CN107011133A - The method that a kind of benzyl position C H keys are direct oxidation into ketone - Google Patents

The method that a kind of benzyl position C H keys are direct oxidation into ketone Download PDF

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CN107011133A
CN107011133A CN201710381003.8A CN201710381003A CN107011133A CN 107011133 A CN107011133 A CN 107011133A CN 201710381003 A CN201710381003 A CN 201710381003A CN 107011133 A CN107011133 A CN 107011133A
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ketone
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CN107011133B (en
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康彦彪
刘杰
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University of Science and Technology of China USTC
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
    • C07C45/32—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with molecular oxygen
    • C07C45/33—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with molecular oxygen of CHx-moieties
    • C07C45/34—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with molecular oxygen of CHx-moieties in unsaturated compounds
    • C07C45/36—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with molecular oxygen of CHx-moieties in unsaturated compounds in compounds containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
    • C07C201/06—Preparation of nitro compounds
    • C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C253/00—Preparation of carboxylic acid nitriles
    • C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C46/00—Preparation of quinones
    • C07C46/02—Preparation of quinones by oxidation giving rise to quinoid structures
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/28—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/29—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group by introduction of oxygen-containing functional groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/30—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom
    • C07D211/32—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
    • C07D213/46—Oxygen atoms
    • C07D213/50—Ketonic radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/22—Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom

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

Abstract

The invention discloses the method that a kind of benzyl position C H keys are direct oxidation into ketone, it is characterized in using the fragrant ethyl class compound of nitrous acid ester catalysis oxidation, using radical initiator and nitrous acid ester concerted catalysis system, use non-metallic catalyst and the catalyst system and catalyzing of oxygen, make the oxidation of the C H keys of the aryl side chains of free radical activation, it is simple to operate, react with petrol ether/ethyl acetate by volume 50~1:1 obtains target product as eluant, eluent, column chromatography for separation.Catalyst system and catalyzing in the present invention uses oxygen as oxygen source, and Atom economy is high.The present invention is non-metal catalyst system, for avoiding the metal residual in synthetic drug from providing a kind of new method.The present invention can be with the double ethylaromatics of selective oxidation into single ketones and diketone for double ethylaromatics.Take the inventive method to efficiently synthesize neuroleptic agent lenperone, a kind of new method is provided for the synthesis of lenperone.

Description

A kind of method that benzyl position C-H key is direct oxidation into ketone
Technical field
The invention belongs to be catalyzed fragrant ethyl synthesis ketone compounds technical field, and in particular to aryl side chains c h bond is direct It is oxidized to the method for ketone.
Background technology
Acyl group generally existing in organic synthesis intermediate and medicine class compound, therefore the direct oxygen of aryl side chains c h bond The reaction of chemical conversion ketone is in chemical industry especially in the field such as pharmacy extensive application.Traditional aryl side chains c h bond is direct oxidation into The method of ketone makes potassium permanganate or potassium bichromate be realized under conditions of harsh, and its byproduct is more, and has two sides Oxidation can not be selectively controlled during chain.Development uses transition metal as catalyst in recent years, because of high Transition metal complexes Thing oxidant limits it in industry and the large-scale application of pharmacy industry plus the residual of metal.Although non-metallic catalyst exists This field also obtains certain development, but unstable peroxide oxidant must be excessively used and limits its hair Exhibition, while the use of excessive oxidant, which limits its method, can not realize selectivity control oxidation.So far, using nonmetallic as urging Agent, oxygen or air aoxidize aryl c h bond and selectivity control oxidation there is still a need for development better method as oxygen source
According to《JACS》A kind of c h bond oxygen that (J.Am.Chem.Soc., 2002,124,2245-2258) is introduced The method of chemical conversion ketone is the IBX with 3 equivalents as oxidant, fluorobenzene/dimethyl sulfoxide (v:V=2:1,3mL) as solvent, 1- phenyl butanes and the like are aoxidized at 85 DEG C, after reacting 12 hours, phenyl propyl ketone and the like are obtained, yield is 70- 80%.Although this method avoids using transition metal, for drawing electron substituent group substrate then to realize conversion.
According to the U.S.《Organic bulletin》A kind of c h bond that (Org.Lett., 2005,7,5167-5170) is introduced is oxidized to ketone Method, is the Rh with 1.0mol%2(cap)4It is used as catalyst, the K of 0.5 equivalent2CO3, the TBHP of 5.0 equivalents, DCM is as molten Agent, after 1 hour of room temperature reaction, obtains acetophenone analog, yield is 30-92%.It the method use the rhodium metal of costliness Catalyst, and largely use unstable peroxide TBHP so that the selective oxidation of single ketones and diketone can be realized, still Selectivity is bad.
According to《German applied chemistry》A kind of c h bond that (Angew.Chem.Int.Ed., 2012,51,2745-2748) is introduced The method of ketone is oxidized to, is the FeCl with 10mol%2·4H2O as catalyst, DMSO as solvent, oxygen as oxidant, Add the AcOH of 1 equivalent, 2- benzyl pyridines and the like aoxidized at 100 DEG C, after 24 hours of reaction, obtain phenyl- 2- pyridine radicals ketones and the like, yield is 59-83%.This method, as oxygen source, but uses metal although with oxygen Catalyst.
According to the U.S.《Organic bulletin》A kind of pyridine side chain c h bond that (Org.Lett., 2014,16,2050-2053) is introduced The method of ketone is oxidized to, is the Cu (OAc) with 10mol%2·H2O is used as solvent, 1atm oxygen conduct as catalyst, DMA Oxidant, 2- benzyl pyridines are aoxidized at 120 DEG C, after 48 hours of reaction, phenyl -2- pyridine radicals ketones are obtained, yield is 89%.This method, as oxygen source, but uses metallic catalyst although with oxygen.
According to《German applied chemistry》A kind of pyridine that (Angew.Chem.Int.Ed., 2015,54,1261-1265) is introduced The method that the step of side chain c h bond one is oxidized to ketone, is the CuCl with 10mol%2·2H2O is used as catalyst, DMF or Isosorbide-5-Nitrae-dioxy six Ring is as solvent, and chloracetate is as additive, using the method for oxygen ball, the pyridine oxide class compound at 130 DEG C, reaction After 24 hours, highest yield is 92%.This method, as oxygen source, but uses metallic catalyst although with oxygen.
According to the U.S.《Organic bulletin》(Org.Lett., 2015,17,2078-2081) and Chinese patent application CN201510105616.X discloses a kind of method that pyridine side chain c h bond is direct oxidation into ketone, is the H with 5mol%4NI, 10mol% AcOH is used as catalyst, 0.1MPaO2It is solvent-free or air is as oxygen source, the pyridine oxide class chemical combination at 100 DEG C Thing, after reacting 24 hours, highest yield is 97%.This method although with oxygen as oxygen source, it is nonmetal catalyzed under realize Conversion, but pyridine compounds and their can only be done.
According to Britain《Chemical science》(Chem.Sci., 2016,7,346-357) reports the side that a kind of c h bond is oxidized to ketone Method, it with 10mol% CuI is catalyst to be, DMSO adds the AcOH of 1 equivalent as solvent, oxygen as oxidant, 2- benzyl pyridines and the like are aoxidized at 100 DEG C, after 24 hours of reaction, phenyl -2- pyridine radicals ketone are obtained and its similar Thing, yield is 59-83%.This method, as oxygen source, but uses metallic catalyst although with oxygen.
According to Britain《Chemical science》(Chem.Sci., 2017,8,1282-1287) reports a kind of c h bond and is oxidized to ketone Method, is to use 1mol%Co (OAc)2·4H2O is catalyst, and 20mol% NHPI is co-catalyst, BuOAc or BuOAc:pyr (v:V=7:3) as solvent, using the method for oxygen ball, at 90-100 DEG C pyridine oxide class or thiophene-based or imidazoles or Benzimidazole or benzothiazole compound, after reacting 12 hours, highest yield is 94%, and this method is made although with oxygen For oxygen source, but use metallic catalyst.
It can be seen that, prior art uses metallic catalyst mostly, so as to be difficult to avoid the metal residual in synthetic drug.It is excessive Unstable peroxide oxidant, it is impossible to realize the selective oxidation of single ketones and diketone well.
The content of the invention
The purpose of the present invention is to propose to a kind of method that benzyl position C-H key is direct oxidation into ketone, take radical initiator and Nitrous acid ester concerted catalysis system, uses non-metallic catalyst and the catalyst system and catalyzing of oxygen, the c h bond of catalysis oxidation aryl side chains Selectivity control is oxidized to ketone, to overcome the drawbacks described above of prior art.
The method that benzyl position C-H key of the present invention is direct oxidation into ketone, it is characterised in that：In oxygen atmosphere, free radical is drawn Send out agent and nitrous acid ester in molar ratio 0.5:As synergistic catalyst after 1~2 mixing, with the fragrant ethyl class compound containing substituent As substrate, it is 0.5~1 with the fragrant ethyl class compound mole ratio containing substituent to make radical initiator:1, nitrous acid ester with Fragrant ethyl class compound mole ratio containing substituent is 1~2:1, in a solvent in 80-90 DEG C react 24-36h, with petroleum ether/ Ethyl acetate by volume 50~1:1 mixing is as eluant, eluent, and column chromatography for separation obtains target product.
The radical initiator is selected from HP, 1,10- ferrosins, neocuproine, 2,6- bis- Tert .-butylpyridine, 2,2,6,6- tetramethyl piperidine oxides, N- hydroxysuccinimides or N- bromo-succinimides.
The nitrous acid ester is selected from nitrite tert-butyl, nitrous acid benzyl ester, isoamyl nitrite or nitrous ether (ethyl nitrite).
The fragrant ethyl class compound containing substituent is selected from 4- ethylo benzenes methyl ether, acetic acid -4- ethylo benzenes phenolic ester, to ethyl Fluorobenzene, to ethyl chlorobenzene, to ethyl bromobenzene, p nitro ethylbenzene, to trifluoromethyl ethylbenzene, to cyano group ethylbenzene, 1-ethylnaphthalene, propyl group Benzene, 1- phenyl-octanes, tridane, 2- benzyl pyridines, diphenyl methane, 2- ethylpyridines, 3-ethylpyridine, 4- ethyl pyrroles Pyridine, 4- benzyl pyridines, 2 acetyl thiophene, p-diethylbenzene, a diethylbenzene, 1- benzyl -4- ethylo benzenes, 1,2,3,4- tetrahydrochysenes Naphthalene, indane, 1,3- diphenyl propanes, 2,2 '-diethyl -1,1 '-biphenyl or 2,6- parvolines.
The solvent is selected from tetrahydrofuran, dimethyl sulfoxide (DMSO), N,N-dimethylformamide, acetonitrile, ethyl acetate, dichloromethane Alkane or 1,4- dioxane.
The method that benzyl position C-H key of the present invention is direct oxidation into ketone, first using the fragrant ethyl class of nitrous acid ester catalysis oxidation Compound, takes aryl side chains c h bond Direct Catalytic Oxidation into ketone, biotransformation method different from the past.Due to present invention use Radical initiator and nitrous acid ester concerted catalysis system, using non-metallic catalyst and the catalyst system and catalyzing of oxygen, make free radical The oxidation of the c h bond of the aryl side chains of activation, has reacted with petrol ether/ethyl acetate by volume 50~1:1 as eluant, eluent, Column chromatography for separation obtains target product.Because the catalyst system and catalyzing in the present invention uses oxygen as oxygen source, Atom economy is high.This Invention is non-metal catalyst system, and metal catalyst system different from the past is of the invention for avoiding the metal in synthetic drug Residual provides a kind of new method.The present invention can be with the double ethylaromatics of selective oxidation into single ketones and double for double ethylaromatics Ketone, it is simple to operate.Neuroleptic agent lenperone can be efficiently synthesized by taking the method for the present invention, be the synthesis of lenperone There is provided a kind of new method.
Embodiment
Embodiment 1：
AcetanisoleSynthesis
The equivalents of NHPI 0.5 are added in 25mL Schlenk reaction tubes, is dried in vacuo 15 minutes, puts oxygen ball, Acetonitrile 1mL, the equivalent of nitrite tert-butyl 1.0, to ethylo benzene methyl ether 0.5mmol, on reaction tube are sequentially added under oxygen atmosphere Plus being put into after polytetrafluoro plug in oil bath pan, 80 DEG C are reacted 24h.After the completion of reaction, be concentrated under reduced pressure removing solvent acetonitrile, post layer Analysis separation, eluant, eluent is petrol ether/ethyl acetate (v:V=20:1) acetanisole, is obtained.Yield 83%, it is faint yellow Solid；1H NMR(CDCl3,400MHz):δ 7.92 (d, J=9.2Hz, 2H), 6.92 (d, J=8.8Hz, 2H), 3.85 (s, 3H), 2.54(s,3H)；13C NMR(CDCl3,100MHz):δ196.7,163.4,130.5,130.3,113.6,55.4,26.3.
Embodiment 2：
4- acetoxy acetophenonesSynthesis
The equivalents of NHPI 1.0 are added in 25mL Schlenk reaction tubes, is dried in vacuo 15 minutes, puts oxygen ball, Acetonitrile 1mL, the equivalent of nitrite tert-butyl 2.0, to Acetoxvethyl benzene 0.5mmol, in reaction are sequentially added under oxygen atmosphere It is put into after adding polytetrafluoro plug on pipe in oil bath pan, 80 DEG C of reaction 24h.After the completion of reaction, be concentrated under reduced pressure removing solvent acetonitrile, Column chromatography for separation, eluant, eluent is petrol ether/ethyl acetate (v:V=10:1) 4- acetoxy acetophenones, are obtained.Yield 72%, White solid；1H NMR(CDCl3,400MHz):δ 7.96 (d, J=6.8Hz, 2H), 7.16 (d, J=6.8Hz, 2H), 2.56 (s, 3H),2.30(s,3H)；13C NMR(CDCl3,100MHz):δ196.8,168.8,154.2,134.5,129.8,121.7, 26.5,21.0.
Embodiment 3：
To fluoro acetophenoneSynthesis
The equivalents of NHPI 0.5 are added in 25mL Schlenk reaction tubes, is dried in vacuo 15 minutes, puts oxygen ball, Acetonitrile 1mL is sequentially added under oxygen atmosphere, the equivalent of nitrite tert-butyl 1.0, to fluoro ethyl benzene 0.5mmol, adds on reaction tube It is put into after upper polytetrafluoro plug in oil bath pan, 80 DEG C of reaction 24h.After the completion of reaction, be concentrated under reduced pressure removing solvent acetonitrile, column chromatography Separation, eluant, eluent is petrol ether/ethyl acetate (v:V=50:1), obtain to fluoro acetophenone.Yield 78%, faint yellow oil；1H NMR(CDCl3,400MHz):δ 7.96 (dd, J=8.2Hz, 5.4Hz, 2H), 7.10 (t, J=8.4Hz, 2H), 2.56 (s, 3H) ；13C NMR(CDCl3,100MHz):δ 196.4,166.9,164.4,133.5 (d, J=3.0Hz), 130.8 (d, J=9.8Hz), 115.6 (d, J=21.9Hz), 26.4.
Embodiment 4：
ParachloroacetophenoneSynthesis
The equivalents of NHPI 0.5 are added in 25mL Schlenk reaction tubes, is dried in vacuo 15 minutes, puts oxygen ball, Acetonitrile 1mL is sequentially added under oxygen atmosphere, the equivalent of nitrite tert-butyl 1.0, to chloroethyl benzene 0.5mmol, adds on reaction tube It is put into after upper polytetrafluoro plug in oil bath pan, 80 DEG C of reaction 24h.After the completion of reaction, be concentrated under reduced pressure removing solvent acetonitrile, column chromatography Separation, eluant, eluent is petrol ether/ethyl acetate (v:V=50:1) parachloroacetophenone, is obtained.Yield 77%, faint yellow oil；1H NMR(CDCl3,400MHz):δ7.87-7.90(m,2H),7.41-7.44(m,2H),2.58(s,3H)；13C NMR(CDCl3, 100MHz):δ196.8,139.5,135.4,129.7,128.9,26.5.
Embodiment 5：
ParabromoacetophenoneSynthesis
The equivalents of NHPI 0.5 are added in 25mL Schlenk reaction tubes, is dried in vacuo 15 minutes, puts oxygen ball, Acetonitrile 1mL is sequentially added under oxygen atmosphere, the equivalent of nitrite tert-butyl 1.0, to bromo ethyl phenenyl 0.5mmol, adds on reaction tube It is put into after upper polytetrafluoro plug in oil bath pan, 80 DEG C of reaction 24h.After the completion of reaction, be concentrated under reduced pressure removing solvent acetonitrile, column chromatography Separation, eluant, eluent is petrol ether/ethyl acetate (v:V=50:1) parabromoacetophenone, is obtained.Yield 73%, white solid；1H NMR(CDCl3,400MHz):δ 7.81 (d, J=8.8Hz, 2H), 7.59 (d, J=9.2Hz, 2H), 2.58 (s, 3H)；13C NMR (CDCl3,100MHz):δ196.9,135.8,131.9,129.8,128.3,26.5.
Embodiment 6：
1- acetyl group naphthalenesSynthesis
The equivalents of NHPI 0.5 are added in 25mL Schlenk reaction tubes, is dried in vacuo 15 minutes, puts oxygen ball, Acetonitrile 1mL is sequentially added under oxygen atmosphere, the equivalent of nitrite tert-butyl 1.0,1-ethylnaphthalene 0.5mmol is added on reaction tube It is put into after polytetrafluoro plug in oil bath pan, 80 DEG C of reaction 24h.After the completion of reaction, be concentrated under reduced pressure removing solvent acetonitrile, column chromatography point From eluant, eluent is petrol ether/ethyl acetate (v:V=50:1) 1- acetyl group naphthalenes, are obtained.Yield 80%, faint yellow oil；1H NMR (CDCl3,400MHz):δ 8.76 (d, J=8.4Hz, 1H), 7.99 (d, J=8.4Hz, 1H), 7.93 (d, J=7.2Hz, 1H), 7.87 (d, J=8.4Hz, 1H), 7.61 (t, J=7.2Hz, 1H), 7.47-7.55 (m.2H), 2.75 (s, 3H)；13C NMR (CDCl3,100MHz):δ201.8,135.4,133.9,132.9,130.1,128.6,128.3,127.9,126.4,125.9, 124.3,29.9.
Embodiment 7：
PropiophenoneSynthesis
The equivalents of NHPI 0.5 are added in 25mL Schlenk reaction tubes, is dried in vacuo 15 minutes, puts oxygen ball, Acetonitrile 1mL, the equivalent of nitrite tert-butyl 1.0, propylbenzene 0.5mmol, plus poly- on reaction tube are sequentially added under oxygen atmosphere It is put into after tetrafluoro plug in oil bath pan, 80 DEG C of reaction 24h.After the completion of reaction, be concentrated under reduced pressure removing solvent acetonitrile, column chromatography point From eluant, eluent is petrol ether/ethyl acetate (v:V=50:1) propiophenone, is obtained.Yield 83%, faint yellow oil；1H NMR (CDCl3,400MHz):δ 7.95-7.97 (m, 2H), 7.52-7.56 (m, 1H), 7.43-7.47 (m, 2H), 2.99 (q, J= 7.2Hz, 2H), 1.22 (t, J=7.2Hz, 3H)；13C NMR(CDCl3,100MHz):δ200.8,136.8,132.8,128.5, 127.9,31.7,8.2.
Embodiment 8：
Octyl group acyl benzeneSynthesis
The equivalents of NHPI 0.5 are added in 25mL Schlenk reaction tubes, is dried in vacuo 15 minutes, puts oxygen ball, Acetonitrile 1mL is sequentially added under oxygen atmosphere, the equivalent of nitrite tert-butyl 1.0,1- phenyl-octane 0.5mmol add on reaction tube It is put into after upper polytetrafluoro plug in oil bath pan, 80 DEG C of reaction 24h.After the completion of reaction, be concentrated under reduced pressure removing solvent acetonitrile, column chromatography Separation, eluant, eluent is petrol ether/ethyl acetate (v:V=50:1) octyl group acyl benzene, is obtained.Yield 71%, white solid；1H NMR (CDCl3,400MHz):δ 7.96 (d, J=7.2Hz, 2H), 7.55 (t, J=7.4Hz, 1H), 7.45 (t, J=7.6Hz, 2H), 2.96 (t, J=7.6Hz, 2H), 1.70-1.77 (m, 2H), 1.29-1.36 (m, 8H), 0.88 (t, J=6.8Hz, 3H)；13C NMR(CDCl3,100MHz):δ200.6,137.1,132.8,128.5,128.0,38.6,31.7,29.3,29.1,24.3, 22.6,14.0.
Embodiment 9：
Benzene n-tridecane base ketoneSynthesis
The equivalents of NHPI 0.5 are added in 25mL Schlenk reaction tubes, is dried in vacuo 15 minutes, puts oxygen ball, Acetonitrile 1mL is sequentially added under oxygen atmosphere, the equivalent of nitrite tert-butyl 2.0, tridane 0.5mmol adds on reaction tube It is put into after upper polytetrafluoro plug in oil bath pan, 80 DEG C of reaction 24h.After the completion of reaction, be concentrated under reduced pressure removing solvent acetonitrile, column chromatography Separation, eluant, eluent is petrol ether/ethyl acetate (v:V=50:1) benzene n-tridecane base ketone, is obtained.Yield 70%, white solid ；1H NMR(CDCl3,400MHz):δ 7.96 (d, J=7.2Hz, 2H), 7.55 (t, J=7.4Hz, 1H), 7.45 (t, J= 7.6Hz, 2H), 2.96 (t, J=7.6Hz, 2H), 1.69-1.77 (m, 2H), 1.26-1.37 (m, 18H), 0.88 (t, J= 7.0Hz,3H)；13C NMR(CDCl3,100MHz):δ200.6,137.1,132.8,128.5,128.0,38.6,31.9,29.6, 29.4,29.3,24.4,22.7,14.1.
Embodiment 10：
P-nitroacetophenoneSynthesis
The equivalents of NHPI 1.0 are added in 25mL Schlenk reaction tubes, is dried in vacuo 15 minutes, puts oxygen ball, Acetonitrile 1mL is sequentially added under oxygen atmosphere, the equivalent of nitrite tert-butyl 2.0, p nitro ethylbenzene 0.5mmol adds on reaction tube It is put into after upper polytetrafluoro plug in oil bath pan, 90 DEG C of reaction 36h.After the completion of reaction, be concentrated under reduced pressure removing solvent acetonitrile, column chromatography Separation, eluant, eluent is petrol ether/ethyl acetate (v:V=20:1) p-nitroacetophenone, is obtained.Yield 66%, faint yellow color is consolidated Body；1H NMR(400MHz,CDCl3) δ 8.29 (d, J=8.8Hz, 2H), 8.10 (d, J=8.8Hz, 2H), 2.67 (s, 3H)；13C NMR(CDCl3,100MHz):δ196.3,150.3,141.4,129.3,123.8,26.9.
Embodiment 11：
To trifluoromethyl acetophenoneSynthesis
The equivalents of NHPI 1.0 are added in 25mL Schlenk reaction tubes, is dried in vacuo 15 minutes, puts oxygen ball, Acetonitrile 1mL, the equivalent of nitrite tert-butyl 2.0, to trifluoromethyl ethylbenzene 0.5mmol, in reaction tube are sequentially added under oxygen atmosphere It is put into after above adding polytetrafluoro plug in oil bath pan, 90 DEG C of reaction 36h.After the completion of reaction, be concentrated under reduced pressure removing solvent acetonitrile, post Chromatography, eluant, eluent is petrol ether/ethyl acetate (v:V=20:1), obtain to trifluoromethyl acetophenone.Yield 73% is light Yellow solid；1H NMR(CDCl3,400MHz):δ 8.05 (d, J=8.4Hz, 2H), 7.72 (d, J=8.4Hz, 2H), 2.64 (s, 3H)；13C NMR(CDCl3,100MHz):δ 196.9,139.7,134.4 (q, J=32.4Hz), 128.6,125.7 (q, J= 3.9Hz),124.9,122.2,26.7.
Embodiment 12：
4-AcetylbenzonitrileSynthesis
The equivalents of NHPI 1.0 are added in 25mL Schlenk reaction tubes, is dried in vacuo 15 minutes, puts oxygen ball, Acetonitrile 1mL is sequentially added under oxygen atmosphere, the equivalent of nitrite tert-butyl 2.0, to cyano group ethylbenzene 0.5mmol, adds on reaction tube It is put into after upper polytetrafluoro plug in oil bath pan, 90 DEG C of reaction 36h.After the completion of reaction, be concentrated under reduced pressure removing solvent acetonitrile, column chromatography Separation, eluant, eluent is petrol ether/ethyl acetate (v:V=20:1) 4-Acetylbenzonitrile, is obtained.Yield 70%, white solid；1H NMR(CDCl3,400MHz):δ 8.03 (d, J=8.8Hz, 2H), 7.76 (d, J=8.4Hz, 2H), 2.63 (s, 3H)；13C NMR (CDCl3,100MHz):δ196.6,139.8,132.5,128.6,117.9,116.3,26.7.
Embodiment 13：
2- acetylpyridinesSynthesis
The equivalents of NHPI 1.0 are added in 25mL Schlenk reaction tubes, is dried in vacuo 15 minutes, puts oxygen ball, Acetonitrile 1mL is sequentially added under oxygen atmosphere, the equivalent of nitrite tert-butyl 2.0,2- ethylpyridine 0.5mmol add on reaction tube It is put into after upper polytetrafluoro plug in oil bath pan, 90 DEG C of reaction 36h.After the completion of reaction, be concentrated under reduced pressure removing solvent acetonitrile, column chromatography Separation, eluant, eluent is petrol ether/ethyl acetate (v:V=10:1) 2- acetylpyridines, are obtained.Yield 70%, faint yellow oil；1H NMR(CDCl3,400MHz):δ 8.61 (d, J=3.6Hz, 1H), 7.96 (d, J=6.8Hz, 1H), 7.74-7.78 (m, 1H), 7.38-7.42(m,1H),2.66(s,3H)；13C NMR(CDCl3,100MHz):δ199.9,153.4,148.8,136.7, 126.9,121.5,25.6.
Embodiment 14：
3- acetylpyridinesSynthesis
The equivalents of NHPI 1.0 are added in 25mL Schlenk reaction tubes, is dried in vacuo 15 minutes, puts oxygen ball, Acetonitrile 1mL is sequentially added under oxygen atmosphere, the equivalent of nitrite tert-butyl 2.0,3-ethylpyridine 0.5mmol adds on reaction tube It is put into after upper polytetrafluoro plug in oil bath pan, 90 DEG C of reaction 36h.After the completion of reaction, be concentrated under reduced pressure removing solvent acetonitrile, column chromatography Separation, eluant, eluent is petrol ether/ethyl acetate (v:V=10:1) 3- acetylpyridines, are obtained.Yield 66%, faint yellow oil；1H NMR(CDCl3,400MHz):δ 9.05 (s, 1H), 8.67 (d, J=4.8Hz, 1H), 8.12 (d, J=6.0Hz, 1H), 7.32 (t, J=8.0Hz, 1H), 2.53 (s, 3H)；13C NMR(CDCl3,100MHz):δ196.5,153.3,149.7,135.2,123.4, 26.4.
Embodiment 15：
4- acetylpyridinesSynthesis
The equivalents of NHPI 1.0 are added in 25mL Schlenk reaction tubes, is dried in vacuo 15 minutes, puts oxygen ball, Acetonitrile 1mL is sequentially added under oxygen atmosphere, the equivalent of nitrite tert-butyl 2.0,4- ethylpyridine 0.5mmol add on reaction tube It is put into after upper polytetrafluoro plug in oil bath pan, 90 DEG C of reaction 36h.After the completion of reaction, be concentrated under reduced pressure removing solvent acetonitrile, column chromatography Separation, eluant, eluent is petrol ether/ethyl acetate (v:V=10:1) 4- acetylpyridines, are obtained.Yield 64%, brown oil；1H NMR (CDCl3,400MHz):δ 8.76 (d, J=4.0Hz, 2H), 7.67-7.69 (m, 2H), 2.58 (s, 3H)；13C NMR(CDCl3, 100MHz):δ197.2,150.8,142.6,121.1,26.3.
Embodiment 16：
2- acetyl thiophenesSynthesis
The equivalents of NHPI 1.0 are added in 25mL Schlenk reaction tubes, is dried in vacuo 15 minutes, puts oxygen ball, Acetonitrile 1mL is sequentially added under oxygen atmosphere, the equivalent of nitrite tert-butyl 2.0,2 acetyl thiophene 0.5mmol adds on reaction tube It is put into after upper polytetrafluoro plug in oil bath pan, 90 DEG C of reaction 36h.After the completion of reaction, be concentrated under reduced pressure removing solvent acetonitrile, column chromatography Separation, eluant, eluent is petrol ether/ethyl acetate (v:V=20:1) 2- acetyl thiophenes, are obtained.Yield 62%, faint yellow oil；1H NMR(CDCl3,400MHz):δ7.67-7.68(m,1H),7.60-7.62(m,1H),7.09-7.12(m,1H),2.53(s, 3H)；13C NMR(CDCl3,100MHz):δ190.6,144.5,133.7,132.4,128.0,26.8.
Embodiment 17：
2- benzoyl pyridinesSynthesis
The equivalents of NHPI 1.0 are added in 25mL Schlenk reaction tubes, is dried in vacuo 15 minutes, puts oxygen ball, Acetonitrile 1mL is sequentially added under oxygen atmosphere, the equivalent of nitrite tert-butyl 2.0,2- benzyl pyridine 0.5mmol add on reaction tube It is put into after upper polytetrafluoro plug in oil bath pan, 90 DEG C of reaction 36h.After the completion of reaction, be concentrated under reduced pressure removing solvent acetonitrile, column chromatography Separation, eluant, eluent is petrol ether/ethyl acetate (v:V=10:1) 2- benzoyl pyridines, are obtained.Yield 67%, white solid ；1H NMR(CDCl3,400MHz):δ8.70(s,1H),7.99-8.06(m,3H),7.85-7.89(m,1H),7.54-7.57 (m,1H),7.45-7.49(m,3H).13C NMR(CDCl3,100MHz):δ193.7,154.9,148.4,136.9,136.1, 132.8,130.8,128.0,126.0,124.4.
Embodiment 18：
BenzophenoneSynthesis
The equivalents of NHPI 0.5 are added in 25mL Schlenk reaction tubes, is dried in vacuo 15 minutes, puts oxygen ball, Acetonitrile 1mL is sequentially added under oxygen atmosphere, the equivalent of nitrite tert-butyl 1.0, diphenyl-methane 0.5mmol is added on reaction tube It is put into after polytetrafluoro plug in oil bath pan, 80 DEG C of reaction 24h.After the completion of reaction, be concentrated under reduced pressure removing solvent acetonitrile, column chromatography point From eluant, eluent is petrol ether/ethyl acetate (v:V=50:1) benzophenone, is obtained.Yield 90%, white solid；1H NMR (CDCl3,400MHz):δ7.80-7.82(m,4H),7.57-7.62(m,2H),7.46-7.51(m,4H)；13C NMR(CDCl3, 100MHz):δ196.7,137.6,132.4,130.0,128.3.
Embodiment 19：
Lenperone
Synthesis
The equivalents of NHPI 1.0 are added in 25mL Schlenk reaction tubes, is dried in vacuo 15 minutes, puts oxygen ball, Acetonitrile 1mL is sequentially added under oxygen atmosphere, the equivalent of nitrite tert-butyl 2.0, fluorobenzene piperazine butane 0.5mmol adds on reaction tube It is put into after upper polytetrafluoro plug in oil bath pan, 90 DEG C of reaction 36h.After the completion of reaction, be concentrated under reduced pressure removing solvent acetonitrile, column chromatography Separation, eluant, eluent is petrol ether/ethyl acetate (v:V=1:1) lenperone, is obtained.Yield 62%, faint yellow solid；1H NMR(CDCl3, 400MHz) and δ 7.93-8.01 (m, 4H), 7.12 (t, J=8.4Hz, 4H), 3.16-3.23 (m, 1H), 2.91- 3.00 (m, 4H), 2.44 (t, J=7.6Hz, 2H), 2.06-2.15 (m, 2H), 1.95 (t, J=7.0Hz, 2H), 1.75-1.85 (m,4H)；13C NMR(CDCl3,100MHz):δ 201.0,198.5,166.8 (d, J=1.3Hz), 164.3 (d, J=2.0Hz), 132.3 (d, J=2.9Hz), 131.3 (d, J=8.1Hz), 130.8 (d, J=8.7Hz), 130.6 (d, J=9.9Hz), 115.9 (d, J=15.7Hz), 115.8 (d, J=14.3Hz), 57.8,53.1,43.3,36.2,28.6,21.6.
Embodiment 20：
A:The synthesis of 4- ethyl acetophenones
The equivalents of NHPI 0.5 are added in 25mL Schlenk reaction tubes, is dried in vacuo 15 minutes, puts oxygen ball, Acetonitrile 1mL is sequentially added under oxygen atmosphere, the equivalent of nitrite tert-butyl 1.0, p-diethylbenzene 0.5mmol adds on reaction tube It is put into after upper polytetrafluoro plug in oil bath pan, 80 DEG C of reaction 24h.After the completion of reaction, be concentrated under reduced pressure removing solvent acetonitrile, column chromatography Separation, eluant, eluent is petrol ether/ethyl acetate (v:V=50:1) 4- ethyl acetophenones, are obtained.Product yield 82%, it is faint yellow Oil；1H NMR(CDCl3,400MHz):δ 7.90 (d, J=8.0Hz, 2H), 7.29 (d, J=8.8Hz, 2H), 2.72 (q, J= 7.6Hz, 2H), 2.59 (s, 3H), 1.27 (t, J=7.8Hz, 3H)；13C NMR(CDCl3,100MHz):δ197.8,149.9, 134.9,128.5,128.0,28.8,26.4,15.1.
B:The synthesis of 1,4- diacetyl benzenes
The equivalents of NHPI 1.0 are added in 25mL Schlenk reaction tubes, is dried in vacuo 15 minutes, puts oxygen ball, Acetonitrile 1mL is sequentially added under oxygen atmosphere, the equivalent of nitrite tert-butyl 2.0, p-diethylbenzene 0.5mmol adds on reaction tube It is put into after upper polytetrafluoro plug in oil bath pan, 90 DEG C of reaction 36h.After the completion of reaction, be concentrated under reduced pressure removing solvent acetonitrile, column chromatography Separation, eluant, eluent is petrol ether/ethyl acetate (v:V=10:1) Isosorbide-5-Nitrae-diacetyl benzene, is obtained.Product yield 71%, white is solid Body；1H NMR(CDCl3,400MHz):δ8.00(s,4H),2.62(s,6H)；13C NMR(CDCl3,100MHz):δ197.4, 140.1,128.4,26.8.
Embodiment 21：
A:The synthesis of 3- ethyl acetophenones
The equivalents of NHPI 0.5 are added in 25mL Schlenk reaction tubes, is dried in vacuo 15 minutes, puts oxygen ball, Acetonitrile 1mL is sequentially added under oxygen atmosphere, the equivalent of nitrite tert-butyl 1.0, a diethylbenzene 0.5mmol adds on reaction tube It is put into after upper polytetrafluoro plug in oil bath pan, 80 DEG C of reaction 24h.After the completion of reaction, be concentrated under reduced pressure removing solvent acetonitrile, column chromatography Separation, eluant, eluent is petrol ether/ethyl acetate (v:V=50:1) 3- ethyl acetophenones, are obtained.Product yield 80%, it is faint yellow Oil；1H NMR(CDCl3,400MHz):δ 7.77 (t, J=8.0Hz, 2H), 7.35-7.41 (m, 2H), 2.70 (q, J=7.6Hz, 2H), 2.60 (s, 3H), 1.26 (t, J=7.6Hz, 3H)；13C NMR(CDCl3,100MHz):δ198.4,144.7,137.2, 132.7,128.5,127.5,125.8,28.7,26.6,15.4.
B:The synthesis of 1,3- diacetyl benzenes
The equivalents of NHPI 1.0 are added in 25mL Schlenk reaction tubes, is dried in vacuo 15 minutes, puts oxygen ball, Acetonitrile 1mL is sequentially added under oxygen atmosphere, the equivalent of nitrite tert-butyl 2.0, a diethylbenzene 0.5mmol adds on reaction tube It is put into after upper polytetrafluoro plug in oil bath pan, 90 DEG C of reaction 36h.After the completion of reaction, be concentrated under reduced pressure removing solvent acetonitrile, column chromatography Separation, eluant, eluent is petrol ether/ethyl acetate (v:V=10:1) 1,3- diacetyl benzenes, are obtained.Product yield 73%, it is faint yellow Oil；1H NMR(CDCl3,400MHz):δ 8.47 (s, 1H), 8.11 (d, J=7.6Hz, 2H), 7.55 (t, J=7.8Hz, 1H), 2.62(s,6H)；13C NMR(CDCl3,100MHz):δ197.3,137.3,132.4,128.9,127.9,26.4.
Embodiment 22：
A:The synthesis of 4- ethylo benzene ketones
The equivalents of NHPI 0.5 are added in 25mL Schlenk reaction tubes, is dried in vacuo 15 minutes, puts oxygen ball, Acetonitrile 1mL, the equivalent of nitrite tert-butyl 1.0,1- benzyl -4- ethylo benzene 0.5mmol, in reaction tube are sequentially added under oxygen atmosphere It is put into after above adding polytetrafluoro plug in oil bath pan, 80 DEG C of reaction 24h.After the completion of reaction, be concentrated under reduced pressure removing solvent acetonitrile, post Chromatography, eluant, eluent is petrol ether/ethyl acetate (v:V=50:1) 4- ethylo benzene ketones, are obtained.Product yield 73% is light Yellow oil；1H NMR(CDCl3,400MHz):δ 7.74-7.81 (m, 4H), 7.58 (t, J=7.4Hz, 1H), 7.47 (t, J= 7.6Hz, 2H), 7.31 (d, J=8.0Hz, 2H), 2.74 (q, J=7.6Hz, 2H), 1.28 (t, J=7.6Hz, 3H)；13C NMR (CDCl3,100MHz):δ196.5,149.4,137.9,135.0,132.1,130.4,129.9,128.1,127.7,28.9, 15.2.
B:The synthesis of 4- acetyl Benzophenones
The equivalents of NHPI 1.0 are added in 25mL Schlenk reaction tubes, is dried in vacuo 15 minutes, puts oxygen ball, Acetonitrile 1mL, the equivalent of nitrite tert-butyl 2.0,1- benzyl -4- ethylo benzene 0.5mmol, in reaction tube are sequentially added under oxygen atmosphere It is put into after above adding polytetrafluoro plug in oil bath pan, 90 DEG C of reaction 36h.After the completion of reaction, be concentrated under reduced pressure removing solvent acetonitrile, post Chromatography, eluant, eluent is petrol ether/ethyl acetate (v:V=10:1) 4- acetyl Benzophenones, are obtained.Product yield 81% is light Yellow solid；1H NMR(CDCl3,400MHz):δ 8.05 (d, J=8.4Hz, 2H), 7.86 (d, J=8.8Hz, 2H), 7.80 (d, J=7.2Hz, 2H), 7.62 (t, J=7.4Hz, 1H), 7.50 (t, J=7.4Hz, 2H), 2.67 (s, 3H)；13C NMR(CDCl3, 100MHz):δ197.5,195.9,141.3,139.5,136.9,132.9,130.1,130.0,128.4,128.1,26.9.
Embodiment 23：
A:The synthesis of ALPHA-tetralone
The equivalents of NHPI 0.5 are added in 25mL Schlenk reaction tubes, is dried in vacuo 15 minutes, puts oxygen ball, Acetonitrile 1mL, the equivalent of nitrite tert-butyl 1.0,1,2,3,4- naphthane 0.5mmol, in reaction tube are sequentially added under oxygen atmosphere It is put into after above adding polytetrafluoro plug in oil bath pan, 80 DEG C of reaction 24h.After the completion of reaction, be concentrated under reduced pressure removing solvent acetonitrile, post Chromatography, eluant, eluent is petrol ether/ethyl acetate (v:V=30:1) ALPHA-tetralone, is obtained.Product yield 86%, it is yellowish Color oil；1H NMR(CDCl3,400MHz):δ 8.03 (d, J=7.6Hz, 1H), 7.44-7.48 (m, 1H), 7.24-7.32 (m, 2H), 2.96 (t, J=6.0Hz, 2H), 2.65 (t, J=6.6Hz, 2H), 2.10-2.16 (m, 2H)13C NMR(CDCl3, 100MHz):δ198.3,144.4,133.3,132.5,128.7,127.1,126.5,39.1,29.6,23.2.
B:The synthesis of 2,3- dihydro -1,4- naphthoquinones
The equivalents of NHPI 1.0 are added in 25mL Schlenk reaction tubes, is dried in vacuo 15 minutes, puts oxygen ball, Acetonitrile 1mL, the equivalent of nitrite tert-butyl 2.0,1,2,3,4- naphthane 0.5mmol, in reaction tube are sequentially added under oxygen atmosphere It is put into after above adding polytetrafluoro plug in oil bath pan, 90 DEG C of reaction 36h.After the completion of reaction, be concentrated under reduced pressure removing solvent acetonitrile, post Chromatography, eluant, eluent is petrol ether/ethyl acetate (v:V=10:1) 2,3- dihydros -1,4-naphthoquinone, is obtained.Product yield 72%, gray solid；1H NMR(CDCl3,400MHz):δ7.99-8.04(m,2H),7.70-7.74(m,2H),3.07(s, 4H)；13C NMR(CDCl3,100MHz):δ195.9,135.2,134.2,126.7,37.5.
Embodiment 24：
A:The synthesis of 1- indones
The equivalents of NHPI 0.5 are added in 25mL Schlenk reaction tubes, is dried in vacuo 15 minutes, puts oxygen ball, Acetonitrile 1mL is sequentially added under oxygen atmosphere, the equivalent of nitrite tert-butyl 1.0, indane 0.5mmol adds poly- four on reaction tube It is put into after fluorine plug in oil bath pan, 80 DEG C of reaction 24h.After the completion of reaction, be concentrated under reduced pressure removing solvent acetonitrile, column chromatography for separation, Eluant, eluent is petrol ether/ethyl acetate (v:V=30:1) 1- indones, are obtained.Product yield 78%, faint yellow solid；1H NMR (CDCl3,400MHz):δ7.74-7.76(m,1H),7.55-7.59(m,1H),7.46-7.48(m,1H),7.34-7.37(m, 1H),3.12-3.15(m,2H),2.66-2.70(m,2H)；13C NMR(CDCl3,100MHz):δ207.0,155.1,137.0, 134.5,127.2,126.7,123.7,36.2,25.7.
B:The synthesis of 1,3- indandiones
The equivalents of NHPI 1.0 are added in 25mL Schlenk reaction tubes, is dried in vacuo 15 minutes, puts oxygen ball, Acetonitrile 1mL is sequentially added under oxygen atmosphere, the equivalent of nitrite tert-butyl 2.0, indane 0.5mmol adds poly- four on reaction tube It is put into after fluorine plug in oil bath pan, 90 DEG C of reaction 36h.After the completion of reaction, be concentrated under reduced pressure removing solvent acetonitrile, column chromatography for separation, Eluant, eluent is petrol ether/ethyl acetate (v:V=10:1) 1,3- indandiones, are obtained.Product yield 61%, brown solid；1H NMR(CDCl3,400MHz):δ7.96-7.99(m,2H),7.83-7.86(m,2H),3.24(s,2H)；13C NMR(CDCl3, 100MHz):δ197.4,143.4,135.6,123.2,45.0.
Embodiment 25：
A:The synthesis of ω-benzyl acetophenone
The equivalents of NHPI 0.5 are added in 25mL Schlenk reaction tubes, is dried in vacuo 15 minutes, puts oxygen ball, Acetonitrile 1mL, the equivalent of nitrite tert-butyl 1.0,1,3- diphenyl propane 0.5mmol, on reaction tube are sequentially added under oxygen atmosphere Plus being put into after polytetrafluoro plug in oil bath pan, 80 DEG C are reacted 24h.After the completion of reaction, be concentrated under reduced pressure removing solvent acetonitrile, post layer Analysis separation, eluant, eluent is petrol ether/ethyl acetate (v:V=30:1) ω-benzyl acetophenone, is obtained.Product yield 74%, white Solid；1H NMR(CDCl3,400MHz):δ 7.98 (t, J=7.2Hz, 2H), 7.58 (t, J=7.4Hz, 1H), 7.48 (t, J= 7.6Hz, 2H), 7.22-7.35 (m, 5H), 3.34 (t, J=7.6Hz, 2H), 3.11 (t, J=7.6Hz, 2H)；13C NMR (CDCl3,100MHz):δ199.2,141.3,136.8,133.0,128.6,128.5,128.4,128.0,126.1,40.4, 30.1.
B:The synthesis of dibenzoyl methane
The equivalents of NHPI 1.0 are added in 25mL Schlenk reaction tubes, is dried in vacuo 15 minutes, puts oxygen ball, Acetonitrile 1mL, the equivalent of nitrite tert-butyl 2.0,1,3- diphenyl propane 0.5mmol, on reaction tube are sequentially added under oxygen atmosphere Plus being put into after polytetrafluoro plug in oil bath pan, 90 DEG C are reacted 36h.After the completion of reaction, be concentrated under reduced pressure removing solvent acetonitrile, post layer Analysis separation, eluant, eluent is petrol ether/ethyl acetate (v:V=10:1) dibenzoyl methane, is obtained.Product yield 62%, in vain Color solid；1H NMR(CDCl3,400MHz):δ 16.9 (s, 1H), 8.00 (d, J=7.6Hz, 4H), 7.57 (t, J=7.2Hz, 2H), 7.50 (t, J=7.2Hz, 4H), 6.87 (s, 1H)；13C NMR(CDCl3,100MHz):δ185.7,135.5,132.4, 128.7,127.1,93.1.
Embodiment 26：
A:The synthesis of 2- -2 '-ethyl biphenyls of acetyl group
The equivalents of NHPI 0.5 are added in 25mL Schlenk reaction tubes, is dried in vacuo 15 minutes, puts oxygen ball, Sequentially add acetonitrile 1mL under oxygen atmosphere, the equivalent of nitrite tert-butyl 1.0,2,2 '-diethyl -1,1 '-biphenyl 0.5mmol, It is put into after adding polytetrafluoro plug on reaction tube in oil bath pan, 80 DEG C of reaction 24h.After the completion of reaction, be concentrated under reduced pressure removing solvent Acetonitrile, column chromatography for separation, eluant, eluent is petrol ether/ethyl acetate (v:V=50:1) 2- -2 '-ethyl biphenyls of acetyl group, are obtained. Product yield 78%, faint yellow oil；1H NMR(CDCl3,400MHz):δ 7.51-7.56 (m, 2H), 7.41 (q, J=8.0Hz, 2H), 7.32 (t, J=7.2Hz, 1H), 7.24 (t, J=7.6Hz, 2H), 7.02-7.07 (m, 1H), 2.76 (q, J=7.6Hz, 2H), 2.65 (s, 3H), 1.23 (t, J=7.4Hz, 3H)；13C NMR(CDCl3,100MHz):δ200.5,143.2,139.0, 132.6,131.9,131.2,130.6,129.4,129.3,127.4,127.3,126.9,124.2,30.7,29.3,14.2； HRMS(ESI)calcd for C16H16O[M+Na]+247.1093,found 247.1096.
B:The synthesis of 2,2 '-diacetyl biphenyl
The equivalents of NHPI 1.0 are added in 25mL Schlenk reaction tubes, is dried in vacuo 15 minutes, puts oxygen ball, Sequentially add acetonitrile 1mL under oxygen atmosphere, the equivalent of nitrite tert-butyl 2.0,2,2 '-diethyl -1,1 '-biphenyl 0.5mmol, It is put into after adding polytetrafluoro plug on reaction tube in oil bath pan, 90 DEG C of reaction 36h.After the completion of reaction, be concentrated under reduced pressure removing solvent Acetonitrile, column chromatography for separation, eluant, eluent is petrol ether/ethyl acetate (v:V=10:1) 2,2 '-diacetyl biphenyl, is obtained.Product is received Rate 73%, brown solid；1H NMR(CDCl3,400MHz):δ 7.72 (d, J=7.6Hz, 2H), 7.42-7.50 (m, 4H), 7.16 (d, J=7.2Hz, 2H), 2.25 (s, 6H)；13C NMR(CDCl3,100MHz):δ201.6,140.5,138.6,130.9, 130.6,128.5,127.5,29.2；HRMS(ESI)calcd for C16H14O2[M+Na]+261.0886,found 261.0888.
Embodiment 27：
A:The synthesis of 2- acetyl group -6- ethylpyridines
The equivalents of NHPI 0.5 are added in 25mL Schlenk reaction tubes, is dried in vacuo 15 minutes, puts oxygen ball, Acetonitrile 1mL, the equivalent of nitrite tert-butyl 1.0,2,6- parvoline 0.5mmol, in reaction tube are sequentially added under oxygen atmosphere It is put into after above adding polytetrafluoro plug in oil bath pan, 80 DEG C of reaction 24h.After the completion of reaction, be concentrated under reduced pressure removing solvent acetonitrile, post Chromatography, eluant, eluent is petrol ether/ethyl acetate (v:V=10:1) 2- acetyl group -6- ethylpyridines, are obtained.Product yield 63%, faint yellow oil；1H NMR(CDCl3,400MHz):δ 7.97 (t, J=7.6Hz, 1H), 7.63-7.71 (m, 2H), 3.42 (q, J=7.3Hz, 2H), 2.69 (s, 3H), 1.66 (t, J=7.6Hz, 3H)；13C NMR(CDCl3,100MHz):δ198.5, 154.1,141.2,139.1,131.7,120.4,28.0,25.7,19.3.
B:The synthesis of 2,6- diacetyl pyridines
The equivalents of NHPI 1.0 are added in 25mL Schlenk reaction tubes, is dried in vacuo 15 minutes, puts oxygen ball, Acetonitrile 1mL, the equivalent of nitrite tert-butyl 2.0,2,6- parvoline 0.5mmol, in reaction tube are sequentially added under oxygen atmosphere It is put into after above adding polytetrafluoro plug in oil bath pan, 90 DEG C of reaction 36h.After the completion of reaction, be concentrated under reduced pressure removing solvent acetonitrile, post Chromatography, eluant, eluent is petrol ether/ethyl acetate (v:V=5:1) DAP, is obtained.Product yield 54%, Yellow solid；1H NMR(CDCl3,400MHz):δ 7.98 (d, J=6.8Hz, 2H), 7.69 (t, J=7.6Hz, 1H), 2.70 (s, 6H)；13C NMR(CDCl3,100MHz):δ197.4,150.9,142.7,121.2,26.7.
The present invention takes aryl side chains c h bond to be directly catalyzed oxygen using the fragrant ethyl class compound of nitrous acid ester catalysis oxidation It is melted into ketone.The a series of experiments of the different substrates cited by ketone is direct oxidation into benzyl position C-H key by above-described embodiment, can be with Conclusion is drawn：It is the equivalent of HP 0.5, nitrous acid uncle for the fragrant ethyl class substrate optimum condition of electron rich The equivalent of butyl ester 1.0,80 DEG C of reaction 24h；It is HP for the fragrant ethyl class substrate optimum condition of electron deficient 1.0 equivalents, the equivalent of nitrite tert-butyl 2.0,90 DEG C of reaction 36h..To the difference cited by selective oxidation into single ketones and diketone A series of embodiments experiment of substrate, can conclude and draw：A conditions are the equivalent of HP 0.5, nitrous acid The equivalent of the tert-butyl ester 1.0,80 DEG C of reaction 24h；B conditions are the equivalent of HP 1.0, nitrite tert-butyl 2.0 Equivalent, 90 DEG C of reaction 36h..The present invention is using non-metallic catalyst and the catalyst system and catalyzing of oxygen, the aryl side for activating free radical The oxidation of the c h bond of chain, it is simple to operate, react with petrol ether/ethyl acetate by volume 50~1:1 is used as eluant, eluent, post Chromatography obtains target product.The above embodiment illustrates that the universal adaptability of substrate of the present invention is good, heterocyclic bottom Thing can also realize conversion.What the present invention took is non-metal catalyst system, it is to avoid the use of transition metal, so as to avoid closing A kind of new method is provided into the metal residual in medicine, while also providing a kind of new side for the synthesis of lenperone Method.Oxidation system different from the past can not selectively control oxidation or selective bad, and the present invention can be controlled selectively Bis oxide ethylaromatics are into single ketones and diketone.

Claims (5)

1. a kind of method that benzyl position C-H key is direct oxidation into ketone, it is characterised in that：In oxygen atmosphere, by radical initiator With nitrous acid ester in molar ratio 0.5:As synergistic catalyst after 1~2 mixing, using the fragrant ethyl class compound containing substituent as Substrate, it is 0.5~1 with the fragrant ethyl class compound mole ratio containing substituent to make radical initiator:1, nitrous acid ester takes with containing Dai Ji fragrant ethyl class compound mole ratio is 1~2:1,24-36h is reacted in 80-90 DEG C in a solvent, with petroleum ether/acetic acid Ethyl ester by volume 50~1:1 mixing is as eluant, eluent, and column chromatography for separation obtains target product.
2. the method that benzyl position C-H key as claimed in claim 1 is direct oxidation into ketone, it is N- to be characterised by the radical initiator Hydroxyphthalimide, 1,10- ferrosins, neocuproine, 2,6 di tert butyl pyridine, 2,2,6,6- tetramethyl piperidine oxygen Compound, N- hydroxysuccinimides or N- bromo-succinimides.
3. the method that benzyl position C-H key as claimed in claim 1 is direct oxidation into ketone, it is nitrous acid to be characterised by the nitrous acid ester The tert-butyl ester, nitrous acid benzyl ester, isoamyl nitrite or nitrous ether (ethyl nitrite).
4. the method that benzyl position C-H key as claimed in claim 1 is direct oxidation into ketone, is characterised by the fragrant ethyl containing substituent Class compound is 4- ethylo benzenes methyl ether, acetic acid -4- ethylo benzenes phenolic ester, to ethyl fluorobenzene, to ethyl chlorobenzene, to ethyl bromobenzene, right Nitro ethylbenzene, to trifluoromethyl ethylbenzene, to cyano group ethylbenzene, 1-ethylnaphthalene, propylbenzene, 1- phenyl-octanes, tridane, 2- benzyls Yl pyridines, diphenyl methane, 2- ethylpyridines, 3-ethylpyridine, 4- ethylpyridines, 4- benzyl pyridines, 2 acetyl thiophene, to two Ethylo benzene, a diethylbenzene, 1- benzyl -4- ethylo benzenes, 1,2,3,4- naphthanes, indane, 1,3- diphenyl propanes, 2,2 '-diethyl Base -1,1 '-biphenyl or 2,6- parvolines.
5. the method that benzyl position C-H key as claimed in claim 1 is direct oxidation into ketone, be characterised by the solvent for tetrahydrofuran, Dimethyl sulfoxide (DMSO), N,N-dimethylformamide, acetonitrile, ethyl acetate, dichloromethane or 1,4- dioxane.
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CN107602393A (en) * 2017-09-28 2018-01-19 安徽省庆云医药股份有限公司 A kind of method that benzyl position C H keys are direct oxidation into ketone or acid
CN108084052A (en) * 2017-12-21 2018-05-29 中国科学技术大学 A kind of method that hydro carbons c h bond is directly translated into oxime
CN111606791A (en) * 2020-06-08 2020-09-01 杭州医学院 Synthetic method of aromatic benzyl ketone
CN111606791B (en) * 2020-06-08 2023-01-03 杭州医学院 Synthetic method of aromatic benzyl ketone
CN111635299A (en) * 2020-06-09 2020-09-08 大连理工大学 Method for preparing aromatic alpha ketone carbonyl compound by continuous visible light catalytic molecular oxygen oxidation in microchannel reactor
CN112679291A (en) * 2020-12-25 2021-04-20 中国科学院西北高原生物研究所 Preparation method of alpha-ketoester compound
CN112679291B (en) * 2020-12-25 2023-03-17 中国科学院西北高原生物研究所 Preparation method of alpha-ketoester compound
CN114292247A (en) * 2022-01-19 2022-04-08 大连理工大学 Disulfide compound and method for catalyzing benzyl oxidation of alkyl aromatic compound by using disulfide compound
CN115611693A (en) * 2022-05-12 2023-01-17 常州大学 Method for catalytically synthesizing isochroman-1-ketone or aromatic ketone compounds
CN115611693B (en) * 2022-05-12 2023-11-28 常州大学 Method for catalytic synthesis of isochroman-1-one or aromatic ketone compound
CN115536498A (en) * 2022-10-24 2022-12-30 遵义医科大学 Method for oxidative coupling of substituted phenol catalyzed by butanedione
CN115536498B (en) * 2022-10-24 2023-10-20 遵义医科大学 Butanedione catalyzed substituted phenol oxidative coupling method

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