CN116947685A - Method for synthesizing N, N-diaryl-O-allylhydroxylamine compound from nitroarene - Google Patents
Method for synthesizing N, N-diaryl-O-allylhydroxylamine compound from nitroarene Download PDFInfo
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- 229910052757 nitrogen Inorganic materials 0.000 title claims abstract description 37
- 238000000034 method Methods 0.000 title claims abstract description 22
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 7
- 238000006243 chemical reaction Methods 0.000 claims abstract description 44
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 19
- 239000003054 catalyst Substances 0.000 claims abstract description 17
- 238000001308 synthesis method Methods 0.000 claims abstract description 15
- 239000002243 precursor Substances 0.000 claims abstract description 12
- 239000003999 initiator Substances 0.000 claims abstract description 8
- 229910052751 metal Inorganic materials 0.000 claims abstract description 8
- 239000002184 metal Substances 0.000 claims abstract description 8
- YHLVIDQQTOMBGN-UHFFFAOYSA-N methyl prop-2-enyl carbonate Chemical compound COC(=O)OCC=C YHLVIDQQTOMBGN-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229910052763 palladium Inorganic materials 0.000 claims abstract description 7
- 239000002994 raw material Substances 0.000 claims abstract description 6
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 claims abstract description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 30
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 24
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
- 239000003960 organic solvent Substances 0.000 claims description 14
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 claims description 12
- 239000003480 eluent Substances 0.000 claims description 12
- 239000003208 petroleum Substances 0.000 claims description 12
- 238000010898 silica gel chromatography Methods 0.000 claims description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 10
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 claims description 9
- 238000003786 synthesis reaction Methods 0.000 claims description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 6
- 230000015572 biosynthetic process Effects 0.000 claims description 6
- 238000013375 chromatographic separation Methods 0.000 claims description 6
- 230000035484 reaction time Effects 0.000 claims description 6
- 239000000741 silica gel Substances 0.000 claims description 6
- 229910002027 silica gel Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- XBHPFCIWRHJDCP-UHFFFAOYSA-N (2-trimethylsilylphenyl) trifluoromethanesulfonate Chemical group C[Si](C)(C)C1=CC=CC=C1OS(=O)(=O)C(F)(F)F XBHPFCIWRHJDCP-UHFFFAOYSA-N 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 4
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 claims description 4
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 claims description 4
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 claims description 4
- 238000001816 cooling Methods 0.000 claims description 3
- 230000008707 rearrangement Effects 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 2
- 101150003085 Pdcl gene Proteins 0.000 claims description 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims description 2
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 235000003270 potassium fluoride Nutrition 0.000 claims description 2
- 239000011698 potassium fluoride Substances 0.000 claims description 2
- 235000013024 sodium fluoride Nutrition 0.000 claims description 2
- 239000011775 sodium fluoride Substances 0.000 claims description 2
- 238000004809 thin layer chromatography Methods 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 6
- 239000007800 oxidant agent Substances 0.000 abstract description 5
- 230000009471 action Effects 0.000 abstract description 4
- 239000002360 explosive Substances 0.000 abstract description 3
- 231100000331 toxic Toxicity 0.000 abstract description 3
- 230000002588 toxic effect Effects 0.000 abstract description 3
- 230000001590 oxidative effect Effects 0.000 abstract description 2
- 239000007858 starting material Substances 0.000 abstract 1
- -1 allyl halide Chemical class 0.000 description 15
- 230000003078 antioxidant effect Effects 0.000 description 9
- 239000003963 antioxidant agent Substances 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 239000004743 Polypropylene Substances 0.000 description 7
- 229920001155 polypropylene Polymers 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 5
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- BGYHLZZASRKEJE-UHFFFAOYSA-N [3-[3-(3,5-ditert-butyl-4-hydroxyphenyl)propanoyloxy]-2,2-bis[3-(3,5-ditert-butyl-4-hydroxyphenyl)propanoyloxymethyl]propyl] 3-(3,5-ditert-butyl-4-hydroxyphenyl)propanoate Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(CCC(=O)OCC(COC(=O)CCC=2C=C(C(O)=C(C=2)C(C)(C)C)C(C)(C)C)(COC(=O)CCC=2C=C(C(O)=C(C=2)C(C)(C)C)C(C)(C)C)COC(=O)CCC=2C=C(C(O)=C(C=2)C(C)(C)C)C(C)(C)C)=C1 BGYHLZZASRKEJE-UHFFFAOYSA-N 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 238000001746 injection moulding Methods 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- KLYCPFXDDDMZNQ-UHFFFAOYSA-N Benzyne Chemical compound C1=CC#CC=C1 KLYCPFXDDDMZNQ-UHFFFAOYSA-N 0.000 description 2
- CKRZKMFTZCFYGB-UHFFFAOYSA-N N-phenylhydroxylamine Chemical compound ONC1=CC=CC=C1 CKRZKMFTZCFYGB-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 238000001125 extrusion Methods 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000006462 rearrangement reaction Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- BNUHAJGCKIQFGE-UHFFFAOYSA-N Nitroanisol Chemical compound COC1=CC=C([N+]([O-])=O)C=C1 BNUHAJGCKIQFGE-UHFFFAOYSA-N 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 150000001412 amines Chemical group 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- LJCIZJORSSYKKN-UHFFFAOYSA-N n-(4-methoxyphenyl)hydroxylamine Chemical compound COC1=CC=C(NO)C=C1 LJCIZJORSSYKKN-UHFFFAOYSA-N 0.000 description 1
- VXLKMBJKPFLBNX-UHFFFAOYSA-N n-methoxy-n-phenylhydroxylamine Chemical compound CON(O)C1=CC=CC=C1 VXLKMBJKPFLBNX-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000010525 oxidative degradation reaction Methods 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 229920000098 polyolefin Polymers 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- MKAUETBYNMSKAN-UHFFFAOYSA-N trimethyl-[2-(trifluoromethyl)phenyl]silane Chemical group C[Si](C)(C)C1=CC=CC=C1C(F)(F)F MKAUETBYNMSKAN-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C239/00—Compounds containing nitrogen-to-halogen bonds; Hydroxylamino compounds or ethers or esters thereof
- C07C239/08—Hydroxylamino compounds or their ethers or esters
- C07C239/20—Hydroxylamino compounds or their ethers or esters having oxygen atoms of hydroxylamino groups etherified
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for synthesizing N, N-diaryl-O-allylhydroxylamine compounds from nitroaromatics, which has the following structural general formula:
Description
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a method for synthesizing N, N-diaryl-O-allylhydroxylamine compounds from nitroaromatics.
Background
N, N-disubstituted-O-allylhydroxylamine compounds are important chemical products, and are usually used as antioxidant stabilizers for organic high polymer materials (such as polyolefin, polyester, polyurethane and elastic polymers) due to good antioxidant activity.
At present, the synthesis of the compounds mainly comprises the following two methods: (1) The first method is that allyl halide and secondary amine are subjected to nucleophilic substitution reaction to prepare a trisubstituted allylamine compound, then N-allyltertiary amine oxynitride is prepared under a strong oxidant, and a rearrangement reaction is performed under a high temperature condition to prepare an N, N-disubstituted-O-allylhydroxylamine compound; (2) The second method is to prepare an N, N-disubstituted-O-allylhydroxylamine compound by nucleophilic substitution reaction of the corresponding hydroxylamine, usually N, N-disubstituted hydroxylamine, with an allylic halide under the action of a strong base.
The two methods have obvious defects: (1) The strong oxidizing agent used in the first method comprises SeO 2 The application range of the method is limited due to the adoption of the extremely toxic compounds, and more side reactions occur due to the higher reaction temperature; (2) The second method has low commercial N, N-disubstituted hydroxylamine content, expensive raw materials and strong alkaline reaction system limits the compatibility of functional groups, and the synthesis chemist seldom selects the method for synthesizing the compounds.
In recent years, studies have shown that N, N-diaryl-O-allylhydroxylamine compounds are useful as antibacterial and anti-inflammatory agents in addition to having better oxidation resistance. However, no report is currently made on the synthesis of such compounds, particularly N, N-asymmetric diaryl-O-allylhydroxylamines.
In view of the defects of the two common synthesis methods, the development of a novel synthesis method with high efficiency, convenience and low cost has higher practical value.
Disclosure of Invention
The invention aims to provide a method for synthesizing N, N-diaryl-O-allylhydroxylamine compounds from nitroaromatics, which can effectively avoid the use of toxic and harmful explosive strong oxidants and solve the problems of limited sources or high price of raw materials, harsh reaction conditions, low reaction selectivity and the like in the existing synthesis method.
The invention adopts the following technical scheme for realizing the purpose:
the structural general formula of the N, N-diaryl-O-allylhydroxylamine compound is as follows:
wherein R is 1 、R 2 Each independently selected from hydrogen, fluoro, methyl, methoxy or acetyl.
The invention also provides a synthesis method of the N, N-diaryl-O-allylhydroxylamine compound, wherein the reaction formula is as follows:
the synthesis method comprises the following specific steps:
step 1, dissolving nitroarene in a first organic solvent, placing the first organic solvent in a high-pressure reaction kettle, and introducing H in the presence of a supported metal catalyst 2 Heating and reacting under stirring; after the reaction is finished, cooling to room temperature, filtering, concentrating under reduced pressure, and separating by silica gel column chromatography to obtain N-aryl hydroxylamine I;
step 2, dissolving N-aryl hydroxylamine I, allyl methyl carbonate and a palladium catalyst in a second organic solvent, and carrying out reaction under the protection of nitrogen, wherein a TLC (thin layer chromatography) plate tracks the reaction progress; concentrating under reduced pressure after the reaction is finished, and separating by silica gel column chromatography to obtain N-aryl-N-allylhydroxylamine II;
and 3, under the protection of nitrogen, taking N-aryl-N-allylhydroxylamine II and aryne precursors as raw materials, taking fluoride as an initiator, dissolving in a third organic solvent, reacting at room temperature, carrying out [2,3] -sigma rearrangement on an allylamine oxide zwitterionic intermediate, and separating by silica gel column chromatography after the reaction is finished to obtain the N, N-diaryl-O-allylhydroxylamine compound III.
Further, the supported metal catalyst in the step 1 is one of Ru-WOx/HZSM-5 and Ru-WOx/HAP, preferably Ru-WOx/HAP.
Further, in step 1: introducing H 2 To a pressure of 0.4-1.2MPa, preferably 0.8MPa; the first organic solvent is tetrahydrofuran or acetone, preferably tetrahydrofuran; the temperature of the heating reaction is 40-80 ℃, the reaction time is 4-8 hours, and the reaction is preferably carried out at 60 ℃ for 5 hours; the ratio of nitroarene to supported metal catalyst was 1mol:5-15mg, preferably 1mol:10mg; eluent V for silica gel column chromatographic separation Petroleum ether ：V Acetic acid ethyl ester 1 to 10:1, preferably 5:1.
further, in step 2: the palladium catalyst is Pd (PPh) 3 ) 4 、PdCl 2 Or Pd (CH) 3 COO) 2 Preferably Pd (PPh) 3 ) 4 The method comprises the steps of carrying out a first treatment on the surface of the The second organic solvent is tetrahydrofuran, acetone or acetonitrile, preferably tetrahydrofuran; the reaction temperature is 20-40 ℃, the reaction time is 1-3 hours, and the reaction is preferably carried out at 25 ℃ for 2 hours; eluent V for silica gel column chromatographic separation Petroleum ether ：V Acetic acid ethyl ester 5 to 20:1, preferably 10:1.
further, in step 2, the N-aryl hydroxylamine I: allyl methyl carbonate: the molar ratio of the palladium catalyst is 1:1-2:0.01-0.05, preferably 1:1.2:0.01.
further, in step 3: the initiator is one of sodium fluoride, potassium fluoride, cesium fluoride and tetrabutylammonium fluoride, preferably cesium fluoride; the aryne precursor is 2- (trimethylsilyl) phenyl trifluoromethane sulfonateAcid salts or R 2 Substituted 2- (trimethylsilyl) phenyl trifluoromethane sulfonate; the third organic solvent is one of tetrahydrofuran, acetonitrile, dichloroethane and N, N-dimethylformamide, preferably acetonitrile; the reaction time at room temperature is 4-12 hours, preferably at 40 ℃ for 6 hours; eluent V for silica gel column chromatographic separation Petroleum ether ：V Acetic acid ethyl ester 10 to 100:1, preferably 80:1.
further, in step 3, N-aryl-N-allylhydroxylamine II: aryne precursor: the molar ratio of the initiator is 1:1-2:1-3, preferably 1:1.2:2.4.
further, the reaction mechanism of step 3 is as follows:
aryne is generated in situ from aryne precursor A under the initiation of fluoride (such as CsF), then nitrogen with stronger nucleophilicity in N-aryl-N-allylhydroxylamine II attacks aryne to obtain aryl anion B, active hydrogen on ortho-oxygen is extracted from generated aryl anion, similar allylamine oxygen zwitterionic intermediate C is generated, and finally [2,3] -sigma rearrangement reaction is carried out at room temperature to obtain the expected product N, N-diaryl-O-allylhydroxylamine III.
Compared with the prior art, the invention has the beneficial effects that:
1. the method has the advantages of high yield, simple post-treatment, suitability for various substrates substituted by functional groups, recycling of the supported metal catalyst for multiple times, and great improvement of the practicability of the method.
2. The aryne precursor generates aryne in situ under the action of an initiator (such as CsF), and can react with N-aryl-N-allylhydroxylamine at room temperature due to the high reactivity of aryne, and the target compound is synthesized through [2,3] -sigma rearrangement of allylamine oxygen zwitterionic intermediate. The reaction is carried out at room temperature, the reaction selectivity is good, the side reaction is less, the reaction yield is higher, and the applicability of the reaction substrate is wider.
3. According to the invention, the N, N-asymmetric diaryl-O-allylhydroxylamine compound is synthesized for the first time by selecting nitroarene containing different substituents and aryne precursors, so that the substrate range of the N, N-disubstituted-O-allylhydroxylamine compound is expanded, and a wider material source is provided for application research of the compound.
4. The synthesis method can effectively avoid the use of toxic and harmful explosive strong oxidants, solves the problems of limited sources or high price of raw materials, harsh reaction conditions, low reaction selectivity and the like in the existing synthesis method, and provides a new idea for developing N, N-diaryl-O-allylhydroxylamine compounds.
Drawings
FIG. 1 is a schematic illustration of N, N-diphenyl-O-allylhydroxylamine prepared in example 1 1 HNMR spectra.
FIG. 2 is a schematic illustration of N, N-diphenyl-O-allylhydroxylamine prepared in example 1 13 CNMR spectra.
FIG. 3 is a schematic illustration of N- (4-methoxyphenyl) -N-phenyl-O-allylhydroxylamine prepared in example 2 1 HNMR spectra.
FIG. 4 is a schematic illustration of N- (4-methoxyphenyl) -N-phenyl-O-allylhydroxylamine prepared in example 2 13 CNMR spectra.
Detailed Description
The following is merely illustrative and explanatory of the principles of the invention, as it would be apparent to those skilled in this art that various modifications or additions may be made to the specific embodiments described or in a similar manner without departing from the principles of the invention or beyond the scope of the claims.
Example 1
A synthesis method of N, N-diphenyl-O-allyl hydroxylamine comprises the following steps:
step 1, nitrobenzene is taken(1.23 g,10 mmol), 100mgRu-WOx/HAP catalyst and 20mL tetrahydrofuran were added to the autoclave, and the mixture was stirred at 60℃for 5 hours while charging hydrogen to 0.8 MPa. After the completion of the reaction, the mixture was cooled to room temperature, saturated brine was poured into the reaction mixture, the mixture was extracted with diethyl ether, the combined organic phases were dried over anhydrous sodium sulfate, and the mixture was subjected to spin-drying and then separation by silica gel column chromatography (eluent V) Petroleum ether ：V Acetic acid ethyl ester 5:1) to give the product N-phenylhydroxylamine (yellow solid, 0.92g, 84% yield).
Step 2, N-phenylhydroxylamine (0.55 g,5 mmol), allyl methyl carbonate (0.70 g,6 mmol) and tetrakis (triphenylphosphine) palladium (57.8 mg,0.05 mmol) were dissolved in tetrahydrofuran, and after three nitrogen charges, the reaction was stirred at room temperature for 2 hours, and then stopped. After the reaction, silica gel column chromatography (eluent V) Petroleum ether ：V Acetic acid ethyl ester 10:1) to give N-phenyl-N-allylhydroxylamine (colorless oil, 0.65g, 87% yield).
Step 3, cesium fluoride (1.46 g,9.6 mmol) was added to a reaction flask containing magneton under nitrogen protection, then N-phenyl-N-allylhydroxylamine (0.60 g,4 mmol) was added respectively, anhydrous acetonitrile (20 mL), a benzyne precursor (i.e., 2- (trimethylsilyl) phenyltrifluoromethane sulfonate) (1.43 g,4.8 mmol) was reacted at room temperature for 6 hours, and cooled to room temperature for silica gel column chromatography (eluent V) Petroleum ether ：V Acetic acid ethyl ester 80:1) to give N, N-diphenyl-O-allylhydroxylamine (pale yellow oil, 0.80g, 89% yield).
The product is characterized by nuclear magnetic resonance spectrum, and the data are as follows:
1 HNMR(400MHz,CDCl 3 )δ7.31(t,J＝7.5Hz,4H),7.20–7.05(m,6H),6.04(dq,J＝11.4,6.0Hz,1H),5.34(d,J＝17.2Hz,1H),5.24(d,J＝10.4Hz,1H),4.44(d,J＝5.9Hz,2H)； 13 CNMR(100MHz,CDCl 3 )δ148.65,133.39,128.88,124.32,120.94,118.80,74.63。
example 2
Synthesis method of N- (4-methoxyphenyl) -N-phenyl-O-allylhydroxylamine
Step 1, p-methoxynitrobenzene (1.53 g,10 mmol), 100mgRu-WOx/HAP catalyst and 20mL tetrahydrofuran are taken and added into a high-pressure reaction kettle, hydrogen is filled to 0.8MPa, and stirring reaction is carried out at 60 ℃ for 5 hours. After the completion of the reaction, the mixture was cooled to room temperature, saturated brine was poured into the reaction mixture, the mixture was extracted with diethyl ether, the combined organic phases were dried over anhydrous sodium sulfate, and the mixture was subjected to spin-drying and then separation by silica gel column chromatography (eluent V) Petroleum ether ：V Acetic acid ethyl ester 5:1) to give the product N-methoxyphenyl hydroxylamine (yellow solid, 1.10g, 79% yield).
Step 2, N-p-methoxyphenyl hydroxylamine (0.70 g,5 mmol), allyl methyl carbonate (0.70 g,6 mmol) and tetrakis (triphenylphosphine) palladium (57.8 mg,0.05 mmol) were dissolved in tetrahydrofuran, and after three times of nitrogen charging, the reaction was stirred at room temperature for 2 hours, and then stopped. After the reaction, silica gel column chromatography (eluent V) Petroleum ether ：V Acetic acid ethyl ester 10:1) to give N-p-methoxyphenyl-N-allylhydroxylamine (yellow oil, 0.82g, 92% yield) in 92%.
Step 3, cesium fluoride (1.46 g,9.6 mmol) was added to a reaction flask containing magneton under nitrogen protection, followed by N-methoxyphenyl-N-allylhydroxylamine (0.72 g,4 mmol), anhydrous acetonitrile (20 mL), a benzyne precursor (i.e., 2- (trimethylsilicon) phenyltrifluoromethane sulfonate) (1.43 g,4.8 mmol), and reacted at room temperature for 6 hours, cooled to room temperature and subjected to silica gel column chromatography (eluent V) Petroleum ether ：V Acetic acid ethyl ester 80:1) to give N- (4-methoxyphenyl) -N-phenyl-O-allylhydroxylamine (colorless oil, 1.01g, 99% yield).
The product is characterized by nuclear magnetic resonance spectrum, and the data are as follows:
1 HNMR(400MHz,CDCl 3 )δ7.18–7.09(m,4H),6.87(dd,J＝7.2,5.0Hz,2H),6.75(t,J＝8.4Hz,3H),5.93(ddt,J＝15.4,10.0,4.9Hz,1H),5.25(dd,J＝17.2,1.6Hz,1H),5.15(dd,J＝10.3,1.5Hz,1H),4.28(dd,J＝3.3,1.6Hz,2H),3.80(s,3H)； 13 CNMR(100MHz,CDCl 3 )δ151.76,137.50,133.46,129.30,128.88,128.20,127.37,122.54,118.14,117.12,74.74,63.75.
example 3
1g of antioxidant and 1kg of polypropylene powder are taken to be premixed in a plastic bag, and then fully mixed by a high-speed mixer, and the mixture is represented by different numbers according to different antioxidants. Then extruding and granulating on a single screw extruder, wherein the rotation speed of a main screw is 60r/min, and the temperatures of all areas of the extruder are 180 ℃, 210 ℃, 220 ℃ and 180 ℃ respectively. Drying at 80 ℃ for 4 hours after granulation, and carrying out injection molding sample preparation, wherein the injection molding temperature is 220 ℃, the injection molding time is 18s, the holding pressure is 30MPa, and the cooling time is 13s.
Wherein, 0# is a sample to which no antioxidant was added, 1# is a sample to which commercially available antioxidant 1010 was added, 2# is a sample to which N, N-diphenyl-O-allylhydroxylamine prepared in example 1 was added, and 3# is a sample to which N- (4-methoxyphenyl) -N-phenyl-O-allylhydroxylamine prepared in example 2 was added.
Melt flow rate test: melt flow rate was measured according to GB/T3682.1-2018. Nitrogen is introduced before testing, after the temperature is raised to 230 ℃, the constant time is 0.5h, a weight of 2.16kg is set, about 4g of sample is taken for testing, the sample is cut every 5 seconds, the total cutting time is 5 times, the weighing calculation is carried out, the average value is taken, and the cycle is 5 times. The test results are shown in Table 1.
TABLE 1
The relative change of the melt flow rate of the polypropylene between the first extrusion and the fifth extrusion shows that after the allylhydroxylamine antioxidant is added, the melt flow rates of the test samples No. 2 and No. 3 are lower than that of a blank, so that the allylhydroxylamine antioxidants can protect the polypropylene from oxidative degradation in the high-temperature processing process, and the antioxidant effect of the two allylhydroxylamines is equivalent to that of the polypropylene antioxidant 1010 commonly used in the current market.
Mechanical property test: the tensile properties of the materials were tested according to GB/T1040-1992, and the tensile strength and elongation at break of polypropylene were tested using an electronic universal tester at a tensile rate of 50mm/min. The test results are shown in Table 2.
TABLE 2
From the above table, the tensile strength and elongation at break of the pure polypropylene are smaller, and the mechanical properties of the polypropylene are improved to different degrees after the allylhydroxylamine antioxidant is added, and the antioxidant is equivalent to the antioxidant effect of the common antioxidant 1010.
The foregoing is illustrative only and is not intended to limit the present invention, and any modifications, equivalents, improvements and modifications falling within the spirit and principles of the invention are intended to be included within the scope of the present invention.
Claims (8)
1. An N, N-diaryl-O-allylhydroxylamine compound is characterized by having the following structural general formula:
wherein R is 1 、R 2 Each independently selected from hydrogen, fluoro, methyl, methoxy or acetyl.
2. A method for synthesizing an N, N-diaryl-O-allylhydroxylamine compound according to claim 1, wherein the reaction formula is as follows:
in the reaction, R 1 、R 2 The same as claim 1;
the synthesis method comprises the following specific steps:
step 1, dissolving nitroarene in a first organic solvent, placing the first organic solvent in a high-pressure reaction kettle, under the existence of a supported metal catalyst,introducing H 2 Heating and reacting under stirring; after the reaction is finished, cooling to room temperature, filtering, concentrating under reduced pressure, and separating by silica gel column chromatography to obtain N-aryl hydroxylamine I;
step 2, dissolving N-aryl hydroxylamine I, allyl methyl carbonate and a palladium catalyst in a second organic solvent, and carrying out reaction under the protection of nitrogen, wherein a TLC (thin layer chromatography) plate tracks the reaction progress; concentrating under reduced pressure after the reaction is finished, and separating by silica gel column chromatography to obtain N-aryl-N-allylhydroxylamine II;
and 3, under the protection of nitrogen, taking N-aryl-N-allylhydroxylamine II and aryne precursors as raw materials, taking fluoride as an initiator, dissolving in a third organic solvent, reacting at room temperature, carrying out [2,3] -sigma rearrangement on an allylamine oxide zwitterionic intermediate, and separating by silica gel column chromatography after the reaction is finished to obtain the N, N-diaryl-O-allylhydroxylamine compound III.
3. The synthesis method according to claim 2, characterized in that: the supported metal catalyst in the step 1 is one of Ru-WOx/HZSM-5 and Ru-WOx/HAP.
4. The method of synthesis according to claim 2, wherein in step 1: introducing H 2 To a pressure of 0.4-1.2MPa; the first organic solvent is tetrahydrofuran or acetone; the temperature of the heating reaction is 40-80 ℃ and the reaction time is 4-8h; the ratio of nitroarene to supported metal catalyst was 1mol:5-15mg; eluent V for silica gel column chromatographic separation Petroleum ether ：V Acetic acid ethyl ester 1 to 10:1.
5. the method of synthesis according to claim 2, wherein in step 2: the palladium catalyst is Pd (PPh) 3 ) 4 、PdCl 2 Or Pd (CH) 3 COO) 2 The method comprises the steps of carrying out a first treatment on the surface of the The second organic solvent is tetrahydrofuran, acetone or acetonitrile; the reaction temperature is 20-40 ℃ and the reaction time is 1-3h; eluent V for silica gel column chromatographic separation Petroleum ether ：V Acetic acid ethyl ester 5 to 20:1.
6. the synthesis method according to claim 2, characterized in that: in step 2, the N-arylhydroxylamine I: allyl methyl carbonate: the molar ratio of the palladium catalyst is 1:1-2:0.01-0.05.
7. The method of synthesis according to claim 2, wherein in step 3: the initiator is one of sodium fluoride, potassium fluoride, cesium fluoride and tetrabutylammonium fluoride; the aryne precursor is 2- (trimethylsilyl) phenyl trifluoro methane sulfonate or R 2 Substituted 2- (trimethylsilyl) phenyl trifluoromethane sulfonate; the third organic solvent is one of tetrahydrofuran, acetonitrile, dichloroethane and N, N-dimethylformamide; the reaction time at room temperature is 4-12 hours; eluent V for silica gel column chromatographic separation Petroleum ether ：V Acetic acid ethyl ester 10 to 100:1.
8. the synthesis method according to claim 2, characterized in that: in step 3, N-aryl-N-allylhydroxylamine II: aryne precursor: the molar ratio of the initiator is 1:1-2:1-3.
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