CN110305160A - A kind of phosphoric acid of copper catalysis mixes the synthetic method of ester type compound - Google Patents

A kind of phosphoric acid of copper catalysis mixes the synthetic method of ester type compound Download PDF

Info

Publication number
CN110305160A
CN110305160A CN201910595417.XA CN201910595417A CN110305160A CN 110305160 A CN110305160 A CN 110305160A CN 201910595417 A CN201910595417 A CN 201910595417A CN 110305160 A CN110305160 A CN 110305160A
Authority
CN
China
Prior art keywords
copper
phosphoric acid
ester
alcohol
mixes
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.)
Granted
Application number
CN201910595417.XA
Other languages
Chinese (zh)
Other versions
CN110305160B (en
Inventor
焦林郁
张泽
殷晓美
洪乾
宁资慧
马晓迅
徐龙
李卓
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.)
Northwest University
Original Assignee
Northwest University
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 Northwest University filed Critical Northwest University
Priority to CN201910595417.XA priority Critical patent/CN110305160B/en
Publication of CN110305160A publication Critical patent/CN110305160A/en
Application granted granted Critical
Publication of CN110305160B publication Critical patent/CN110305160B/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 System
    • C07F9/02—Phosphorus compounds
    • C07F9/06—Phosphorus compounds without P—C bonds
    • C07F9/08—Esters of oxyacids of phosphorus
    • C07F9/09—Esters of phosphoric acids
    • C07F9/12—Esters of phosphoric acids with hydroxyaryl 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 System
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/30—Phosphinic acids R2P(=O)(OH); Thiophosphinic acids, i.e. R2P(=X)(XH) (X = S, Se)
    • C07F9/32—Esters thereof
    • C07F9/3205—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/3229—Esters of aromatic acids (P-C aromatic linkage)
    • 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 System
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/30—Phosphinic acids R2P(=O)(OH); Thiophosphinic acids, i.e. R2P(=X)(XH) (X = S, Se)
    • C07F9/32—Esters thereof
    • C07F9/3258—Esters thereof the ester moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/3288—Esters with arylalkanols

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)

Abstract

A kind of phosphoric acid of copper catalysis mixes the synthetic method of ester type compound, and azido acid ester class compound and fatty alcohol are mixed, copper catalyst is then added, adds alkali, react 3 at 20~100 DEG C~for 24 hours, phosphoric acid is obtained after post treatment mixes ester type compound.The present invention is synthesized phosphoric acid using azido acid ester class compound and fatty alcohol for the first time and mixes ester type compound; the synthesis process only needs to be added the alkali of copper catalyst and catalytic amounts; it is easy to operate, and the shortcomings that needing inert gas shielding is overcome, it is a kind of novel high-efficiency synthesis method.

Description

A kind of phosphoric acid of copper catalysis mixes the synthetic method of ester type compound
Technical field
The present invention relates to organic syntheses and fine organic chemical industry field, and in particular to a kind of mixed esters of phosphoric acid of copper catalysis Close the synthetic method of object.
Background technique
Phosphate compounds are a kind of very important organic phosphorus compounds, and it is wherein very important that phosphoric acid, which mixes ester, One kind, has good market prospects and application value, is a current research hotspot.
Phosphate compounds play an important role in the natural products and bioactive compound of various structures, phosphorus The introducing of acidic group substantially changes the physics and chemical property of parent molecule, to change molecular polarization and intermolecular key Close feature.Phosphate compounds have been widely used in biology, medicine, pesticide, macromolecule and material science, especially prominent Be its good bioactivity (D.Kim, et.al.Chemistry of Materials, 2010,22,247； N.H.Williams,et.al.Archives of Toxicology,2007,81,627；H.H.Chou,et.al.Advanced Materials,2010,22,2468；D.K.C.Nomura,et.al.Bioorganic&Medicinal Chemistry Letters, 2008,18,5875.) and flame retardant property.Currently, phosphate compounds industrially obtained it is more and more Application, study its synthetic method with very important social effect and economic significance.
Some traditional preparation methods of Reofos compound, as Michaelis-Arbuzov reacts (A.E.J.Arbuzov,Russian Journal of Physical Chemistry,1906,38,687.)、Atherton- Todd reaction (F.R.Atherto, et.al.Journal of the Chemical Society, 1945,382.), P (O)-Cl Nucleophilic substitution (B.R.Sculimbrene, Journal of the American occurs with nucleopilic reagent (such as alcohol, phenol) Chemical Society,2001,123,10125；D.S.Panmand,et.al.Tetrahedron Letters,2014, 55,5898.), P (O)-OH and alcohol reaction (B.Xiong, et.al.ACS Catalysis, 2015,5,537；G.Keglevich, Et.al.Organic&Biomolecular Chemistry, 2012,10,2011.) etc., these reactions are in the past few decades Good development is obtained, but there is also some limitations for these traditional synthetic methods, such as the tolerance to functional group Property it is poor, it usually needs expensive activating reagent, and using to the reagent of air and water sensitive or toxic reagent etc..Cause This, it is necessary to develop new efficient synthesis technology.
In conclusion Reofos compound is usually with P (O)-H, P (O)-Cl, P in previous report (O)-OH functional group is as raw material, using alcohol, phenol, amine etc. as nucleopilic reagent, needs to react under conditions of anhydrous and oxygen-free, sometimes Metallic catalyst or base catalyst need to be added.These methods have the disadvantage that, as economic cost is relatively high, reaction condition is severe It carves, even corrode equipment etc. using toxic reagent.Therefore, the technique for developing the mixed ester type compound of new efficient synthesis phosphoric acid is compeled In the eyebrows and eyelashes.
Summary of the invention
To overcome the problems of the prior art, the purpose of the present invention is to provide a kind of phosphoric acid of copper catalysis to mix esters chemical combination The synthetic method of object.
To achieve the above object, the present invention adopts the following technical scheme that:
A kind of phosphoric acid of copper catalysis mixes the synthetic method of ester type compound, and azido acid ester class compound and fatty alcohol are mixed Close, copper catalyst is then added, adds alkali, at 20~100 DEG C react 3~for 24 hours, obtain after post treatment phosphoric acid mix esters Compound.
A further improvement of the present invention lies in that azido acid ester class compound is diphenyl phosphate azide, diphenylphosphine is folded Nitride, nitrine di(2-ethylhexyl)phosphate (the bromo- phenyl of 4-) ester bis- to toluene ester, nitrine phosphoric acid, nitrine phosphoric acid are bis- (4- methoxyl group-phenyl) Ester, nitrine di(2-ethylhexyl)phosphate m-tolyl ester or nitrine di(2-ethylhexyl)phosphate o-toluene ester.
A further improvement of the present invention lies in that fatty alcohol be methanol, ethyl alcohol, 2,2,2 ,-trifluoroethanol, normal propyl alcohol, isopropyl Alcohol, n-butanol, isobutanol or n-amyl alcohol.
A further improvement of the present invention lies in that fatty alcohol be isoamyl alcohol, cyclopentanol, n-hexyl alcohol, cyclohexanol, cyclohexanemethanol, When benzyl alcohol, n-heptanol, 2- cyclohexyl ethyl alcohol, benzyl carbinol or citronellol, azido acid ester class compound and fatty alcohol are mixed, Solvent is added, copper catalyst is then added.
A further improvement of the present invention lies in that in solvent azido acid ester class compound molar concentration be 0.25~ 0.5mol/L。
A further improvement of the present invention lies in that solvent is hexamethylene, methylene chloride, n,N-Dimethylformamide, Isosorbide-5-Nitrae-two One of six ring of oxygen, ether.
A further improvement of the present invention lies in that copper catalyst is copper powder, stannous chloride, cuprous iodide, copper chloride, fluorination One of copper, copper oxide, copper sulphate, copper trifluoromethanesulfcomposite, copper acetate, copper nitrate.
A further improvement of the present invention lies in that alkali is sodium hydroxide, in sodium carbonate, sodium bicarbonate, sodium acetate, sodium phosphate It is a kind of.
A further improvement of the present invention lies in that the mass ratio of the material of azido acid ester class compound and fatty alcohol is 1:(2.2 ~100), the mass ratio of the material of azido acid ester class compound and copper catalyst is 1:(0.05~0.2), azido acid ester class The mass ratio of the material for closing object and alkali is 1:(0.2~0.5).
Compared with prior art, the invention has the benefit that the present invention uses azido acid ester class compound for the first time Phosphoric acid is synthesized with fatty alcohol mixes ester type compound；Reaction process needs that copper catalyst and alkali is added, it is ensured that reaction it is suitable Benefit carries out, which is simple and efficient；Reaction process can carry out under air atmosphere, be not necessarily to inert gas shielding, entire to synthesize Process is simple and efficient, is easy to operate, realizes phosphoric acid by one kettle way and mixes ester type compound synthesis；This synthetic route selectivity By force, combined coefficient is high；Reaction raw materials are cheap and easy to get；With wide potential application foreground.
Specific embodiment
In order to deepen the understanding of the present invention, below in conjunction with embodiment, the present invention is described further, the implementation Example for explaining only the invention, does not restrict the protection scope of the present invention.
Using azido acid ester class compound and fatty alcohol as raw material in the present invention, catalyst is mantoquita, and catalytic amounts are added Alkali, prepare at a certain temperature corresponding phosphoric acid mix ester type compound.
A kind of reaction equation of the synthetic method of the mixed ester type compound of phosphoric acid of copper catalysis are as follows:
Azido acid ester class compound and fatty alcohol are added in solvent or directly by azido acid ester class compound and Fatty alcohol mixing, using fatty alcohol as solvent；
Then be added copper catalyst and catalytic amounts alkali, at 20~100 DEG C react 3~for 24 hours, obtain after post treatment Phosphoric acid mixes ester type compound.
Wherein, azido acid ester class compound is diphenyl phosphate azide, diphenylphosphine azide, nitrine di(2-ethylhexyl)phosphate pair Bis- (the bromo- phenyl of the 4-) esters of toluene ester, nitrine phosphoric acid, bis- (4- methoxyl group-phenyl) esters of nitrine phosphoric acid, nitrine di(2-ethylhexyl)phosphate m-tolyl ester Or nitrine di(2-ethylhexyl)phosphate o-toluene ester.
Fatty alcohol be methanol, ethyl alcohol, 2,2,2 ,-trifluoroethanol, normal propyl alcohol, isopropanol, n-butanol, isobutanol, n-amyl alcohol, Isoamyl alcohol, cyclopentanol, n-hexyl alcohol, cyclohexanol, cyclohexanemethanol, benzyl alcohol, n-heptanol, 2- cyclohexyl ethyl alcohol, benzyl carbinol or lemongrass Alcohol.
Copper catalyst be copper or mantoquita, specially copper powder, stannous chloride, cuprous iodide, copper chloride, copper fluoride, copper oxide, One of copper sulphate, copper trifluoromethanesulfcomposite, copper acetate, copper nitrate.
Alkali is one of sodium hydroxide, sodium carbonate, sodium bicarbonate, sodium acetate, sodium phosphate.
Solvent is one of hexamethylene, methylene chloride, N,N-dimethylformamide, 1,4- dioxane, ether；
Fatty alcohol is methanol, ethyl alcohol, 2,2,2 ,-trifluoroethanol, normal propyl alcohol, isopropanol, n-butanol, isobutanol or n-amyl alcohol When Deng the relatively small fatty alcohol of viscosity as reactant, fatty alcohol is excessive, it is not necessary that other solvents are added；
When fatty alcohol is isoamyl alcohol, cyclopentanol, n-hexyl alcohol, cyclohexanol, cyclohexanemethanol, benzyl alcohol, n-heptanol, 2- cyclohexyl When the biggish fatty alcohol of the viscosity such as ethyl alcohol, benzyl carbinol or citronellol is as reactant, need to be added solvent, and solvent is hexamethylene One of alkane, methylene chloride, N,N-dimethylformamide, 1,4- dioxane, ether.Azido acid ester class compound is molten Molar concentration in agent is 0.25~0.5mol/L；
The mass ratio of the material of azido acid ester class compound and fatty alcohol is 1:(2.2~100)；
The mass ratio of the material of azido acid ester class compound and copper catalyst is 1:(0.05~0.2)；
The mass ratio of the material of azido acid ester class compound and alkali is 1:(0.2~0.5)；
The pressure of reaction is 0.1MPa.
It is below specific embodiment.
Embodiment 1
The synthesis of methyl orthophosphoric acid diphenyl ester: 108 μ L (0.5mmol) of diphenyl phosphate azide, methanol 2mL are weighed respectively (49.4mmol), stannous chloride, sodium carbonate；The mass ratio of the material of diphenyl phosphate azide and stannous chloride is 1:0.1；Mazidox The mass ratio of the material of diphenyl phthalate and sodium carbonate is 1:0.2；It is anti-that load weighted reactant is sequentially added into the 25mL with magneton Ying Guanzhong is stirred on magnetic stirring apparatus under room temperature, is then slowly heated to 40 DEG C, with thin-layer chromatography monitoring reaction into Journey.At 0.1MPa, stops reaction after 3h, be cooled to room temperature.Mixture is diluted with water (5mL), and uses ethyl acetate (10mL × 3) extraction, merges organic phase.Organic phase is washed with saturated salt solution (5mL), and anhydrous sodium sulfate is added and dries, filters Concentration, is separated with column chromatography chromatogram, using the silica gel of 300~400 mesh as stationary phase, ethyl acetate and petroleum in varing proportions The mixed solvent of ether carries out purifies and separates to product as eluant, eluent.
The physical property and characterize data of gained compound are as follows:
Colorless oil；IR(ATR):2958(vw),1592(w),1484(m),1456 (vw),1289(m),1221(w),1187(s),1163(m),1044(s),1009(m),936(vs),821(m),755(s), 686(s)；1H NMR(400MHz,CDCl3, 298K): δ=3.89 (dd, J=11.6Hz, J=1.6Hz, 3H), 7.15 (dd, J= 8.0Hz, J=7.8Hz, 2H), 7.22 (d, J=8.0Hz, 4H), 7.30 (dd, J=8.0Hz, J=7.8Hz, 4H) ppm；13C NMR(101MHz,CDCl3, 298K): δ=55.5 (d, J=6.0Hz), 120.0 (d, J=4.0Hz), 125.5 (d, J= 1.0Hz), 129.9,150.5 (d, J=7.1Hz) ppm；31P NMR(162MHz,CDCl3, 298K): δ=- 10.79ppm.
Embodiment 2
The synthesis of phosphoric acid pentyl ester diphenyl ester: 108 μ L (0.5mmol) of diphenyl phosphate azide, n-amyl alcohol 2mL are weighed respectively (18.4mmol), copper nitrate, sodium carbonate；The mass ratio of the material of diphenyl phosphate azide and copper nitrate is 1:0.1；Nitrine di(2-ethylhexyl)phosphate The mass ratio of the material of phenyl ester and sodium carbonate is 1:0.5；Load weighted reactant is sequentially added to the 25mL reaction tube with magneton In, it is stirred on magnetic stirring apparatus under room temperature, is then slowly heated to 60 DEG C, with the process of thin-layer chromatography monitoring reaction. At 0.1MPa, stops reaction afterwards for 24 hours, be cooled to room temperature.By mixture with 0.1mol/L hydrochloric acid (5mL), and use acetic acid Ethyl ester (10mL × 3) extraction, merges organic phase.Organic phase is washed with saturated salt solution (5mL), and anhydrous sodium sulfate drying is added, Filtering and concentrating is separated with column chromatography chromatogram, using the silica gel of 300~400 mesh as stationary phase, ethyl acetate in varing proportions and The mixed solvent of petroleum ether carries out purifies and separates to product as eluant, eluent.
The physical property and characterize data of gained compound are as follows:
Colorless oil；IR(ATR):2958(vw),1590(w),1488(m),1457 (vw),1287(m),1220(w),1189(s),1163(m),1024(s),941(vs),903(m),827(w),754(s),688 (s)；1H NMR(400MHz,CDCl3, 298K): δ=0.89 (t, J=7.2Hz, 3H), 1.24-1.40 (m, 4H), 1.66-1.74 (m,2H),4.23–4.28(m,2H),7.14–7.20(m,2H),7.22–7.26(m,4H),7.31–7.36(m,4H)ppm；13C NMR(101MHz,CDCl3, 298K): δ=13.9,22.1,27.4,29.9 (d, J=7.0Hz), 69.5 (d, J=6.0Hz), 120.1 (d, J=4.0Hz), 125.3 (d, J=1.0Hz), 129.8,150.6 (d, J=7.0Hz) ppm；31P NMR(162MHz, CDCl3, 298K): δ=- 11.76ppm.
Embodiment 3
The synthesis of phosphoric acid 3- methylbutyl butenoate diphenyl ester: 108 μ L (0.5mmol) of diphenyl phosphate azide, isoamyl are weighed respectively Alcohol 0.2mL (1.84mmol), copper chloride, sodium carbonate, hexamethylene；The mass ratio of the material of diphenyl phosphate azide and copper chloride is 1: 0.1；The mass ratio of the material of diphenyl phosphate azide and sodium carbonate is 1:0.5；The volume ratio of hexamethylene and isoamyl alcohol is 9:1；It will Load weighted reactant sequentially adds in the 25mL reaction tube with magneton, stirs on magnetic stirring apparatus under room temperature, so After be slowly heated to 60 DEG C, with thin-layer chromatography monitoring reaction process.At 0.1MPa, stops reaction afterwards for 24 hours, be cooled to room Temperature.It by mixture with 0.1mol/L hydrochloric acid (5mL), and is extracted with ethyl acetate (10mL × 3), merges organic phase.It is organic Mutually being washed with saturated salt solution (5mL), addition anhydrous sodium sulfate dries, filters concentration, it is separated with column chromatography chromatogram, with 300~ The silica gel of 400 mesh is as stationary phase, and the mixed solvent of ethyl acetate and petroleum ether in varing proportions is as eluant, eluent to product Carry out purifies and separates.
The physical property and characterize data of gained compound are as follows:
Colorless oil；IR(ATR):2960(vw),1591(w),1488(m),1469 (vw),1389(vw),1288(m),1221(w),1188(s),1162(m),1052(m),1008(s),938(vs),754(s), 687(s)；1H NMR(400MHz,CDCl3, 298K): δ=0.88-0.95 (m, 6H), 1.59-1.64 (m, 2H), 1.69-1.77 (m,1H),4.28–4.34(m,2H),7.18–7.22(m,2H),7.23–7.28(m,4H),7.34–7.39(m,4H)ppm；13C NMR(101MHz,CDCl3, 298K): δ=22.3,24.4,38.8 (d, J=6.0Hz), 67.9 (d, J=6.0Hz), 120.1 (d, J=4.0Hz), 125.3 (d, J=2.0Hz), 129.8,150.6 (d, J=7.0Hz) ppm；31P NMR(162MHz, CDCl3, 298K): δ=- 11.56ppm.
Embodiment 4
The synthesis of phosphoric acid ring pentyl ester diphenyl ester: 108 μ L (0.5mmol) of diphenyl phosphate azide, cyclopentanol are weighed respectively 0.2mL (2.20mmol), cuprous iodide, sodium carbonate, hexamethylene；The mass ratio of the material of diphenyl phosphate azide and cuprous iodide is 1:0.1；The mass ratio of the material of diphenyl phosphate azide and sodium carbonate is 1:0.5；The volume ratio of hexamethylene and cyclopentanol is 9:1； Load weighted reactant is sequentially added in the 25mL reaction tube with magneton, is stirred on magnetic stirring apparatus under room temperature, 60 DEG C are then slowly heated to, with the process of thin-layer chromatography monitoring reaction.At 0.1MPa, stops reaction afterwards for 24 hours, be cooled to room Temperature.It by mixture with 0.1mol/L hydrochloric acid (5mL), and is extracted with ethyl acetate (10mL × 3), merges organic phase.It is organic Mutually being washed with saturated salt solution (5mL), addition anhydrous sodium sulfate dries, filters concentration, it is separated with column chromatography chromatogram, with 300~ The silica gel of 400 mesh is as stationary phase, and the mixed solvent of ethyl acetate and petroleum ether in varing proportions is as eluant, eluent to product Carry out purifies and separates.
The physical property and characterize data of gained compound are as follows:
Colorless oil；IR(ATR):2965(vw),2875(vw),1591(w),1488 (m),1456(vw),1284(m),1221(w),1188(s),1162(m),1071(w),1009(s),936(vs),753(s), 688(s)；1H NMR(400MHz,CDCl3, 298K): δ=1.57-1.66 (m, 2H), 1.71-1.96 (m, 6H), 5.14-5.18 (m, 1H), 7.18-7.29 (m, 6H), 7.35 (dd, J=8.0Hz, J=8.0Hz, 4H) ppm；13C NMR(101MHz,CDCl3, 298K): δ=22.9,33.9 (d, J=5.0Hz), 83.5 (d, J=7.0Hz), 120.1 (d, J=5.0Hz), 125.2 (d, J= 1.0Hz), 129.7,150.6 (d, J=7.0Hz) ppm；31P NMR(162MHz,CDCl3, 298K): δ=- 12.43ppm.
Embodiment 5
The synthesis of the own ester diphenyl ester of phosphoric acid: 108 μ L (0.5mmol) of diphenyl phosphate azide, n-hexyl alcohol 0.2mL are weighed respectively (1.61mmol), copper sulphate, sodium carbonate, methylene chloride；The mass ratio of the material of diphenyl phosphate azide and copper sulphate is 1:0.1； The mass ratio of the material of diphenyl phosphate azide and sodium carbonate is 1:0.5；The volume ratio of methylene chloride and n-hexyl alcohol is 9:1；It will claim Measured reactant sequentially adds in the 25mL reaction tube with magneton, stirs on magnetic stirring apparatus under room temperature, then 60 DEG C are slowly heated to, with the process of thin-layer chromatography monitoring reaction.At 0.1MPa, stops reaction afterwards for 24 hours, be cooled to room temperature. It by mixture with 0.1mol/L hydrochloric acid (5mL), and is extracted with ethyl acetate (10mL × 3), merges organic phase.Organic phase is used Saturated salt solution (5mL) washing is added anhydrous sodium sulfate and dries, filters concentration, separated with column chromatography chromatogram, with 300~400 mesh Silica gel as stationary phase, the mixed solvent of ethyl acetate and petroleum ether in varing proportions carries out product as eluant, eluent pure Change separation.
The physical property and characterize data of gained compound are as follows:
Colorless oil；IR(ATR):2958(vw),1590(w),1488(m),1457 (vw),1290(m),1220(w),1189(s),1163(m),1024(s),945(vs),904(m),755(s),688(s)；1H NMR(400MHz,CDCl3, 298K): δ=0.88-0.93 (m, 3H), 1.26-1.48 (m, 6H), 1.68-1.77 (m, 2H), 4.24–4.33(m,2H),7.19–7.28(m,6H),7.35–7.42(m,4H)ppm；13C NMR(101MHz,CDCl3,298K): δ=14.3,25.5,26.2,29.0,38.3 (d, J=7.0Hz), 68.7,120.1 (d, J=9.0Hz), 125.3 (d, J= 2.0Hz), 129.8,133.2 (d, J=12Hz), 150.6 (d, J=7.0Hz) ppm；31P NMR(162MHz,CDCl3,298K): δ=- 11.80ppm.
Embodiment 6
The synthesis of phosphoric acid cyclohexyl diphenyl ester: 108 μ L (0.5mmol) of diphenyl phosphate azide, cyclohexanol are weighed respectively 0.2mL (1.89mmol), copper oxide, sodium carbonate, hexamethylene；The mass ratio of the material of diphenyl phosphate azide and copper oxide is 1: 0.1；The mass ratio of the material of diphenyl phosphate azide and sodium carbonate is 1:0.3；The volume ratio of hexamethylene and cyclohexanol is 4:1；It will Load weighted reactant sequentially adds in the 25mL reaction tube with magneton, stirs on magnetic stirring apparatus under room temperature, so After be slowly heated to 60 DEG C, with thin-layer chromatography monitoring reaction process.At 0.1MPa, stops reaction afterwards for 24 hours, be cooled to room Temperature.It by mixture with 0.1mol/L hydrochloric acid (5mL), and is extracted with ethyl acetate (10mL × 3), merges organic phase.It is organic Mutually being washed with saturated salt solution (5mL), addition anhydrous sodium sulfate dries, filters concentration, it is separated with column chromatography chromatogram, with 300~ The silica gel of 400 mesh is as stationary phase, and the mixed solvent of ethyl acetate and petroleum ether in varing proportions is as eluant, eluent to product Carry out purifies and separates.
The physical property and characterize data of gained compound are as follows:
Colorless oil；IR(ATR):2936(vw),2858(vw),1590(w),1488 (m),1455(w),1284(m),1221(w),1189(s),1163(m),1001(s),938(vs),836(w),754(s),688 (s)；1H NMR(400MHz,CDCl3, 298K): δ=1.24-1.39 (m, 3H), 1.49-1.63 (m, 3H), 1.70-1.77 (m, 2H),1.86–1.97(m,2H),4.62–4.67(m,1H),7.17–7.30(m,6H),7.33–7.42(m,4H)ppm；13C NMR (101MHz,CDCl3, 298K): δ=23.4,25.0,33.2 (d, J=5.0Hz), 79.5,120.2 (d, J=5.0Hz), 125.2,129.8 (d, J=17Hz), 150.7 (d, J=8.0Hz) ppm；31P NMR(162MHz,CDCl3, 298K): δ=- 12.61ppm。
Embodiment 7
The synthesis of phosphoric acid cyclohexylmethyl diphenyl ester: 108 μ L (0.5mmol) of diphenyl phosphate azide, hexamethylene are weighed respectively Methanol 0.2mL (1.63mmol), stannous chloride, sodium carbonate, 1,4- dioxane；The object of diphenyl phosphate azide and stannous chloride The amount ratio of matter is 1:0.1；The mass ratio of the material of diphenyl phosphate azide and sodium carbonate is 1:0.4；1,4- dioxane and hexamethylene The volume ratio of methanol is 9:1；Load weighted reactant is sequentially added in the 25mL reaction tube with magneton, is existed under room temperature It is stirred on magnetic stirring apparatus, is then slowly heated to 60 DEG C, with the process of thin-layer chromatography monitoring reaction.At 0.1MPa, for 24 hours after Stop reaction, is cooled to room temperature.By mixture with 0.1mol/L hydrochloric acid (5mL), and extracted with ethyl acetate (10mL × 3) It takes, merges organic phase.Organic phase is washed with saturated salt solution (5mL), and anhydrous sodium sulfate is added and dries, filters concentration, with column layer Chromatographic isolation is analysed, using the silica gel of 300~400 mesh as stationary phase, the mixing of ethyl acetate and petroleum ether in varing proportions is molten Agent carries out purifies and separates to product as eluant, eluent.
The physical property and characterize data of gained compound are as follows:
Colorless oil；IR(ATR):2925(vw),2853(vw),1590(w),1488 (w),1450(w),1288(m),1221(w),1189(s),1163(m),1111(vw),1019(s),938(vs),857(w), 754(s),688(s)；1H NMR(400MHz,CDCl3, 298K): δ=0.94-0.99 (m, 2H), 1.01-1.28 (m, 4H), 1.65–1.82(m,5H),4.05–4.08(m,2H),7.18–7.40(m,10H)ppm；13C NMR(101MHz,CDCl3, 298K): δ=25.5,26.2,29.0,38.3,74.3 (d, J=7.0Hz), 120.1 (d, J=6.0Hz), 125.3 (d, J= 2.0Hz), 129.8,150.6 (d, J=7.0Hz) ppm；31P NMR(162MHz,CDCl3, 298K): δ=- 11.70ppm.
Embodiment 8
The synthesis of phosphoric acid heptyl ester diphenyl ester: 108 μ L (0.5mmol) of diphenyl phosphate azide, n-heptanol 0.2mL are weighed respectively (1.41mmol), stannous chloride, sodium carbonate, ether；The mass ratio of the material of diphenyl phosphate azide and stannous chloride is 1:0.1； The mass ratio of the material of diphenyl phosphate azide and sodium carbonate is 1:0.5；The volume ratio of ether and n-heptanol is 9:1；It will weigh Reactant sequentially add in the 25mL reaction tube with magneton, stirred on magnetic stirring apparatus under room temperature, then slowly 50 DEG C are heated to, with the process of thin-layer chromatography monitoring reaction.At 0.1MPa, stops reaction afterwards for 24 hours, be cooled to room temperature.It will mix Object is closed with 0.1mol/L hydrochloric acid (5mL), and extracted with ethyl acetate (10mL × 3), merging organic phase.Organic phase saturation Saline solution (5mL) washing is added anhydrous sodium sulfate and dries, filters concentration, separated with column chromatography chromatogram, with the silicon of 300~400 mesh For glue as stationary phase, the mixed solvent of ethyl acetate and petroleum ether in varing proportions carries out purifying point to product as eluant, eluent From.
The physical property and characterize data of gained compound are as follows:
Colorless oil；IR(ATR):2928(vw),2857(vw),1591(w),1489 (m),1457(w),1285(m),1221(w),1190(s),1163(m),1023(m),942(vs),823(vw),754(s), 688(s)；1H NMR(400MHz,CDCl3, 298K): δ=0.86-0.92 (m, 4H), 1.24-1.35 (m, 6H), 1.51-1.55 (m, 1H), 1.66-1.71 (m, 2H), 4.25 (dt, J=8.0Hz, J=7.6Hz, 2H), 7.17 (dd, J=8.0Hz, J= 8.0Hz, 2H), 7.23-7.28 (m, 4H), 7.33 (dd, J=8.0Hz, J=8.0Hz, 4H) ppm；13C NMR(101MHz, CDCl3, 298K): δ=14.1 (d, J=5.0Hz), 22.5,25.3,28.7,30.2 (d, J=7.0Hz), 31.7,69.5 (d, J =6.0Hz), 120.0 (d, J=5.0Hz), 125.3 (d, J=1.0Hz), 129.8,150.6 (d, J=7.0Hz) ppm；31P NMR(162MHz,CDCl3, 298K): δ=- 11.60ppm.
Embodiment 9
The synthesis of phosphoric acid phenethyl ester diphenyl ester: 108 μ L (0.5mmol) of diphenyl phosphate azide, benzyl carbinol are weighed respectively 0.2mL (1.67mmol), stannous chloride, sodium carbonate, hexamethylene；The mass ratio of the material of diphenyl phosphate azide and stannous chloride is 1:0.2；The mass ratio of the material of diphenyl phosphate azide and sodium carbonate is 1:0.5；The volume ratio of hexamethylene and benzyl carbinol is 9:1； Load weighted reactant is sequentially added in the 25mL reaction tube with magneton, is stirred on magnetic stirring apparatus under room temperature, 90 DEG C are then slowly heated to, with the process of thin-layer chromatography monitoring reaction.At 0.1MPa, stops reaction afterwards for 24 hours, be cooled to room Temperature.It by mixture with 0.1mol/L hydrochloric acid (5mL), and is extracted with ethyl acetate (10mL × 3), merges organic phase.It is organic Mutually being washed with saturated salt solution (5mL), addition anhydrous sodium sulfate dries, filters concentration, it is separated with column chromatography chromatogram, with 300~ The silica gel of 400 mesh is as stationary phase, and the mixed solvent of ethyl acetate and petroleum ether in varing proportions is as eluant, eluent to product Carry out purifies and separates.
The physical property and characterize data of gained compound are as follows:
Colorless oil；IR(ATR):1590(w),1488(m),1455(w),1286(m), 1187(s),1163(m),1018(m),943(vs),751(s),687(s)；1H NMR(400MHz,CDCl3, 298K): δ= 3.06 (t, J=3.6Hz, 2H), 4.49 (dt, J=3.6Hz, J=1.2Hz, 2H), 7.19-7.25 (m, 7H), 7.27-7.38 (m,8H)ppm；13C NMR(101MHz,CDCl3, 298K): δ=36.6 (d, J=7.0Hz), 69.5 (d, J=6.0Hz), 120.1 (d, J=4.0Hz), 125.4 (d, J=1.0Hz), 126.9,128.6,129.1,129.8,136.7,150.5 (d, J= 7.0Hz)ppm；31P NMR(162MHz,CDCl3, 298K): δ=- 11.99ppm.
Embodiment 10
The synthesis of phosphoric acid 3,7- dimethyl -6- octenylester diphenyl ester: 108 μ L of diphenyl phosphate azide is weighed respectively (0.5mmol), citronellol 0.2mL (1.10mmol), stannous chloride, sodium carbonate, hexamethylene；Diphenyl phosphate azide and protochloride The mass ratio of the material of copper is 1:0.1；The mass ratio of the material of diphenyl phosphate azide and sodium carbonate is 1:0.5；Hexamethylene and lemongrass The volume ratio of alcohol is 9:1；Load weighted reactant is sequentially added in the 25mL reaction tube with magneton, under room temperature in magnetic It is stirred on power blender, is then slowly heated to 100 DEG C, with the process of thin-layer chromatography monitoring reaction.At 0.1MPa, for 24 hours after Stop reaction, is cooled to room temperature.By mixture with 0.1mol/L hydrochloric acid (5mL), and extracted with ethyl acetate (10mL × 3) It takes, merges organic phase.Organic phase is washed with saturated salt solution (5mL), and anhydrous sodium sulfate is added and dries, filters concentration, with column layer Chromatographic isolation is analysed, using the silica gel of 300~400 mesh as stationary phase, the mixing of ethyl acetate and petroleum ether in varing proportions is molten Agent carries out purifies and separates to product as eluant, eluent.
The physical property and characterize data of gained compound are as follows:
Colorless oil；IR(ATR):2914(w),2855(vw),1592(w),1488(m), 1457(w),1378(vw),1285(m),1221(w),1189(s),1163(m),1009(m),948(vs),829(vw),754 (s),688(s)；1H NMR(400MHz,CDCl3, 298K): δ=0.85-0.90 (m, 3H), 1.13-1.19 (m, 2H), 1.29- 1.39(m,2H),1.66–1.69(m,6H),1.90–2.01(m,3H),4.27–4.32(m,1H),5.05–5.11(m,2H), 7.16–7.24(m,6H),7.29–7.36(m,4H)ppm；13C NMR(101MHz,CDCl3, 298K): δ=19.5,25.7, (28.8,29.2,36.9,37.3,39.8,60.8,120.0 d, J=5.0Hz), 124.4,124.8,125.3,129.8,150.5 (d, J=7.0Hz) ppm；31P NMR(162MHz,CDCl3, 298K): δ=- 11.80ppm.
Embodiment 11
The synthesis of etherophosphoric acid diphenyl ester: 108 μ L (0.5mmol) of diphenyl phosphate azide, ethyl alcohol 2mL are weighed respectively (34.3mmol), stannous chloride, sodium carbonate；The mass ratio of the material of diphenyl phosphate azide and stannous chloride is 1:0.05；Nitrine The mass ratio of the material of diphenyl phosphate and sodium carbonate is 1:0.5；Load weighted reactant is sequentially added into the 25mL with magneton It in reaction tube, is stirred on magnetic stirring apparatus under room temperature, is then slowly heated to 40 DEG C, with thin-layer chromatography monitoring reaction Process.At 0.1MPa, stops reaction after 15h, be cooled to room temperature.Mixture is diluted with water (5mL), and uses ethyl acetate (10mL × 3) extraction, merges organic phase.Organic phase is washed with saturated salt solution (5mL), and anhydrous sodium sulfate is added and dries, filters Concentration, is separated with column chromatography chromatogram, using the silica gel of 300~400 mesh as stationary phase, ethyl acetate and petroleum in varing proportions The mixed solvent of ether carries out purifies and separates to product as eluant, eluent.
The physical property and characterize data of gained compound are as follows:
Colorless oil；IR(ATR):2985(vw),1589(w),1488(m),1282(m), 1219(w),1187(s),1163(m),1024(s),1008(m),942(vs),793(m),755(s),688(s)；1H NMR (400MHz,CDCl3, 298K): δ=1.39 (dt, J=7.2Hz, J=1.2Hz, 3H), 4.36 (dq, J=7.2Hz, J= 1.2Hz,2H),7.19–7.28(m,6H),7.34–7.42(m,4H)ppm；13C NMR(101MHz,CDCl3, 298K): δ= 16.1 (d, J=6.0Hz), 65.5 (d, J=6.0Hz), 120.0 (d, J=5.0Hz), 125.3,129.8,150.6 (d, J=J =8.0Hz) ppm；31P NMR(162MHz,CDCl3, 298K): δ=- 11.88ppm.
Embodiment 12
The synthesis of phosphoric acid 2,2,2- trifluoro ethyl ester diphenyl ester: respectively weigh 108 μ L (0.5mmol) of diphenyl phosphate azide, 2,2,2 tfifluoroethyl alcohol 2mL (27.8mmol), copper powder, sodium carbonate；The mass ratio of the material of diphenyl phosphate azide and copper powder is 1: 0.1；The mass ratio of the material of diphenyl phosphate azide and sodium carbonate is 1:0.5；Load weighted reactant is sequentially added with magnetic In the 25mL reaction tube of son, is stirred on magnetic stirring apparatus under room temperature, be then slowly heated to 60 DEG C, supervised with thin-layer chromatography Survey the process of reaction.At 0.1MPa, stops reaction afterwards for 24 hours, be cooled to room temperature.By mixture 0.1mol/L hydrochloric acid (5mL), and extracted with ethyl acetate (10mL × 3), merge organic phase.Organic phase is washed with saturated salt solution (5mL), and nothing is added Aqueous sodium persulfate dries, filters concentration, is separated with column chromatography chromatogram, using the silica gel of 300~400 mesh as stationary phase, with not year-on-year The ethyl acetate of example and the mixed solvent of petroleum ether carry out purifies and separates to product as eluant, eluent.
The physical property and characterize data of gained compound are as follows:
Colorless oil；IR(ATR):3048(vw),1594(w),1489(w),1273(m), 1162(s),1084(s),1026(m),1012(m),959(vs),906(w),844(w),754(s),688(s),657(m)；1H NMR(400MHz,CDCl3, 298K): δ=4.42-4.56 (m, 2H), 6.85-6.99 (m, 4H), 7.23-7.43 (m, 6H) ppm ；13C NMR(101MHz,CDCl3, 298K): δ=64.2,115.3,120.0 (dd, J=62Hz, J=10Hz), 126.1, 130.0 (dd, J=20Hz, J=10Hz), 155.7ppm；31P NMR(162MHz,CDCl3, 298K): δ=- 12.51ppm.
Embodiment 13
The synthesis of phosphoric acid propyl ester diphenyl ester: 108 μ L (0.5mmol) of diphenyl phosphate azide, normal propyl alcohol 2mL are weighed respectively (26.8mmol), stannous chloride, sodium hydroxide；The mass ratio of the material of diphenyl phosphate azide and stannous chloride is 1:0.1；Nitrine The mass ratio of the material of diphenyl phosphate and sodium hydroxide is 1:0.2；Load weighted reactant is sequentially added with magneton It in 25mL reaction tube, is stirred on magnetic stirring apparatus under the conditions of 20 DEG C, with the process of thin-layer chromatography monitoring reaction.In 0.1MPa Under, stop reaction after 8h.It by mixture with 0.1mol/L hydrochloric acid (5mL), and is extracted, is closed with ethyl acetate (10mL × 3) And organic phase.Organic phase is washed with saturated salt solution (5mL), and anhydrous sodium sulfate is added and dries, filters concentration, uses column chromatography chromatogram Separation, using the silica gel of 300~400 mesh as stationary phase, the mixed solvent conduct of ethyl acetate and petroleum ether in varing proportions Eluant, eluent carries out purifies and separates to product.
The physical property and characterize data of gained compound are as follows:
Colorless oil；IR(ATR):2971(vw),1592(w),1488(m),1457 (vw),1284(m),1220(w),1188(s),1162(m),1057(w),1009(s),938(vs),849(w),754(s), 688(s)；1H NMR(400MHz,CDCl3, 298K): δ=0.96 (t, J=7.2Hz, 3H), 1.70-1.79 (m, 2H), 4.20- 4.28(m,2H),7.18–7.28(m,4H),7.33–7.39(m,6H)ppm；13C NMR(101MHz,CDCl3, 298K): δ= 9.96,23.6 (d, J=7.0Hz), 70.9 (d, J=7.0Hz), 120.0 (d, J=5.0Hz), 125.3,129.8,150.6 (d, J=7.0Hz) ppm；31P NMR(162MHz,CDCl3, 298K): δ=- 11.79ppm.
Embodiment 14
The synthesis of p isopropylbenzoic acid ester diphenyl ester: 108 μ L (0.5mmol) of diphenyl phosphate azide, isopropanol 2mL are weighed respectively (26.1mmol), copper trifluoromethanesulfcomposite, sodium bicarbonate；The mass ratio of the material of diphenyl phosphate azide and copper trifluoromethanesulfcomposite is 1: 0.1；The mass ratio of the material of diphenyl phosphate azide and sodium bicarbonate is 1:0.5；Load weighted reactant is sequentially added and is had It in the 25mL reaction tube of magneton, is stirred on magnetic stirring apparatus under room temperature, is then slowly heated to 60 DEG C, uses thin-layer chromatography Monitor the process of reaction.At 0.1MPa, stops reaction after 12h, be cooled to room temperature.By mixture 0.1mol/L hydrochloric acid (5mL), and extracted with ethyl acetate (10mL × 3), merge organic phase.Organic phase is washed with saturated salt solution (5mL), and nothing is added Aqueous sodium persulfate dries, filters concentration, is separated with column chromatography chromatogram, using the silica gel of 300~400 mesh as stationary phase, with not year-on-year The ethyl acetate of example and the mixed solvent of petroleum ether carry out purifies and separates to product as eluant, eluent.
The physical property and characterize data of gained compound are as follows:
Colorless oil；IR(ATR):2983(vw),1591(w),1488(m),1388 (vw),1284(m),1222(w),1189(s),1106(vw),1072(vw),1000(s),938(vs),755(s),688(s) ；1H NMR(400MHz,CDCl3, 298K): δ=1.37 (dd, J=6.4Hz, J=1.0Hz, 6H), 4.87-4.95 (m, 1H), 7.19 (ddd, J=8.0Hz, J=8.0Hz, J=1.6Hz, 2H), 7.24 (dd, J=8.0Hz, J=2.0Hz, 4H), 7.35 (ddd, J=8.0Hz, J=8.0Hz, J=1.2Hz, 4H) ppm；13C NMR(101MHz,CDCl3, 298K): δ=23.6 (d, J =5.0Hz), 74.9 (d, J=7.0Hz), 120.1 (d, J=5.0Hz), 125.2 (d, J=1.0Hz), 129.8,150.6 (d, J =7.0Hz) ppm；31P NMR(162MHz,CDCl3, 298K): δ=- 12.72ppm.
Embodiment 15
The synthesis of butylphosphoric acid ester diphenyl ester: 108 μ L (0.5mmol) of diphenyl phosphate azide, n-butanol 2mL are weighed respectively (21.9mmol), copper acetate, sodium acetate；The mass ratio of the material of diphenyl phosphate azide and copper acetate is 1:0.1；Nitrine di(2-ethylhexyl)phosphate The mass ratio of the material of phenyl ester and sodium acetate is 1:0.5；Load weighted reactant is sequentially added to the 25mL reaction tube with magneton In, it is stirred on magnetic stirring apparatus under room temperature, is then slowly heated to 80 DEG C, with the process of thin-layer chromatography monitoring reaction. At 0.1MPa, stops reaction after 16h, be cooled to room temperature.By mixture with 0.1mol/L hydrochloric acid (5mL), and use acetic acid Ethyl ester (10mL × 3) extraction, merges organic phase.Organic phase is washed with saturated salt solution (5mL), and anhydrous sodium sulfate drying is added, Filtering and concentrating is separated with column chromatography chromatogram, using the silica gel of 300~400 mesh as stationary phase, ethyl acetate in varing proportions and The mixed solvent of petroleum ether carries out purifies and separates to product as eluant, eluent.
The physical property and characterize data of gained compound are as follows:
Colorless oil；IR(ATR):2961(vw),1590(w),1489(m),1457 (vw),1287(m),1220(w),1189(s),1163(m),1024(s),1008(m),938(vs),800(w),755(s), 688(s)；1H NMR(400MHz,CDCl3, 298K): δ=0.92 (t, J=7.2Hz, 3H), 1.36-1.45 (m, 2H), 1.67- 1.74(m,2H),4.26–4.31(m,2H),7.18–7.28(m,6H),7.34–7.40(m,4H)ppm；13C NMR(101MHz, CDCl3, 298K): δ=13.5,18.6,32.2 (d, J=7.0Hz), 69.2 (d, J=6.0Hz), 120.1 (d, J=4.0Hz), 125.3 (d, J=2.0Hz), 129.8,150.6 (d, J=8.0Hz) ppm；31P NMR(162MHz,CDCl3, 298K): δ=- 11.77ppm。
Embodiment 16
The synthesis of phosphoric acid isobutyl ester diphenyl ester: 108 μ L (0.5mmol) of diphenyl phosphate azide, isobutanol 2mL are weighed respectively (21.6mmol), copper fluoride, sodium phosphate；The mass ratio of the material of diphenyl phosphate azide and copper fluoride is 1:0.1；Nitrine di(2-ethylhexyl)phosphate The mass ratio of the material of phenyl ester and sodium phosphate is 1:0.5；Load weighted reactant is sequentially added to the 25mL reaction tube with magneton In, it is stirred on magnetic stirring apparatus under room temperature, is then slowly heated to 60 DEG C, with the process of thin-layer chromatography monitoring reaction. At 0.1MPa, stops reaction after 20h, be cooled to room temperature.By mixture with 0.1mol/L hydrochloric acid (5mL), and use acetic acid Ethyl ester (10mL × 3) extraction, merges organic phase.Organic phase is washed with saturated salt solution (5mL), and anhydrous sodium sulfate drying is added, Filtering and concentrating is separated with column chromatography chromatogram, using the silica gel of 300~400 mesh as stationary phase, ethyl acetate in varing proportions and The mixed solvent of petroleum ether carries out purifies and separates to product as eluant, eluent.
The physical property and characterize data of gained compound are as follows:
Colorless oil；IR(ATR):2965(vw),1589(w),1489(vw),1371 (vw),1288(m),1220(w),1189(s),1163(m),1021(s),940(vs),956(w),755(s),688(s)；1H NMR(400MHz,CDCl3, 298K): δ=0.93 (dd, J=6.4Hz, J=0.8Hz, 6H), 1.95-2.05 (m, 1H), 4.01- 4.06 (m, 2H), 7.19 (ddd, J=8.0Hz, J=7.6Hz, J=1.2Hz, 2H), 7.25 (dd, J=8.0Hz, J=1.6Hz, 4H), 7.34 (ddd, J=8.0Hz, J=7.2Hz, J=1.2Hz, 4H) ppm；13C NMR(101MHz,CDCl3, 298K): δ= 18.6,29.1 (d, J=8.0Hz), 75.2 (d, J=7.0Hz), 120.1 (d, J=5.0Hz), 125.3 (d, J=1.0Hz), (129.8,150.6 d, J=8.0Hz) ppm；31P NMR(162MHz,CDCl3, 298K): δ=- 11.61ppm.
Embodiment 17
The synthesis of two o-toluene ester of methyl orthophosphoric acid: nitrine di(2-ethylhexyl)phosphate o-toluene ester 152mg (0.5mmol), first are weighed respectively Alcohol 2mL (49.4mmol), stannous chloride, sodium carbonate；The mass ratio of the material of nitrine di(2-ethylhexyl)phosphate o-toluene ester and stannous chloride is 1: 0.1；The mass ratio of the material of nitrine di(2-ethylhexyl)phosphate o-toluene ester and sodium carbonate is 1:0.5；Load weighted reactant is sequentially added into band Have in the 25mL reaction tube of magneton, stirred on magnetic stirring apparatus under room temperature, be then slowly heated to 40 DEG C, with thin layer color The process of spectrum monitoring reaction.At 0.1MPa, stops reaction after 3h, be cooled to room temperature.Mixture is dilute with 0.1mol/L hydrochloric acid It releases (5mL), and is extracted with ethyl acetate (10mL × 3), merge organic phase.Organic phase is washed with saturated salt solution (5mL), is added Anhydrous sodium sulfate dries, filters concentration, is separated with column chromatography chromatogram, using the silica gel of 300~400 mesh as stationary phase, with difference The ethyl acetate of ratio and the mixed solvent of petroleum ether carry out purifies and separates to product as eluant, eluent.
The physical property and characterize data of gained compound are as follows:
Colorless oil；IR(ATR):2958(vw),1586(w),1491(m),1461(w), 1289(m),1223(m),1167(s),1108(s),1041(s),948(vs),829(m),810(m),788(w),758(s), 709(m)；1H NMR(400MHz,CDCl3, 298K): δ=2.28 (s, 6H), 3.97 (dd, J=8.0Hz, J=1.2Hz, 3H), 7.10 (dd, J=8.0Hz, J=7.6Hz, 2H), 7.16-7.22 (m, 4H), 7.34 (d, J=7.8Hz, 2H) ppm；13C NMR (101MHz,CDCl3, 298K): δ=16.3,55.5 (d, J=7.0Hz), 119.8 (d, J=2.0Hz), 125.4 (d, J= 1.0Hz), 127.1 (d, J=1.0Hz), 129.4 (d, J=6.0Hz), 131.5,149.1 (d, J=7.0Hz) ppm；31P NMR (162MHz,CDCl3, 298K): δ=- 10.25ppm.
Embodiment 18
The synthesis of two m-tolyl ester of methyl orthophosphoric acid: nitrine di(2-ethylhexyl)phosphate m-tolyl ester 152mg (0.5mmol), first are weighed respectively Alcohol 2mL (49.4mmol), stannous chloride, sodium carbonate；The mass ratio of the material of nitrine di(2-ethylhexyl)phosphate m-tolyl ester and stannous chloride is 1: 0.1；The mass ratio of the material of nitrine di(2-ethylhexyl)phosphate m-tolyl ester and sodium carbonate is 1:0.5；Load weighted reactant is sequentially added into band Have in the 25mL reaction tube of magneton, stirred on magnetic stirring apparatus under room temperature, be then slowly heated to 40 DEG C, with thin layer color The process of spectrum monitoring reaction.At 0.1MPa, stops reaction after 3h, be cooled to room temperature.Mixture is dilute with 0.1mol/L hydrochloric acid It releases (5mL), and is extracted with ethyl acetate (10mL × 3), merge organic phase.Organic phase is washed with saturated salt solution (5mL), is added Anhydrous sodium sulfate dries, filters concentration, is separated with column chromatography chromatogram, using the silica gel of 300~400 mesh as stationary phase, with difference The ethyl acetate of ratio and the mixed solvent of petroleum ether carry out purifies and separates to product as eluant, eluent.
The physical property and characterize data of gained compound are as follows:
Colorless oil；IR(ATR):2958(vw),1611(w),1585(w),1487(m), 1453(w),1288(m),1240(m),1139(s),1046(s),1011(s),958(vs),864(s),778(s),722(w), 686(s)；1H NMR(400MHz,CDCl3, 298K): δ=2.35 (d, J=1.2Hz, 6H), 3.95 (dd, J=8.8Hz, J= 2.0Hz, 3H), 7.00-7.09 (m, 6H), 7.23 (ddd, J=8.0Hz, J=8.0Hz, J=1.2Hz, 2H) ppm；13C NMR (101MHz,CDCl3, 298K): δ=21.3,55.4 (d, J=6.0Hz), 117.0 (d, J=5.0Hz), 120.6 (d, J= 6.0Hz), 126.2 (d, J=1.0Hz), 129.5,140.1,150.5 (d, J=7.0Hz) ppm；31P NMR(162MHz, CDCl3, 298K): δ=- 10.72ppm.
Embodiment 19
Synthesis of the methyl orthophosphoric acid two to toluene ester: nitrine di(2-ethylhexyl)phosphate is weighed respectively to toluene ester 152mg (0.5mmol), first Alcohol 2mL (49.4mmol), stannous chloride, sodium carbonate；Nitrine di(2-ethylhexyl)phosphate is 1 to the mass ratio of the material of toluene ester and stannous chloride: 0.1；Nitrine di(2-ethylhexyl)phosphate is 1:0.5 to the mass ratio of the material of toluene ester and sodium carbonate；Load weighted reactant is sequentially added into band Have in the 25mL reaction tube of magneton, stirred on magnetic stirring apparatus under room temperature, be then slowly heated to 40 DEG C, with thin layer color The process of spectrum monitoring reaction.At 0.1MPa, stops reaction after 3h, be cooled to room temperature.Mixture is dilute with 0.1mol/L hydrochloric acid It releases (5mL), and is extracted with ethyl acetate (10mL × 3), merge organic phase.Organic phase is washed with saturated salt solution (5mL), is added Anhydrous sodium sulfate dries, filters concentration, is separated with column chromatography chromatogram, using the silica gel of 300~400 mesh as stationary phase, with difference The ethyl acetate of ratio and the mixed solvent of petroleum ether carry out purifies and separates to product as eluant, eluent.
The physical property and characterize data of gained compound are as follows:
Colorless oil；IR(ATR):2958(vw),1609(vw),1504(s),1449 (vw),1291(m),1190(s),1164(m),1105(w),1045(s),1018(m),945(vs),817(s),788(m), 699(w)；1H NMR(400MHz,CDCl3, 298K): δ=2.32 (s, 6H), 3.93 (d, J=8.4Hz, 3H), 7.10-7.18 (m,8H)ppm；13C NMR(101MHz,CDCl3, 298K): δ=20.7,55.4 (d, J=6.0Hz), 119.7 (d, J= 5.0Hz), 130.3,135.0 (d, J=2.0Hz), 148.4 (d, J=7.0Hz) ppm；31P NMR(162MHz,CDCl3, 298K): δ=- 10.30ppm.
Embodiment 20
The synthesis of bis- (4- methoxyl group-phenyl) esters of methyl orthophosphoric acid: bis- (4- methoxyl group-phenyl) esters of nitrine phosphoric acid are weighed respectively 168mg (0.5mmol), methanol 2mL (49.4mmol), stannous chloride, sodium carbonate；Bis- (4- methoxyl group-phenyl) esters of nitrine phosphoric acid The mass ratio of the material with stannous chloride is 1:0.1；The mass ratio of the material of nitrine phosphoric acid bis- (4- methoxyl group-phenyl) esters and sodium carbonate For 1:0.5；Load weighted reactant is sequentially added in the 25mL reaction tube with magneton, under room temperature in magnetic stirring apparatus Upper stirring is then slowly heated to 40 DEG C, with the process of thin-layer chromatography monitoring reaction.At 0.1MPa, stop reaction after 3h, it is cold But to room temperature.It by mixture with 0.1mol/L hydrochloric acid (5mL), and is extracted, is merged organic with ethyl acetate (10mL × 3) Phase.Organic phase is washed with saturated salt solution (5mL), and anhydrous sodium sulfate is added and dries, filters concentration, is separated with column chromatography chromatogram, Using the silica gel of 300~400 mesh as stationary phase, the mixed solvent of ethyl acetate and petroleum ether in varing proportions is as eluant, eluent Purifies and separates are carried out to product.
The physical property and characterize data of gained compound are as follows:
Colorless oil；IR(ATR):2958(vw),2838(vw),1598(vw),1501 (s),1464(w),1289(m),1250(m),1214(m),1178(s),1104(w),1031(s),1008(m),943(vs), 829(s),788(m),702(w)；1H NMR(400MHz,CDCl3, 298K): δ=3.73 (d J=8.0Hz, 6H), 3.92 (dd, J=9.2Hz, J=3.6Hz, 3H), 6.80-6.86 (m, 4H), 7.10-7.16 (m, 4H) ppm；13C NMR(101MHz,CDCl3, 298K): δ=55.4 (dd, J=6.0Hz, J=1.0Hz), 55.5 (d, J=3.0Hz), 114.7,120.9 (d, J=5.0Hz), 144.1 (d, J=7.0Hz), 156.9 (d, J=2.0Hz) ppm；31P NMR(162MHz,CDCl3, 298K): δ=- 9.51ppm.
Embodiment 21
The synthesis of bis- (the bromo- phenyl of the 4-) esters of methyl orthophosphoric acid: bis- (the bromo- phenyl of 4-) the ester 216mg of nitrine phosphoric acid are weighed respectively (0.5mmol), methanol 2mL (49.4mmol), stannous chloride, sodium carbonate；Bis- (the bromo- phenyl of the 4-) esters of nitrine phosphoric acid and stannous chloride The mass ratio of the material be 1:0.1；The mass ratio of the material of bis- (the bromo- phenyl of the 4-) esters of nitrine phosphoric acid and sodium carbonate is 1:0.5；It will weigh Good reactant sequentially adds in the 25mL reaction tube with magneton, stirs on magnetic stirring apparatus, then delays under room temperature Slowly 40 DEG C are heated to, with the process of thin-layer chromatography monitoring reaction.At 0.1MPa, stop reaction after 3h.Mixture is used 0.1mol/L hydrochloric acid (5mL), and extracted with ethyl acetate (10mL × 3), merge organic phase.Organic phase saturated salt solution (5mL) washing, be added anhydrous sodium sulfate dry, filter concentration, separated with column chromatography chromatogram, using the silica gel of 300~400 mesh as The mixed solvent of stationary phase, ethyl acetate and petroleum ether in varing proportions carries out purifies and separates to product as eluant, eluent.
The physical property and characterize data of gained compound are as follows:
Colorless oil；IR(ATR):2958(vw),2855(vw),1583(vw),1481 (s),1401(vw),1301(m),1230(w),1191(s),1163(m),1096(w),1045(s),1011(m),943(vs), 825(s),774(m),699(w)；1H NMR(400MHz,CDCl3, 298K): δ=3.97 (dd, J=8.0Hz, J=1.2Hz, 3H), 7.12 (dd, J=8.0Hz, J=1.2Hz, 4H), 7.47 (d, J=8.0Hz, 4H) ppm；13C NMR(101MHz,CDCl3, 298K): δ=55.8 (d, J=6.0Hz), 118.6 (d, J=2.0Hz), 121.8 (d, J=5.0Hz), 132.9,149.4 (d, J =7.0Hz) ppm；31P NMR(162MHz,CDCl3, 298K): δ=- 11.24ppm.
Embodiment 22
The synthesis of diphenylphosphine acid benzyl ester: diphenylphosphine azide 122mg (0.5mmol), benzyl alcohol are weighed respectively 0.2mL (1.93mmol), stannous chloride, sodium carbonate, hexamethylene；The mass ratio of the material of diphenylphosphine azide and stannous chloride For 1:0.1；The mass ratio of the material of diphenylphosphine azide and sodium carbonate is 1:0.5；The volume ratio of hexamethylene and benzyl alcohol is 9:1；Load weighted reactant is sequentially added in the 25mL reaction tube with magneton, is stirred on magnetic stirring apparatus under room temperature It mixes, is then slowly heated to 30 DEG C, with the process of thin-layer chromatography monitoring reaction.At 0.1MPa, stop reaction afterwards for 24 hours, it is cooling To room temperature.It by mixture with 0.1mol/L hydrochloric acid (5mL), and is extracted with ethyl acetate (10mL × 3), merges organic phase. Organic phase is washed with saturated salt solution (5mL), and anhydrous sodium sulfate is added and dries, filters concentration, is separated with column chromatography chromatogram, with The silica gel of 300~400 mesh is as stationary phase, and the mixed solvent of ethyl acetate and petroleum ether in varing proportions is as eluant, eluent pair Product carries out purifies and separates, obtains diphenylphosphine acid benzyl ester.
Embodiment 23
The synthesis of phosphoric acid 2- cyclohexyl ethyl ester diphenyl ester: 108 μ L (0.5mmol) of diphenyl phosphate azide, 2- are weighed respectively Cyclohexyl ethyl alcohol 0.2mL (1.43mmol), stannous chloride, sodium carbonate, N,N-dimethylformamide；Diphenyl phosphate azide and chlorine Changing cuprous the mass ratio of the material is 1:0.15；The mass ratio of the material of diphenyl phosphate azide and sodium carbonate is 1:0.5；N, N- diformazan The volume ratio of base formamide and 2- cyclohexyl ethyl alcohol is 9:1；It is anti-that load weighted reactant is sequentially added into the 25mL with magneton Ying Guanzhong is stirred on magnetic stirring apparatus under room temperature, is then slowly heated to 70 DEG C, with thin-layer chromatography monitoring reaction into Journey.At 0.1MPa, stops reaction afterwards for 24 hours, be cooled to room temperature.By mixture with 0.1mol/L hydrochloric acid (5mL), and use second Acetoacetic ester (10mL × 3) extraction, merges organic phase.Organic phase is washed with saturated salt solution (5mL), and it is dry that anhydrous sodium sulfate is added Dry, filtering and concentrating is separated with column chromatography chromatogram, using the silica gel of 300~400 mesh as stationary phase, acetic acid second in varing proportions The mixed solvent of ester and petroleum ether carries out purifies and separates to product as eluant, eluent, obtains phosphoric acid 2- cyclohexyl ethyl ester diphenyl ester.
The present invention by azido acid ester class compound and fatty alcohol are added in solvent or directly using fatty alcohol as Solvent is then respectively adding the alkali of copper catalyst and catalytic amounts, react 3 at 20~100 DEG C~for 24 hours, after post treatment Ester type compound is mixed to phosphoric acid.The present invention is synthesized phosphoric acid using azido acid ester class compound and fatty alcohol for the first time and mixes esters Object is closed, which only needs to be added the alkali of copper catalyst and catalytic amounts, and it is easy to operate, and overcome and need indifferent gas The shortcomings that body is protected is a kind of novel high-efficiency synthesis method.
The above is merely a preferred embodiment of the present invention, it is noted that for those skilled in the art For, under the premise of not departing from core of the invention technology, improvements and modifications can also be made, what retouching these, which improve, is also answered When belonging to scope of patent protection of the invention.With any change in the comparable meaning and scope of claims of the present invention, It is all considered as including within Claims scope.

Claims (9)

1. the synthetic method that a kind of phosphoric acid of copper catalysis mixes ester type compound, which is characterized in that by azido acid ester class compound With fatty alcohol mix, copper catalyst is then added, adds alkali, at 20~100 DEG C react 3~for 24 hours, obtain after post treatment Phosphoric acid mixes ester type compound.
2. the synthetic method that a kind of phosphoric acid of copper catalysis according to claim 1 mixes ester type compound, which is characterized in that folded Nitrogen phosphate compounds are diphenyl phosphate azide, diphenylphosphine azide, nitrine di(2-ethylhexyl)phosphate to toluene ester, nitrine phosphoric acid Bis- (4- methoxyl group-phenyl) esters of bis- (the bromo- phenyl of 4-) esters, nitrine phosphoric acid, nitrine di(2-ethylhexyl)phosphate m-tolyl ester or nitrine di(2-ethylhexyl)phosphate are adjacent Toluene ester.
3. the synthetic method that a kind of phosphoric acid of copper catalysis according to claim 1 mixes ester type compound, which is characterized in that rouge Fat alcohol is methanol, ethyl alcohol, 2,2,2 ,-trifluoroethanol, normal propyl alcohol, isopropanol, n-butanol, isobutanol or n-amyl alcohol.
4. the synthetic method that a kind of phosphoric acid of copper catalysis according to claim 1 mixes ester type compound, which is characterized in that rouge Fat alcohol is isoamyl alcohol, cyclopentanol, n-hexyl alcohol, cyclohexanol, cyclohexanemethanol, benzyl alcohol, n-heptanol, 2- cyclohexyl ethyl alcohol, benzyl carbinol Or when citronellol, azido acid ester class compound and fatty alcohol are mixed, solvent is added, copper catalyst is then added.
5. the synthetic method that a kind of phosphoric acid of copper catalysis according to claim 4 mixes ester type compound, which is characterized in that molten The molar concentration of azido acid ester class compound is 0.25~0.5mol/L in agent.
6. a kind of phosphoric acid of copper catalysis according to claim 4 or 5 mixes the synthetic method of ester type compound, feature exists In solvent is one of hexamethylene, methylene chloride, n,N-Dimethylformamide, Isosorbide-5-Nitrae-dioxane, ether.
7. the synthetic method that a kind of phosphoric acid of copper catalysis according to claim 1 mixes ester type compound, which is characterized in that copper Catalyst is copper powder, stannous chloride, cuprous iodide, copper chloride, copper fluoride, copper oxide, copper sulphate, copper trifluoromethanesulfcomposite, acetic acid One of copper, copper nitrate.
8. the synthetic method that a kind of phosphoric acid of copper catalysis according to claim 1 mixes ester type compound, which is characterized in that alkali For one of sodium hydroxide, sodium carbonate, sodium bicarbonate, sodium acetate, sodium phosphate.
9. the synthetic method that a kind of phosphoric acid of copper catalysis according to claim 1 mixes ester type compound, which is characterized in that folded The mass ratio of the material of nitrogen phosphate compounds and fatty alcohol is 1:(2.2~100), azido acid ester class compound and copper are catalyzed The mass ratio of the material of agent is 1:(0.05~0.2), the mass ratio of the material of azido acid ester class compound and alkali be 1:(0.2~ 0.5)。
CN201910595417.XA 2019-07-03 2019-07-03 Synthesis method of copper-catalyzed phosphate mixed ester compound Active CN110305160B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201910595417.XA CN110305160B (en) 2019-07-03 2019-07-03 Synthesis method of copper-catalyzed phosphate mixed ester compound

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201910595417.XA CN110305160B (en) 2019-07-03 2019-07-03 Synthesis method of copper-catalyzed phosphate mixed ester compound

Publications (2)

Publication Number Publication Date
CN110305160A true CN110305160A (en) 2019-10-08
CN110305160B CN110305160B (en) 2021-07-23

Family

ID=68079037

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201910595417.XA Active CN110305160B (en) 2019-07-03 2019-07-03 Synthesis method of copper-catalyzed phosphate mixed ester compound

Country Status (1)

Country Link
CN (1) CN110305160B (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111732605A (en) * 2020-06-30 2020-10-02 西北大学 Method for synthesizing phosphate mixed ester compound by chitosan loaded copper catalysis

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111732605A (en) * 2020-06-30 2020-10-02 西北大学 Method for synthesizing phosphate mixed ester compound by chitosan loaded copper catalysis
CN111732605B (en) * 2020-06-30 2021-10-01 西北大学 Method for synthesizing phosphate mixed ester compound by chitosan loaded copper catalysis

Also Published As

Publication number Publication date
CN110305160B (en) 2021-07-23

Similar Documents

Publication Publication Date Title
ES2351376T3 (en) METHOD FOR LITHIUM EXCHANGE REACTIONS.
CN102276481A (en) Calixarene derivative and metal complex thereof, and preparation method and application of calixarene derivative and metal complex thereof
CN104829493B (en) A kind of method of synthesizing amino formic acid aromatic ester
CN106365986B (en) Compound and preparation method thereof and the purposes in synthesis Bu Waxitan
CN108947894A (en) Novel biaryl structure chirality N- methylpyridoxal catalyst and its synthesis and application
CN109293468A (en) A method of it being catalyzed the decarboxylation coupling reaction synthesizing cis alkene of NHP ester and terminal aryl group alkynes by iridium
CN101148456A (en) Organic phosphoric acid catalyst and its preparation method and application
CN110305160A (en) A kind of phosphoric acid of copper catalysis mixes the synthetic method of ester type compound
CN108178770A (en) A kind of method for synthesizing alpha-amido boron compound
CN104829465B (en) A kind of preparation method of 4- isopropylaminos-n-butyl alcohol
CN110172028A (en) A kind of method of industrialized production tulobuterol
Batista et al. Synthesis and characterization of the mer-[RuCl3 (NO)(dppb)] isomer. X-ray structures of fac-[RuCl3 (NO)(dppm)], cis-[RuCl2 (dppm) 2] and mer-[RuCl3 (NO)(dppb)][dppm= 1, 2-bis (diphenylphosphino) methane and dppb= 1, 4-bis (diphenylphosphino) butane]
CN110156721A (en) Utilize diazotate, cyclic ethers, amine and CO2The method of synthesis of carbamates
CN103508999B (en) Maxacalcitol synthesizing intermediate and preparation method and application thereof
CN111039767B (en) Method for preparing deuterated aldehyde by using triazole carbene as catalyst
CN104945345A (en) Chiral morpholine compounds and preparation method thereof as well as chiral amino acid compounds and preparation method and application thereof
CN109824553A (en) 2-((tert-butoxycarbonyl) amino) ethyl-1- sulfonic acid and preparation method thereof
CN104892372B (en) A kind of synthetic method of little molecule Polyethylene Glycol
CN104910195B (en) A kind of difluorocarbene's DDTC and its preparation and application
CN104771392A (en) Histone deacetylase inhibitor and applications thereof
CN105801578B (en) A kind of synthetic method of semi-saturation pyrazines derivatives and application
JP3738225B2 (en) Novel chiral copper catalyst and method for producing N-acylated amino acid derivative using the same
CN110627718B (en) Synthesis method of (E) -beta-monofluoroalkyl-beta, gamma-unsaturated amide
CN108484451A (en) A kind of method that one kettle way prepares 1,2- alkamine compounds
Falshaw et al. Ruthenium complexes that incorporate a chiro-inositol derived diphosphinite ligand as catalysts for asymmetric hydrogenation reactions

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