CN114591364B - Synthesis method of thiophosphonate compound - Google Patents
Synthesis method of thiophosphonate compound Download PDFInfo
- Publication number
- CN114591364B CN114591364B CN202210263763.XA CN202210263763A CN114591364B CN 114591364 B CN114591364 B CN 114591364B CN 202210263763 A CN202210263763 A CN 202210263763A CN 114591364 B CN114591364 B CN 114591364B
- Authority
- CN
- China
- Prior art keywords
- reaction
- thiophosphonate
- compound
- formula
- synthesizing
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 150000001875 compounds Chemical class 0.000 title claims description 19
- 238000001308 synthesis method Methods 0.000 title abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims abstract description 62
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 20
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 17
- 239000011593 sulfur Substances 0.000 claims abstract description 17
- 238000000034 method Methods 0.000 claims abstract description 13
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 150000008049 diazo compounds Chemical class 0.000 claims abstract description 4
- 238000005286 illumination Methods 0.000 claims abstract description 4
- 239000000047 product Substances 0.000 claims abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 54
- -1 diaryl phosphorus oxide compound Chemical class 0.000 claims description 31
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 27
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 125000001624 naphthyl group Chemical group 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 239000012044 organic layer Substances 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 229910001392 phosphorus oxide Inorganic materials 0.000 claims description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 239000012467 final product Substances 0.000 claims 1
- 238000003756 stirring Methods 0.000 claims 1
- 238000005406 washing Methods 0.000 claims 1
- 239000003054 catalyst Substances 0.000 abstract description 7
- VWBYXJRDIQCSLW-UHFFFAOYSA-N O=[P](c1ccccc1)c1ccccc1 Chemical class O=[P](c1ccccc1)c1ccccc1 VWBYXJRDIQCSLW-UHFFFAOYSA-N 0.000 abstract description 6
- 239000000758 substrate Substances 0.000 abstract description 6
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical class OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 abstract description 3
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 abstract description 3
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 abstract description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract 2
- 239000006227 byproduct Substances 0.000 abstract 1
- 229910052757 nitrogen Inorganic materials 0.000 abstract 1
- 231100000252 nontoxic Toxicity 0.000 abstract 1
- 230000003000 nontoxic effect Effects 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 28
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- 230000015572 biosynthetic process Effects 0.000 description 11
- 238000003786 synthesis reaction Methods 0.000 description 11
- 239000012043 crude product Substances 0.000 description 10
- 239000007788 liquid Substances 0.000 description 10
- 239000003208 petroleum Substances 0.000 description 10
- 238000010898 silica gel chromatography Methods 0.000 description 10
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
- LXCYSACZTOKNNS-UHFFFAOYSA-N diethoxy(oxo)phosphanium Chemical compound CCO[P+](=O)OCC LXCYSACZTOKNNS-UHFFFAOYSA-N 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 239000007800 oxidant agent Substances 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 238000006276 transfer reaction Methods 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 230000001590 oxidative effect Effects 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- NJLHHACGWKAWKL-UHFFFAOYSA-N ClP(Cl)=O Chemical compound ClP(Cl)=O NJLHHACGWKAWKL-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 2
- BEWOQXVDCFTBAQ-UHFFFAOYSA-N P(OC1=CC=CC=C1)(OC1=CC=CC=C1)=S Chemical compound P(OC1=CC=CC=C1)(OC1=CC=CC=C1)=S BEWOQXVDCFTBAQ-UHFFFAOYSA-N 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 150000001989 diazonium salts Chemical class 0.000 description 2
- NFORZJQPTUSMRL-UHFFFAOYSA-N dipropan-2-yl hydrogen phosphite Chemical compound CC(C)OP(O)OC(C)C NFORZJQPTUSMRL-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 150000003573 thiols Chemical class 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- OHVLMTFVQDZYHP-UHFFFAOYSA-N 1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-2-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]ethanone Chemical compound N1N=NC=2CN(CCC=21)C(CN1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)=O OHVLMTFVQDZYHP-UHFFFAOYSA-N 0.000 description 1
- CWPKTBMRVATCBL-UHFFFAOYSA-N 3-[1-[1-[(2-methylphenyl)methyl]piperidin-4-yl]piperidin-4-yl]-1h-benzimidazol-2-one Chemical compound CC1=CC=CC=C1CN1CCC(N2CCC(CC2)N2C(NC3=CC=CC=C32)=O)CC1 CWPKTBMRVATCBL-UHFFFAOYSA-N 0.000 description 1
- CRTMHFYHYMQVSB-UHFFFAOYSA-N CC=1C=C(C=C(C1)C)[P](C1=CC(=CC(=C1)C)C)=O Chemical compound CC=1C=C(C=C(C1)C)[P](C1=CC(=CC(=C1)C)C)=O CRTMHFYHYMQVSB-UHFFFAOYSA-N 0.000 description 1
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- 239000012954 diazonium Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- AQSJGOWTSHOLKH-UHFFFAOYSA-N phosphite(3-) Chemical class [O-]P([O-])[O-] AQSJGOWTSHOLKH-UHFFFAOYSA-N 0.000 description 1
- 239000011941 photocatalyst Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 1
- VSAISIQCTGDGPU-UHFFFAOYSA-N tetraphosphorus hexaoxide Chemical compound O1P(O2)OP3OP1OP2O3 VSAISIQCTGDGPU-UHFFFAOYSA-N 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/16—Esters of thiophosphoric acids or thiophosphorous acids
- C07F9/165—Esters of thiophosphoric acids
- C07F9/17—Esters of thiophosphoric acids with hydroxyalkyl compounds without further substituents on alkyl
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or 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)
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02B—CLIMATE CHANGE MITIGATION TECHNOLOGIES RELATED TO BUILDINGS, e.g. HOUSING, HOUSE APPLIANCES OR RELATED END-USER APPLICATIONS
- Y02B20/00—Energy efficient lighting technologies, e.g. halogen lamps or gas discharge lamps
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
The invention discloses a method for synthesizing phosphorothioate compounds by light promotion, which takes diazo compounds and settled sulfur as reaction substrates, and reacts with diphenyl phosphorus oxide compounds or dialkyl phosphite compounds under illumination conditions, wherein the reaction conditions are mild, no catalyst is needed, and the phosphorothioate products can be obtained by reacting in a water phase or solvent-free state. The synthesis method disclosed by the invention has the advantages of wide substrate universality, higher yield, environment friendliness and the like by taking generated nitrogen as the only byproduct in the reaction process, and being nontoxic and harmless.
Description
Technical Field
The invention relates to a method for synthesizing a thiophosphonate compound directly promoted by illumination without a catalyst.
Background
The thiophosphonate compound has the effects of killing insects, sterilizing and the like, is widely used for agricultural medicines, and has important significance for the development of agriculture at home and abroad. However, in recent years, due to the continuous improvement of environmental protection requirements and the continuous enhancement of public health consciousness, the pesticide industry faces more challenges, and the development of novel low-toxicity low-residue high-efficiency thiophosphonate drugs and an environment-friendly synthetic route of the thiophosphonate compounds has great significance.
The traditional synthesis mode of the compound is to prepare the compound by the reaction of the phosphonic chloride and the mercaptan, but the preparation process of the phosphonic chloride compound is complex, and the compound has the defects of easy decomposition, difficult storage and toxicity. In recent years, the use of phosphorus oxide (HP (O) R) has evolved 2 ) And thiol Cross Dehydrogenation Coupling (CDC) reaction to synthesize thiophosphonate compound. In 2014, the literature reported a method using CuBr 2 As a catalyst, DDQ is an oxidant, and diphenyl phosphorus oxide and thiophenol are used as raw materials to prepare diphenyl thiophosphonate (chem. Commun.2014, 50, 10879); in 2015, the literature reports a method for preparing diphenyl thiophosphonate compounds by reacting diphenyl phosphorus oxide and mercaptan for 5-8 hours at room temperature by using KI as a catalyst and TBPB as an oxidant (Green chem.2015, 17, 314), and both the above methods need to be usedA catalyst and an oxidant. In 2017, the literature reported one example of Cs 2 CO 3 Catalytic reaction of diethyl phosphite and thiol under oxygen conditions to prepare thiophosphonate (angel. Chem. Int. Ed.2017,56,2487), which is simple and high yield, but uses thiol compounds with malodor and certain toxicity as sulfur source.
Settled sulfur (S) 8 ) As a simple, readily available, safe and harmless sulfur source, compounds used for synthesizing thiophosphonates have been used in recent years. In 2016, the literature reported a reaction for preparing phosphorothioates by copper-catalyzed reaction of dialkyl phosphites with elemental sulfur and phenylboronic acid (org. Lett.2016,18, 1266-1269), which was mild in reaction conditions and high in yield, but required a metal catalyst and limited in substrate. In 2019, the literature reports a reaction (adv. Synth. Catalyst. 2019,361, 3210-3216.) for preparing phosphorothioate by reacting dialkyl phosphite with elemental sulfur and indole compounds catalyzed by iodine and TBHP, which reaction is efficient for preparing indole heterocyclic phosphorothioate, but requires elemental iodine and an oxidizing agent. In 2020, the literature reports a reaction of dialkyl phosphite, elemental sulfur and fluoroalkyl amine with the preparation of thiophosphonate via a 1, 5-hydrogen transfer process (org. Lett.2020,22, 1760-1764.) but the preparation of the reaction substrate is difficult and the range of application is limited.
Disclosure of Invention
Aiming at the problems in the prior art, the invention aims to provide a method for synthesizing a thiophosphonate compound, which is efficient, simple, mild in reaction condition and strong in substrate universality.
The invention discloses a method for synthesizing thiophosphonate compounds, which is characterized in that diaryl phosphorus oxide compounds or phosphite ester compounds shown in a formula (I) and settled sulfur are added into a reaction vessel, uniformly stirred in the presence or absence of a solvent, then diazonium compounds shown in a formula (II-1) or (II-2) are added, the reaction is carried out for 10-24 hours under the condition of illumination at a certain temperature, ethyl acetate is added for extraction after the reaction is finished, and an organic layer is washed and purified by saturated saline water to obtain a product thiophosphonate compound shown in a formula (III-1) or a formula (III-2), wherein the reaction equation is as follows:
wherein R is phenyl, naphthyl, substituted phenyl or alkoxy, the substituted phenyl is mono-substituted or multi-substituted by hydrogen substituent groups on a benzene ring, and each substituent group is independently selected from halogen, methyl and methoxy; r is R 1 Methyl, halogen or methoxy; r is R 2 Is methyl, ethyl or isopropyl.
Further, the invention also defines that the alkoxy group is methoxy, ethoxy or isopropoxy.
Further, the invention also defines that the solvent is one or more of acetonitrile, dichloromethane, ethyl acetate, water, preferably water when R is phenyl, naphthyl or substituted phenyl, and preferably in the absence of solvent when R is alkoxy.
Further, the invention also defines that the reacted light source is one or two of a blue LED lamp and a white CFL lamp, when R is phenyl, naphthyl or substituted phenyl, the reacted light source is preferably a blue LED, and when R is alkoxy, the reacted light source is preferably a white CFL lamp.
Further, the invention also defines a reaction time of 12-16 hours; the reaction temperature is 25 to 80 ℃, preferably room temperature when R is phenyl, naphthyl or substituted phenyl, and preferably 80 ℃ when R is alkoxy.
Further, the invention also defines that the extractant is dichloromethane or ethyl acetate.
Furthermore, the invention also defines diaryl phosphorus oxide compound or phosphite ester compound shown in the formula (I) and settled sulfur S 8 The molar ratio of the diazo compound shown in the formula (II-1) or (II-2) is 1:1.5-2:1.5-2.
By adopting the limiting technology, compared with the prior art, the invention has the following beneficial effects: the invention adopts the diazonium compound as the raw material, does not need the transition metal to participate in the reaction with the photocatalyst, and has the advantages of environmental protection, simple and convenient operation, mild condition, good substrate universality and the like.
Detailed Description
The synthetic scheme of the present invention is described below with reference to specific examples, but the scope of the present invention is not limited thereto.
Example 12 Synthesis of ethyl- ((diphenylphosphoryl) thio) -2-phenylacetate
To a 10mL reaction tube were added settled sulfur (0.3 mmol, 0.010g) and diphenyl phosphorus oxide (0.2 mmol,0.040 g), water (1 mL), the reaction was stirred at room temperature for 10 minutes, then ethyl 2-diazonium-2-phenylacetate (0.3 mmol,0.058 g) was added, the reaction was stirred under blue LED lamp irradiation for 12 hours, and the reaction solution was extracted with 3mL ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and distilled under reduced pressure. The crude product was purified by silica gel chromatography using petroleum ether: ethyl acetate=5:1 volume ratio to give 58mg of ethyl 2- ((diphenylphosphoryl) thio) -2-phenylacetate as a pale yellow oily liquid in 74% yield. 1 H NMR(400MHz,Chloroform-d)δ7.92–7.80(m,2H),7.74–7.64(m,2H),7.57–7.50(m,1H),7.51–7.41(m,3H),7.37–7.28(m,4H),7.22–7.14(m,3H),5.12(d,J=10.5Hz,1H),4.02–3.87(m,2H),1.08(t,J=7.1Hz,3H).; 13 C NMR(100MHz,Chloroform-d)δ169.86(d,J=3.5Hz),135.80(d,J=3.6Hz),132.55(d,J=107.6Hz),132.51(d,J=2.9Hz),132.26(d,J=2.8Hz),131.57(d,J=5.9Hz),131.46(d,J=5.8Hz),128.57,128.57(d,J=13.3Hz),128.47,128.27,128.26(d,J=14.4Hz),128.16(d,J=109.7Hz),62.01,49.52,13.74.; 31 P NMR(162MHz,Chloroform-d)δ42.08.;ESI-MS[M+H]m/z 397.1031.
Example 22 Synthesis of Ethyl 2- ((diphenylphosphoryl) thio) acetate
To a 10mL reaction tube were added settled sulfur (0.4 mmol,0.012 g) and diphenyl phosphorus oxide (0.2 mmol,0.040 g), water (1 mL), the reaction was stirred at room temperature for 10 minutes, then ethyl 2- (4-chlorophenyl) -2-diazonoacetate (0.4 mmol,0.090 g), the reaction was stirred under irradiation of a blue LED lamp for 12 hours, and the reaction solution was extracted twice with 3mL ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, distilled under reduced pressure, and the crude product was purified by silica gel chromatography using petroleum ether: ethyl acetate=5:1 volume ratio to give 57mg of ethyl 2- (4-chlorophenyl) -2- ((diphenylphosphoryl) thio) acetate as a yellow oily liquid in 66% yield. 1 H NMR(400MHz,Chloroform-d)δ7.88–7.79(m,2H),7.70–7.61(m,2H),7.58–7.52(m,1H),7.51–7.43(m,3H),7.37–7.29(m,2H),7.26–7.20(m,2H),7.15–7.06(m,2H),5.12(d,J=10.1Hz,1H),4.05–3.92(m,2H),1.11(t,J=7.1Hz,3H).; 13 C NMR(100MHz,Chloroform-d)δ169.52(d,J=4.3Hz),134.53(d,J=2.9Hz),134.14,132.63(d,J=2.7Hz),132.62(d,J=107.6Hz),132.24(d,J=2.8Hz),131.84(d,J=107.8Hz),131.60(d,J=10.7Hz),131.49(d,J=10.9Hz),129.78,128.66(d,J=13.2Hz),128.65,128.43(d,J=13.4Hz),62.25,49.07,13.79.; 31 PNMR(162MHz,Chloroform-d)δ41.90.;ESI-MS[M+Na]m/z 453.0461.
Example 32 Synthesis of isopropyl- ((diphenylphosphoryl) thio) -2-phenylacetate
To a 10mL reaction tube were added settled sulfur (0.4 mmol,0.012 g) and diphenyl phosphorus oxide (0.2 mmol,0.040 g), water (1 mL), the reaction was stirred at room temperature for 10 minutes, then isopropyl 2-diazonium-2-phenylacetate (0.4 mmol,0.082 g) was added, the reaction was stirred under blue LED lamp irradiation for 12 hours, and the reaction solution was extracted twice with 3mL ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and distilled under reduced pressure. The crude product was purified by silica gel chromatography using petroleum ether: ethyl acetate=5:1 volume ratio to give a yellowish oily liquid 2- ((diphenyl)Phosphoryl) thio) -2-phenylacetic acid isopropyl ester 66mg in 72% yield. 1 H NMR(400MHz,Chloroform-d)δ7.91–7.80(m,2H),7.72–7.63(m,2H),7.57–7.51(m,1H),7.50–7.40(m,3H),7.35–7.28(m,4H),7.22–7.12(m,3H),5.10(d,J=10.7Hz,1H),4.85(hept,J=6.2Hz,1H),1.08(dd,J=10.0,6.3Hz,6H).; 13 C NMR(100MHz,Chloroform-d)δ169.31(d,J=4.1Hz),136.15(d,J=3.3Hz),132.86(d,J=107.1Hz),132.51(d,J=2.9Hz),132.18(d,J=3.0Hz),132.13(d,J=107.1Hz),131.61,131.50,128.56(d,J=23.2Hz),128.55,128.53,128.24,128.20(d,J=23.8Hz),69.86,50.06,21.33(d,J=6.7Hz).; 31 P NMR(162MHz,Chloroform-d)δ42.07.;ESI-MS[M+Na]m/z 433.0999.
Example 4 2 Synthesis of ethyl- ((bis (3, 5-dimethylphenyl) phosphoryl) thio) -2-phenylacetate
To a 10mL reaction tube were added settled sulfur (0.4 mmol,0.013 g) and bis (3, 5-dimethylphenyl) phosphorus oxide (0.2 mmol,0.046 g), water (1 mL), the reaction was stirred at room temperature for 10 minutes, then ethyl 2-diazonium-2-phenylacetate (0.4 mmol,0.076 g) was added, the reaction was stirred under irradiation of a blue LED lamp for 12 hours, and the reaction solution was extracted twice with 3mL ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and distilled under reduced pressure. The crude product was purified by silica gel chromatography using petroleum ether: ethyl acetate=5:1 volume ratio to give 62mg of ethyl 2- ((bis (3, 5-dimethylphenyl) phosphoryl) thio) -2-phenylacetate as a colourless oily liquid in 68% yield. 1 H NMR(600MHz,Chloroform-d)δ7.47–7.42(m,2H),7.33–7.29(m,3H),7.27(s,1H),7.21–7.16(m,3H),7.13(s,1H),7.03(s,1H),5.08(d,J=10.7Hz,1H),4.03–3.94(m,2H),2.32(s,6H),2.22(s,6H),1.10(t,J=7.1Hz,3H).; 13 C NMR(150MHz,Chloroform-d)δ169.96(d,J=3.9Hz),138.28(d,J=13.8Hz),138.05(d,J=13.9Hz),136.21(d,J=3.3Hz),134.09(d,J=3.2Hz),133.88(d,J=3.2Hz),132.61(d,J=105.9Hz),131.81(d,J=106.1Hz),129.12(d,J=10.6Hz),128.89(d,J=10.9Hz),128.35,128.26,128.02,61.87,49.48,21.16,21.05,13.72.; 31 PNMR(243MHz,Chloroform-d)δ43.31.;ESI-MS[M+H]m/z 453.1663.
Example 52 Synthesis of Ethyl- ((diethoxyphosphoryl) thio) -2-phenylacetate
To a 10mL reaction tube were added settled sulfur (0.8 mmol,0.026 g) and diethyl phosphite (0.4 mmol,0.0552 g), the reaction was stirred at room temperature for 10 minutes, then ethyl 2-diazonium-2-phenylacetate (0.8 mmol,0.152 g) was added, the reaction was heated to 80℃under irradiation of a white CFL lamp and stirred for 18 hours, the reaction solution was transferred with 3mL of dichloromethane, and distilled under reduced pressure. The crude product was purified by silica gel chromatography using petroleum ether: ethyl acetate=5:1 volume ratio to give 93mg of ethyl 2- ((diethoxyphosphoryl) thio) -2-phenylacetate as a colourless oily liquid in 64% yield. 1 H NMR(400MHz,Chloroform-d)δ7.45(m,2H),7.38–7.28(m,3H),4.99(d,J=11.2Hz,1H),4.26–3.90(m,6H),1.23(m,9H).
Example 62 Synthesis of Ethyl (4-bromophenyl) -2- ((diethoxyphosphoryl) thio) acetate
To a 10mL reaction tube were added settled sulfur (0.8 mmol,0.026 g) and diethyl phosphite (0.4 mmol,0.0552 g), the reaction was stirred at room temperature for 10 minutes, then ethyl 2- (4-bromophenyl) -2-diazonium acetate (0.8 mmol,0.214 g), the reaction was heated to 80℃under irradiation of a white CFL lamp and stirred for 18 hours, the transfer reaction solution was dissolved with 3mL of methylene chloride and distilled under reduced pressure. The crude product was purified by silica gel chromatography using petroleum ether: ethyl acetate=5:1 volume ratio to give 103mg of ethyl 2- (4-bromophenyl) -2- ((diethoxyphosphoryl) thio) acetate as a yellow oily liquid in 63% yield. 1 H NMR(400MHz,Chloroform-d)δ7.53–7.44(m,2H),7.39–7.30(m,2H),4.97(d,J=11.2Hz,1H),4.26–3.91(m,6H),1.30–1.18(m,9H).; 13 C NMR(100MHz,Chloroform-d)δ169.39(d,J=7.2Hz),135.46(d,J=4.8Hz),131.90,129.95,122.67,63.95(d,J=5.7Hz),63.79(d,J=6.0Hz),62.44,51.47(d,J=2.8Hz),15.83(d,J=5.7Hz),15.76(d,J=5.8Hz),13.90.; 31 PNMR(162MHz,Chloroform-d)δ23.66.;ESI-MS[M+H]m/z 411.0027.
Example 72 Synthesis of isopropyl- ((diethoxyphosphoryl) thio) -2-phenylacetate
To a 10mL reaction tube were added settled sulfur (0.8 mmol,0.026 g) and diethyl phosphite (0.4 mmol,0.0552 g), the reaction was stirred at room temperature for 10 minutes, then isopropyl 2-diazonium-2-phenylacetate (0.8 mmol,0.164 g) was added, the reaction was heated to 80℃under irradiation of a white CFL lamp and stirred for 18 hours, the transfer reaction solution was dissolved with 3mL of methylene chloride and distilled under reduced pressure. The crude product was purified by silica gel chromatography using petroleum ether: ethyl acetate=5:1 volume ratio to give 75mg of isopropyl 2- ((diethoxyphosphoryl) thio) -2-phenylacetate as a colourless oily liquid in 54% yield. 1 H NMR(400MHz,Chloroform-d)δ7.43(dd,J=7.9,1.7Hz,2H),7.36–7.26(m,3H),5.06–4.92(m,1H),4.95(d,J=11.3Hz,1H),4.19–3.86(m,4H),1.26–1.10(m,12H).; 13 C NMR(101MHz,Chloroform-d)δ169.24(d,J=7.0Hz),136.46(d,J=4.7Hz),128.72,128.43,128.21,69.99,63.76(d,J=5.5Hz),63.64(d,J=5.7Hz),52.37(d,J=2.7Hz),21.52,21.34,15.84(d,J=1.8Hz),15.76(d,J=1.8Hz).; 31 PNMR(162MHz,Chloroform-d)δ24.33.;ESI-MS[M+H]m/z 347.1089.
Example 82 Synthesis of Ethyl 2-phenylacetate- ((diisopropyloxyphosphoryl) thio) -2
Sedimentation was added to a 10mL reaction tubeSulfur (0.8 mmol,0.026 g) and diisopropyl phosphite (0.4 mmol,0.066 g) were reacted at room temperature for 10 minutes, then ethyl 2-diazonium-2-phenylacetate (0.8 mmol,0.152 g) was added, the reaction was heated to 80℃under white CFL lamp irradiation and stirred for 18h, the transfer reaction was dissolved in 3mL of dichloromethane and distilled under reduced pressure. The crude product was purified by silica gel chromatography using petroleum ether: ethyl acetate=5:1 volume ratio to give 84mg of ethyl 2- ((diisopropyloxyphosphoryl) thio) -2-phenylacetate as a colourless oily liquid in 55% yield. 1 H NMR(400MHz,Chloroform-d)δ7.51–7.42(m,2H),7.37–7.27(m,3H),5.05(d,J=11.6Hz,1H),4.79–4.65(m,1H),4.58–4.44(m,1H),4.25–4.09(m,2H),1.33(d,J=6.2Hz,3H),1.25–1.17(m,12H).; 13 C NMR(100MHz,Chloroform-d)δ169.98(d,J=7.0Hz),136.49(d,J=4.8Hz),128.74,128.41,128.28,73.13(d,J=6.2Hz),72.93(d,J=6.2Hz),62.14,52.33(d,J=2.9Hz),23.78(d,J=3.7Hz),23.56(d,J=4.0Hz),23.31(d,J=5.9Hz),13.90.; 31 PNMR(162MHz,Chloroform-d)δ21.70.;ESI-MS[M+Na]m/z 383.1063.
EXAMPLE 9 Synthesis of O, O-diisopropylS- (2-oxo-2-phenethyl) thiophosphonate
To a 10mL reaction tube were added settled sulfur (0.8 mmol,0.026 g) and diisopropyl phosphite (0.4 mmol,0.066 g), the reaction was stirred at room temperature for 10 minutes, then 2-diazonium-1-acetophenone (0.8 mmol,0.117 g) was added, the reaction was heated to 80℃under irradiation of a white CFL lamp and stirred for 18 hours, the transfer reaction solution was dissolved with 3mL of dichloromethane, and distilled under reduced pressure. The crude product was purified by silica gel chromatography using petroleum ether: ethyl acetate=5:1 volume ratio to give a yellow oily liquid O, O-diisopropyl S- (2-oxo-2-phenethyl) thiophosphonate 70mg in 55% yield. 1 H NMR(600MHz,Chloroform-d)δ8.02–7.94(m,2H),7.62–7.57(m,1H),7.51–7.44(m,2H),4.82–4.71(m,2H),4.37(d,J=11.6Hz,1H),1.40–1.30(m,12H).; 13 C NMR(150MHz,Chloroform-d)δ193.22(d,J=6.6Hz),135.17,133.80,128.78,128.52,73.17(d,J=6.5Hz),38.31(d,J=2.8Hz),23.80(d,J=4.3Hz),23.54(d,J=5.7Hz).; 31 PNMR(243MHz,Chloroform-d)δ23.54.;ESI-MS[M+H]m/z 317.0984.
EXAMPLE 10 Synthesis of ethyl 2- ((diethoxyphosphoryl) thio) -2- (4-methoxyphenyl) acetate
To a 10mL reaction tube were added settled sulfur (0.6 mmol,0.019 g) and diethyl phosphite (0.4 mmol,0.0552 g), the reaction was stirred at room temperature for 10 minutes, then ethyl 2-diazonium-2- (4-methoxyphenyl) acetate (0.6 mmol,0.132 g), and the reaction was heated to 80℃under irradiation of a white CFL lamp, stirred for 12 hours, and the reaction solution was transferred with 3mL of dichloromethane and distilled under reduced pressure. The crude product was purified by silica gel chromatography using petroleum ether: ethyl acetate=5:1 volume ratio to give 62mg of ethyl 2- ((diethoxyphosphoryl) thio) -2- (4-methoxyphenyl) acetate as a colourless oily liquid in 43% yield. 1 H NMR(400MHz,Chloroform-d)δ7.44–7.33(m,2H),6.93–6.81(m,2H),4.97(d,J=11.0Hz,1H),4.26–3.93(m,6H),3.80(s,3H),1.30–1.20(m,9H). 13 C NMR(101MHz,Chloroform-d)δ170.05(d,J=6.5Hz),159.71,129.50,128.17(d,J=5.4Hz),114.15,63.80(d,J=5.6Hz),63.66(d,J=5.7Hz),62.19,55.30,51.63(d,J=2.9Hz),15.91,15.82(d,J=3.6Hz),13.96. 31 P NMR(162MHz,Chloroform-d)δ24.30.ESI-MS[M+H]m/z 363.1034.
Claims (5)
1. A method for synthesizing thiophosphonate compound is characterized in that diaryl phosphorus oxide compound or phosphite ester compound shown in formula (I) and settled sulfur S 8 Adding into a reaction vessel, stirring uniformly in the presence or absence of solvent, adding diazo compound represented by formula (II-1) or (II-2), reacting at a certain temperature under illumination for 10-24 hr, adding extractant after reaction, extracting, washing the organic layer with saturated saline, and purifying to obtain the final product of formula (I)II-1) or a product thiophosphonate compound shown in a formula (III-2), wherein the reaction equation is as follows:
,
wherein R is phenyl, naphthyl, substituted phenyl or alkoxy, the substituted phenyl is mono-substituted or multi-substituted by hydrogen substituent groups on a benzene ring, and each substituent group is independently selected from halogen, methyl and methoxy; r is R 1 Methyl, halogen or methoxy; r is R 2 Methyl, ethyl or isopropyl;
when R is phenyl, naphthyl or substituted phenyl, the solvent is water, and the light source for the reaction is blue LED; when R is alkoxy, the reaction is carried out under the condition of no solvent, the light source of the reaction is a white CFL lamp, and the alkoxy is methoxy, ethoxy or isopropoxy.
2. The method for synthesizing a thiophosphonate compound according to claim 1, wherein the reaction time is 12-24 hours; the reaction temperature is 25-80 ℃.
3. The method for synthesizing a thiophosphonate compound according to claim 2, wherein when R is phenyl, naphthyl or substituted phenyl, the reaction temperature is room temperature, and when R is alkoxy, the reaction temperature is 80 ℃.
4. The method for synthesizing a thiophosphonate compound according to claim 1, wherein the extractant is dichloromethane or ethyl acetate.
5. The method for synthesizing the thiophosphonate compound, according to claim 1, wherein the molar ratio of the diaryl phosphorus oxide compound or phosphite ester compound shown in the formula (I) to the settled sulfur to the diazo compound shown in the formula (II-1) or (II-2) is 1:1.5-2:1.5-2.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210263763.XA CN114591364B (en) | 2022-03-15 | 2022-03-15 | Synthesis method of thiophosphonate compound |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202210263763.XA CN114591364B (en) | 2022-03-15 | 2022-03-15 | Synthesis method of thiophosphonate compound |
Publications (2)
Publication Number | Publication Date |
---|---|
CN114591364A CN114591364A (en) | 2022-06-07 |
CN114591364B true CN114591364B (en) | 2023-11-14 |
Family
ID=81817619
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202210263763.XA Active CN114591364B (en) | 2022-03-15 | 2022-03-15 | Synthesis method of thiophosphonate compound |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN114591364B (en) |
-
2022
- 2022-03-15 CN CN202210263763.XA patent/CN114591364B/en active Active
Non-Patent Citations (2)
Title |
---|
3-芳基磺酰化喹啉衍生物及硫磷酸酯的合成;张亮亮;《中国优秀硕士学位论文全文数据库工程科技I辑》;B014-137 * |
Visible-light-driven multicomponent reactions to access S-alkyl phosphorothioates using elemental sulfur as the sulfur source;Chengming Qu等;《Green Chem.》;第24卷;第4915-4920页,特别是表1,第4916页右栏倒数第11行,第4918页左栏倒数第1段,Scheme 3 * |
Also Published As
Publication number | Publication date |
---|---|
CN114591364A (en) | 2022-06-07 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN109456362B (en) | Novel method for efficiently preparing diaryl methyl substituted organic phosphonate by using P (O) -H compound | |
CA2860493A1 (en) | Process for the asymmetric oxidation of organic compounds with peroxides in the presence of a chiral acid catalyst | |
CN111468191A (en) | Synthetic method of ruthenium carbene catalyst | |
CN114591364B (en) | Synthesis method of thiophosphonate compound | |
CN110229187B (en) | Method for preparing alkyl phosphonyl compound from peroxide | |
CN111187298B (en) | C2-phosphono methylene indole compound and preparation method and application thereof | |
CN108948077A (en) | A kind of the a-amino acid esters compound and its synthetic method of α-phosphorylated | |
CN116199713A (en) | Chiral alpha-aminophosphonic acid derivative and preparation method thereof | |
US6627758B2 (en) | Compositions and methods for hydration of terminal alkynes | |
JPS603317B2 (en) | Method for producing chlorinated phosphite | |
US4094873A (en) | Process for preparing phosphorothioates and phenylphosphonothioates | |
US11891409B2 (en) | Trifluoromethyl alkenylphosphonate and preparation method therefor | |
CN107226829B (en) | Preparation method of ferrocenyl-group-containing phosphine oxide ligand | |
CN117700455A (en) | Carbon-phosphorus (C-P) coupling reactions involving alkylsilyl peroxides | |
US6407290B2 (en) | Process for the production of substituted 10-chloro-phenoxaphosphines or 10-bromo-phenoxaphosphines | |
Savignac et al. | Homoallylic Phosphonates: Useful Precursors for 3, 4-Epoxyalkanephosphonates | |
CN115490732B (en) | Synthesis method of chiral biphenyl diol catalyst | |
CN114805430B (en) | Preparation method of selenophosphide and thiophosphoride | |
CN112724060B (en) | Novel process for producing prostaglandin and intermediate | |
CN110256489B (en) | Preparation method of alkyl phosphonyl | |
CN113292599B (en) | Benzylphosphine oxide compound and preparation method and application thereof | |
CN110330526B (en) | Green synthesis method of thiophosphite | |
US4028439A (en) | Process for preparing phosphorothioates and phenylphosphonothioates | |
FI86732B (en) | FOERFARANDE FOER FRAMSTAELLNING AV O-ALKYL-S, S-DIALKYLFOSFORDITIOATER. | |
CN115651017A (en) | Method for selectively preparing benzyl or alkyl phosphine oxide compound based on benzyl thioether derivative |
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 |