.1A priority patent/CN110218229B/en
Priority to CN201910606595.8A priority patent/CN110272450B/en
Publication of CN107501328A publication Critical patent/CN107501328A/en
Application granted granted Critical
Publication of CN107501328B publication Critical patent/CN107501328B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
    • C07F9/32—Esters thereof
    • 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
    • C07F9/4071—Esters thereof the ester moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/4075—Esters with hydroxyalkyl compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/50—Organo-phosphines
    • C07F9/53—Organo-phosphine oxides; Organo-phosphine thioxides
    • C07F9/5304—Acyclic saturated phosphine oxides or thioxides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/50—Organo-phosphines
    • C07F9/53—Organo-phosphine oxides; Organo-phosphine thioxides
    • C07F9/5316—Unsaturated acyclic phosphine oxides or thioxides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/50—Organo-phosphines
    • C07F9/53—Organo-phosphine oxides; Organo-phosphine thioxides
    • C07F9/5325—Aromatic phosphine oxides or thioxides (P-C aromatic linkage)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/572—Five-membered rings
    • C07F9/5728—Five-membered rings condensed with carbocyclic rings or carbocyclic ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/576—Six-membered rings
    • C07F9/58—Pyridine rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms
    • C07F9/655345—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms the sulfur atom being part of a five-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
    • C07F9/6581—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms
    • C07F9/6584—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms having one phosphorus atom as ring hetero atom
    • C07F9/65842—Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring
    • C07F9/65846—Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring the phosphorus atom being part of a six-membered ring which may be condensed with another ring system

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)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The invention discloses one kindβThiocyanogen alkenyl phosphinylidyne analog derivative and preparation method thereof.The present invention is starting material using alkynes, and raw material is easy to get, and type is extensive；The product types multiplicity obtained using the method for the present invention, it is widely used, it can be directly used for synthesis of organo-phosphines drug；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 β-thiocyanogen alkenyl phosphono analog derivative and preparation method thereof
Technical field
The invention belongs to the preparation technical fields of organic compound, and in particular to a kind of β-thiocyanogen alkenyl phosphono class is derivative Object and preparation method.
Background technique
Organic phosphine drug has important application value in fields such as treating cancer, anti-inflammatory, anti-osteoporosis；Organic phosphine closes It is a kind of important anticancer drug at enzyme, it can accelerate the apoptosis speed of tumour cell, to play the role of anticancer.This Outside, organic phosphine compound also has antiinflammation, to polyarthirtis have good therapeutic effect (Kamel, A. A., Geronikaki, A., Abdou, W. M. Inhibitory effect of novel S, N-bisphosphonates on some carcinoma cell lines, osteoarthritis, and chronic inflammation. Eur. J. Med. Chem2012,51,239.).
W. M. Abdou et al. discloses a kind of containing S, the synthetic method of the bis phosphoric acid ester type compound of N, and to chemical combination The anticancer and antiphlogistic activity of object are tested, testing in vitro the result shows that, compound is thin to the breast cancer cell of test, cervical carcinoma Born of the same parents, liver cancer cells, colon cancer cell all show apparent anticancer activity；In addition, they also have to polyarthirtis compared with Good antiphlogistic activity, it is worth mentioning at this point that, compound does not show apparent toxicity to normal cell, has preferable application Prospect.This method, for raw material, by two phosphoryl methylenations, takes off CS with benzothiazine -2,4- dithione2, cyclisation etc. processes Obtain compound；Raw material is rare, route is long, severe reaction conditions, non-selectivity, and releases toxic liquid CS in reaction2, pole Volatile, foul smelling taste can invade human body through respiratory tract and skin, injure nervous system and blood vessel, cause cardiovascular disease.Cause This synthetic method that exploitation reaction condition is mild, applied widely, reaction step is succinct, raw material are simple and easy to get is very heavy It wants.
Summary of the invention
The object of the present invention is to provide a kind of sides for preparing β-thiocyanogen alkenyl phosphono analog derivative and related derivative product Method has many advantages, such as that raw material sources are simple, reaction condition is mild, post-processing is simple, yield is high.
To achieve the above object of the invention, the technical solution adopted by the present invention is that: it is a kind of to prepare β-thiocyanogen alkenyl phosphono class The method of derivative, comprising the following steps: by alkynes, phosphorus reagent, isothiocyanic acid trimethylsilyl group, copper catalyst and peroxide It is dissolved in solvent, is reacted at 30 ~ 70 DEG C, obtain β-thiocyanogen alkenyl phosphono analog derivative.
The invention also discloses a kind of β-thiocarbonyl group phosphono analog derivative preparation methods, comprising the following steps: by alkynes, Phosphorus reagent, isothiocyanic acid trimethylsilyl group, copper catalyst and peroxide are dissolved in solvent, are reacted at 30 ~ 70 DEG C, and β-is obtained Thiocyanogen alkenyl phosphono analog derivative；Then using β-thiocyanogen alkenyl phosphono analog derivative as raw material, in zinc catalyst and acetic acid In the presence of, β-thiocarbonyl group phosphono analog derivative is prepared.
The invention also discloses a kind of preparation methods of the double phosphono analog derivatives of β-thiocarbonyl group, comprising the following steps: by alkynes Hydrocarbon, phosphorus reagent, isothiocyanic acid trimethylsilyl group, copper catalyst and peroxide are dissolved in solvent, are reacted, are obtained at 30 ~ 70 DEG C Obtain β-thiocyanogen alkenyl phosphono analog derivative；Then using β-thiocyanogen alkenyl phosphono analog derivative as raw material, in zinc catalyst and In the presence of acetic acid, β-thiocarbonyl group phosphono analog derivative is prepared；Then using β-thiocarbonyl group phosphono analog derivative as raw material, Phosphite ester, trifluoromethanesulfonic acid be cuprous, in the presence of di-tert-butyl peroxide, and it is derivative that the double phosphono classes of β-thiocarbonyl group are prepared Object.
The invention also discloses a kind of β-sulfydryl azepine phosphorus heterocycle analog derivative preparation methods, comprising the following steps: will Alkynes, phosphorus reagent, isothiocyanic acid trimethylsilyl group, copper catalyst and peroxide are dissolved in solvent, are reacted at 30 ~ 70 DEG C, Obtain β-thiocyanogen alkenyl phosphono analog derivative；Then using β-thiocyanogen alkenyl phosphono analog derivative as raw material, in zinc catalyst In the presence of acetic acid, β-thiocarbonyl group phosphono analog derivative is prepared；Then using β-thiocarbonyl group phosphono analog derivative as raw material, In phosphite ester, trifluoromethanesulfonic acid is cuprous, di-tert-butyl peroxide in the presence of, it is derivative that the double phosphono classes of β-thiocarbonyl group are prepared Object；Finally using the double phosphono analog derivatives of β-thiocarbonyl group as raw material, in the presence of sodium ethoxide, hydrochloric acid, β-sulfydryl azepine is prepared Phosphorus heterocycle analog derivative.
The invention also discloses a kind of β-thioindole ketones derivant preparation methods, comprising the following steps: by alkynes, Phosphorus reagent, isothiocyanic acid trimethylsilyl group, copper catalyst and peroxide are dissolved in solvent, are reacted at 30 ~ 70 DEG C, and β-is obtained Thiocyanogen alkenyl phosphono analog derivative；Then using β-thiocyanogen alkenyl phosphono analog derivative as raw material, in zinc catalyst and acetic acid In the presence of, β-thiocarbonyl group phosphono analog derivative is prepared；Then using β-thiocarbonyl group phosphono analog derivative as raw material, in phosphorous Acid esters, trifluoromethanesulfonic acid be cuprous, in the presence of di-tert-butyl peroxide, and the double phosphono analog derivatives of β-thiocarbonyl group are prepared；Most Afterwards using the double phosphono analog derivatives of β-thiocarbonyl group as raw material, in the presence of iodosobenzene, tetra-n-butyl iodate amine, β-sulphur is prepared For indole ketone derivative.
The invention also discloses alkynes, phosphorus reagent, isothiocyanic acid trimethylsilyl group as raw material in preparation β-thiocyanogen alkene Application in base phosphono analog derivative；Or copper catalyst, peroxide are preparing β-thiocyanogen alkenyl phosphono as additive Application in analog derivative.
In above-mentioned application, alkynes, phosphorus reagent, isothiocyanic acid trimethylsilyl group, copper catalyst and peroxide are dissolved in molten It in agent, is reacted at 30 ~ 70 DEG C, obtains β-thiocyanogen alkenyl phosphono analog derivative.
In the present invention, the chemical structural formula of the alkynes is one of the following chemical structure:
、
Wherein, R is selected from one of alkyl, N- alkyl phthalic imide base, aryl alkyl, ethyl acetate base；X is H or, wherein R2Selected from one of alkyl, alkoxy；Ar is selected from one of the following chemical structure:
、、、、
Wherein, R1Selected from one of alkyl, alkoxy, halogen, nitro, cyano, ester group；Y in O, S, N one Kind；R3Selected from one of alkyl, alkoxy, halogen.
Phosphorus reagent of the present invention is as shown in having structure general formula:
Wherein R4Selected from alkoxy or aryl.
The chemical formula of copper catalyst of the present invention is CuXn, wherein X is one of Cl, Br, I or SCN；N is 1 or 2；
β of the present invention-thiocyanogen alkenyl phosphono analog derivative is as shown in following general formula of the chemical structure:
。
β of the present invention-thiocarbonyl group phosphono analog derivative is as shown in following general formula of the chemical structure:
The double phosphono analog derivatives of β-thiocarbonyl group of the present invention are as shown in following general formula of the chemical structure:
β of the present invention-sulfydryl azepine phosphorus heterocycle analog derivative is as shown in following chemical structural formula:
β of the present invention-thioindole ketones derivant is as shown in following chemical structural formula:
Solvent of the present invention is selected from ethyl alcohol, acetonitrile, tetrahydrofuran, acetone, toluene, N,N-dimethylformamide or N- first One of base pyrrolidones.
Alkynes of the present invention can be such as following chemical structural formula:
、、、、
Preferably, the alkynes is selected from: phenylacetylene, 2- methylamino phenylacetylene, 4- methyl phenylacetylene, 4- methoxybenzene Acetylene, 4- fluorobenzene acetylene, 4- chlorobenzene acetylene, 4- bromobenzene acetylene, 4- nitrobenzene acetylene, 4- ethynyl-benzoate, 3- methyl Phenylacetylene, 3- Methoxy-phenylacetylene, 3- chlorobenzene acetylene, 2- chlorobenzene acetylene, tolans, 2- thiophene acetylene, 2- acetenyl pyrrole Pyridine, 4- phenyl butine, 5- phenyl pentyne, 1- phenyl butine -3- ketone, 2- cyclopropyl acethlene, positive hept- 1- alkynes, positive nonyl- 1- alkynes, just One of decyl- 1- alkynes, hex- 3- alkynes, methyl propargyl ether, two (propargyl) ethers, trimethyl silicane ethyl-acetylene；The phosphorus reagent choosing From: dimethyl phosphite, diethyl phosphite, diphenyl phosphine oxide, two (4- methoxyphenyl) phosphine oxides or two (4- cyano benzene One of base) phosphine oxide.
In above-mentioned technical proposal, using thin-layer chromatography chromatography (TLC) tracking reaction until being fully completed.
In above-mentioned technical proposal, in molar ratio, alkynes: phosphorus reagent: isothiocyanic acid trimethylsilyl group: copper catalyst: peroxide Compound is 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 may be expressed as:
Due to the application of the above technical scheme, compared with the prior art, the invention has the following advantages:
1, the present invention is starting material using alkynes derivative, and raw material is easy to get, toxicity is low, low in cost, type is more.
2, the present invention is applied widely, is applicable not only to aryl alkynes, equally applicable to common alkyl alkynes.
3, thiocyanogen reagent used in the present invention is easy to get, is inexpensive.
4, in method disclosed by the invention, reaction condition is mild, and the reaction time is short, the high income of target product, reaction behaviour Make and last handling process is simple, is suitable for industrialized production.
Specific embodiment
The present invention will be further described below with reference to examples:
Embodiment one: the synthesis of (2- phenyl -2- thiocyanogen) vinyl diphenyl phosphine oxide
Using phenylacetylene, diphenyl phosphine oxide as raw material, reaction step is as follows:
Phenylacetylene (0.041 gram, 0.4 mmol) is added in reaction flask, hexichol oxygen phosphorus (0.081 gram, 0.4 mmol), Isothiocyanic acid trimethylsilyl group (0.052 gram, 0.4 mmol), CuCl (0.04g, 0.04 mmol), tertbutanol peroxide (0.051 gram, 0.4 mmol) and ethyl alcohol (3 mL), 70 DEG C of reactions；
TLC tracking reaction is until be fully completed；
The crude by column chromatography separation (ethyl acetate: petroleum ether=1:1) obtained after reaction, obtains target Product (yield 84%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.85 – 7.71 (m, 4H), 7.67 – 7.39 (m, 11H), 6.62 (d, J = 19.1 Hz, 1H)。
Embodiment two: (2-(4- tolyl) -2- thiocyanogen)) synthesis of vinyl diphenyl phosphine oxide
Using 4- methyl phenylacetylene, diphenyl phosphine oxide as raw material, reaction step is as follows:
4- methyl phenylacetylene (0.046 gram, 0.4 mmol) is added in reaction flask, and hexichol oxygen phosphorus (0.162 gram, 0.8 Mmol), isothiocyanic acid trimethylsilyl group (0.104 gram, 0.8 mmol), CuCl (0.08g, 0.08 mmol), the tertiary fourth of peroxidating Alcohol (0.102 gram, 0.8 mmol) and acetonitrile (3 mL), 60 DEG C of reactions；
TLC tracking reaction is until be fully completed；
The crude by column chromatography separation (ethyl acetate: petroleum ether=1:1) obtained after reaction, obtains target Product (yield 86%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.81 – 7.71 (m, 4H), 7.61 – 7.49 (m, 6H), 7.44 – 7.40 (d, J = 8.1 Hz, 2H), 7.24 (s, 2H), 6.60 (d, J = 19.1 Hz, 1H), 2.39 (s, 3H)。
Embodiment three: (2-(3- tolyl) -2- thiocyanogen)) synthesis of vinyl diphenyl phosphine oxide
Using 3- methyl phenylacetylene, diphenyl phosphine oxide as raw material, reaction step is as follows:
3- methyl phenylacetylene (0.046 gram, 0.4 mmol) is added in reaction flask, and hexichol oxygen phosphorus (0.243 gram, 1.2 Mmol), isothiocyanic acid trimethylsilyl group (0.154 gram, 1.2 mmol), CuCl (0.12g, 0.12 mmol), the tertiary fourth of peroxidating Alcohol (0.154 gram, 1.2 mmol) and acetone (3 mL), 50 DEG C of reactions；
TLC tracking reaction is until be fully completed；
The crude by column chromatography separation (ethyl acetate: petroleum ether=1:1) obtained after reaction, obtains target Product (yield 89%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.88 – 7.79 (m, 4H), 7.66 – 7.54 (m, 6H), 7.48 – 7.30 (m, 3H), 7.24 (d, J = 19.0 Hz,1H), 2.37 (s, 3H)。
Example IV: (2-(3- methoxyphenyl) -2- thiocyanogen)) synthesis of vinyl diphenyl phosphine oxide
Using 3- Methoxy-phenylacetylene, diphenyl phosphine oxide as raw material, reaction step is as follows:
3- Methoxy-phenylacetylene (0.053 gram, 0.4 mmol) is added in reaction flask, and hexichol oxygen phosphorus (0.081 gram, 0.4 Mmol), isothiocyanic acid trimethylsilyl group (0.052 gram, 0.4 mmol), CuBr (0.056g, 0.04 mmol), the tertiary fourth of peroxidating Alcohol (0.154 gram, 1.2 mmol) and tetrahydrofuran (3 mL), 40 DEG C of reactions；
TLC tracking reaction is until be fully completed；
The crude by column chromatography separation (ethyl acetate: petroleum ether=1:1) obtained after reaction, obtains target Product (yield 83%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.73 – 7.70 (m, 4H), 7.62 – 7.47 (m, 6H), 7.39 – 7.33 (m, 1H), 7.10 (d, J = 7.7 Hz, 1H), 7.05 – 6.95 (m, 2H), 6.63 (d, J = 19.2 Hz, 1H), 3.85 (s, 3H)。
Embodiment five: (2-(4- methoxyphenyl) -2- thiocyanogen)) synthesis of vinyl diphenyl phosphine oxide
Using 4- Methoxy-phenylacetylene, diphenyl phosphine oxide as raw material, reaction step is as follows:
4- Methoxy-phenylacetylene (0.053 gram, 0.4 mmol) is added in reaction flask, and hexichol oxygen phosphorus (0.081 gram, 0.4 Mmol), isothiocyanic acid trimethylsilyl group (0.052 gram, 0.4 mmol), CuBr (0.112g, 0.08 mmol), the tertiary fourth of peroxidating Alcohol (0.154 gram, 1.2 mmol) and toluene (3 mL), 30 DEG C of reactions；
TLC tracking reaction is until be fully completed；
The crude by column chromatography separation (ethyl acetate: petroleum ether=1:1) obtained after reaction, obtains target Product (yield 91%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.8 – 7.72 (m, 4H), 7.60 – 7.48 (m, 8H), 6.95 (d, J = 8.8 Hz, 2H), 6.58 (d, J = 18.9 Hz, 2H), 3.85 (s, 3H)。
Embodiment six: (2-(2- chlorphenyl) -2- thiocyanogen)) synthesis of vinyl diphenyl phosphine oxide
Using 2- chlorobenzene acetylene, diphenyl phosphine oxide as raw material, reaction step is as follows:
2- chlorobenzene acetylene (0.054 gram, 0.4 mmol) is added in reaction flask, and hexichol oxygen phosphorus (0.081 gram, 0.4 Mmol), isothiocyanic acid trimethylsilyl group (0.052 gram, 0.4 mmol), CuBr (0.056g, 0.04 mmol), the tertiary fourth of peroxidating Alcohol (0.154 gram, 1.2 mmol) and n,N-Dimethylformamide (3 mL), 50 DEG C of reactions；
TLC tracking reaction is until be fully completed；
The crude by column chromatography separation (ethyl acetate: petroleum ether=1:1) obtained after reaction, obtains target Product (yield 82%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.81 – 7.70 (m, 4H), 7.62 – 7.56(m, 2H), 7.55 – 7.48 (m, 5H), 7.41 – 7.34 (m, 3H), 6.49 (d, J = 19.8 Hz, 1H)。
Embodiment seven: (2-(3- chlorphenyl) -2- thiocyanogen)) synthesis of vinyl diphenyl phosphine oxide
Using 3- chlorobenzene acetylene, diphenyl phosphine oxide as raw material, reaction step is as follows:
3- chlorobenzene acetylene (0.054 gram, 0.4 mmol) is added in reaction flask, and hexichol oxygen phosphorus (0.162 gram, 0.8 Mmol), isothiocyanic acid trimethylsilyl group (0.104 gram, 0.8 mmol), CuI (0.076g, 0.04 mmol), the tertiary fourth of peroxidating Alcohol (0.154 gram, 1.2 mmol) and N-Methyl pyrrolidone (3 mL), 50 DEG C of reactions；
TLC tracking reaction is until be fully completed；
The crude by column chromatography separation (ethyl acetate: petroleum ether=1:1) obtained after reaction, obtains target Product (yield 80%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.90 – 7.79 (m, 4H), 7.77 (s, 1H), 7.66 – 7.52 (m, 9H), 7.38 (d, J = 18.6 Hz, 1H)。
Embodiment eight: (2-(4- chlorphenyl) -2- thiocyanogen)) synthesis of vinyl diphenyl phosphine oxide
Using 4- chlorobenzene acetylene, diphenyl phosphine oxide as raw material, reaction step is as follows:
4- chlorobenzene acetylene (0.054 gram, 0.4 mmol) is added in reaction flask, and hexichol oxygen phosphorus (0.162 gram, 0.8 Mmol), isothiocyanic acid trimethylsilyl group (0.104 gram, 0.8 mmol), CuI (0.152g, 0.08 mmol), the tertiary fourth of peroxidating Alcohol (0.154 gram, 1.2 mmol) and N-Methyl pyrrolidone (3 mL), 60 DEG C of reactions；
TLC tracking reaction is until be fully completed；
The crude by column chromatography separation (ethyl acetate: petroleum ether=1:1) obtained after reaction, obtains target Product (yield 85%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.79 – 7.71 (m, 4.3H), 7.66 – 7.56 (m, 4.3H), 7.55 – 7.49 (m,4.3H), 7.48 – 7.42 (m, 4.3H), 7.39 (dd, J = 7.6, 2.8 Hz, 1.45H), 7.30 (d, J = 8.4 Hz, 0.8H), 7.16 (d, J = 8.3 Hz, 0.8H), 7.01 (d, J = 13.6 Hz, 0.4H), 6.62 (d, J = 18.8 Hz, 1H)。
Embodiment nine: (2-(4- fluorophenyl) -2- thiocyanogen)) synthesis of vinyl diphenyl phosphine oxide
Using 4- fluorobenzene acetylene, diphenyl phosphine oxide as raw material, reaction step is as follows:
4- fluorobenzene acetylene (0.048 gram, 0.4 mmol) is added in reaction flask, and hexichol oxygen phosphorus (0.162 gram, 0.8 Mmol), isothiocyanic acid trimethylsilyl group (0.104 gram, 0.8 mmol), CuI (0.076g, 0.04 mmol), the tertiary fourth of peroxidating Alcohol (0.154 gram, 1.2 mmol) and acetonitrile (3 mL), 70 DEG C of reactions；
TLC tracking reaction is until be fully completed；
The crude by column chromatography separation (ethyl acetate: petroleum ether=1:1) obtained after reaction, obtains target Product (yield 75%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.82 – 7.71 (m, 4H), 7.64 – 7.45 (m, 8H), 7.19 – 7.07 (m, 2H), 6.60 (d, J = 18.9 Hz, 1H)。
Embodiment ten: (2-(4- bromophenyl) -2- thiocyanogen)) synthesis of vinyl diphenyl phosphine oxide
Using 4- bromobenzene acetylene, diphenyl phosphine oxide as raw material, reaction step is as follows:
4- bromobenzene acetylene (0.072 gram, 0.4 mmol) is added in reaction flask, and hexichol oxygen phosphorus (0.081 gram, 0.4 Mmol), isothiocyanic acid trimethylsilyl group (0.052 gram, 0.4 mmol), CuCl2(0.056g, 0.04 mmol), peroxidating uncle Butanol (0.154 gram, 1.2 mmol) and acetonitrile (3 mL), 50 DEG C of reactions；
TLC tracking reaction is until be fully completed；
The crude by column chromatography separation (ethyl acetate: petroleum ether=1:1) obtained after reaction, obtains target Product (yield 72%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.89 – 7.69 (m, 5H), 7.66 – 7.30 (m, 16.7H), 7.24 – 7.14 (m, 1.6H), 7.01 (d, J = 13.6 Hz, 0.7H) 6.62 (d, J = 18.8 Hz, 1H)。
Embodiment 11: (2-(4- nitrobenzophenone) -2- thiocyanogen)) synthesis of vinyl diphenyl phosphine oxide
Using 4- nitrobenzene acetylene, diphenyl phosphine oxide as raw material, reaction step is as follows:
4- nitrobenzene acetylene (0.059 gram, 0.4 mmol) is added in reaction flask, and hexichol oxygen phosphorus (0.243 gram, 1.2 Mmol), isothiocyanic acid trimethylsilyl group (0.154 gram, 1.2 mmol), CuCl2(0.112g, 0.08 mmol), peroxidating uncle Butanol (0.154 gram, 1.2 mmol) and acetonitrile (3 mL), 50 DEG C of reactions；
TLC tracking reaction is until be fully completed；
The crude by column chromatography separation (ethyl acetate: petroleum ether=1:1) obtained after reaction, obtains target Product (yield 70%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.82 – 7.71 (m, 4H), 7.64 – 7.45 (m, 8H), 7.19 – 7.07 (m, 2H), 6.60 (d, J = 18.9 Hz, 1H)。
Embodiment 12: (2-(4- methoxycarbonyl-phenyl) -2- thiocyanogen)) synthesis of vinyl diphenyl phosphine oxide
Using 4- ethynyl-benzoate, diphenyl phosphine oxide as raw material, reaction step is as follows:
4- ethynyl-benzoate (0.064,0.4 mmol) is added in reaction flask, hexichol oxygen phosphorus (0.243 gram, 1.2 mmol), isothiocyanic acid trimethylsilyl group (0.154 gram, 1.2 mmol), CuCl2(0.056g, 0.04 mmol), peroxide Change the tert-butyl alcohol (0.154 gram, 1.2 mmol) and n,N-Dimethylformamide (3 mL), 50 DEG C of reactions；
TLC tracking reaction is until be fully completed；
The crude by column chromatography separation (ethyl acetate: petroleum ether=1:1) obtained after reaction, obtains target Product (yield 73%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.8 – 7.72 (m, 4H), 7.60 – 7.48 (m, 8H), 6.95 (d, J = 8.8 Hz, 2H), 6.58 (d, J = 18.9 Hz, 1H), 3.89 (s, 3H)。
Embodiment 13: the synthesis of (1,2- diphenyl -2- thiocyanogen) vinyl diphenyl phosphine oxide
Using tolans, diphenyl phosphine oxide as raw material, reaction step is as follows:
Tolans (0.071 gram, 0.4 mmol) is added in reaction flask, and hexichol oxygen phosphorus (0.243 gram, 1.2 Mmol), isothiocyanic acid trimethylsilyl group (0.154 gram, 1.2 mmol), CuI2(0.128g, 0.04 mmol), the tertiary fourth of peroxidating Alcohol (0.154 gram, 1.2 mmol) and n,N-Dimethylformamide (3 mL), 50 DEG C of reactions；
TLC tracking reaction is until be fully completed；
The crude by column chromatography separation (ethyl acetate: petroleum ether=1:1) obtained after reaction, obtains target Product (yield 82%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.85 – 7.71 (m, 8H), 7.67 – 7.39 (m, 12H)。
Embodiment 14: the synthesis of (1- acetyl group -2- phenyl -2- thiocyanogen) vinyl diphenyl phosphine oxide
Using 1- phenyl butine -3- ketone, diphenyl phosphine oxide as raw material, reaction step is as follows:
1- phenyl butine -3- ketone (0.058 gram, 0.4 mmol) is added in reaction flask, hexichol oxygen phosphorus (0.081 gram, 0.4 mmol), isothiocyanic acid trimethylsilyl group (0.052 gram, 0.4 mmol), CuI2(0.256g, 0.08 mmol), peroxidating The tert-butyl alcohol (0.154 gram, 1.2 mmol) and n,N-Dimethylformamide (3 mL), 50 DEG C of reactions；
TLC tracking reaction is until be fully completed；
The crude by column chromatography separation (ethyl acetate: petroleum ether=1:1) obtained after reaction, obtains target Product (yield 74%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.91 – 7.82 (m, 4H), 7.64 – 7.58 (m, 2H), 7.56 – 7.46 (m, 7H), 7.43 – 7.39 (m, 2H), 1.38 (s, 3H)。
Embodiment 15: (2-(pyridine -2- base) -2- thiocyanogen) vinyl diphenyl phosphine oxide synthesis
Using 2- ethynyl pyridine, diphenyl phosphate oxygen as raw material, reaction step is as follows:
2- ethynyl pyridine (0.041 gram, 0.4 mmol) is added in reaction flask, and hexichol oxygen phosphorus (0.081 gram, 0.4 Mmol), isothiocyanic acid trimethylsilyl group (0.052 gram, 0.4 mmol), CuBr2(0.088g, 0.04 mmol), peroxidating uncle Butanol (0.154 gram, 1.2 mmol) and N-Methyl pyrrolidone (3 mL), 40 DEG C of reactions；
TLC tracking reaction is until be fully completed；
The crude by column chromatography separation (ethyl acetate: petroleum ether=1:1) obtained after reaction, obtains target 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, 5H), 7.53 – 7.36 (m, 8H), 6.55 (d, J = 15.9 Hz, 1H)。
Embodiment 16: (2-(thiophene -2- base) -2- thiocyanogen) vinyl diphenyl phosphine oxide synthesis
Using 2- thiophene acetylene, diphenyl phosphate oxygen as raw material, reaction step is as follows:
2- thiophene acetylene (0.042 gram, 0.4 mmol) is added in reaction flask, and hexichol oxygen phosphorus (0.081 gram, 0.4 Mmol), isothiocyanic acid trimethylsilyl group (0.052 gram, 0.4 mmol), CuBr2(0.176g, 0.08 mmol), peroxidating uncle Butanol (0.154 gram, 1.2 mmol) and N-Methyl pyrrolidone (3 mL), 40 DEG C of reactions；
TLC tracking reaction is until be fully completed；
The crude by column chromatography separation (ethyl acetate: petroleum ether=1:1) obtained after reaction, obtains target Product (yield 82%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.78 – 7.72 (m, 4H), 7.53 – 7.47 (m, 6H), 7.39-7.37 (m, 1H), 7.01-6.81 (m, 2H), 6.59 (d, J = 15.7 Hz, 1H)。
Embodiment 17: (2-(2- phenylethyl) -2- thiocyanogen) vinyl diphenyl phosphine oxide synthesis
Using 4- phenyl butyl- 1- alkynes, diphenyl phosphate oxygen as raw material, reaction step is as follows:
4- phenyl butyl- 1- alkynes (0.053 gram, 0.4 mmol) is added in reaction flask, and hexichol oxygen phosphorus (0.081 gram, 0.4 Mmol), isothiocyanic acid trimethylsilyl group (0.052 gram, 0.4 mmol), CuBr2(0.088g, 0.04 mmol), peroxidating uncle Butanol (0.154 gram, 1.2 mmol) and N-Methyl pyrrolidone (3 mL), 40 DEG C of reactions；
TLC tracking reaction is until be fully completed；
The crude by column chromatography separation (ethyl acetate: petroleum ether=1:1) obtained after reaction, obtains target Product (yield 75%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.73 – 7.64 (m, 4.3H), 7.61 – 7.39 (m, 10.7H), 7.24 – 7.04 (m,6.4H), 6.49 (d, J = 17.6 Hz, 1H), 6.06 (d, J = 19.4 Hz, 0.4H), 3.32 – 3.26 (m, 2.1H), 3.08 – 3.01 (m, 2.1H), 2.91 – 2.84 (m, 2.1H)。
Embodiment 18: (2-(3- phenyl propyl) -2- thiocyanogen) vinyl diphenyl phosphine oxide synthesis
Using the amyl- 1- alkynes of 5- phenyl, diphenyl phosphate oxygen as raw material, reaction step is as follows:
The amyl- 1- alkynes of 5- phenyl (0.058 gram, 0.4 mmol) is added in reaction flask, and hexichol oxygen phosphorus (0.081 gram, 0.4 Mmol), isothiocyanic acid trimethylsilyl group (0.052 gram, 0.4 mmol), CuSCN (0.05 gram, 0.04 mmol), peroxidating uncle Butanol (0.154 gram, 1.2 mmol) and N-Methyl pyrrolidone (3 mL), 50 DEG C of reactions；
TLC tracking reaction is until be fully completed；
The crude by column chromatography separation (ethyl acetate: petroleum ether=1:1) obtained after reaction, obtains target Product (yield 77%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.73 – 7.64 (m, 2H), 7.61 – 7.39 (m, 9H), 7.24 – 7.04 (m, 4H), 6.49 (d, J = 17.6 Hz, 1H), 3.32 – 3.26 (m, 2H), 3.08 – 3.01 (m, 2H), 2.91 – 2.84 (m, 4H)。
Embodiment 19: the synthesis of (2- n-pentyl -2- thiocyanogen) vinyl diphenyl phosphine oxide
Using hept- 1- alkynes, diphenyl phosphate oxygen as raw material, reaction step is as follows:
Hept- 1- alkynes (0.038 gram, 0.4 mmol) is added in reaction flask, hexichol oxygen phosphorus (0.081 gram, 0.4 mmol), Isothiocyanic acid trimethylsilyl group (0.052 gram, 0.4 mmol), CuSCN (0.10 gram, 0.08 mmol), tertbutanol peroxide (0.154 gram, 1.2 mmol) and acetone (3 mL), 50 DEG C of reactions；
TLC tracking reaction is until be fully completed；
The crude by column chromatography separation (ethyl acetate: petroleum ether=1:1) obtained after reaction, obtains target Product (yield 81%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.95 – 7.86 (m, 0.9H), 7.78 – 7.69 (m, 5.5H), 7.66 – 7.52 (m, 10H), 7.45 – 7.25 (m, 1.8H), 7.01 (d, J = 19.9 Hz, 0.8H), 6.89 (d, J = 18.0 Hz, 1H), 2.99 – 2.89 (m, 3H), 2.80 – 2.63 (m, 3H), 1.70 – 1.58 (m, 2H), 1.53 – 1.35 (m, 4H), 1.20 – 1.15 (m, 4H), 0.89 – 0.72 (dt, J = 43.5, 6.9 Hz, 6H)。
Embodiment 20: the synthesis of (2- cyclopropyl -2- thiocyanogen) vinyl diphenyl phosphine oxide
Using cyclopropyl acethlene, diphenyl phosphate oxygen as raw material, reaction step is as follows:
Cyclopropyl acethlene (0.095 gram, 0.4 mmol) is added in reaction flask, and hexichol oxygen phosphorus (0.081 gram, 0.4 Mmol), isothiocyanic acid trimethylsilyl group (0.052 gram, 0.4 mmol), CuSCN (0.05 gram, 0.04 mmol), peroxidating uncle Butanol (0.154 gram, 1.2 mmol) and acetone (3 mL), 60 DEG C of reactions；
TLC tracking reaction is until be fully completed；
The crude by column chromatography separation (ethyl acetate: petroleum ether=1:1) obtained after reaction, obtains target Product (yield 71%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.73 – 7.64 (m, 4H), 7.61 – 7.39 (m, 6H), 6.49 (d, J = 15.6 Hz, 1H), 3.32 – 3.26 (m, 1H), 3.08 – 3.01 (m, 2H), 2.91 – 2.84 (m, 2H)。
Embodiment 21: the synthesis of (2- phenyl -2- thiocyanogen) vinyl phosphoric acid dimethyl ester
Using phenylacetylene, dimethyl phosphite as raw material, reaction step is as follows:
Phenylacetylene (0.041 gram, 0.4 mmol) is added in reaction flask, and dimethyl phosphite (0.088 gram, 0.8 Mmol), isothiocyanic acid trimethylsilyl group (0.052 gram, 0.4 mmol), CuSCN (0.05 gram, 0.04 mmol), peroxidating uncle Butanol (0.154 gram, 1.2 mmol) and acetone (3 mL), 30 DEG C of reactions；
TLC tracking reaction is until be fully completed；
The crude by column chromatography separation (ethyl acetate: petroleum ether=1:1) obtained after reaction, obtains target Product (yield 84%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.33-7.17 (m, 5H), 6.62 (d, J = 18.1 Hz, 1H), 3.25 (d, J = 7.8 Hz, 6H)。
Embodiment 22: the synthesis of (2- phenyl -2- thiocyanogen) vinyl phosphoric acid diethylester
Using phenylacetylene, diethyl phosphite as raw material, reaction step is as follows:
Phenylacetylene (0.041 gram, 0.4 mmol) is added in reaction flask, and diethyl phosphite (0.110 gram, 0.8 Mmol), isothiocyanic acid trimethylsilyl group (0.052 gram, 0.4 mmol), CuSCN (0.05 gram, 0.04 mmol), peroxidating uncle Butanol (0.154 gram, 1.2 mmol) and N-Methyl pyrrolidone (3 mL), 50 DEG C of reactions；
TLC tracking reaction is until be fully completed；
The crude by column chromatography separation (ethyl acetate: petroleum ether=1:1) obtained after reaction, obtains target Product (yield 86%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.33-7.17 (m, 5H), 6.62 (d, J = 18.1 Hz, 1H), 4.24-4.14 (m, 4H), 1.36 (t, J = 7.5 Hz, 6H)。
Embodiment 23: (2- phenyl -2- thiocyanogen)) vinyl two (4- methoxyphenyl) phosphine oxide synthesis
Using phenylacetylene, diphenyl phosphine oxide as raw material, reaction step is as follows:
Phenylacetylene (0.041 gram, 0.4 mmol) is added in reaction flask, hexichol oxygen phosphorus (0.081 gram, 0.4 mmol), Isothiocyanic acid trimethylsilyl group (0.052 gram, 0.4 mmol), CuSCN (0.05 gram, 0.04 mmol), tertbutanol peroxide (0.154 gram, 1.2 mmol) and N-Methyl pyrrolidone (3 mL), 50 DEG C of reactions；
TLC tracking reaction is until be fully completed；
The crude by column chromatography separation (ethyl acetate: petroleum ether=1:1) obtained after reaction, obtains target Product (yield 88%).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), 6.62 (d, J = 19.1 Hz, 1H), 3.81 (s, 6H)。
24: 2- ethyoxyl -4- sulfydryl -1- methyl -2- oxo -1 of embodimentHBenzo [1,2] azepine phosphorus heterocycle -3- The synthesis of diethyl phosphite (4)
Using 2- methylamino phenylacetylene, diethyl phosphite as raw material, reaction step is as follows:
2- methylamino phenylacetylene (0.104 gram, 0.8 mmol) is added in reaction flask, diethyl phosphite is added (0.110 gram, 0.8 mmol), isothiocyanic acid trimethylsilyl group (0.104 gram, 0.8 mmol), CuSCN (0.10 gram, 0.08 Mmol), tertbutanol peroxide (0.154 gram, 1.2 mmol) and N-Methyl pyrrolidone (5 mL), 50 DEG C of reactions；
TLC tracking reaction is until be fully completed；
The crude by column chromatography separation (ethyl acetate: petroleum ether=1:1) obtained after reaction, obtains target Product 24-1(yield 81%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ9.81 (s, 1H), 7.33-7.17 (m, 5H), 6.62 (d, J = 18.9 Hz, 1H), 4.24-4.14 (m, 4H), 3.86 (s, 3H), 1.36 (t, J= 7.5 Hz, 6H)；
(4) 24-1 (0.978 gram, 3 mmol) and acetic acid (30 mL) are added in reaction flask, zinc powder (3.0 is added thereto Gram, 45 mmol), then mixed solution is heated to reflux 24 h.Ether is added after filtrate concentration in diatomite filtering, washes twice, Anhydrous sodium sulfate is dry, is concentrated to give product 24-2(yield 98%).The analysis data of product are as follows:1H NMR (300 MHz, CDCl3): δ9.81 (s, 1H), 7.33-7.17 (m, 5H), 4.54 (d, J = 13.9 Hz, 2H), 4.14- 4.04 (m, 4H), 3.86 (s, 3H), 1.36 (t, J= 7.5 Hz, 6H)；
In reaction flask be added 24-2(0.301 grams, 1 mmol), triethyl phosphorite (0.498 gram, 7 mmol), Trifluoromethanesulfonic acid cuprous (0.021 gram, 0.1 mmol), di-tert-butyl peroxide (1.022 grams, 7 mmol) and N, N- dimethyl Formamide (5 mL), 80 DEG C of reactions are to terminating.20 mL water, ethyl acetate extraction, dry, concentration, crude by column chromatography is added It separates (ethyl acetate: petroleum ether=1:1), obtains target compound 3(yield 78%).The analysis data of product are as follows:1H NMR (300 MHz, CDCl3): δ9.81 (s, 1H), 7.33-7.17 (m, 5H), 4.61 – 4.58 (m, 1H), 4.14-4.04 (m, 8H), 3.86 (s, 3H), 1.39 – 1.30 (m, 12H)；
(6) alcohol sodium solution (0.2 gram of sodium (9 mmol) is dissolved in 30 mL ethyl alcohol) and compound 3 are added in reaction flask (1.748 grams, 4 mmol), after being heated to reflux 15 hours, are cooled to room temperature, and dilute hydrochloric acid is added and adjusts pH to neutrality, ethyl acetate Extraction, dry, concentration, crude by column chromatography separates (ethyl acetate: petroleum ether=1:1), obtains target compound 4(yield 78%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.46 (d, J = 8.4 Hz, 2H), 7.84 (d, J = 8.4 Hz, 2H), 4.01 – 3.88 (m, 6H), 3.23 (d, J = 4.7 Hz, 3H), 1.91 (d, J = 3.8 Hz, 1H), 1.12 (dt, J = 6.6, 3.6 Hz, 6H), 0.99 (dt, J = 6.6, 3.5 Hz, 3H)。
The synthesis of 25: 1- methyl -3- thioindole ketone -2,2- diphosphorous acid tetra-ethyl ester (5) of embodiment
Using compound 3 as raw material, reaction step is as follows:
(1) in reaction flask be added 3(0.087 grams of compound, 0.2 mmol), iodosobenzene (0.088 gram, 0.4 ), mmol tetra-n-butyl iodate amine (0.089 gram, 0.24 mmol) and toluene (1 mL).Room temperature reaction；
(2) TLC tracking reaction is until be fully completed；
(3) the crude by column chromatography separation (ethyl acetate: petroleum ether=1:1) obtained after reaction, obtains target Compound 5(yield 81%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 7.42 (d, J = 8.1 Hz, 2H), 7.85 (d, J = 8.1 Hz, 2H), 4.01 – 3.84 (m, 8H), 3.14 (d, J = 3.3 Hz, 3H), 1.41 – 1.11 (m, 12H)。
Embodiment 26: 1,1- bis- (diethyl phosphonate base) thioketones -2(26-3 in heptan) synthesis
Using heptyne, diethyl phosphite as raw material, reaction step is as follows:
Heptyne (0.077 gram, 0.8 mmol) is added in reaction flask, and addition diethyl phosphite (0.220 gram, 1.6 Mmol), isothiocyanic acid trimethylsilyl group (0.208 gram, 1.6 mmol), CuSCN (0.10 gram, 0.08 mmol), peroxidating uncle Butanol (0.205 gram, 1.6 mmol) and N-Methyl pyrrolidone (5 mL), 50 DEG C of reactions；
TLC tracking reaction is until be fully completed；
The crude by column chromatography separation (ethyl acetate: petroleum ether=1:1) obtained after reaction, obtains target Product 26-1(yield 82%).The analysis data of product are as follows:1H NMR (400 MHz, CDCl3): δ 6.43 (d, J = 13.9 Hz, 1H), 4.24 – 4.14 (m, 4H), 3.08 (t, J = 4.7 Hz, 2H), 1.41 – 1.30 (m, 6H), 1.24 (dd, J = 9.3, 7.6 Hz, 6H), 0.85 (t, J = 6.9 Hz, 3H);
(4) 26-1 (0.873 gram, 3 mmol) and acetic acid (30 mL) are added in reaction flask, zinc powder (3.0 is added thereto Gram, 45 mmol), then mixed solution is heated to reflux 24 h.Ether is added after filtrate concentration in diatomite filtering, washes twice, Anhydrous sodium sulfate is dry, is concentrated to give product 26-2(yield 95%).The analysis data of product are as follows:1H NMR (300 MHz, CDCl3): δ4.24 – 4.14 (m, 4H), 3.34 (d, J = 15.3 Hz, 2H), 3.08 (t, J = 4.7 Hz, 2H), 1.41 – 1.30 (m, 6H), 1.24 (dd, J = 9.3, 7.6 Hz, 6H), 0.85 (t, J = 6.9 Hz, 3H);
In reaction flask be added 26-2(0.266 grams, 1 mmol), triethyl phosphorite (0.498 gram, 7 mmol), Trifluoromethanesulfonic acid cuprous (0.021 gram, 0.1 mmol), di-tert-butyl peroxide (1.022 grams, 7 mmol) and N, N- dimethyl Formamide (5 mL), 80 DEG C of reactions are to terminating.20 mL water, ethyl acetate extraction, dry, concentration, crude by column chromatography is added It separates (ethyl acetate: petroleum ether=1:1), obtains target compound 26-3(yield 78%).The analysis data of product are as follows:1H NMR (300 MHz, CDCl3): δ 4.24 – 4.14 (m, 8H), 3.34 (d, J = 15.3 Hz, 1H), 3.08 (t, J = 4.7 Hz, 2H), 1.41 – 1.30 (m, 6H), 1.34 – 1.01 (m, 12H), 0.85 (t, J = 6.9 Hz, 3H)。

Claims (3)

1. a kind of β-thiocyanogen alkenyl phosphono analog derivative preparation method, comprising the following steps: by alkynes, phosphorus reagent, different sulphur Cyanic acid trimethylsilyl group, copper catalyst and peroxide are dissolved in solvent, are reacted at 30 ~ 70 DEG C, and β-thiocyanogen alkenyl is obtained Phosphono analog derivative；
The chemical structural formula of the alkynes is one of the following chemical structure:
、、
Wherein, R is selected from one of alkyl, N- alkyl phthalic imide base, aryl alkyl, ethyl acetate base；X be H or Person, wherein R2Selected from one of alkyl, alkoxy；Ar is selected from one of the following chemical structure:
、、、
Wherein, R1Selected from one of alkyl, alkoxy, halogen, nitro, cyano, ester group；Y is selected from one of O, S, N；R3Choosing From one of alkyl, alkoxy, halogen；
The phosphorus reagent is as shown in having structure general formula:
Wherein R4Selected from alkoxy or aryl；
The chemical formula of the copper catalyst is CuXn, wherein X is one of Cl, Br, I or SCN；N is 1 or 2.
2. a kind of β-thiocarbonyl group phosphono analog derivative preparation method, comprising the following steps: by alkynes, phosphorus reagent, isothiocyanic acid Trimethylsilyl group, copper catalyst and peroxide are dissolved in solvent, are reacted at 30 ~ 70 DEG C, and β-thiocyanogen alkenyl phosphono is obtained Analog derivative；Then it using β-thiocyanogen alkenyl phosphono analog derivative as raw material, in the presence of zinc catalyst and acetic acid, is prepared into To β-thiocarbonyl group phosphono analog derivative；
The chemical structural formula of the alkynes is one of the following chemical structure:
、、
Wherein, R is selected from one of alkyl, N- alkyl phthalic imide base, aryl alkyl, ethyl acetate base；X be H or Person, wherein R2Selected from one of alkyl, alkoxy；Ar is selected from one of the following chemical structure:
、、、
Wherein, R1Selected from one of alkyl, alkoxy, halogen, nitro, cyano, ester group；Y is selected from one of O, S, N；R3Choosing From one of alkyl, alkoxy, halogen；
The phosphorus reagent is as shown in having structure general formula:
Wherein R4Selected from alkoxy or aryl；
The chemical formula of the copper catalyst is CuXn, wherein X is one of Cl, Br, I or SCN；N is 1 or 2.
3. preparation method described in any one according to claims 1 to 2, it is characterised in that: in molar ratio, alkynes: phosphorus Reagent: isothiocyanic acid trimethylsilyl group: copper catalyst: peroxide 1: (1~3): (1~3): (0.1~0.3): (1~3)； It is reacted using thin-layer chromatography chromatogram tracking until being fully completed；Column chromatography for separation purification processes are carried out to product after reaction； The solvent is in ethyl alcohol, acetonitrile, tetrahydrofuran, acetone, toluene, N,N-dimethylformamide or N-Methyl pyrrolidone It is a kind of；The peroxide is tertbutanol peroxide.
CN201710808044.0A 2017-09-08 2017-09-08 A kind of β-thiocyanogen alkenyl phosphono analog derivative and preparation method thereof Active CN107501328B (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
CN201910606597.7A CN110256496B (en) 2017-09-08 2017-09-08 Beta-thioindolone derivative and preparation method thereof
CN201710808044.0A CN107501328B (en) 2017-09-08 2017-09-08 A kind of β-thiocyanogen alkenyl phosphono analog derivative and preparation method thereof
CN201910606598.1A CN110218229B (en) 2017-09-08 2017-09-08 Beta-mercapto azaphospho heterocyclic derivative and preparation method thereof
CN201910606595.8A CN110272450B (en) 2017-09-08 2017-09-08 Beta-thiocarbonyl diphosphonic acid derivative and preparation method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201710808044.0A CN107501328B (en) 2017-09-08 2017-09-08 A kind of β-thiocyanogen alkenyl phosphono analog derivative and preparation method thereof

Related Child Applications (3)

Application Number Title Priority Date Filing Date
CN201910606598.1A Division CN110218229B (en) 2017-09-08 2017-09-08 Beta-mercapto azaphospho heterocyclic derivative and preparation method thereof
CN201910606595.8A Division CN110272450B (en) 2017-09-08 2017-09-08 Beta-thiocarbonyl diphosphonic acid derivative and preparation method thereof
CN201910606597.7A Division CN110256496B (en) 2017-09-08 2017-09-08 Beta-thioindolone derivative and preparation method thereof

Publications (2)

Publication Number Publication Date
CN107501328A CN107501328A (en) 2017-12-22
CN107501328B true CN107501328B (en) 2019-09-03

Family

ID=60696002

Family Applications (4)

Application Number Title Priority Date Filing Date
CN201710808044.0A Active CN107501328B (en) 2017-09-08 2017-09-08 A kind of β-thiocyanogen alkenyl phosphono analog derivative and preparation method thereof
CN201910606598.1A Active CN110218229B (en) 2017-09-08 2017-09-08 Beta-mercapto azaphospho heterocyclic derivative and preparation method thereof
CN201910606595.8A Active CN110272450B (en) 2017-09-08 2017-09-08 Beta-thiocarbonyl diphosphonic acid derivative and preparation method thereof
CN201910606597.7A Active CN110256496B (en) 2017-09-08 2017-09-08 Beta-thioindolone derivative and preparation method thereof

Family Applications After (3)

Application Number Title Priority Date Filing Date
CN201910606598.1A Active CN110218229B (en) 2017-09-08 2017-09-08 Beta-mercapto azaphospho heterocyclic derivative and preparation method thereof
CN201910606595.8A Active CN110272450B (en) 2017-09-08 2017-09-08 Beta-thiocarbonyl diphosphonic acid derivative and preparation method thereof
CN201910606597.7A Active CN110256496B (en) 2017-09-08 2017-09-08 Beta-thioindolone derivative and preparation method thereof

Country Status (1)

Country Link
CN (4) CN107501328B (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109096336B (en) * 2018-10-08 2019-09-27 南通纺织丝绸产业技术研究院 A kind of preparation method and application of benzo phospha naphthalene derivatives
CN109096330B (en) * 2018-10-08 2020-08-14 苏州大学 Trifluoromethyl alkenyl phosphonate and preparation method thereof
WO2020073208A1 (en) * 2018-10-09 2020-04-16 南通纺织丝绸产业技术研究院 Method for preparing benzophospho naphthalene derivative, and use thereof
CN112010722B (en) * 2020-09-14 2023-01-06 南通大学 Synthesis method of E-type beta-thiocyanatelamide derivative

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1704423A (en) * 1998-09-09 2005-12-07 症变治疗公司 Novel heteroaromatic inhibitors of fructose 1,6-bisphosphatase
CN105017312A (en) * 2015-06-26 2015-11-04 苏州大学 Preparation method of beta-aminoethylphosphonyl derivatives
CN106432329A (en) * 2016-09-09 2017-02-22 苏州大学 Beta-cyano phosphoryl derivatives as well as preparation method and application thereof

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105503945B (en) * 2015-12-14 2017-09-05 苏州大学 A kind of method for preparing the Dicarbonyl derivatives of 2 phosphonate group 1,3

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1704423A (en) * 1998-09-09 2005-12-07 症变治疗公司 Novel heteroaromatic inhibitors of fructose 1,6-bisphosphatase
CN105017312A (en) * 2015-06-26 2015-11-04 苏州大学 Preparation method of beta-aminoethylphosphonyl derivatives
CN106432329A (en) * 2016-09-09 2017-02-22 苏州大学 Beta-cyano phosphoryl derivatives as well as preparation method and application thereof

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Inhibitory effect of novel S,N-bisphosphonates on some carcinoma cell lines, osteoarthritis, and chronic inflammation;Kamel, Azza A. et al.;《European Journal of Medicinal Chemistry》;20121231;第239-249页
Vinyl esters of phosphorus acids. XVIII. Phosphorylation of thiocyanatoacetone;Ivanova, Zh. M. et al.;《Zhurnal Obshchei Khimii》;19791231;第1464-1470页

Also Published As

Publication number Publication date
CN110272450A (en) 2019-09-24
CN110256496A (en) 2019-09-20
CN110256496B (en) 2021-08-17
CN107501328A (en) 2017-12-22
CN110218229A (en) 2019-09-10
CN110272450B (en) 2021-08-17
CN110218229B (en) 2021-08-17

Similar Documents

Publication Publication Date Title
CN107501328B (en) A kind of β-thiocyanogen alkenyl phosphono analog derivative and preparation method thereof
Reddy et al. PEG-SO3H catalyzed synthesis and cytotoxicity of α-aminophosphonates
SU1447284A3 (en) Method of producing derivative of [3h]-imidazo-[5,1-alpha]-1,2,3,5-tetrazin-4-none
CN114524701B (en) N-axis chiral pyrrole derivative and synthesis method thereof
CN109336866A (en) A kind of polysubstituted pyridine cyclics preparation method and application
CN115385916B (en) Chiral indoline pyrrole compound and synthesis method thereof
CN111892608B (en) Spiroheterocyclic 2, 3-dihydrobenzofuran compound with optical activity and application thereof
Gallienne et al. Short synthesis of new salacinol analogues and their evaluation as glycosidase inhibitors
CN112920173A (en) Chiral chroman compound and synthesis method thereof
CN106146560A (en) A kind of process for purification of high-purity phosphoric acid specially azoles amine
CN103288801A (en) Preparation method for high-purity esomeprazole sodium
JP7096559B2 (en) Triptolide derivatives and their manufacturing methods and uses
CN102746295B (en) Preparation method for 4-substituted-7-azaindole
CN107629039B (en) The preparation method and intermediate of deuterated acrylamide
CN105732758B (en) Cholic acid α aminophosphonate ester derivatives and its synthetic method
CN114989214B (en) Shikonin phosphoramidate hybrid and synthetic method and application thereof
CN109021014B (en) Method for synthesizing 2-O- (3-aminopropyl hydrogen phosphoryl) -ascorbic acid
CN116082217B (en) N-axis chiral bisindole compound and synthesis method thereof
WO2023216317A1 (en) Method for synthesizing nirmatrelvir intermediate
CN106928224B (en) Indoles Sophoridine derivative and preparation method thereof
CN113712961B (en) Application of beta-selenoether imidazole compound in preparation of antitumor drugs
CN108191736A (en) A kind of 2,3- disubstituted indoles analog derivative and preparation method thereof
CN107629052B (en) A kind of pyrrolo- [3,4b] quinoline -9- aminated compounds and its preparation method and application
CN116332902A (en) 1, 3-dithiacyclobutane-2, 4-dichotomous compound and synthesis and application thereof
CN110105364A (en) The rubigan substituted maleimide amine of N- containing pyrrazole structure α-terpinene cycloaddition derivative and its preparation method and application

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant