CN107011133B - Method for directly oxidizing benzylic C-H bond into ketone - Google Patents
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- 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
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- 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
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- 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
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- 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
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- 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
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Abstract
The invention discloses a method for directly oxidizing a benzylic C-H bond into ketone, which is characterized in that nitrite is used for catalyzing and oxidizing benzylic CH-containing compounds2The aromatic hydrocarbon compound is prepared by adopting a free radical initiator and nitrite ester synergistic catalysis system and a nonmetal catalyst and oxygen catalysis system to oxidize C-H bonds of aryl side chains activated by free radicals, the operation is simple, petroleum ether/ethyl acetate is used as an eluent according to the volume ratio of 50-1: 1 after the reaction is finished, and the target product is obtained by column chromatography separation. The catalytic system of the invention uses oxygen as an oxygen source, and has high atom economy. The invention is a non-metal catalytic system, and provides a new method for avoiding metal residues in synthetic drugs. The invention contains CH for double benzyl position2The aromatic hydrocarbon compound can selectively oxidize double benzyl containing CH2The aromatic compounds of (a) are mono-ketones and di-ketones. The method can efficiently synthesize the diazepam drug paroxetine, and provides a new method for synthesizing paroxetine.
Description
Technical Field
The invention belongs to the field of catalyzing benzyl containing CH2The technical field of synthesizing ketone compounds from aromatic hydrocarbon compounds, in particular to a method for directly oxidizing aryl side chain C-H bonds into ketone.
Background
Acyl is ubiquitous in organic synthesis intermediates and pharmaceutical compounds, so that the reaction of directly oxidizing aryl side chain C-H bond into ketone is widely applied in chemical industry, particularly in the fields of pharmacy and the like. The traditional method for directly oxidizing aryl side chain C-H bond into ketone is realized by potassium permanganate or potassium dichromate under severe conditions, the number of byproducts is large, and the oxidation cannot be selectively controlled when two side chains exist. The use of transition metals as catalysts has been developed in recent years, and the high residual content of transition metal complex oxidants plus metals has limited their use on a large scale in the industrial and pharmaceutical industries. Although non-metal catalysts have also been developed in this field, the necessity of using an excess of unstable peroxide oxidants limits their development, while the use of excess oxidants limits their process from achieving selectively controlled oxidation. To date, the oxidation of aryl C-H bonds using a non-metal as a catalyst, oxygen or air as the source of oxygen, and the selective control of the oxidation, still requires the development of better processes
A C-H bond oxidation to ketones is described in the J.Am.chem.Soc.,2002,124, 2245-. This approach, while avoiding the use of transition metals, does not allow for conversion for electron-withdrawing substrates.
A method for the oxidation of C-H bonds to ketones, which is described in the U.S. Kuntze et al (org. Lett.,2005,7,5167-5170), uses 1.0 mol% Rh to form the C-H bond2(cap)4As catalyst, 0.5 equivalent of K2CO3Reacting 5.0 equivalent of TBHP and DCM as solvent at room temperature for 1 hour to obtain the acetophenone analog with the yield of 30-92%. The process uses expensive rhodium metal catalysts and uses a large amount of unstable peroxide TBHP, making it possible to achieve selective oxidation of mono-and diketones, but with poor selectivity.
A method for the oxidation of C-H bonds to ketones, which is described in German applied chemistry (Angew. chem. int. Ed.,2012,51, 2745-2748), uses 10 mol% FeCl2·4H2O is used as a catalyst, DMSO is used as a solvent, oxygen is used as an oxidant, 1 equivalent of AcOH is added, 2-benzyl pyridine and analogues thereof are oxidized at 100 ℃, and after 24 hours of reaction, phenyl-2-pyridyl ketone and analogues thereof are obtained with the yield of 59-83%. This method uses a metal catalyst although oxygen is used as the oxygen source.
A method for oxidation of the C-H bond in the pyridine side chain to ketones, which is described in U.S. Kuntze, Ong.Lett., 2014,16,2050-2053, is carried out using 10 mol% Cu (OAc)2·H2O is used as a catalyst, DMA is used as a solvent, 1atm of oxygen is used as an oxidant, 2-benzyl pyridine is oxidized at 120 ℃ for 48 hours, and phenyl-2-pyridyl ketone is obtained with the yield of 89%. This method uses a metal catalyst although oxygen is used as the oxygen source.
According to German applicationA one-step oxidation of the C-H bond of the pyridine side chain to ketones, using 10 mol% of CuCl, is described in chemistry (Angew. chem. int. Ed.,2015,54, 1261-2·2H2O is used as a catalyst, DMF or 1, 4-dioxane is used as a solvent, chloroacetate is used as an additive, the pyridine compounds are oxidized at 130 ℃ by using an oxygen balloon method, and the highest yield is 92 percent after the reaction is carried out for 24 hours. This method uses a metal catalyst although oxygen is used as the oxygen source.
U.S. patent application No. Org.Lett.,2015,17,2078-2081 and Chinese patent application No. CN201510105616.X disclose a method for direct oxidation of C-H bond of pyridine side chain into ketone by using 5 mol% of H4NI, 10 mol% AcOH as catalyst, 0.1MPaO2Or air is used as an oxygen source, no solvent is used, the pyridine compounds are oxidized at 100 ℃, and after 24 hours of reaction, the highest yield is 97%. Although the method adopts oxygen as an oxygen source and realizes conversion under the catalysis of nonmetal, the method only can be used for preparing pyridine compounds.
According to the British chemical science (chem.Sci.,2016,7, 346-one 357), a method for oxidizing C-H bond into ketone is reported, which comprises using 10 mol% of CuI as catalyst, DMSO as solvent, oxygen as oxidant, adding 1 equivalent of AcOH, and oxidizing 2-benzyl pyridine and analogues thereof at 100 ℃ for 24 hours to obtain phenyl-2-pyridyl ketone and analogues thereof, wherein the yield is 59-83%. This method uses a metal catalyst although oxygen is used as the oxygen source.
A method for the oxidation of C-H bonds to ketones is reported in the United kingdom by chemical sciences (chem. Sci.,2017,8,1282-1287) using 1 mol% Co (OAc)2·4H2O is a catalyst, 20 mol% NHPI is a co-catalyst, BuOAc or BuOAc: pyr (v: v ═ 7:3) is used as a solvent, pyridine or thiophene or imidazole or benzimidazole or benzothiazole compounds are oxidized at 90-100 ℃ for 12 hours using an oxygen balloon method, the maximum yield is 94%, and the method uses a metal catalyst although oxygen is used as an oxygen source.
It can be seen that the prior art mostly uses metal catalysts, so that it is difficult to avoid metal residues in the synthesized drug. The selective oxidation of mono-and diketones cannot be well achieved by an excess of unstable peroxide oxidizing agents.
Disclosure of Invention
The invention aims to provide a method for directly oxidizing a benzylic C-H bond into ketone, which adopts a synergistic catalytic system of a free radical initiator and nitrite and uses a catalytic system of a nonmetal catalyst and oxygen to catalyze and oxidize the C-H bond of an aryl side chain into ketone in a selectively controlled manner so as to overcome the defects in the prior art.
The invention relates to a method for directly oxidizing a benzylic C-H bond into ketone, which is characterized by comprising the following steps: in an oxygen atmosphere, mixing a free radical initiator and nitrite according to a molar ratio of 0.5: 1-2 to serve as a synergistic catalyst, wherein the benzyl position contains CH2Using the aromatic hydrocarbon compound as a substrate, and allowing the radical initiator to contain CH at the benzyl position2The aromatic hydrocarbon compound has a molar ratio of 0.5-1: 1, and the nitrous acid ester and benzyl position contain CH2The aromatic hydrocarbon compound is 1-2: 1, the reaction is carried out in a solvent at the temperature of 80-90 ℃ for 24-36h, petroleum ether/ethyl acetate mixture is used as an eluent according to the volume ratio of 50-1: 1, and the target product is obtained through column chromatography separation.
The free radical initiator is selected from N-hydroxyphthalimide, 2,6, 6-tetramethylpiperidine oxide, N-hydroxysuccinimide or N-bromosuccinimide.
The nitrite is selected from tert-butyl nitrite, benzyl nitrite, isoamyl nitrite or ethyl nitrite.
The benzyl position contains CH2The aromatic hydrocarbon compound is selected from 4-ethyl methyl ether, 4-ethyl phenol acetate, p-ethyl fluorobenzene, p-ethyl chlorobenzene, p-ethyl bromobenzene, p-nitroethylbenzene, p-trifluoromethyl ethylbenzene, p-cyanoethylbenzene, 1-ethyl naphthalene, propylbenzene, 1-phenyl octane, tridecylbenzene, 2-benzyl pyridine, diphenylmethane, 2-ethyl pyridine, 3-ethyl pyridine, 4-benzyl pyridine, 2-ethyl thiophene, p-diethyl benzene, m-diethyl benzene, 1-benzyl-4-ethyl benzene, 1,2,3, 4-tetrahydronaphthalene, indane, 1, 3-diphenylpropane, 2, 4-tetrahydronaphthalene’-diethyl-1, 1' -biphenyl or 2, 6-diethylpyridine.
The solvent is selected from tetrahydrofuran, dimethyl sulfoxide, N-dimethylformamide, acetonitrile, ethyl acetate, dichloromethane or 1, 4-dioxane.
The method for directly oxidizing benzylic C-H bond into ketone firstly uses nitrite to catalyze and oxidize benzylic CH-containing2The aromatic hydrocarbon compound is directly oxidized into ketone by adopting aryl side chain C-H bond as a catalyst, which is different from the prior biological conversion method. According to the invention, a free radical initiator and nitrite ester synergistic catalysis system is adopted, a nonmetal catalyst and oxygen catalysis system is used, the C-H bond of the aryl side chain activated by the free radical is oxidized, petroleum ether/ethyl acetate is used as an eluent according to the volume ratio of 50-1: 1 after the reaction is finished, and the target product is obtained by column chromatography separation. Because the catalytic system in the invention uses oxygen as the oxygen source, the atom economy is high. The invention is a non-metal catalytic system, which is different from the prior metal catalytic system and provides a new method for avoiding metal residue in synthetic drugs. The invention contains CH for double benzyl position2The aromatic hydrocarbon compound can selectively oxidize double benzyl containing CH2The aromatic hydrocarbon compounds are mono-ketone and di-ketone, and the operation is simple. The method can efficiently synthesize the diazepam drug paroxetine, and provides a new method for synthesizing paroxetine.
Detailed Description
Example 1:
p-methoxyacetophenone
Synthesis of (2)
Adding 0.5 equivalent of NHPI into a 25mL Schlenk reaction tube, drying in vacuum for 15 minutes, sleeving an oxygen balloon, sequentially adding 1mL of acetonitrile, 1.0 equivalent of tert-butyl nitrite and 0.5mmol of p-ethyl phenyl ether in an oxygen atmosphere, adding a polytetrafluoroethylene plug on the reaction tube, putting the reaction tube into an oil bath, and reacting at 80 ℃ for 24 hours. After the reaction is finished, the solvent acetonitrile is removed by decompression and concentration, column chromatography separation is carried out, and an eluent is petroleum ether/ethyl acetate (v: v ═ 20:1), so that the p-methoxyacetophenone is obtained. Yield 83%, light yellow solid;1H NMR(CDCl3,400MHz):δ7.92(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.
example 2:
4-acetoxyacetophenone
Synthesis of (2)
Adding 1.0 equivalent of NHPI into a 25mL Schlenk reaction tube, drying in vacuum for 15 minutes, sleeving an oxygen balloon, sequentially adding 1mL of acetonitrile, 2.0 equivalent of tert-butyl nitrite and 0.5mmol of p-acetoxyethylbenzene into the reaction tube under the oxygen atmosphere, adding a polytetrafluoroethylene plug into the reaction tube, putting the reaction tube into an oil bath, and reacting for 24 hours at 80 ℃. After the reaction is finished, the solvent acetonitrile is removed by decompression and concentration, column chromatography separation is carried out, and the eluent is petroleum ether/ethyl acetate (v: v ═ 10:1), so as to obtain the 4-acetoxyacetophenone. Yield 72%, white solid;1H NMR(CDCl3,400MHz):δ7.96(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.
example 3:
p-fluoro acetophenone
Synthesis of (2)
Adding 0.5 equivalent of NHPI into a 25mL Schlenk reaction tube, drying in vacuum for 15 minutes, sleeving an oxygen balloon, sequentially adding 1mL of acetonitrile, 1.0 equivalent of tert-butyl nitrite and 0.5mmol of p-fluoroethylbenzene in an oxygen atmosphere, adding a polytetrafluoroethylene plug on the reaction tube, putting the reaction tube into an oil bath, and reacting at 80 ℃ for 24 hours. After the reaction is finished, the solvent acetonitrile is removed by decompression and concentration, column chromatography separation is carried out, and an eluent is petroleum ether/ethyl acetate (v: v ═ 50:1), so that the p-fluoro acetophenone is obtained. Yield 78%, light yellow oil;1H NMR(CDCl3,400MHz):δ7.96(dd,J＝8.2Hz,5.4Hz,2H),7.10(t,J＝8.4Hz,2H),2.56(s,3H)；13C NMR(CDCl3,100MHz):δ196.4,166.9,164.4,133.5(d,J＝3.0Hz),130.8(d,J＝9.8Hz),115.6(d,J＝21.9Hz),26.4.
example 4:
p-chloroacetophenone
Synthesis of (2)
Adding 0.5 equivalent of NHPI into a 25mL Schlenk reaction tube, drying in vacuum for 15 minutes, sleeving an oxygen balloon, sequentially adding 1mL of acetonitrile, 1.0 equivalent of tert-butyl nitrite and 0.5mmol of p-chloroethylbenzene in an oxygen atmosphere, adding a polytetrafluoroethylene plug on the reaction tube, putting the reaction tube into an oil bath, and reacting at 80 ℃ for 24 hours. After the reaction is finished, the solvent acetonitrile is removed by decompression and concentration, column chromatography separation is carried out, and the eluent is petroleum ether/ethyl acetate (v: v ═ 50:1), so as to obtain the p-chloro acetophenone. Yield 77% as pale 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.
example 5:
p-bromoacetophenone
Synthesis of (2)
Adding 0.5 equivalent of NHPI into a 25mL Schlenk reaction tube, drying in vacuum for 15 minutes, sleeving an oxygen balloon, sequentially adding 1mL of acetonitrile, 1.0 equivalent of tert-butyl nitrite and 0.5mmol of p-bromoethylbenzene into the reaction tube in an oxygen atmosphere, adding a polytetrafluoroethylene plug into the reaction tube, putting the reaction tube into an oil bath, and reacting for 24 hours at 80 ℃. After the reaction is finished, the solvent acetonitrile is removed by decompression and concentration, column chromatography separation is carried out, and an eluent is petroleum ether/ethyl acetate (v: v ═ 50:1), so that the p-bromoacetophenone is obtained. Yield 73%, white solid;1H NMR(CDCl3,400MHz):δ7.81(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.
example 6:
1-acetyl naphthalene
Synthesis of (2)
Into a 25mL Schlenk reaction tubeNHPI 0.5 equivalent, vacuum drying for 15 minutes, sleeving an oxygen balloon, sequentially adding acetonitrile 1mL, tert-butyl nitrite 1.0 equivalent and 1-ethylnaphthalene 0.5mmol in the oxygen atmosphere, adding a polytetrafluoroethylene plug on a reaction tube, putting the reaction tube into an oil bath, and reacting for 24 hours at 80 ℃. After the reaction is finished, the solvent acetonitrile is removed by decompression and concentration, column chromatography separation is carried out, and the eluent is petroleum ether/ethyl acetate (v: v ═ 50:1), so as to obtain the 1-acetyl naphthalene. Yield 80%, light yellow oil;1H NMR(CDCl3,400MHz):δ8.76(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.
example 7:
propiophenoneSynthesis of (2)
Adding 0.5 equivalent of NHPI into a 25mL Schlenk reaction tube, drying in vacuum for 15 minutes, sleeving an oxygen balloon, sequentially adding 1mL of acetonitrile, 1.0 equivalent of tert-butyl nitrite and 0.5mmol of propylbenzene into the reaction tube under the oxygen atmosphere, adding a polytetrafluoroethylene plug into the reaction tube, putting the reaction tube into an oil bath, and reacting for 24 hours at 80 ℃. After the reaction is finished, the solvent acetonitrile is removed by decompression and concentration, column chromatography separation is carried out, and the eluent is petroleum ether/ethyl acetate (v: v ═ 50:1), so that the propiophenone is obtained. Yield 83%, light yellow oil;1H NMR(CDCl3,400MHz):δ7.95-7.97(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.
example 8:
octyl benzene acylateSynthesis of (2)
Adding 0.5 equivalent of NHPI into a 25mL Schlenk reaction tube, drying in vacuum for 15 minutes, covering with an oxygen balloon, and sequentially adding 1mL of acetonitrile and 1.0 equivalent of tert-butyl nitrite into the Schlenk reaction tube under the oxygen atmosphere0.5mmol of 1-phenyloctane, adding a polytetrafluoroethylene plug on the reaction tube, putting the reaction tube into an oil bath pot, and reacting for 24 hours at 80 ℃. After the reaction is finished, the solvent acetonitrile is removed by decompression and concentration, column chromatography separation is carried out, and an eluent is petroleum ether/ethyl acetate (v: v ═ 50:1), so as to obtain the octyl acyl benzene. Yield 71%, white solid;1H NMR(CDCl3,400MHz):δ7.96(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.
example 9:
benzene n-tridecyl ketone
Synthesis of (2)
Adding 0.5 equivalent of NHPI into a 25mL Schlenk reaction tube, drying in vacuum for 15 minutes, sleeving an oxygen balloon, sequentially adding 1mL of acetonitrile, 2.0 equivalent of tert-butyl nitrite and 0.5mmol of tridecylbenzene in an oxygen atmosphere, adding a polytetrafluoroethylene plug on the reaction tube, putting the reaction tube into an oil bath, and reacting at 80 ℃ for 24 hours. After the reaction is finished, the solvent acetonitrile is removed by decompression and concentration, column chromatography separation is carried out, and the eluent is petroleum ether/ethyl acetate (v: v ═ 50:1), so that the benzene-n-tridecyl ketone is obtained. Yield 70%, white solid;1H NMR(CDCl3,400MHz):δ7.96(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.
example 10:
p-nitroacetophenone
Synthesis of (2)
Adding 1.0 equivalent of NHPI into a 25mL Schlenk reaction tube, drying in vacuum for 15 minutes, covering with an oxygen balloon, and sequentially adding 1mL of acetonitrile, 2.0 equivalents of tert-butyl nitrite and p-nitro in an oxygen atmosphere0.5mmol of ethylbenzene, adding a polytetrafluoroethylene plug on the reaction tube, putting the reaction tube into an oil bath pot, and reacting for 36 hours at 90 ℃. After the reaction is finished, the solvent acetonitrile is removed by decompression and concentration, column chromatography separation is carried out, and an eluent is petroleum ether/ethyl acetate (v: v ═ 20:1), so that the p-nitroacetophenone is obtained. Yield 66%, light yellow solid;1H NMR(400MHz,CDCl3)δ8.29(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.
example 11:
p-trifluoromethyl acetophenone
Synthesis of (2)
Adding 1.0 equivalent of NHPI into a 25mL Schlenk reaction tube, drying in vacuum for 15 minutes, sleeving an oxygen balloon, sequentially adding 1mL of acetonitrile, 2.0 equivalent of tert-butyl nitrite and 0.5mmol of p-trifluoromethylethylbenzene into the reaction tube under the oxygen atmosphere, adding a polytetrafluoroethylene plug into the reaction tube, putting the reaction tube into an oil bath, and reacting for 36 hours at 90 ℃. After the reaction is finished, the solvent acetonitrile is removed by decompression and concentration, column chromatography separation is carried out, and the eluent is petroleum ether/ethyl acetate (v: v ═ 20:1), so that the p-trifluoromethyl acetophenone is obtained. Yield 73%, light yellow solid;1H NMR(CDCl3,400MHz):δ8.05(d,J＝8.4Hz,2H),7.72(d,J＝8.4Hz,2H),2.64(s,3H)；13C NMR(CDCl3,100MHz):δ196.9,139.7,134.4(q,J＝32.4Hz),128.6,125.7(q,J＝3.9Hz),124.9,122.2,26.7.
example 12:
p-cyanoacetophenone
Synthesis of (2)
Adding 1.0 equivalent of NHPI into a 25mL Schlenk reaction tube, drying in vacuum for 15 minutes, sleeving an oxygen balloon, sequentially adding 1mL of acetonitrile, 2.0 equivalent of tert-butyl nitrite and 0.5mmol of p-cyanoethylbenzene into the reaction tube in an oxygen atmosphere, adding a polytetrafluoroethylene plug into the reaction tube, putting the reaction tube into an oil bath, and reacting for 36 hours at 90 ℃. After the reaction is finished, decompressing and concentrating to remove the solvent acetonitrile, separating by column chromatography, and eluting with stoneOleyl ether/ethyl acetate (v: v ═ 20:1) gave p-cyanoacetophenone. Yield 70%, white solid;1H NMR(CDCl3,400MHz):δ8.03(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.
example 13:
2-acetylpyridine
Synthesis of (2)
Adding 1.0 equivalent of NHPI into a 25mL Schlenk reaction tube, drying in vacuum for 15 minutes, sleeving an oxygen balloon, sequentially adding 1mL of acetonitrile, 2.0 equivalent of tert-butyl nitrite and 0.5mmol of 2-ethylpyridine into the reaction tube under the oxygen atmosphere, adding a polytetrafluoroethylene plug into the reaction tube, putting the reaction tube into an oil bath, and reacting for 36 hours at 90 ℃. After the reaction is finished, the solvent acetonitrile is removed by decompression and concentration, column chromatography separation is carried out, and the eluent is petroleum ether/ethyl acetate (v: v ═ 10:1), so as to obtain the 2-acetylpyridine. Yield 70%, light yellow oil;1H NMR(CDCl3,400MHz):δ8.61(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.
example 14:
3-acetylpyridine
Synthesis of (2)
Adding 1.0 equivalent of NHPI into a 25mL Schlenk reaction tube, drying in vacuum for 15 minutes, sleeving an oxygen balloon, sequentially adding 1mL of acetonitrile, 2.0 equivalent of tert-butyl nitrite and 0.5mmol of 3-ethylpyridine into the reaction tube under the oxygen atmosphere, adding a polytetrafluoroethylene plug into the reaction tube, putting the reaction tube into an oil bath, and reacting for 36 hours at 90 ℃. After the reaction is finished, the solvent acetonitrile is removed by decompression and concentration, column chromatography separation is carried out, and the eluent is petroleum ether/ethyl acetate (v: v ═ 10:1), so that the 3-acetylpyridine is obtained. Yield 66%, light yellow oil;1H NMR(CDCl3,400MHz):δ9.05(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.
example 15:
4-acetylpyridine
Synthesis of (2)
Adding 1.0 equivalent of NHPI into a 25mL Schlenk reaction tube, drying in vacuum for 15 minutes, sleeving an oxygen balloon, sequentially adding 1mL of acetonitrile, 2.0 equivalent of tert-butyl nitrite and 0.5mmol of 4-ethylpyridine into the reaction tube under the oxygen atmosphere, adding a polytetrafluoroethylene plug into the reaction tube, putting the reaction tube into an oil bath, and reacting for 36 hours at 90 ℃. After the reaction is finished, the solvent acetonitrile is removed by decompression and concentration, column chromatography separation is carried out, and an eluent is petroleum ether/ethyl acetate (v: v ═ 10:1), so that 4-acetylpyridine is obtained. Yield 64% brown oil;1H NMR(CDCl3,400MHz):δ8.76(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.
example 16:
2-acetylthiophene
Synthesis of (2)
Adding 1.0 equivalent of NHPI into a 25mL Schlenk reaction tube, drying in vacuum for 15 minutes, sleeving an oxygen balloon, sequentially adding 1mL of acetonitrile, 2.0 equivalent of tert-butyl nitrite and 0.5mmol of 2-ethylthiophene into the reaction tube in an oxygen atmosphere, adding a polytetrafluoroethylene plug into the reaction tube, putting the reaction tube into an oil bath, and reacting for 36 hours at 90 ℃. After the reaction is finished, the solvent acetonitrile is removed by decompression and concentration, column chromatography separation is carried out, and the eluent is petroleum ether/ethyl acetate (v: v ═ 20:1), so as to obtain the 2-acetylthiophene. Yield 62% as a pale 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.
example 17:
2-benzoylpyridines
Synthesis of (2)
Adding 1.0 equivalent of NHPI into a 25mL Schlenk reaction tube, drying in vacuum for 15 minutes, sleeving an oxygen balloon, sequentially adding 1mL of acetonitrile, 2.0 equivalent of tert-butyl nitrite and 0.5mmol of 2-benzyl pyridine into the reaction tube under the oxygen atmosphere, adding a polytetrafluoroethylene plug into the reaction tube, putting the reaction tube into an oil bath, and reacting for 36 hours at 90 ℃. After the reaction is finished, the solvent acetonitrile is removed by decompression and concentration, column chromatography separation is carried out, and the eluent is petroleum ether/ethyl acetate (v: v ═ 10:1), so as to obtain the 2-benzoylpyridine. 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.
example 18:
benzophenones as fungicides
Synthesis of (2)
Adding 0.5 equivalent of NHPI into a 25mL Schlenk reaction tube, drying in vacuum for 15 minutes, sleeving an oxygen balloon, sequentially adding 1mL of acetonitrile, 1.0 equivalent of tert-butyl nitrite and 0.5mmol of diphenylmethane into the reaction tube under the oxygen atmosphere, adding a polytetrafluoroethylene plug into the reaction tube, putting the reaction tube into an oil bath, and reacting for 24 hours at 80 ℃. After the reaction is finished, the solvent acetonitrile is removed by decompression and concentration, column chromatography separation is carried out, and an eluant is petroleum ether/ethyl acetate (v: v ═ 50:1), so that the 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.
example 19:
flubenoxanone
Synthesis of (2)
Adding NHPI 1.0 equivalent into a 25mL Schlenk reaction tube, vacuum drying for 15 minutes, covering with an oxygen balloon, and sequentially adding into the Schlenk reaction tube under the oxygen atmosphereAdding 1mL of acetonitrile, 2.0 equivalent of tert-butyl nitrite and 0.5mmol of paroxetine, adding a polytetrafluoroethylene plug on a reaction tube, putting the reaction tube into an oil bath, and reacting for 36h at 90 ℃. After the reaction is finished, the solvent acetonitrile is removed by decompression and concentration, column chromatography separation is carried out, and the eluent is petroleum ether/ethyl acetate (v: v ═ 1:1), so that the paroxetine is obtained. Yield 62%, light yellow solid;1H NMR(CDCl3,400MHz)δ7.93-8.01(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):δ201.0,198.5,166.8(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.
example 20:
synthesis of A: 4-ethyl acetophenone
Adding 0.5 equivalent of NHPI into a 25mL Schlenk reaction tube, drying in vacuum for 15 minutes, sleeving an oxygen balloon, sequentially adding 1mL of acetonitrile, 1.0 equivalent of tert-butyl nitrite and 0.5mmol of p-diethylbenzene into the reaction tube under the oxygen atmosphere, adding a polytetrafluoroethylene plug into the reaction tube, putting the reaction tube into an oil bath, and reacting for 24 hours at 80 ℃. After the reaction is finished, the solvent acetonitrile is removed by decompression and concentration, column chromatography separation is carried out, and the eluent is petroleum ether/ethyl acetate (v: v ═ 50:1), so as to obtain the 4-ethyl acetophenone. Product yield 82%, light yellow oil;1H NMR(CDCl3,400MHz):δ7.90(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.
synthesis of 1, 4-diacetylbenzene
Adding 1.0 equivalent of NHPI into a 25mL Schlenk reaction tube, drying in vacuum for 15 minutes, covering with an oxygen balloon, sequentially adding 1mL of acetonitrile, 2.0 equivalent of tert-butyl nitrite and 0.5mmol of p-diethylbenzene into the reaction tube under the oxygen atmosphereAdding a polytetrafluoroethylene plug, putting into an oil bath pot, and reacting for 36 hours at 90 ℃. After the reaction is finished, the solvent acetonitrile is removed by decompression and concentration, column chromatography separation is carried out, and the eluent is petroleum ether/ethyl acetate (v: v ═ 10:1), so as to obtain the 1, 4-diacetylbenzene. Product yield 71%, white solid;1H NMR(CDCl3,400MHz):δ8.00(s,4H),2.62(s,6H)；13C NMR(CDCl3,100MHz):δ197.4,140.1,128.4,26.8.
example 21:
synthesis of A: 3-ethyl acetophenone
Adding 0.5 equivalent of NHPI into a 25mL Schlenk reaction tube, drying in vacuum for 15 minutes, sleeving an oxygen balloon, sequentially adding 1mL of acetonitrile, 1.0 equivalent of tert-butyl nitrite and 0.5mmol of m-diethylbenzene into the reaction tube under the oxygen atmosphere, adding a polytetrafluoroethylene plug into the reaction tube, putting the reaction tube into an oil bath, and reacting for 24 hours at 80 ℃. After the reaction is finished, the solvent acetonitrile is removed by decompression and concentration, column chromatography separation is carried out, and the eluent is petroleum ether/ethyl acetate (v: v ═ 50:1), so that the 3-ethyl acetophenone is obtained. Product yield 80%, light yellow oil;1H NMR(CDCl3,400MHz):δ7.77(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.
synthesis of 1, 3-diacetylbenzene
Adding 1.0 equivalent of NHPI into a 25mL Schlenk reaction tube, drying in vacuum for 15 minutes, sleeving an oxygen balloon, sequentially adding 1mL of acetonitrile, 2.0 equivalent of tert-butyl nitrite and 0.5mmol of m-diethylbenzene into the reaction tube under the oxygen atmosphere, adding a polytetrafluoroethylene plug into the reaction tube, putting the reaction tube into an oil bath, and reacting for 36 hours at 90 ℃. After the reaction is finished, the solvent acetonitrile is removed by decompression and concentration, column chromatography separation is carried out, and the eluent is petroleum ether/ethyl acetate (v: v ═ 10:1), so as to obtain the 1, 3-diacetylbenzene. Product yield 73%, light yellow oil;1H NMR(CDCl3,400MHz):δ8.47(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.
example 22:
synthesis of A: 4-ethyl benzophenone
Adding 0.5 equivalent of NHPI into a 25mL Schlenk reaction tube, drying in vacuum for 15 minutes, sleeving an oxygen balloon, sequentially adding 1mL of acetonitrile, 1.0 equivalent of tert-butyl nitrite and 0.5mmol of 1-benzyl-4-ethyl benzene into the reaction tube in an oxygen atmosphere, adding a polytetrafluoroethylene plug into the reaction tube, putting the reaction tube into an oil bath, and reacting for 24 hours at 80 ℃. After the reaction is finished, the solvent acetonitrile is removed by decompression and concentration, column chromatography separation is carried out, and the eluent is petroleum ether/ethyl acetate (v: v ═ 50:1), so as to obtain the 4-ethyl benzophenone. Product yield 73%, light yellow oil;1H NMR(CDCl3,400MHz):δ7.74-7.81(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.
synthesis of B, 4-acetyl benzophenone
Adding 1.0 equivalent of NHPI into a 25mL Schlenk reaction tube, drying in vacuum for 15 minutes, sleeving an oxygen balloon, sequentially adding 1mL of acetonitrile, 2.0 equivalent of tert-butyl nitrite and 0.5mmol of 1-benzyl-4-ethylbenzene into the reaction tube in the oxygen atmosphere, adding a polytetrafluoroethylene plug into the reaction tube, putting the reaction tube into an oil bath, and reacting for 36 hours at 90 ℃. After the reaction is finished, the solvent acetonitrile is removed by decompression and concentration, column chromatography separation is carried out, and the eluent is petroleum ether/ethyl acetate (v: v ═ 10:1), so as to obtain the 4-acetylbenzophenone. The yield of the product is 81 percent, and the product is light yellow solid;1H NMR(CDCl3,400MHz):δ8.05(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.
example 23:
synthesis of A: 1-tetralone
Adding 0.5 equivalent of NHPI into a 25mL Schlenk reaction tube, drying in vacuum for 15 minutes, sleeving an oxygen balloon, sequentially adding 1mL of acetonitrile, 1.0 equivalent of tert-butyl nitrite and 0.5mmol of 1,2,3, 4-tetrahydronaphthalene in an oxygen atmosphere, adding a polytetrafluoroethylene plug on the reaction tube, putting the reaction tube into an oil bath, and reacting at 80 ℃ for 24 hours. After the reaction is finished, the solvent acetonitrile is removed by decompression and concentration, column chromatography separation is carried out, and the eluent is petroleum ether/ethyl acetate (v: v ═ 30:1), so as to obtain the 1-tetralone. Product yield 86%, light yellow oil;1H NMR(CDCl3,400MHz):δ8.03(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, synthesis of 2, 3-dihydro-1, 4-naphthoquinone
Adding 1.0 equivalent of NHPI into a 25mL Schlenk reaction tube, drying in vacuum for 15 minutes, sleeving an oxygen balloon, sequentially adding 1mL of acetonitrile, 2.0 equivalent of tert-butyl nitrite and 0.5mmol of 1,2,3, 4-tetrahydronaphthalene into the reaction tube under the oxygen atmosphere, adding a polytetrafluoroethylene plug into the reaction tube, putting the reaction tube into an oil bath, and reacting for 36 hours at 90 ℃. After the reaction is finished, the solvent acetonitrile is removed by decompression and concentration, column chromatography separation is carried out, and the eluent is petroleum ether/ethyl acetate (v: v ═ 10:1), so as to obtain the 2, 3-dihydro-1, 4-naphthoquinone. Product yield 72%, grey 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.
example 24:
synthesis of A: 1-indanone
A25 mL Schlenk reaction tube was charged with NHPI 0.5 eq, dried under vacuum for 15 minutes, fitted with an oxygen balloon and charged with oxygenUnder the atmosphere, 1mL of acetonitrile, 1.0 equivalent of tert-butyl nitrite and 0.5mmol of indane are sequentially added, a polytetrafluoroethylene plug is added on a reaction tube, and then the reaction tube is placed in an oil bath pot to react for 24 hours at 80 ℃. After the reaction is finished, the solvent acetonitrile is removed by decompression and concentration, column chromatography separation is carried out, and the eluent is petroleum ether/ethyl acetate (v: v ═ 30:1), so as to obtain the 1-indanone. The yield of the product is 78 percent, and the product is light 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.
synthesis of 1, 3-indandione
Adding 1.0 equivalent of NHPI into a 25mL Schlenk reaction tube, drying in vacuum for 15 minutes, sleeving an oxygen balloon, sequentially adding 1mL of acetonitrile, 2.0 equivalent of tert-butyl nitrite and 0.5mmol of indane into the reaction tube under the oxygen atmosphere, adding a polytetrafluoroethylene plug into the reaction tube, putting the reaction tube into an oil bath, and reacting for 36 hours at 90 ℃. After the reaction is finished, the solvent acetonitrile is removed by decompression and concentration, column chromatography separation is carried out, and the eluent is petroleum ether/ethyl acetate (v: v ═ 10:1), so as to obtain the 1, 3-indandione. 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.
example 25:
synthesis of omega-benzyl acetophenone
Adding 0.5 equivalent of NHPI into a 25mL Schlenk reaction tube, drying in vacuum for 15 minutes, sleeving an oxygen balloon, sequentially adding 1mL of acetonitrile, 1.0 equivalent of tert-butyl nitrite and 0.5mmol of 1, 3-diphenyl propane under the oxygen atmosphere, adding a polytetrafluoroethylene plug on the reaction tube, putting the reaction tube into an oil bath, and reacting for 24 hours at 80 ℃. After the reaction is finished, the solvent acetonitrile is removed by decompression and concentration, column chromatography separation is carried out, and the eluent is petroleum ether/ethyl acetate (v: v ═ 30:1), so that omega-benzyl acetophenone is obtained. Product yield 74%, white solid;1H NMR(CDCl3,400MHz):δ7.98(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, synthesis of dibenzoylmethane
Adding 1.0 equivalent of NHPI into a 25mL Schlenk reaction tube, drying in vacuum for 15 minutes, sleeving an oxygen balloon, sequentially adding 1mL of acetonitrile, 2.0 equivalent of tert-butyl nitrite and 0.5mmol of 1, 3-diphenyl propane under the oxygen atmosphere, adding a polytetrafluoroethylene plug on the reaction tube, putting the reaction tube into an oil bath, and reacting for 36 hours at 90 ℃. After the reaction is finished, the solvent acetonitrile is removed by decompression and concentration, and column chromatography separation is carried out, wherein an eluent is petroleum ether/ethyl acetate (v: v ═ 10:1), and dibenzoyl methane is obtained. Product yield 62%, white solid;1H NMR(CDCl3,400MHz):δ16.9(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.
example 26:
synthesis of A, 2-acetyl-2' -ethyl biphenyl
Adding 0.5 equivalent of NHPI into a 25mL Schlenk reaction tube, drying in vacuum for 15 minutes, sleeving an oxygen balloon, sequentially adding 1mL of acetonitrile, 1.0 equivalent of tert-butyl nitrite and 0.5mmol of 2,2 '-diethyl-1, 1' -biphenyl into the reaction tube in an oxygen atmosphere, adding a polytetrafluoroethylene plug into the reaction tube, putting the reaction tube into an oil bath, and reacting for 24 hours at 80 ℃. After the reaction is finished, the solvent acetonitrile is removed by decompression and concentration, column chromatography separation is carried out, and the eluent is petroleum ether/ethyl acetate (v: v ═ 50:1), so as to obtain the 2-acetyl-2' -ethyl biphenyl. Product yield 78%, light yellow oil;1H NMR(CDCl3,400MHz):δ7.51-7.56(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.
synthesis of B, 2' -diacetylbiphenyl
Adding 1.0 equivalent of NHPI into a 25mL Schlenk reaction tube, drying in vacuum for 15 minutes, sleeving an oxygen balloon, sequentially adding 1mL of acetonitrile, 2.0 equivalent of tert-butyl nitrite and 0.5mmol of 2,2 '-diethyl-1, 1' -biphenyl into the reaction tube in the oxygen atmosphere, adding a polytetrafluoroethylene plug into the reaction tube, putting the reaction tube into an oil bath, and reacting for 36 hours at 90 ℃. After the reaction is finished, the solvent acetonitrile is removed by decompression and concentration, column chromatography separation is carried out, and the eluent is petroleum ether/ethyl acetate (v: v ═ 10:1), so as to obtain the 2, 2' -diacetylbiphenyl. Product yield 73%, brown solid;1H NMR(CDCl3,400MHz):δ7.72(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.
example 27:
synthesis of A: 2-acetyl-6-ethylpyridine
Adding 0.5 equivalent of NHPI into a 25mL Schlenk reaction tube, drying in vacuum for 15 minutes, sleeving an oxygen balloon, sequentially adding 1mL of acetonitrile, 1.0 equivalent of tert-butyl nitrite and 0.5mmol of 2, 6-diethyl pyridine into the reaction tube under the oxygen atmosphere, adding a polytetrafluoroethylene plug into the reaction tube, putting the reaction tube into an oil bath, and reacting for 24 hours at 80 ℃. After the reaction is finished, the solvent acetonitrile is removed by decompression and concentration, column chromatography separation is carried out, and the eluent is petroleum ether/ethyl acetate (v: v ═ 10:1), so that 2-acetyl-6-ethyl pyridine is obtained. Product yield 63%, light yellow oil;1H NMR(CDCl3,400MHz):δ7.97(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.
synthesis of 2, 6-diacetylpyridine
Adding 1.0 equivalent of NHPI into a 25mL Schlenk reaction tube, drying in vacuum for 15 minutes, sleeving an oxygen balloon, sequentially adding 1mL of acetonitrile, 2.0 equivalent of tert-butyl nitrite and 0.5mmol of 2, 6-diethylpyridine into the reaction tube under the oxygen atmosphere, adding a polytetrafluoroethylene plug into the reaction tube, putting the reaction tube into an oil bath, and reacting for 36 hours at 90 ℃. After the reaction is finished, the solvent acetonitrile is removed by decompression and concentration, column chromatography separation is carried out, and the eluent is petroleum ether/ethyl acetate (v: v ═ 5:1), so as to obtain the 2, 6-diacetylpyridine. Product yield 54%, yellow solid;1H NMR(CDCl3,400MHz):δ7.98(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 invention uses nitrite to catalyze and oxidize benzyl containing CH2The aromatic hydrocarbon compound is directly catalyzed and oxidized into ketone by adopting an aryl side chain C-H bond. Through a series of experiments performed in the above examples on the different substrates listed for the direct oxidation of the C-H bond at the benzylic position to a ketone, it can be concluded that: for electron-rich benzylic positions containing CH2The preferable conditions of the aromatic hydrocarbon compound are 0.5 equivalent of N-hydroxyphthalimide and 1.0 equivalent of tert-butyl nitrite, and the aromatic hydrocarbon compound reacts for 24 hours at the temperature of 80 ℃; for electron-deficient benzylic position containing CH2The preferable conditions of the aromatic hydrocarbon compound are 1.0 equivalent of N-hydroxyphthalimide, 2.0 equivalents of tert-butyl nitrite and 36h of reaction at 90 ℃. A series of examples of experiments with different substrates listed for the selective oxidation to monoketones and diketones can be summarized as follows: the condition A is that N-hydroxyphthalimide is 0.5 equivalent, tert-butyl nitrite is 1.0 equivalent, and the reaction lasts 24 hours at 80 ℃; the condition B is that N-hydroxyphthalimide is 1.0 equivalent, nitrosyl tert-butyl ester is 2.0 equivalents, and the reaction is carried out for 36h at 90 ℃. The method uses a non-metal catalyst and oxygen catalytic system to oxidize C-H bonds of aryl side chains activated by free radicals, is simple to operate, uses petroleum ether/ethyl acetate as an eluent according to a volume ratio of 50-1: 1 after reaction, and obtains a target product through column chromatography separation. The above examples illustrate the generally good adaptability of the substrates of the invention, heterocyclesSubstrates can also effect the conversion. The invention adopts a non-metal catalytic system, avoids the use of transition metal, thereby providing a new method for avoiding metal residue in the synthetic drug and simultaneously providing a new method for synthesizing the paroxetine. Different from the prior oxidation system which can not selectively control oxidation or has poor selectivity, the invention can selectively control the oxidation of the bis-ethyl aromatic hydrocarbon into the mono-ketone and the bis-ketone.
Claims (1)
1. A method for directly oxidizing a benzylic C-H bond into ketone is characterized in that: in an oxygen atmosphere, mixing a free radical initiator and nitrite according to a molar ratio of 0.5: 1-2 to serve as a synergistic catalyst, wherein the benzyl position contains CH2Using the aromatic hydrocarbon compound as a substrate, and allowing the radical initiator to contain CH at the benzyl position2The aromatic hydrocarbon compound has a molar ratio of 0.5-1: 1, and the nitrous acid ester and benzyl position contain CH2The aromatic hydrocarbon compound has a molar ratio of 1-2: 1, reacts in a solvent at 80-90 ℃ for 24-36h, is mixed with petroleum ether/ethyl acetate according to a volume ratio of 50-1: 1 to serve as an eluent, and is subjected to column chromatography separation to obtain a target product;
the free radical initiator is N-hydroxyphthalimide, 2,6, 6-tetramethylpiperidine oxide, N-hydroxysuccinimide or N-bromosuccinimide;
the nitrite is tert-butyl nitrite, benzyl nitrite, isoamyl nitrite or ethyl nitrite;
the benzyl position contains CH2The aromatic hydrocarbon compound is 4-ethyl methyl ether, 4-ethyl phenol acetate, p-ethyl fluorobenzene, p-ethyl chlorobenzene, p-ethyl bromobenzene, p-nitroethylbenzene, p-trifluoromethyl ethylbenzene, p-cyanoethylbenzene, 1-ethyl naphthalene, propylbenzene, 1-phenyl octane, tridecylbenzene, 2-benzyl pyridine, diphenylmethane, 2-ethyl pyridine, 3-ethyl pyridine, 4-benzyl pyridine, 2-ethyl thiophene, p-diethyl benzene, m-diethyl benzene, 1-benzyl-4-ethyl benzene, 1,2,3, 4-tetrahydronaphthalene, indane, 1, 3-diphenylpropane, 2, 4-tetrahydronaphthalene’-diethyl-1, 1' -biphenyl or 2, 6-diethylpyridine;
the solvent is tetrahydrofuran, dimethyl sulfoxide, N-dimethylformamide, acetonitrile, ethyl acetate, dichloromethane or 1, 4-dioxane.
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| 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 |
| 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 |
| 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 |
| CN115611693B (en) * | 2022-05-12 | 2023-11-28 | 常州大学 | Method for catalytic synthesis of isochroman-1-one or aromatic ketone compound |
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