CN104059103A - Synthesis method of arylphosphate compounds - Google Patents
Synthesis method of arylphosphate compounds Download PDFInfo
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Abstract
The invention relates to a synthesis method of arylphosphate compounds. An arylation reagent used as aryl carboxylic acid and dialkyl phosphite used as a reaction substrate directly react under the actions of the catalyst, alkali and additive to prepare the arylphosphates by one step. The method has the advantages of mild conditions, cheap and accessible raw materials and higher yield, and is simple to operate. The aryl carboxylic acid is an arylation reagent with very high efficiency and favorable universality.
Description
Technical field
The present invention relates to a kind of synthetic method of arylphosphonic acid ester compound.
Background technology
Arylphosphonic acid ester compound is the very important pharmaceutical-chemical intermediate of a class, and they are in field widespread uses such as organic synthesis, medicine, bioactive molecules, agricultural chemicals, Materials science.Particularly, at medical pesticide field, arylphosphonic acid ester cpds occupies consequence, and the representative aryl phosphine acid esters of some of them skeleton structure is as follows:
Linked reaction based on aryl substrate and dialkyl phosphite class substrate is the synthetic universal methods of these aryl phosphine acid esters skeletons.In these methods, most popular aryl substrate is halogenated aryl hydrocarbon (as iodine, bromine and chlorinated aromatic hydrocarbons), and wherein iodo aromatic hydrocarbons and aryl bromide is most widely used ((a) Beletskaya, I.P.; Kazankova, M.A.Russ J Org Chem, 2002,38,1391; (b) Baillie, C.; Xiao, J.Curr Org Chem, 2003,7,477; (c) Schwan, A.L.Chem Soc Rev, 2004,33,218; (d) Tappe, F.M.J.; Trepohl, V.T.; Oestreich, M.Synthesis, 2010,12,3037; Demmer, C.S.; Krogsgaard-Larsen, N.; Bunch, L.ChemRev, 2011,111,7981.).Although the linked reaction research that halogenated aryl hydrocarbon participates in is very ripe, halo substrate activity is relatively high, poor to the universality of functional group, and halo substrate is large to harm, and environmental pollution is serious.
In recent years, chemists expand for aryl substrate, have developed the synthetic method of some new arylphosphonic acid ester compounds.Wherein the widely used method of a class is that triflate derivative with phenol and that come is aryl coupling substrate (Petrakis, K.S.; Nagabhushan, T.L.J Am Chem Soc, 1987,109,2831.).But aryl substrate requires that phenolic compound is carried out to functional group's conversion in advance and just can obtain, this has just extended synthetic route undoubtedly, has increased synthetic cost.
Adopting aryl boric acid is that substrate carrys out synthesizing aryl phosphonate ester compound, and the method all has good compatibility ((a) Andaloussi, M. to the functional group of aryl boric acid; Lindh, J.;
, J.; J.R.
, P.; Larhed, M.Chem Eur J, 2009,15,13069; (b) Zhuang, R.; Xu, J.; Cai, Z.; Tang, G.; Fang, M.; Zhao, Y.Org Lett, 2011,13,2110.).But it is pre-synthesis that aryl boric acid needs, and boric acid is more expensive, and this has just limited the application of the method.
Aryl diazonium salts also can be well and trialkyl phosphite compound generation coupling generate arylphosphonic acid ester compound (Berrino, R.; Cacchi, S.; Fabrizi, G.; Goggiamani, A.; Stabile, P.Org Biomol Chem, 2010,8,4518.).Similarly, aryl diazonium salts also needs pre-synthesis, and diazonium compound is dangerous, easily blasts.
Utilize C-H activation strategy, from aromatic hydrocarbons and the dialkyl phosphite of inertia, a direct step builds arylphosphonic acid ester compound, beyond doubt the most green synthetic method.Report ((a) Effenberger, the F. of at present more existing these class methods; Kottmann, H.Tetrahedron, 1985,41,4171; (b) Kagayama, T.; Nakano, A.; Sakaguchi, S.; Ishii, Y.Org Lett2006,8,407; (c) Xu, W.; Zou, J.-P.; Zhang, W.TetrahedronLett, 2010,51,2639; (d) Kuninobu, Y; Yoshida, T; Takai, K.J Org Chem, 2011,76,7370; (e) Feng, C.-G.; Ye, M.Xiao, K.-J.; Li, S.; Yu, J.-Q.J Am Chem Soc, 2013,135,9322; (f) Li, C.; Yano, T.; Ishida, N.; Murakami, M.Angew Chem Int Ed, 2013,52,9801.).Utilize these methods, all synthesizing aryl phosphonate ester compound effectively.Yet these methods still have some flaws: poor selectivity or need homing device.
Summary of the invention
The present invention is directed to the above defect of prior art, be intended to utilize the extensive aryl carboxylic acid existing of occurring in nature as a kind of potential aromatic yl reagent-ing, arylation reaction for to dialkyl phosphite, carrys out synthesizing aryl phosphonate ester compound, and overcomes the problem of this current existence in field.
The invention provides a kind of synthetic method of arylphosphonic acid ester compound, its reaction formula is as follows:
In reaction formula, R
1hydrogen, halogen, heteroatoms or alkyl; R
2it is alkyl;
Its concrete synthetic method is as follows:
In reaction flask, add successively aryl carboxylic acid, palladium catalyst, alkali, additive, dialkyl phosphite and solvent, wherein the mol ratio of aryl carboxylic acid, palladium catalyst, alkali, additive and dialkyl phosphite is 1-2: 0.05-0.4: 0.05-3: 0.5-3: 1; Then, stirring at room 5-30 minute, mixes reactant; In 80-140 ℃ of reacting by heating, type of heating is microwave heating or conventional stirring heating again, and microwave heating power is 20-140 watt, and be 8-20 minute heat-up time; The conventional stirring heating time is 5-20 hour; Thin-layer chromatography monitoring raw material reaction is complete; After solution is cooled to room temperature, with siliceous earth column, filter, and by washed with dichloromethane; Collect filtrate, be spin-dried for rear rapid column chromatography and obtain product;
Described palladium catalyst is acid chloride, Palladous chloride, palladium bromide, palladium trifluoroacetate, tetrakis triphenylphosphine palladium or two (diphenylphosphine) Palladous chloride; Described alkali is silver carbonate, Silver Nitrate, silver acetate, silver molybdate, silver suboxide or Trisilver phosphate; Described additive is lithium nitrate, lithium chloride, trifluoromethanesulfonic acid lithium, lithium hydroxide, lithium fluoride, lithiumbromide or lithium iodide; Described solvent is DMF, N,N-dimethylacetamide, dimethyl sulfoxide (DMSO), N-Methyl pyrrolidone, acetonitrile, tetrahydrofuran (THF), or DMF and the dimethyl sulfoxide (DMSO) volume ratio mixed solvent that is 19: 1.
The present invention compared with prior art has the following advantages:
The present invention uses aryl carboxylic acid for aromatic yl reagent-ing, under the effect of metal palladium catalyst and alkali, its lose a part carbonic acid gas and with dialkyl phosphite generation linked reaction, obtain corresponding product.Compare with existing aryl coupling substrate, aryl carboxylic acid is at occurring in nature ubiquity, and stable in properties, without special preservation condition.
Synthesising method reacting condition of the present invention is gentle, and catalyst system is simple, and without part, without protection of inert gas, all insensitive to atmospheric moisture, easy and simple to handle, this has important Research Significance and using value undoubtedly.
The efficient aryl phosphine acid esters skeleton building of the present invention is the important skeleton of many medicines, bioactive molecules etc., and synthetic method of the present invention is this compounds syntheticly provides a widely used preparation method.
Embodiment
Synthesizing of embodiment 1. O-Nitrophenylfluorone diethyl phosphonates
In the 10mL reaction flask of magneton is housed, add successively o-Carboxynitrobenzene (61.4mg, 0.36mmol), silver carbonate (168.0mg, 0.6mmol), lithium nitrate (20.9mg, 0.3mmol), acid chloride (10.6mg, 0.06mmol), diethyl phosphite (39.04 μ L, 0.3mmol), DMF (2mL).Be placed under room temperature and stir 20min.Then, under the heating power of 40 watts, microwave reaction instrument, in 120 ℃, react 10min.Thin-layer chromatography monitoring raw material reaction is complete.Until product solution, be cooled to after room temperature, with siliceous earth column, filter, and use washed with dichloromethane.Be spin-dried for rear rapid column chromatography and obtain oily liquids 42.0mg, productive rate 54%.
R
f=0.18 (V
normal hexane/ V
ethyl acetate=1/2).
1H NMR(600MHz，CDCl
3)：δ8.10(d，1H，ArH，J
ArH-P＝14.0Hz)，7.88(s，1H，ArH)，7.71(m，2H，ArH)，4.24(m，4H，CH
2)，1.37(t，6H，CH
3，J＝6.6Hz).
13C NMR(150MHz，CDCl
3)：δ152.16(d，J＝3.0Hz)，135.25(d，J＝6.0Hz)，133.32(d，J＝2.1Hz)，132.32(d，J＝13.0Hz)，124.32(d，J＝8.7Hz)，123.44(d，J＝190.2Hz)，63.48(d，J＝6.0Hz)，16.33(d，J＝6.5Hz).
31P NMR(242MHz，CDCl
3)：δ11.61.MS(70eV，EI)m/z(％)：260(M
++1，5)，238(2)，214(22)，204(71)，186(100)，171(72)，157(75).
Synthesizing of embodiment 2. O-Nitrophenylfluorone diethyl phosphonates
Working method is with embodiment 1.Difference is, use Palladous chloride (10.6mg, 0.06mmol) substitute acid chloride as catalyzer, use lithium chloride (12.8mg, 0.3mmol) substitute lithium nitrate as additive, (volume ratio is 19/1 to use DMF/dimethyl sulfoxide (DMSO), 2mL) substitute DMF as solvent.Obtain oily liquids 17.1mg, productive rate 22%.Its R
f,
1h NMR,
13c NMR,
31p NMR, the analytical data such as MS are same as embodiment 1.
Synthesizing of embodiment 3. O-Nitrophenylfluorone diethyl phosphonates
Working method is with embodiment 2.Difference is, uses lithium hydroxide (14.0mg, 0.3mmol) to substitute lithium chloride as additive.Obtain oily liquids 9.6mg, productive rate 12%.Its R
f,
1h NMR,
13c NMR,
31p NMR, the analytical data such as MS are same as embodiment 1.
Synthesizing of embodiment 4. O-Nitrophenylfluorone diethyl phosphonates
Working method is with embodiment 2.Difference is, uses trifluoromethanesulfonic acid lithium (48.3mg, 0.3mmol) to substitute lithium chloride as additive.Obtain oily liquids 11.7mg, productive rate 15%.Its R
f,
1h NMR,
13c NMR,
31p NMR, the analytical data such as MS are same as embodiment 1.
Synthesizing of embodiment 5. O-Nitrophenylfluorone diethyl phosphonates
Working method is with embodiment 2.Difference is, uses lithium fluoride (7.8mg, 0.3mmol) to substitute lithium chloride as additive.Obtain oily liquids 8.4mg, productive rate 11%.Its R
f,
1h NMR,
13c NMR,
31p NMR, the analytical data such as MS are same as embodiment 1.
Synthesizing of embodiment 6. O-Nitrophenylfluorone diethyl phosphonates
Working method is with embodiment 2.Difference is, uses lithiumbromide (26.3mg, 0.3mmol) to substitute lithium chloride as additive.Obtain oily liquids 11.4mg, productive rate 15%.Its R
f,
1h NMR,
13c NMR,
31p NMR, the analytical data such as MS are same as embodiment 1.
Synthesizing of embodiment 7. O-Nitrophenylfluorone diethyl phosphonates
Working method is with embodiment 2.Difference is, uses lithium iodide (40.8mg, 0.3mmol) to substitute lithium chloride as additive.Obtain oily liquids 8.2mg, productive rate 8%.Its R
f,
1h NMR,
13c NMR,
31p NMR, the analytical data such as MS are same as embodiment 1.
Synthesizing of embodiment 8. O-Nitrophenylfluorone diethyl phosphonates
Working method is with embodiment 2.Difference is, uses lithium nitrate (10.5mg, 0.15mmol) to substitute lithium chloride as additive.Obtain oily liquids 24.4mg, productive rate 32%.Its R
f,
1h NMR,
13c NMR,
31p NMR, the analytical data such as MS are same as embodiment 1.
Synthesizing of embodiment 9. O-Nitrophenylfluorone diethyl phosphonates
Working method is with embodiment 2.Difference is, uses lithium nitrate (20.9mg, 0.3mmol) to substitute lithium chloride as additive.Obtain oily liquids 22.6mg, productive rate 29%.Its R
f,
1h NMR,
13c NMR,
31p NMR, the analytical data such as MS are same as embodiment 1.
Synthesizing of embodiment 10. O-Nitrophenylfluorone diethyl phosphonates
Working method is with embodiment 2.Difference is, uses lithium nitrate (62.7mg, 0.9mmol) to substitute lithium chloride as additive.Obtain oily liquids 2.4mg, productive rate 3%.Its R
f,
1h NMR,
13c NMR,
31p NMR, the analytical data such as MS are same as embodiment 1.
Synthesizing of embodiment 11. O-Nitrophenylfluorone diethyl phosphonates
Working method is with embodiment 9.Difference is, uses acid chloride (13.6mg, 0.06mmol) to substitute Palladous chloride as catalyzer.Obtain oily liquids 32.4mg, productive rate 42%.Its R
f,
1h NMR,
13c NMR,
31p NMR, the analytical data such as MS are same as embodiment 1.
Synthesizing of embodiment 12. O-Nitrophenylfluorone diethyl phosphonates
Working method is with embodiment 9.Difference is, uses palladium bromide (16.2mg, 0.06mmol) to substitute Palladous chloride as catalyzer.Obtain oily liquids 5.5mg, productive rate 7%.Its R
f,
1h NMR,
13c NMR,
31p NMR, the analytical data such as MS are same as embodiment 1.
Synthesizing of embodiment 13. O-Nitrophenylfluorone diethyl phosphonates
Working method is with embodiment 9.Difference is, uses palladium trifluoroacetate (20.6mg, 0.06mmol) to substitute Palladous chloride as catalyzer.Obtain oily liquids 26.0mg, productive rate 33%.Its R
f,
1h NMR,
13c NMR,
31p NMR, the analytical data such as MS are same as embodiment 1.
Synthesizing of embodiment 14. O-Nitrophenylfluorone diethyl phosphonates
Working method is with embodiment 9.Difference is, uses tetrakis triphenylphosphine palladium (69.3mg, 0.06mmol) to substitute Palladous chloride as catalyzer.Obtain oily liquids 4.7mg, productive rate 6%.Its R
f,
1h NMR,
13c NMR,
31p NMR, the analytical data such as MS are same as embodiment 1.
Synthesizing of embodiment 15. O-Nitrophenylfluorone diethyl phosphonates
Working method is with embodiment 9.Difference is, uses two (diphenylphosphine) Palladous chlorides (43.0mg, 0.06mmol) to substitute Palladous chloride as catalyzer.Obtain oily liquids 6.2mg, productive rate 8%.Its R
f,
1h NMR,
13c NMR,
31p NMR, the analytical data such as MS are same as embodiment 1.
Synthesizing of embodiment 16. O-Nitrophenylfluorone diethyl phosphonates
Working method is with embodiment 1.Difference is, uses dimethyl sulfoxide (DMSO) (2mL) to substitute DMF as solvent, uses the heating power of 20 watts to substitute 40 watts.Obtain oily liquids 7.9mg, productive rate 10%.Its R
f,
1h NMR,
13c NMR,
31p NMR, the analytical data such as MS are same as embodiment 1.
Synthesizing of embodiment 17. O-Nitrophenylfluorone diethyl phosphonates
Working method is with embodiment 1.Difference is, uses N,N-dimethylacetamide (2mL) to substitute DMF as solvent.Obtain oily liquids 18.7mg, productive rate 24%.Its R
f,
1h NMR,
13c NMR,
31p NMR, the analytical data such as MS are same as embodiment 1.
Synthesizing of embodiment 18. O-Nitrophenylfluorone diethyl phosphonates
Working method is with embodiment 1.Difference is, uses N-Methyl pyrrolidone (2mL) to substitute DMF as solvent.Obtain oily liquids 4.8mg, productive rate 6%.Its R
f,
1h NMR,
13c NMR,
31p NMR, the analytical data such as MS are same as embodiment 1.
Synthesizing of embodiment 19. O-Nitrophenylfluorone diethyl phosphonates
Working method is with embodiment 1.Difference is, uses acetonitrile (2mL) to substitute DMF as solvent.Obtain oily liquids 3.8mg, productive rate 5%.Its R
f,
1h NMR,
13c NMR,
31p NMR, the analytical data such as MS are same as embodiment 1.
Synthesizing of embodiment 20. O-Nitrophenylfluorone diethyl phosphonates
Working method is with embodiment 1.Difference is, uses tetrahydrofuran (THF) (2mL) to substitute DMF as solvent, uses the heating power of 140 watts to substitute 40 watts.Obtain oily liquids 3.1mg, productive rate 4%.Its R
f,
1h NMR,
13c NMR,
31p NMR, the analytical data such as MS are same as embodiment 1.
Synthesizing of embodiment 21. O-Nitrophenylfluorone diethyl phosphonates
Working method is with embodiment 1.Difference is, uses the temperature of reaction of 80 ℃ to substitute 120 ℃.Obtain oily liquids 10.1mg, productive rate 13%.Its R
f,
1h NMR,
13c NMR,
31p NMR, the analytical data such as MS are same as embodiment 1.
Synthesizing of embodiment 22. O-Nitrophenylfluorone diethyl phosphonates
Working method is with embodiment 1.Difference is, uses the temperature of reaction of 140 ℃ to substitute 120 ℃.Obtain oily liquids 18.7mg, productive rate 24%.Its R
f,
1h NMR,
13c NMR,
31p NMR, the analytical data such as MS are same as embodiment 1.
Synthesizing of embodiment 23. O-Nitrophenylfluorone diethyl phosphonates
Working method is with embodiment 1.Difference is, uses Silver Nitrate (103.0mg, 0.6mmol) to substitute silver carbonate as alkali.Obtain oily liquids 1.2mg, productive rate 2%.Its R
f,
1h NMR,
13c NMR,
31p NMR, the analytical data such as MS are same as embodiment 1.
Synthesizing of embodiment 24. O-Nitrophenylfluorone diethyl phosphonates
Working method is with embodiment 1.Difference is, uses silver acetate (101.2mg, 0.6mmol) to substitute silver carbonate as alkali.Obtain oily liquids 8.4mg, productive rate 11%.Its R
f,
1h NMR,
13c NMR,
31p NMR, the analytical data such as MS are same as embodiment 1.
Synthesizing of embodiment 25. O-Nitrophenylfluorone diethyl phosphonates
Working method is with embodiment 1.Difference is, uses silver molybdate (232.4mg, 0.6mmol) to substitute silver carbonate as alkali.Obtain oily liquids 6.4mg, productive rate 8%.Its R
f,
1h NMR,
13c NMR,
31p NMR, the analytical data such as MS are same as embodiment 1.
Synthesizing of embodiment 26. O-Nitrophenylfluorone diethyl phosphonates
Working method is with embodiment 1.Difference is, uses silver suboxide (140.4mg, 0.6mmol) to substitute silver carbonate as alkali.Obtain oily liquids 1.0mg, productive rate 1%.Its R
f,
1h NMR,
13c NMR,
31p NMR, the analytical data such as MS are same as embodiment 1.
Synthesizing of embodiment 27. O-Nitrophenylfluorone diethyl phosphonates
Working method is with embodiment 1.Difference is, uses Trisilver phosphate (253.7mg, 0.6mmol) to substitute silver carbonate as alkali.Obtain oily liquids 6.0mg, productive rate 8%.Its R
f,
1h NMR,
13c NMR,
31p NMR, the analytical data such as MS are same as embodiment 1.
Synthesizing of embodiment 28. O-Nitrophenylfluorone diethyl phosphonates
Working method is with embodiment 1.Difference is, uses o-Carboxynitrobenzene (51.2mg, 0.3mmol) to substitute o-Carboxynitrobenzene (61.4mg, 0.36mmol) as aromatic yl reagent-ing.Obtain oily liquids 26.5mg, productive rate 34%.Its R
f,
1h NMR,
13c NMR,
31p NMR, the analytical data such as MS are same as embodiment 1.
Synthesizing of embodiment 29. O-Nitrophenylfluorone diethyl phosphonates
Working method is with embodiment 1.Difference is, uses o-Carboxynitrobenzene (122.8mg, 0.6mmol) to substitute o-Carboxynitrobenzene (61.4mg, 0.36mmol) as aromatic yl reagent-ing.Obtain oily liquids 15.6mg, productive rate 20%.Its R
f,
1h NMR,
13c NMR,
31p NMR, the analytical data such as MS are same as embodiment 1.
Synthesizing of embodiment 30. O-Nitrophenylfluorone diethyl phosphonates
Working method is with embodiment 1.Difference is, uses acid chloride (3.4mg, 0.015mmol) to substitute acid chloride (13.6mg, 0.06mmol) as aromatic yl reagent-ing.Obtain oily liquids 13.2mg, productive rate 17%.Its R
f,
1h NMR,
13c NMR,
31p NMR, the analytical data such as MS are same as embodiment 1.
Synthesizing of embodiment 31. O-Nitrophenylfluorone diethyl phosphonates
Working method is with embodiment 1.Difference is, uses acid chloride (27.2mg, 0.12mmol) to substitute acid chloride (13.6mg, 0.06mmol) as aromatic yl reagent-ing.Obtain oily liquids 28.0mg, productive rate 36%.Its R
f,
1h NMR,
13c NMR,
31p NMR, the analytical data such as MS are same as embodiment 1.
Synthesizing of embodiment 32. O-Nitrophenylfluorone diethyl phosphonates
Working method is with embodiment 1.Difference is, uses conventional stirring and refluxing heating to substitute microwave as type of heating, uses 6h to substitute 10min as the reaction times.Obtain oily liquids 23.3mg, productive rate 30%.Its R
f,
1h NMR,
13c NMR,
31p NMR, the analytical data such as MS are same as embodiment 1.
Synthesizing of embodiment 33. O-Nitrophenylfluorone phosphonic acids dipropyls
Working method is with embodiment 1.Difference is, uses phosphorous acid dipropyl (48.87 μ L, 0.3mmol) to substitute diethyl phosphite as phosphine acylating reagent.Obtain oily liquids 48.0mg, productive rate 56%.
R
f=0.37 (V
normal hexane/ V
ethyl acetate=1/2).
1H NMR(600MHz，CDCl
3)：δ8.11(d，1H，ArH，J
ArH-P＝14.0Hz)，7.88(s，1H，ArH)，7.71(s，2H，ArH)，4.12(m，4H，OCH
2)，1.74(dd，4H，CH
2CH
3，J
ArH-P＝13.8Hz，J＝6.8Hz)，0.97(t，6H，CH
3，J＝7.2Hz).
13C NMR(150MHz，CDCl
3)：δ152.09，135.28(d，J＝6.0Hz)，133.30(d，J＝2.1Hz)，132.31(d，J＝13.1Hz)，124.33(d，J＝8.6Hz)，123.37(d，J＝190.6Hz)，68.93(d，J＝6.4Hz)，23.82(d，J＝6.7Hz)，10.12.
31P NMR(242MHz，CDCl
3)：δ11.88.MS(70eV，EI)m/z(％)：288(M
++1，2)，246(11)，228(4)，204(100)，186(59)，171(13)，156(20).
Synthesizing of embodiment 34. O-Nitrophenylfluorone phosphonic acids diisopropyl esters
Working method is with embodiment 1.Difference is, uses diisopropyl phosphite (50.50 μ L, 0.3mmol) to substitute diethyl phosphite as phosphine acylating reagent.Obtain oily liquids 39.1mg, productive rate 46%.
R
f=0.34 (V
normal hexane/ V
ethyl acetate=1/2).
1H NMR(600MHz，CDCl
3)：δ8.15(m，1H，ArH)，7.83(dd，1H，ArH，J
ArH-P＝8.7Hz，J＝5.1Hz)，7.68(s，2H，ArH)，4.83(m，2H，CH)，1.40(d，6H，CH
3，J＝6.1Hz)，1.29(d，6H，CH
3，J＝6.2Hz).
13C NMR(150MHz，CDCl
3)：δ152.22(d，J＝2.3Hz)，135.40(d，J＝6.2Hz)，133.05(d，J＝2.5Hz)，132.07(d，J＝13.2Hz)，124.56(d，J＝189.8Hz)，124.16(d，J＝8.6Hz)，72.39(d，J＝6.3Hz)，24.05(d，J＝4.3Hz)，23.81(d，J＝4.9Hz).
31P NMR(242MHz，CDCl
3)：δ9.23.MS(70eV，EI)m/z(％)：288(M
++1，2)，246(2.5)，228(4)，204(100)，186(84)，171(10)，156(26).
Synthesizing of embodiment 35. O-Nitrophenylfluorone phosphonic acids dibutyl esters
Working method is with embodiment 1.Difference is, uses dibutyl phosphite (61.00 μ L, 0.3mmol) to substitute diethyl phosphite as phosphine acylating reagent.Obtain oily liquids 45.8mg, productive rate 48%.
R
f=0.47 (V
normal hexane/ V
ethyl acetate=1/2).
1H NMR(600MHz，CDCl
3)：δ8.10(m，1H，ArH)，7.88(d，1H，ArH，J
ArH-P＝8.6Hz，J＝5.1Hz)，7.70(m，2H，ArH)，4.16(m，4H，OCH
2)，1.69(m，4H，OCH
2CH
2)，1.41(m，4H，CH
2CH
3)，0.93(t，6H，CH
3，J＝7.4Hz).
13C NMR(150MHz，CDCl
3)：δ152.12，135.31(d，J＝5.9Hz)，133.28(d，J＝2.4Hz)，132.30(d，J＝13.1Hz)，124.34(d，J＝8.5Hz)，123.43(d，J＝190.4Hz)，67.17(d，J＝6.2Hz)，32.46(d，J＝6.5Hz)，18.79，13.69.
31P NMR(242MHz，CDCl
3)：δ11.85.MS(70eV，EI)m/z(％)：316(M
++1，1.5)，260(7)，204(100)，186(48)，171(10)，156(15).
Synthesizing of embodiment 36. O-Nitrophenylfluorone phosphonic acids diisobutyl esters
Working method is with embodiment 1.Difference is, uses phosphorous acid diisobutyl ester (62.58 μ L, 0.3mmol) to substitute diethyl phosphite as phosphine acylating reagent.Obtain oily liquids 45.7mg, productive rate 48%.
R
f=0.47 (V
normal hexane/ V
ethyl acetate=1/2).
1H NMR(600MHz，CDCl
3)：δ8.11(m，1H，ArH)，7.88(dd，1H，ArH，J
ArH-P＝8.8Hz，J＝5.5Hz)，7.71(m，2H，ArH)，3.93(m，4H，CH
2)，1.98(m，2H，CH)，0.95(d，12H，CH
3，J＝6.7Hz).
13C NMR(150MHz，CDCl
3)：δ152.12，135.36(d，J＝6.0Hz)，133.26(d，J＝2.2Hz)，132.29(d，J＝13.1Hz)，124.37(d，J＝8.6Hz)，123.43(d，J＝190.7Hz)，73.25(d，J＝6.6Hz)，29.30(d，J＝6.8Hz)，14.27(d，J＝9.1Hz).
31P NMR(242MHz，CDCl
3)：δ11.80.MS(70eV，EI)m/z(％)：316(M
++1，1.5)，260(3)，204(100)，186(38)，171(10)，156(10).
Synthesizing of embodiment 37.5-methyl-2-nitro-phenyl-phosphonic acid diethyl ester
Working method is with embodiment 1.Difference is, uses 5-methyl-2-nitrobenzoic acid (66.5mg, 0.36mmol) to substitute o-Carboxynitrobenzene as aromatic yl reagent-ing.Obtain oily liquids 39.2mg, productive rate 48%.
R
f=0.25 (V
normal hexane/ V
ethyl acetate=1/2).
1H NMR(600MHz，CDCl
3)：δ7.92(dd，1H，ArH，J
ArH-P＝14.9Hz，J＝1.0Hz)，7.82(dd，1H，ArH，J＝8.1Hz，J
ArH-P＝6.0Hz)，7.47(d，1H，ArH，J＝8.1Hz)，4.23(m，4H，CH
2)，2.49(s，ArCH
3)，1.36(m，6H，CH
2CH
3).
13C NMR(150MHz，CDCl
3)：δ149.88，143.62(d，J＝12.9Hz)，136.02(d，J＝6.4Hz)，133.56(d，J＝2.1Hz)，124.63(d，J＝9.2Hz)，123.37(d，J＝189.9Hz)，63.42(d，J＝6.0Hz)，21.53，16.37(d，J＝6.5Hz).
31P NMR(242MHz，CDCl
3)：δ12.14.MS(70eV，EI)m/z(％)：274(M
++1，11)，246(13)，228(35)，218(76)，200(100)，185(94)，171(87)，153(72).
Synthesizing of embodiment 38.3-methyl-2-nitro-phenyl-phosphonic acid diethyl ester
Working method is with embodiment 1.Difference is, uses 3-methyl-2-nitrobenzoic acid (66.5mg, 0.36mmol) to substitute o-Carboxynitrobenzene as aromatic yl reagent-ing.Obtain oily liquids 31.6g, productive rate 39%.
R
f=0.31 (V
normal hexane/ V
ethyl acetate=1/2).
1H NMR(600MHz，CDCl
3)：δ7.86(dd，1H，ArH，J
ArH-P＝14.7Hz，J＝7.6Hz)，7.49(m，2H，ArH)，4.15(m，4H，CH
2)，2.34(s，3H，ArCH
3)，1.34(t，6H，CH
2CH
3，J＝7.1Hz).
13C NMR(150MHz，CDCl
3)：δ152.57，135.66(d，J＝2.1Hz)，132.25(d，J＝6.1Hz)，130.23(d，J＝9.3Hz)，129.82(d，J＝14.2Hz)，121.19(d，J＝186.4Hz)，63.23(d，J＝5.6Hz)，17.28，16.09(d，J＝6.6Hz).
31PNMR(242MHz，CDCl
3)：δ11.62.MS(70eV，EI)m/z(％)：274(M
++1，9)，246(19)，227(74)，218(33)，200(88)，185(60)，171(100)，153(91).
Embodiment 39.4,5-dimethoxy-2-nitro-phenyl-phosphonic acid diethyl ester synthetic
Working method is with embodiment 1.Difference is, uses 4,5-Dimethoxy-2-nitrobenzoic Acid (83.5mg, 0.36mmol) to substitute o-Carboxynitrobenzene as aromatic yl reagent-ing.Obtain oily liquids 21.0mg, productive rate 22%.
R
f=0.23 (V
normal hexane/ V
ethyl acetate=1/2).
1H NMR(400MHz，CDCl
3)：δ7.58(d，1H，ArH，J
ArH-P＝15.4Hz)，7.55(d，1H，ArH，J
ArH-P＝6.1Hz)，4.23(m，2H，CH
2)，4.01(s，3H，OCH
3)，3.99(s，3H，OCH
3)，1.36(t，6H，CH
2CH
3，J＝7.1Hz).
13C NMR(100MHz，CDCl
3)：δ151.87(d，J＝15.8Hz)，151.64(d，J＝3.1Hz)，145.38(d，J＝2.3Hz)，116.71(d，J＝195.3Hz)，116.82(d，J＝8.0Hz)，108.33(d，J＝10.8Hz)，63.42(d，J＝6.1Hz)，56.77，56.74，16.43(d，J＝6.5Hz).
31P NMR(162MHz，CDCl
3)：δ12.71.MS(70eV，EI)m/z(％)：319(M
+，100)，291(17)，274(15)，262(16)，247(40)，230(17)，216(80)，199(18).
Synthesizing of the chloro-phenyl-phosphonic acid diethyl ester of embodiment 40.5-nitro-2-
Working method is with embodiment 1.Difference is, uses 5-nitro-2-chloro-benzoic acid (73.3mg, 0.36mmol) to substitute o-Carboxynitrobenzene as aromatic yl reagent-ing.Obtain oily liquids 22.9mg, productive rate 26%.
R
f=0.46 (V
normal hexane/ V
ethyl acetate=1/2).
1H NMR(400MHz，CDCl
3)：δ8.82(dd，1H，ArH，J
ArH-P＝14.8Hz，J＝2.8Hz)，8.31(dd，1H，ArH，J＝8.7Hz，J＝2.8Hz)，7.65(dd，1H，ArH，J＝8.7Hz，J
ArH-P＝5.1Hz)，4.24(m，4H，CH
2)，1.39(t，6H，CH
3，J＝7.1Hz).
13C NMR(100MHz，CDCl
3)＝δ146.24(d，J＝16.9Hz)，143.82(d，J＝3.3Hz)，132.12(d，J＝10.6Hz)，130.67(d，J＝9.5Hz)，130.37(d，J＝192.9Hz)，127.99(d，J＝2.5Hz)，63.46(d，J＝5.9Hz)，16.46(d，J＝6.3Hz).
31P NMR(162MHz，CDCl
3)：δ10.68.MS(70eV，EI)m/z(％)：294(M
++1，4.5)，266(21)，258(44)，238(100)，230(85)，220(32).
Synthesizing of the chloro-2-nitro-phenyl-phosphonic acid of embodiment 41.4-diethyl ester
Working method is with embodiment 1.Difference is, uses the chloro-2-nitrobenzoic acid of 4-(73.3mg, 0.36mmol) to substitute o-Carboxynitrobenzene as aromatic yl reagent-ing.Obtain oily liquids 10.6mg, productive rate 12%.
R
f=0.34 (V
normal hexane/ V
ethyl acetate=1/2).
1H NMR(400MHz，CDCl
3)：δ8.05(dd，1H，ArH，J
ArH-P＝14.0Hz，J＝8.3Hz)，7.86(dd，1H，ArH，J
ArH-P＝4.7Hz，J＝2.0Hz)，7.66(ddd，1H，H5，J
ArH-P＝J＝8.3Hz，J＝2.0Hz)，4.23(m，4H，CH
2)，1.36(t，6H，CH
3，J＝7.1Hz).
13C NMR(100MHz，CDCl
3)：δ152.66，139.64(d，J＝3.4Hz)，136.54(d，J＝6.7Hz)，132.38(d，J＝13.6Hz)，124.69(d，J＝9.2Hz)，122.08(d，J＝191.9Hz)，63.70(d，J＝6.1Hz)，17.28，16.36(d，J＝6.4Hz).
31P NMR(162MHz，CDCl
3)：δ10.66.MS(70eV，EI)m/z(％)：294(M
++1，4)，266(12)，248(18)，238(70)，220(89)，205(100)，191(63)，173(40).
Synthesizing of embodiment 42.5-methyl-2-nitro-dibutyl phenyl phosphonate
Working method is with embodiment 1.Difference is; use 5-methyl-2-nitrobenzoic acid (66.5mg; 0.36mmol) substitute o-Carboxynitrobenzene as aromatic yl reagent-ing; use dibutyl phosphite (61.00 μ L; 0.3mmol) substitute diethyl phosphite as phosphine acylating reagent; use silver carbonate (16.8mg, 0.06mmol) to substitute silver carbonate (168.0mg, 0.6mmol) as alkali.Obtain oily liquids 46.4g, productive rate 47%.
R
f=0.56 (V
normal hexane/ V
ethyl acetate=1/2).
1H NMR(400MHz，CDCl
3)：δ7.92(d，1H，ArH，J
ArH-P＝14.9Hz)，7.81(d，1H，ArH，J＝8.0Hz，J
ArH-P＝6.0Hz)，7.46(d，1H，ArH，J＝8.0Hz)，4.15(m，4H，OCH
2)，3.93(s，3H，OCH
3)，2.47(s，3H，ArCH
3)，1.68(m，4H，OCH
2CH
2)，1.41(m，4H，CH
2CH
3)，0.92(t，6H，CH
3，J＝7.4Hz).
13C NMR(100MHz，CDCl
3)：δ149.87(d，J＝1.8Hz)，143.57(d，J＝13.0Hz)，136.11(d，J＝6.2Hz)，133.51(d，J＝2.6Hz)，124.65(d，J＝9.0Hz)，123.39(d，J＝189.6Hz)，67.11(d，J＝6.4Hz)，32.53(d，J＝6.5Hz)，21.53，18.83，13.71.
31P NMR(162MHz，CDCl
3)：δ13.03.MS(70eV，EI)m/z(％)：330(M
++1，3)，274(5)，218(100)，200(64)，188(20)，170(19).
Synthesizing of embodiment 43.3-methyl-2-nitro-dibutyl phenyl phosphonate
Working method is with embodiment 42.Difference is, uses 3-methyl-2-nitrobenzoic acid (66.5mg, 0.36mmol) to substitute 5-methyl-2-nitrobenzoic acid as aromatic yl reagent-ing.Obtain oily liquids 24.7mg, productive rate 25%.
R
f=0.55 (V
normal hexane/ V
ethyl acetate=1/2).
1H NMR(400MHz，CDCl
3)：δ7.87(ddd，1H，ArH，J
ArH-P＝14.1Hz，J＝6.5Hz，J＝2.2Hz)，7.48(m，2H，ArH)，4.08(m，4H，OCH
2)，2.35(d，3H，ArCH
3，J＝2.9Hz)，1.67(m，4H，OCH
2CH
2)，1.40(m，4H，CH
2CH
3)，0.92(t，6H，CH
3，J＝7.4Hz).
13C NMR(100MHz，CDCl
3)：δ152.65(d，J＝3.9Hz)，135.83(d，J＝2.6Hz)，132.43(d，J＝6.2Hz)，130.38(d，J＝9.2Hz)，129.98(d，J＝14.2Hz)，121.14(d，J＝187.6Hz)，67.15(d，J＝6.1Hz)，32.37(d，J＝6.6Hz)，18.78，17.46，13.7.
31P NMR(162MHz，CDCl
3)：δ12.79.MS(70eV，EI)m/z(％)：330(M
++1，1.5)，274(4)，218(100)，200(54)，185(14)，170(20).
Embodiment 44.4,5-dimethoxy-2-nitro-dibutyl phenyl phosphonate synthetic
Working method is with embodiment 42.Difference is, uses 4,5-Dimethoxy-2-nitrobenzoic Acid (83.5mg, 0.36mmol) to substitute 5-methyl-2-nitrobenzoic acid as aromatic yl reagent-ing.Obtain oily liquids 39.4mg, productive rate 35%.
R
f=0.40 (V
normal hexane/ V
ethyl acetate=1/2).
1H NMR(400MHz，CDCl
3)：δ7.57(m，2H，ArH)，4.15(m，4H，OCH
2)，4.01(s，3H，ArOCH
3)，3.99(s，3H，ArOCH
3)，1.68(m，4H，OCH
2CH
2)，1.41(m，4H，CH
2CH
3)，0.93(t，6H，CH
3，J＝7.4Hz).
13C NMR(100MHz，CDCl
3)：δ151.82(d，J＝15.9Hz)，151.57(d，J＝3.0Hz)，145.30(d，J＝2.2Hz)，116.86(d，J＝8.0Hz)，116.68(d，J＝195.3Hz)，108.33(d，J＝10.8Hz)，67.10(d，J＝6.4Hz)，56.74，56.71，32.55(d，J＝6.6Hz)，18.86，13.72.
31P NMR(162MHz，CDCl
3)：δ12.89.MS(70eV，EI)m/z(％)：376(M
++1，5)，305(18)，264(100)，246(70)，231(57)，216(48).
Synthesizing of the chloro-dibutyl phenyl phosphonate of embodiment 45.5-nitro-2-
Working method is with embodiment 42.Difference is, uses 5-nitro-2-chloro-benzoic acid (73.3mg, 0.36mmol) to substitute 5-methyl-2-nitrobenzoic acid as aromatic yl reagent-ing.Obtain oily liquids 31.5mg, productive rate 30%.
R
f=0.76 (V
normal hexane/ V
ethyl acetate=1/2).
1H NMR(400MHz，CDCl
3)：δ8.83(dd，1H，ArH，J
ArH-P＝14.8Hz，J＝2.8Hz)，8.31(dd，1H，ArH，J＝8.7Hz，J＝2.8Hz)，7.65(dd，1H，ArH，J＝8.7Hz，J
ArH-P＝5.1Hz)，4.16(m，4H，OCH
2)，1.71(m，4H，OCH
2CH
2)，1.43(m，4H，CH
2CH
3)，0.93(t，6H，CH
3，J＝7.4Hz).
13C NMR(100MHz，CDCl
3)：δ146.19(d，J＝16.2Hz)，143.79(d，J＝3.2Hz)，132.08(d，J＝10.7Hz)，130.70(d，J＝9.4Hz)，130.32(d，J＝192.7Hz)，127.95(d，J＝2.5Hz)，67.10(d，J＝6.1Hz)，32.53(d，J＝6.4Hz)，18.87，13.68.
31P NMR(162MHz，CDCl
3)：δ11.55.MS(70eV，EI)m/z(％)：350(M
++1，1.5)，314(2)，294(5)，258(6)，238(100)，220(13).
Synthesizing of the fluoro-2-nitro-dibutyl phenyl phosphonate of embodiment 46.5-
Working method is with embodiment 42.Difference is, uses the fluoro-2-nitrobenzoic acid of 5-(68.0mg, 0.36mmol) to substitute 5-methyl-2-nitrobenzoic acid as aromatic yl reagent-ing.Obtain oily liquids 43.0mg, productive rate 43%.
R
f=0.80 (V
normal hexane/ V
ethyl acetate=1/2).
1H NMR(400MHz，CDCl
3)：δ7.99(ddd，1H，ArH，J
ArH-P＝8.9Hz，J＝6.4Hz，J＝4.6Hz)，7.80(ddd，1H，ArH，J
ArH-P＝15.3Hz，J
ArH-F＝8.4Hz，J＝2.8Hz)，7.35(m，1H，ArH)，4.18(m，4H，OCH
2)，1.70(m，4H，OCH
2CH
2)，1.41(m，4H，CH
2CH
3)，0.93(t，6H，CH
3，J＝7.4Hz).
13C NMR(100MHz，CDCl
3)：δ163.96(dd，J
C-F＝258.3Hz，J＝18.2Hz)，147.96(d，J＝1.4Hz)，127.46(dd，J＝189.5Hz，J
C-F＝7.3Hz)，127.43(t，J＝J
C-F＝9.3Hz)，122.45(dd，J
C-F＝25.3Hz，J＝6.3Hz)，119.81(dd，J
C-F＝23.1Hz，J＝2.7Hz)，67.54(d，J＝6.4Hz)，32.52(d，J＝6.5Hz)，18.82，13.70.
31P NMR(162MHz，CDCl
3)：δ9.77(d，J
F-P＝5.1Hz).MS(70eV，EI)m/z(％)：334(M
++1，3)，278(6)，222(100)，204(38)，189(12).
Synthesizing of the chloro-2-nitro-dibutyl phenyl phosphonate of embodiment 47.5-
Working method is with embodiment 42.Difference is, uses the chloro-2-nitrobenzoic acid of 5-(74.0mg, 0.36mmol) to substitute 5-methyl-2-nitrobenzoic acid as aromatic yl reagent-ing.Obtain oily liquids 50.4mg, productive rate 48%.
R
f=0.79 (V
normal hexane/ V
ethyl acetate=1/2).
1H NMR(400MHz，CDCl
3)：δ8.07(dd，1H，ArH，J
ArH-P＝14.7Hz，J＝2.3Hz)，7.86(dd，1H，ArH，J＝8.6Hz，J
ArH-P＝6.0Hz)，7.64(dd，1H，ArH，J＝8.6Hz，J＝2.3Hz)，4.17(m，4H，OCH
2)，1.69(m，4H，OCH
2CH
2)，1.41(m，4H，CH
2CH
3)，0.93(t，6H，CH
3，J＝7.4Hz).
13C NMR(100MHz，CDCl
3)：δ150.19(d，J＝1.7Hz)，139.15(d，J＝17.2Hz)，135.42(d，J＝6.7Hz)，133.06(d，J＝2.5Hz)，125.99(d，J＝188.5Hz)，125.98(d，J＝9.5Hz)，67.54(d，J＝6.4Hz)，32.51(d，J＝6.4Hz)，18.82，13.70.
31P NMR(162MHz，CDCl
3)：δ9.91.MS(70eV，EI)m/z(％)：350(M
++1，4)，294(5)，238(100)，220(48)，205(14)，190(16).
Synthesizing of the chloro-2-nitro-dibutyl phenyl phosphonate of embodiment 48.4-
Working method is with embodiment 42.Difference is, uses the chloro-2-nitrobenzoic acid of 4-(74.8mg, 0.36mmol) to substitute 5-methyl-2-nitrobenzoic acid as aromatic yl reagent-ing.Obtain oily liquids 64.0mg, productive rate 61%.
R
f=0.63 (V
normal hexane/ V
ethyl acetate=1/2).
1H NMR(400MHz，CDCl
3)：δ8.04(dd，1H，ArH，J
ArH-P＝14.0Hz，J＝8.3Hz)，7.86(dd，1H，ArH，J
ArH-P＝4.7Hz，J＝2.0Hz)，7.66(ddd，1H，ArH，J
ArH-P＝J＝8.2Hz，J＝2.0Hz)，4.14(m，4H，OCH
2)，1.68(m，4H，OCH
2CH
2)，1.40(m，4H，CH
2CH
3)，0.93(t，6H，CH
3，J＝7.4Hz).
13C NMR(100MHz，CDCl
3)：δ152.59(d，J＝3.5Hz)，139.58(d，J＝3.5Hz)，136.57(d，J＝6.7Hz)，132.35(d，J＝13.6Hz)，124.69(d，J＝9.2Hz)，122.05(d，J＝192.0Hz)，67.35(d，J＝6.3Hz)，32.48(d，J＝6.5Hz)，18.81，13.69.
31P NMR(162MHz，CDCl
3)：δ10.78.MS(70eV，EI)m/z(％)：350(M
++1，3)，294(7)，238(100)，220(40)，205(8)，190(9).
Synthesizing of the bromo-2-nitro-dibutyl phenyl phosphonate of embodiment 49.4-
Working method is with embodiment 42.Difference is, uses the bromo-2-nitrobenzoic acid of 4-(90.4mg, 0.36mmol) to substitute 5-methyl-2-nitrobenzoic acid as aromatic yl reagent-ing.Obtain oily liquids 46.1mg, productive rate 39%.
R
f=0.69 (V
normal hexane/ V
ethyl acetate=1/2).
1H NMR(400MHz，CDCl
3)：δ8.00(dd，1H，ArH，J
ArH-P＝4.8Hz，J＝2.0Hz)，7.96(dd，1H，ArH，J
ArH-P＝13.9Hz，J＝8.2Hz)，7.82(ddd，1H，ArH，J
ArH-P＝J＝8.2Hz，J＝2.0Hz)，4.14(m，4H，OCH
2)，1.67(m，4H，OCH
2CH
2)，1.41(m，4H，CH
2CH
3)，0.93(t，6H，CH
3，J＝7.3Hz).
13C NMR(100MHz，CDCl
3)：δ152.45(d，J＝3.3Hz)，136.59(d，J＝6.6Hz)，135.38(d，J＝13.5Hz)，133.09，127.49(d，J＝9.0Hz)，122.49(d，J＝191.5Hz)，67.38(d，J＝6.4Hz)，32.48(d，J＝6.5Hz)，18.82，13.70.
31P NMR(162MHz，CDCl
3)：δ10.96.MS(70eV，EI)m/z(％)：396(M
++1，3)，394(M
+-1，2)，340(6)，282(100)，266(50)，251(14)，236(26)，219(14).
Synthesizing of the fluoro-2-nitro-dibutyl phenyl phosphonate of embodiment 50.4-
Working method is with embodiment 42.Difference is, uses the fluoro-2-nitrobenzoic acid of 4-(68.0mg, 0.36mmol) to substitute 5-methyl-2-nitrobenzoic acid as aromatic yl reagent-ing.Obtain oily liquids 70.0mg, productive rate 70%.
R
f=0.61 (V
normal hexane/ V
ethyl acetate=1/2).
1H NMR(400MHz，CDCl
3)：δ8.13(ddd，1H，ArH，J
ArH-P＝14.1Hz，J＝8.6Hz，J
ArH-F＝5.7Hz)，7.60(m，1H，ArH)，7.39(m，1H，ArH)，4.15(m，4H，OCH
2)，1.68(m，4H，OCH
2CH
2)，1.41(m，4H，CH
2CH
3)，0.93(t，6H，CH
3，J＝7.4Hz).
13C NMR(100MHz，CDCl
3)：δ164.55(dd，J
C-F＝258.6Hz，J＝3.4Hz)，153.36(dd，J
C-F＝9.4Hz，J＝4.0Hz)，137.78(dd，J＝8.7Hz，J
C-F＝7.1Hz)，119.79(dd，J＝193.6Hz，J
C-F＝4.2Hz)，119.41(dd，J
C-F＝20.5Hz，J＝14.0Hz)，112.67(dd，J
C-F＝26.5Hz，J＝9.8Hz)，67.29(d，J＝6.4Hz)，32.48(d，J＝6.5Hz)，18.81，13.69.
31P NMR(162MHz，CDCl
3)：δ10.85.MS(70eV，EI)m/z(％)：334(M
++1，4)，278(4)，222(100)，204(39)，189(7)，174(8).
Synthesizing of embodiment 51.5-methoxyl group-2-nitro-dibutyl phenyl phosphonate
Working method is with embodiment 42.Difference is, uses 5-methoxyl group-2-nitrobenzoic acid (73.2mg, 0.36mmol) to substitute 5-methyl-2-nitrobenzoic acid as aromatic yl reagent-ing.Obtain oily liquids 48.7mg, productive rate 47%.
R
f=0.84 (V
normal hexane/ V
ethyl acetate=1/2).
1H NMR(400MHz，CDCl
3)：δ8.03(dd，1H，ArH，J＝8.9Hz，J
ArH-P＝6.8Hz)，7.61(dd，1H，ArH，J
ArH-P＝16.2Hz，J＝2.8Hz)，7.09(dd，1H，ArH，J＝9.0Hz，J＝2.8Hz)，4.18(m，4H，OCH
2)，3.93(s，3H，OCH
3)，1.69(m，4H，OCH
2CH
2)，1.42(m，4H，CH
2CH
3)，0.93(t，6H，CH
3，J＝7.4Hz).
13C NMR(100MHz，CDCl
3)：δ162.60(d，J＝16.2Hz)，144.58(d，J＝1.8Hz)，127.47(d，J＝10.0Hz)，126.33(d，J＝189.5Hz)，121.09(d，J＝6.9Hz)，117.10(d，J＝2.7Hz)，67.26(d，J＝6.5Hz)，56.28，32.56(d，J＝6.5Hz)，18.85，13.72.
31P NMR(162MHz，CDCl
3)：δ12.62.MS(70eV，EI)m/z(％)：346(M
++1，1.5)，290(9)，234(100)，216(56)，201(27)，186(21).
Claims (1)
1. a synthetic method for arylphosphonic acid ester compound, is characterized in that, its reaction formula is as follows:
In reaction formula, R
1hydrogen, halogen, heteroatoms or alkyl; R
2it is alkyl;
Its concrete synthetic method is as follows:
In reaction flask, add successively aryl carboxylic acid, palladium catalyst, alkali, additive, dialkyl phosphite and solvent, wherein the mol ratio of aryl carboxylic acid, palladium catalyst, alkali, additive and dialkyl phosphite is 1-2: 0.05-0.4: 0.05-3: 0.5-3: 1; Then, stirring at room 5-30 minute, mixes reactant; In 80-140 ℃ of reacting by heating, type of heating is microwave heating or conventional stirring heating again, and microwave heating power is 20-140 watt, and be 8-20 minute heat-up time; The conventional stirring heating time is 5-20 hour; Thin-layer chromatography monitoring raw material reaction is complete; After solution is cooled to room temperature, with siliceous earth column, filter, and by washed with dichloromethane; Collect filtrate, be spin-dried for rear rapid column chromatography and obtain product;
Described palladium catalyst is acid chloride, Palladous chloride, palladium bromide, palladium trifluoroacetate, tetrakis triphenylphosphine palladium or two (diphenylphosphine) Palladous chloride; Described alkali is silver carbonate, Silver Nitrate, silver acetate, silver molybdate, silver suboxide or Trisilver phosphate; Described additive is lithium nitrate, lithium chloride, trifluoromethanesulfonic acid lithium, lithium hydroxide, lithium fluoride, lithiumbromide or lithium iodide; Described solvent is that DMF, N,N-dimethylacetamide, dimethyl sulfoxide (DMSO), N-Methyl pyrrolidone, acetonitrile, tetrahydrochysene furan are fed, or DMF and the dimethyl sulfoxide (DMSO) volume ratio mixed solvent that is 19: 1.
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| GASTON LAVÉN ET AL.: "Palladium（0）-Catalyzed Benzylation of H-Phosphonate Diesters: An Efficient Entry to Benzylphosphonates", 《SYNLETT》 * |
| MARCIN KALEK ET AL.: "Preparation of Arylphosphonates by Palladium（0）-Catalyzed Cross-Coupling in the Presence of Acetate Additives: Synthetic and Mechanistic Studies", 《ADVANCED SYNTHESIS & CATALYSIS》 * |
| 朱茂根等: "钯/Dabco体系催化芳基膦酸酯的合成", 《湖南师范大学自然科学学报》 * |
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